bluuebunny/crossref_metadata_2025 huggingface dataset:
Prevalence of Modifiable Breast Cancer Risk Factors and Potential Opportunities for Primary Prevention Among Women Engaged in Screening Mammography: National Health Interview Survey Results
Authors: Chowdhry Divya N , Miles Randy C , Escamilla Guevara Antonio , Flores Efren J , Narayan Anand K
Published: July 2023

Objective

To determine the prevalence of modifiable breast cancer risk factors among women engaged in screening mammography using nationally representative cross-sectional survey data and to inform potential opportunities for breast facilities to contribute to primary prevention.

Methods

2018 National Health Interview Survey respondents who were women ages 40–74 years without history of breast cancer were included and then categorized based on whether they reported screening mammography within the prior two years. Proportions of these women reporting evidence-based modifiable breast cancer risk factors, including elevated body mass index (BMI), lack of physical activity, or moderate or heavy alcohol consumption were calculated and stratified by demographics. Multivariable logistic regression was used to estimate the association between these risk factors and sociodemographic characteristics.

Results

Among 4989 women meeting inclusion criteria and reporting screening mammography, 79% reported at least one modifiable risk factor. Elevated BMI was the most reported risk factor (67%), followed by lack of physical activity (24%) and alcohol consumption (16%). The majority of each race/ethnicity category reported at least one modifiable risk factor, with the highest proportion reported by Black respondents (90%). Asian, college educated, and higher-income participants were less likely to have at least one modifiable risk factor.

Conclusion

Modifiable breast cancer risk factors are prevalent among women engaged in screening mammography. This provides potential opportunities for breast imaging facilities to contribute to the primary prevention of breast cancer by providing resources for lifestyle modification at the time of screening mammography.
Metaheuristic algorithms for a sustainable saffron supply chain network considering government policies and product quality under uncertainty
Authors: Sogandi Fatemeh , Shiri Mahdyeh
Published: July 2023

Iranian saffron products hold a unique place in the global market as the most highly valued agricultural and medicinal commodities. The various uses of saffron make it clear that there is a need for special attention to the supply chain network. Unfortunately, the absence of an integrated supply chain network within the saffron industry has resulted in significant challenges related to supply management and demand fulfillment. Addressing real-world uncertainties is paramount when developing models for optimization problems. Therefore, this research proposes a multi-objective optimization model for designing a saffron supply chain network under uncertainty. The model objectives are to decrease the total cost of the supply chain, increase job opportunities and economic development in regions, and improve the quality of products. The proposed mathematical model is solved using the interactive fuzzy method to deal with multiple functions. Furthermore, possibilistic chance constrained programming is employed to effectively manage uncertain variables such as demand, cost, and social parameters within the model. To demonstrate the applicability and validity of the proposed model and solution method, a real case study was conducted in Khorasan Razavi province, Iran. Additionally, because of the complexity of the proposed model in large-scale networks, non-dominated sorting genetic algorithm-II and multi-objective simulated annealing algorithms are proposed. Different parameters are analyzed to determine their impact on the results so that decision-makers can choose values more accurately. The sensitivity analysis and statistical tests performed on the results support the performance of the proposed model. Overall, the results demonstrate that the exact method and metaheuristic algorithms are capable of solving the problem in different dimensions. The computational results derived from this model offer invaluable managerial insights, empowering decision-makers to align their strategies and preferences more effectively.
Species differences in hormonally mediated gene expression underlie the evolutionary loss of sexually dimorphic coloration inSceloporuslizards
Authors: Robinson Christopher D , Hale Matthew D , Wittman Tyler N , Cox Christian L , John-Alder Henry B , Cox Robert M
Published: July 2023

Phenotypic sexual dimorphism often involves the hormonal regulation of sex-biased expression for underlying genes. However, it is generally unknown whether the evolution of hormonally mediated sexual dimorphism occurs through upstream changes in tissue sensitivity to hormone signals, downstream changes in responsiveness of target genes, or both. Here, we use comparative transcriptomics to explore these possibilities in 2 species of Sceloporus lizards exhibiting different patterns of sexual dichromatism. Sexually dimorphic S. undulatus develops blue and black ventral coloration in response to testosterone, while sexually monomorphic S. virgatus does not, despite exhibiting similar sex differences in circulating testosterone levels. We administered testosterone implants to juveniles of each species and used RNAseq to quantify gene expression in ventral skin. Transcriptome-wide responses to testosterone were stronger in S. undulatus than in S. virgatus, suggesting species differences in tissue sensitivity to this hormone signal. Species differences in the expression of genes for androgen metabolism and sex hormone-binding globulin were consistent with this idea, but expression of the androgen receptor gene was higher in S. virgatus, complicating this interpretation. Downstream of androgen signaling, we found clear species differences in hormonal responsiveness of genes related to melanin synthesis, which were upregulated by testosterone in S. undulatus, but not in S. virgatus. Collectively, our results indicate that hormonal regulation of melanin synthesis pathways contributes to the development of sexual dimorphism in S. undulatus, and that changes in the hormonal responsiveness of these genes in S. virgatus contribute to the evolutionary loss of ventral coloration.
Multigrid accelerated projection method on GPU cluster for the simulation of turbulent flows
Authors: Chiu Tzu-Hsuan , Lin Chao-An
Published: July 2023

A graphics processing unit (GPU)-enabled numerical procedure based on the projection method is developed for simulating incompressible turbulent flows. The pressure Poisson equation is efficiently solved using the V-cycle geometric multigrid method. Additionally, the coarse grid aggregation (CGA) technique enhances the multigrid level of multi-GPU simulations, resulting in significant performance improvements. The validity of the proposed method is confirmed through direct numerical simulations of the turbulent lid-driven cavity flows at a Reynolds number of 3200. The computed mean, and turbulence quantities closely match the available measured data, validating the accuracy of the approach. For the cubic cavity under consideration, the optimized minimum grid sizes for multigrid and CGA are determined to be 83 and 323, respectively. An additional speedup of approximately ≈2.3 to ≈2.6 is achieved by employing CGA. In terms of performance, the current implementation demonstrates compatibility with the lattice Boltzmann method while also being three times faster than the explicit weakly compressible scheme. The superior performance of the GPU implementation over CPU is further highlighted, with a remarkable one thousandfold speedup observed between the Nvidia Tesla V100 and a single core of the Intel I7-6900K (8 cores). Specifically, the performance of one Tesla V100 is found to be equivalent to 125 I7-6900K central processing units.
Cystic squamous metaplasia in a giant benign phyllodes tumor of the breast: a case report
Authors: Niyonkuru Evrard , Nisabwe Simon , Sami Zineb , Faizi Issam , Mazti Asmae , Elkarroumi Mohamed , Karkouri Mehdi
Published: July 2023

Phyllodes tumor is a rare tumor of the breast, which encompasses both stromal and epithelial components. In these components, metaplastic changes can be observed occasionally. We report the case of a 51-year-old woman nulligest menopaused who presented a huge mass, largely ulcerated in her right breast. The radiological examination revealed a large tumor with microcalcifications classified as Breast Imaging and Reporting Data System Category 5. The patient undergone right mastectomy and the histological analysis revealed benign phyllodes tumor with cystic squamous metaplasia. Therefore, we aim to present this uncommon event occasionally occurring in phyllodes tumor of the breast.
Paradoxical embolism: a rare cause of acute upper limb ischemia
Authors: Cunha Roberto , Silva Manuel , Henrique Alberto , Maximiano Pedro , Correia Mafalda , Vieira Isabel , Cássio Isabel , Oliveira Nelson , Dias Emanuel
Published: July 2023

Paradoxical embolism is a rare cause of arterial embolism, even more those resulting in acute ischemia of the upper limb. A case of a 45-year-old patient with acute paradoxical upper limb embolization and acute limb ischemia is presented. A review of the most recent evidence on the diagnosis and management of paradoxical embolism were explored. The cardiac defect most associated with paradoxical embolism is a patent foramen oval. The diagnosis can be performed by transthoracic or transesophageal echocardiography. Closure of the foramen oval is a safe and effective procedure; however, there is no clear consensus on when it should be performed, so the strategy should be individualized. A high level of suspicion of paradoxical embolism should exist in the presence of simultaneous venous and arterial embolism. The investigation of the embolic source is fundamental to avoid the recurrence of events.
Polymerase chain reaction for the in vitro detection of the pESI plasmid associated with the globally circulating Salmonella Infantis outbreak strain
Authors: McMillan Elizabeth A , Hiott Lari M , Carrico Joao A , Machado Miguel P , Pouseele Hannes , Jackson Charlene R , Frye Jonathan G
Published: July 2023

A globally circulating strain of Salmonella enterica serotype Infantis containing the pESI plasmid has increased in prevalence in poultry meat samples and cases of human infections. In this study, a polymerase chain reaction (PCR) protocol was designed to detect the pESI plasmid and confirm the Infantis serotype of Salmonella isolates. Primers were tested bioinformatically to predict specificity, sensitivity, and precision. A total of 54 isolates of Salmonella serotypes Infantis, Senftenberg, and Alachua were tested, with and without the pESI plasmid carriage. Isolates of 31 additional serotypes were also screened to confirm specificity to Infantis. Specificity, sensitivity, and precision of each primer were >0.95. All isolates tested produced the expected band sizes. This PCR protocol provides a rapid and clear result for the detection of the pESI plasmid and serotype Infantis and will allow for the in vitro detection for epidemiological studies where whole-genome sequencing is not available.
Women's Group Treatment for Substance Use Disorder
Authors: Epstein Elizabeth E. , McCrady Barbara S.
Published: July 2023

Women’s Group Treatment for Substance Use Disorder: Evidence-Based Cognitive Behavioral Therapy—Client Workbook is a session-by-session guide to treat the unique challenges and needs of women with alcohol and/or drug use problems. This step-by-step program is designed to help women achieve and maintain abstinence from alcohol and drugs, learn skills to prevent relapse, and achieve improvements in quality of life, self-care, coping skills, self-compassion, relationships with others, and wellness. The program also teaches skills to alleviate depression, anxiety, and trauma symptoms. Written to be used in a therapeutic setting and in conjunction with the companion Therapist Guide, the program includes easy instructions and materials to help clients identify their drinking patterns and triggers, take control of their behavior, seek social network support, understand and experience the rewards of sobriety, and find positive alternatives to drinking and drug use. Clients also will learn useful techniques for managing strong negative emotions and negative thoughts. Overcoming alcohol or drug problems is an attainable goal with this effective and comprehensive program.
A complete catalogue of broad-line AGNs and double-peaked emission lines from MaNGA integral-field spectroscopy of 10K galaxies: stellar population of AGNs, supermassive black holes, and dual AGNs
Authors: Fu Youquan , Cappellari Michele , Mao Shude , Lu Shengdong , Zhu Kai , Li Ran
Published: July 2023

We analyse the integral field spectroscopy data for the ≈10 000 galaxies in final data release of the MaNGA survey. We identify 188 galaxies for which the emission lines cannot be described by single Gaussian components. These galaxies can be classified into (1) 38 galaxies with broad $\rm H\alpha$ and [O iii] $\rm \lambda$5007 lines, (2) 101 galaxies with broad $\rm H\alpha$ lines but no broad [O iii] $\rm \lambda$5007 lines, and (3) 49 galaxies with double-peaked narrow emission lines. Most of the broad-line galaxies are classified as active galactic nuclei (AGNs) from their line ratios. The catalogue helps us further understand the AGN-galaxy coevolution through the stellar population of broad-line region host galaxies and the relation between broad lines’ properties and the host galaxies’ dynamical properties. The stellar population properties (including mass, age, and metallicity) of broad-line host galaxies suggest there is no significant difference between narrow-line Seyfert-2 galaxies and Type-1 AGNs with broad $\rm H\alpha$ lines. We use the broad-$\rm H\alpha$ line width and luminosity to estimate masses of black hole in these galaxies, and test the MBH–σe relation in Type-1 AGN host galaxies. Furthermore, we find three dual AGN candidates supported by radio images from the VLA FIRST survey. This sample may be useful for further studies on AGN activities and feedback processes.
astraeus – VIII. A new framework for Lyman-α emitters applied to different reionization scenarios
Authors: Hutter Anne , Trebitsch Maxime , Dayal Pratika , Gottlöber Stefan , Yepes Gustavo , Legrand Laurent
Published: July 2023

We use the astraeus framework to investigate how the visibility and spatial distribution of Lyman-α (Lyα) emitters (LAEs) during reionization is sensitive to a halo mass-dependent fraction of ionizing radiation escaping from the galactic environment (fesc) and the ionization topology. To this end, we consider the two physically plausible bracketing scenarios of fesc increasing and decreasing with rising halo mass. We derive the corresponding observed Lyα luminosities of galaxies for three different analytic Lyα line profiles and associated Lyα escape fraction ($f_\mathrm{esc}^\mathrm{Ly\alpha }$) models: importantly, we introduce two novel analytic Lyα line profile models that describe the surrounding interstellar medium (ISM) as dusty gas clumps. They are based on parameterizing results from radiative transfer simulations, with one of them relating $f_\mathrm{esc}^\mathrm{Ly\alpha }$ to fesc by assuming the ISM of being interspersed with low-density tunnels. Our key findings are: (i) for dusty gas clumps, the Lyα line profile develops from a central to double peak dominated profile as a galaxy’s halo mass increases; (ii) LAEs are galaxies with $M_h\gtrsim 10^{10}\, {\rm \rm M_\odot }$ located in overdense and highly ionized regions; (iii) for this reason, the spatial distribution of LAEs is primarily sensitive to the global ionization fraction and only weakly in second-order to the ionization topology or a halo mass-dependent fesc; (iv) furthermore, as the observed Lyα luminosity functions reflect the Lyα emission from more massive galaxies, there is a degeneracy between the fesc-dependent intrinsic Lyα luminosity and the Lyα attenuation by dust in the ISM if fesc does not exceed $\sim 50~{{\ \rm per \, cent}}$.
Relaxation of the turbulent magnetosheath
Authors: Pecora F , Yang Y , Chasapis A , Servidio S , Cuesta M E , Roy S , Chhiber R , Bandyopadhyay R , Gershman D J , Giles B L , Burch J L , Matthaeus W H
Published: July 2023

In turbulence, non-linear terms drive energy transfer from large-scale eddies into small scales through the so-called energy cascade. Turbulence often relaxes toward states that minimize energy; typically these states are considered globally. However, turbulence can also relax toward local quasi-equilibrium states, creating patches or cells where the magnitude of non-linearity is reduced and the energy cascade is impaired. We show, using data from the Magnetospheric Multiscale (MMS) mission, and for the first time, compelling observational evidence that this ‘cellularization’ of turbulence can occur due to local relaxation in a strongly turbulent natural environment such as the Earth’s magnetosheath.
A new 2D stochastic methodology for simulating variable accretion discs: propagating fluctuations and epicyclic motion
Authors: Turner Samuel G D , Reynolds Christopher S
Published: July 2023

Accretion occurs across a large range of scales and physical regimes. Despite this diversity in the physics, the observed properties show remarkable similarity. The theory of propagating fluctuations, in which broad-band variability within an accretion disc travel inwards and combine, has long been used to explain these phenomena. Recent numerical work has expanded on the extensive analytical literature but has been restricted to using the 1D diffusion equation for modelling the disc behaviour. In this work we present a novel numerical approach for 2D (vertically integrated), stochastically driven α-disc simulations, generalizing existing 1D models. We find that the theory of propagating fluctuations translates well to 2D. However, the presence of epicyclic motion in 2D (which cannot be captured within the diffusion equation) is shown to have an important impact on local disc dynamics. Additionally, there are suggestions that for sufficiently thin discs the log-normality of the light curves changes. As in previous work, we find that the break frequency in the luminosity power spectrum is strongly dependent on the driving time-scale of the stochastic perturbations within the disc, providing a possible observational signature for probing the magnetorotational instability dynamo. We also find that thinner discs are significantly less variable than thicker ones, providing a compelling explanation for the greater variability seen in the hard state versus the soft state of X-ray binaries. Finally, we consider the wide-ranging applications of our numerical model for use in other simulations.
Cosmic web dissection in fuzzy dark matter cosmologies
Authors: Dome Tibor , Fialkov Anastasia , Sartorio Nina , Mocz Philip
Published: July 2023

On large cosmological scales, anisotropic gravitational collapse is manifest in the dark cosmic web. Its statistical properties are little known for alternative dark matter (DM) models such as fuzzy dark matter (FDM). In this work, we assess for the first time the relative importance of cosmic nodes, filaments, walls, and voids in a cosmology with primordial small-scale suppression of power. We post-process N-body simulations of FDM-like cosmologies with varying axion mass m at redshifts z ∼ 1.0−5.6 using the NEXUS+ Multiscale Morphology Filter technique at smoothing scale Δx = 0.04 h−1 Mpc. The formation of wall and void halos is more suppressed than naively expected from the half-mode mass M1/2. Also, we quantify the mass- and volume-filling fractions of cosmic environments and find that 2D cosmic sheets host a larger share of the matter content of the Universe as m is reduced, with an ∼8−12 per cent increase for the m = 7 × 10−22 eV model compared to cold dark matter (CDM). We show that in FDM-like cosmologies, filaments, walls, and voids are cleaner and more pronounced structures than in CDM, revealed by a strong mid-range peak in the conditioned overdensity PDFs P(δ). At high redshift, low-density regions are more suppressed than high-density regions. Furthermore, skewness estimates S3 of the total overdensity PDF in FDM-like cosmologies are consistently higher than in CDM, especially at high redshift z ∼ 5.6 where the m = 10−22 eV model differs from CDM by ∼6σ. Accordingly, we advocate for the usage of P(δ) as a testbed for constraining FDM and other alternative DM models.
The first evidence of tidally induced activity in a brown dwarf-M dwarf pair: a Chandra study of the NLTT 41135/41136 system
Authors: Ilić Nikoleta , Poppenhaeger Katja , Dsouza Desmond , Wolk Scott J , Agüeros Marcel A , Stelzer Beate
Published: July 2023

The magnetic activity of low-mass stars changes as they age. The primary process decreasing the stellar activity level is the angular momentum loss via magnetized stellar wind. However, processes like tidal interactions between stars and their close companions may slow down the braking effect and the subsequent decrease of the activity level. Until now, the tidal impact of substellar objects like brown dwarfs on the evolution of their central stars has not been quantified. Here, we analyse the X-ray properties of NLTT 41135, an M dwarf tightly orbited by a brown dwarf, to determine the impact of tidal interactions between them. We find that NLTT 41135 is more than an order of magnitude brighter in the X-ray regime than its stellar companion, NLTT 41136, also an M dwarf star, with whom it forms a wide binary system. To characterize the typical intrinsic activity scatter between coeval M dwarf stars, we analyse a control sample of 25 M dwarf wide binary systems observed with the XMM–Newton and Chandra telescopes and the eROSITA instrument onboard the Spectrum Röntgen Gamma satellite. The activity difference in the NLTT 41135/41136 system is a 3.44σ outlier compared to the intrinsic activity scatter of the control systems. Therefore, the most convincing explanation for the observed activity discrepancy is tidal interactions between the M dwarf and its brown dwarf. This shows that tidal interactions between a star and a substellar companion can moderately alter the expected angular-momentum evolution of the star, making standard observational proxies for its age, such as X-ray emission, unreliable.
Breaking the τT–f degeneracy of the kinetic Sunyaev–Zel’dovich cosmology in redshift space
Authors: Xiao Liang , Zheng Yi
Published: July 2023

The ‘optical depth–linear growth rate’ (τT − f) degeneracy is a long-standing problem in the kinetic Sunyaev–Zel’dovich (kSZ) cosmology. It can be broken in redshift space, where the velocity field leaves its own distinct imprint on the galaxies’ redshift space positions and provides valuable information of the linear growth rate. We validate this idea with the Fisher matrix and Monte Carlo Markov chain techniques in this work, finding that the level of this degeneracy breaking is further enhanced on non-linear scales due to the non-linear evolution of the density and velocity fields, if we have a good prior knowledge of the non-linear bias of galaxies. This result emphasizes the importance of the redshift space analysis of the kSZ effect and its potential as a powerful cosmological probe, especially on non-linear scales. As a by-product, we develop a non-linear model of the redshift space density-weighted pairwise kSZ power spectrum. The fitted f and τT values from this model are shown to be accurate within 1σ–2σ ranges of the fiducial ones when confronted to the mock galaxies mimicking a DESI + CMB-S4 survey combination, even on small scales of k ∼ 0.5h Mpc−1.
The nature of the X-ray sources in dwarf galaxies in nearby clusters from the KIWICS
Authors: Şen Şeyda , Göğüş Ersin , Peletier Reynier F , Choque-Challapa Nelvy , Amiri Amirnezam
Published: July 2023

We present a deep search for and analysis of X-ray sources in a sample of dwarf galaxies (Mr < −15.5 mag) located within twelve galaxy clusters from the Kapteyn IAC WHT Enhanced Area Velocity Explores Isaac Newton Telescope Cluster Survey of photometric observations in the r and g using the Wide Field Camera at the 2.5-m Isaac Newton telescope. We first investigated the optical data, identified 2720 dwarf galaxies in all fields and determined their characteristics; namely, their colours, effective radii, and stellar masses. We then searched the Chandra data archive for X-ray counterparts of optically detected dwarf galaxies. We found a total of 20 X-ray emitting dwarf galaxies, with X-ray flux ranging from 1.7 × 10−15 to 4.1 × 10−14 erg cm−2 s−1 and X-ray luminosities varying from 2 × 1039 to 5.4 × 1041 erg s−1. Our results indicate that the X-ray luminosity of the sources in our sample is larger than the Eddington luminosity limit for a typical neutron star, even at the lowest observed levels. This leads us to conclude that the sources emitting X-rays in our sample are likely black holes. Additionally, we have employed a scaling relation between black hole and stellar mass to estimate the masses of the black holes in our sample, and have determined a range of black hole masses from 4.6 × 104 to 1.5 × 106 M⊙. Finally, we find a trend between X-ray to optical flux ratio and X-ray flux. We discuss the implications of our findings and highlight the importance of X-ray observations in studying the properties of dwarf galaxies.
Wave modes and instabilities in gravitating magnetized polytropic quantum plasmas including viscosity tensor and FLR corrections
Authors: Sangwan Vinesh Kumar , Prajapati Ram Prasad
Published: July 2023

The present analytical study extends the problems of pressure anisotropy-driven instabilities and gravitational instability in space plasmas to mixed quantum polytropic gas in the interior of dense stars accounting for the effects of viscosity, finite Larmor radius (FLR) and self-gravitational effects. The generalized polytrope pressure laws are considered as adiabatic equations in which the pressure components depend upon the plasma density, magnitude of the magnetic field, and the polytrope indices. The modified properties of waves and instabilities in gravitating quantum plasmas have been analysed using the quantum magnetohydrodynamic (QMHD) fluid description in the magnetohydrodynamic (MHD) and Chew–Goldberger–Low (CGL) limits. In the parallel propagation, the Jeans instability modified by quantum diffraction parameters and firehose mode modified by FLR parameter is obtained separately. The Jeans instability condition depends upon the quantum diffraction term and polytrope index β, and it remains unaffected due to viscosity and ion Larmor frequency. The growth rate of the Jeans instability decreases due to viscosity and quantum diffraction parameters, while the growth rate of the firehose instability increases due to FLR corrections. In the transverse mode, a similar nature is observed in the growth rates; however, the instability region decreases significantly due to polytrope indices and different dispersion properties of MHD and CGL viscous quantum plasmas. The analytical results have been applied in dense degenerate stars to measure the characteristic parameters and understand the MHD wave propagation, pressure anisotropy-driven, and gravitationally driven instabilities.
Co-Evolution vs. Co-existence: The effect of accretion modelling on the evolution of black holes and host galaxies
Authors: Soliman Nadine H , Macciò Andrea V , Blank Marvin
Published: July 2023

We append two additional black hole (BH) accretion models, namely viscous disc and gravitational torque-driven accretion, into the Numerical Investigation of a Hundred Astrophysical Objects (NIHAO) project of galaxy simulations. We show that these accretion models, characterized by a weaker dependence on the BH mass compared to the commonly used Bondi-Hoyle accretion, naturally create a common evolutionary track (co-existence) between the mass of the BH and the stellar mass of the galaxy, even without any direct coupling via feedback (FB). While FB is indeed required to control the final BH and stellar mass of the galaxies, our results suggest that FB might not be the leading driver of the cosmic co-evolution between these two quantities; in these models, co-evolution is simply determined by the shared central gas supply. Conversely, simulations using Bondi-Hoyle accretion show a two-step evolution, with an early growth of stellar mass followed by exponential growth of the central supermassive black hole (SMBH). Our results show that the modelling of BH accretion (sometimes overlooked) is an extremely important part of BH evolution and can improve our understanding of how scaling relations emerge and evolve, and whether SMBH and stellar mass co-exist or co-evolve through cosmic time.
Human serum albumin as a copper source for anticancer thiosemicarbazones
Authors: Schaier Martin , Falcone Enrico , Prstek Tomas , Vileno Bertrand , Hager Sonja , Keppler Bernhard K , Heffeter Petra , Koellensperger Gunda , Faller Peter , Kowol Christian R
Published: July 2023

Thiosemicarbazones (TSCs) are a class of biologically active compounds with promising anticancer activity. Their typical mechanism, especially of the clinically far developed representative Triapine, is chelation of iron (Fe), with the Fe-containing enzyme ribonucleotide reductase as primary intracellular target. However, for the subclass of terminally disubstituted, nanomolar-active derivatives like Dp44mT and Me2NNMe2, recent findings suggest that the chelation, stability, and reduction properties of the copper(II) (Cu) complexes are essential for their modes of action. Consequently, it is important to elucidate whether blood serum Cu(II) is a potential metal source for these TSCs. To gain more insights, the interaction of Triapine, Dp44mT or Me2NNMe2 with purified human serum albumin (HSA) as the main pool of labile Cu(II) was investigated by UV-vis and electron paramagnetic resonance measurements. Subsequently, a size-exclusion chromatography inductively coupled plasma mass spectrometry method for the differentiation of Cu species in serum was developed, especially separating the non-labile Cu enzyme ceruloplasmin from HSA. The results indicate that the TSCs specifically chelate copper from the N-terminal Cu-binding site of HSA. Furthermore, the Cu(II)-TSC complexes were shown to form ternary HSA conjugates, most likely via histidine. Noteworthy, Fe-chelation from transferrin was not overserved, even not for Triapine. In summary, the labile Cu pool of HSA is a potential source for Cu-TSC complex formation and, consequently, distinctly influences the anticancer activity and pharmacological behavior of TSCs.
Evolution of molecular switches for regulation of transgene expression by clinically licensed gluconate
Authors: Teixeira Ana Palma , Xue Shuai , Huang Jinbo , Fussenegger Martin
Published: July 2023

Synthetic biology holds great promise to improve the safety and efficacy of future gene and engineered cell therapies by providing new means of endogenous or exogenous control of the embedded therapeutic programs. Here, we focused on gluconate as a clinically licensed small-molecule inducer and engineered gluconate-sensitive molecular switches to regulate transgene expression in human cell cultures and in mice. Several switch designs were assembled based on the gluconate-responsive transcriptional repressor GntR from Escherichia coli. Initially we assembled OFF- and ON-type switches by rewiring the native gluconate-dependent binding of GntR to target DNA sequences in mammalian cells. Then, we utilized the ability of GntR to dimerize in the presence of gluconate to activate gene expression from a split transcriptional activator. By means of random mutagenesis of GntR combined with phenotypic screening, we identified variants that significantly enhanced the functionality of the genetic devices, enabling the construction of robust two-input logic gates. We also demonstrated the potential utility of the synthetic switch in two in vivo settings, one employing implantation of alginate-encapsulated engineered cells and the other involving modification of host cells by DNA delivery. Then, as proof-of-concept, the gluconate-actuated genetic switch was connected to insulin secretion, and the components encoding gluconate-induced insulin production were introduced into type-1 diabetic mice as naked DNA via hydrodynamic tail vein injection. Normoglycemia was restored, thereby showcasing the suitability of oral gluconate to regulate in situ production of a therapeutic protein.
CDK2 regulates collapsed replication fork repair in CCNE1-amplified ovarian cancer cells via homologous recombination
Authors: Brown Victoria E , Moore Sydney L , Chen Maxine , House Nealia , Ramsden Philip , Wu Hsin-Jung , Ribich Scott , Grassian Alexandra R , Choi Yoon Jong
Published: July 2023

CCNE1 amplification is a common alteration in high-grade serous ovarian cancer and occurs in 15–20% of these tumors. These amplifications are mutually exclusive with homologous recombination deficiency, and, as they have intact homologous recombination, are intrinsically resistant to poly (ADP-ribose) polymerase inhibitors or chemotherapy agents. Understanding the molecular mechanisms that lead to this mutual exclusivity may reveal therapeutic vulnerabilities that could be leveraged in the clinic in this still underserved patient population. Here, we demonstrate that CCNE1-amplified high-grade serous ovarian cancer cells rely on homologous recombination to repair collapsed replication forks. Cyclin-dependent kinase 2, the canonical partner of cyclin E1, uniquely regulates homologous recombination in this genetic context, and as such cyclin-dependent kinase 2 inhibition synergizes with DNA damaging agents in vitro and in vivo. We demonstrate that combining a selective cyclin-dependent kinase 2 inhibitor with a DNA damaging agent could be a powerful tool in the clinic for high-grade serous ovarian cancer.
Phylogenetic signal in gut microbial community rather than in rodent metabolic traits
Authors: Zhang Xue-Ying , Khakisahneh Saeid , Liu Wei , Zhang Xinyi , Zhai Weiwei , Cheng Jilong , Speakman John R , Wang De-Hua
Published: July 2023

Host phylogeny and environment have all been implicated in shaping the gut microbiota and host metabolic traits of mammals. However, few studies have evaluated phylogeny-associated microbial assembly and host metabolic plasticity concurrently, and their relationships on both short-term and evolutionary timescales. We report that the branching order of a gut microbial dendrogram was nearly congruent with phylogenetic relationships of seven rodent species, and this pattern of phylosymbiosis was intact after diverse laboratory manipulations. Laboratory rearing, diet or air temperature (Ta) acclimation induced alterations in gut microbial communities, but could not override host phylogeny in shaping microbial community assembly. A simulative heatwave reduced core microbiota diversity by 26% in these species, and led to an unmatched relationship between the microbiota and host metabolic phenotypes in desert species. Moreover, the similarity of metabolic traits across species at different Tas was not correlated with phylogenetic distance. These data demonstrated that the gut microbial assembly showed strong concordance with host phylogeny and may be shaped by environmental variables, whereas host metabolic traits did not seem to be linked with phylogeny.
Enablers and barriers to mental health initiatives in construction SMEs
Authors: Blake H , Bullock H , Chouliara N
Published: July 2023

Background

Mental ill-health is prevalent in the construction industry, and workers in small- to medium-sized enterprises (SMEs) are at high risk. Knowledge about the implementation of mental health initiatives in construction SMEs is limited.

Aims

To explore enablers and barriers to implementing mental health initiatives within UK SME construction firms from the perspective of the business owners, directors and managers with responsibilities for workplace mental health.

Methods

Qualitative study involving semi-structured interviews conducted with company owners/managers with responsibilities for workforce mental health. Participants were sampled from construction SMEs in the UK.

Results

Eleven construction professionals were interviewed (10 men, 1 woman; aged 34–55 years, M = 40.6) representing UK SME construction firms that were micro (<10 employees, n = 8), small (<50 employees, n = 1) and medium (<250 employees, n = 2) sized organizations. Reflexive thematic analysis generated four themes: (i) traditional views and macho culture, identified as barriers to implementation; (ii) mental health awareness, knowledge and education; (iii) valuing good mental health and (iv) a reactive or proactive approach to mental health, which all served as both enablers and barriers depending on perspective and context.

Conclusions

This study sheds light on an under-researched but high-risk category of workers experiencing poor mental health. We provide recommendations for policy and practice with a ‘call to action’ for SME owners, industry and policymakers to embark on workplace mental health implementation projects in SME settings.
Long-term Outcomes of Patients With HIV and Pneumocystis jirovecii Pneumonia in the Antiretroviral Therapy Era
Authors: Epling Brian P , Manion Maura , Sirajuddin Arlene , Laidlaw Elizabeth , Galindo Frances , Anderson Megan , Roby Gregg , Rocco Joseph M , Lisco Andrea , Sheikh Virginia , Kovacs Joseph A , Sereti Irini
Published: July 2023

Background

Pneumocystis jirovecii pneumonia (PCP) is one of the most frequent opportunistic infections in people with HIV (PWH). However, there are limited data on long-term outcomes of PCP in the antiretroviral therapy (ART) era.

Methods

We conducted a secondary analysis of 2 prospective studies on 307 PWH, 81 with prior PCP, with a median follow-up of 96 weeks. Laboratory data were measured at protocol-defined intervals. We reviewed clinically indicated chest computerized tomography imaging in 63 patients with prior PCP at a median of 58 weeks after PCP diagnosis and pulmonary function tests (PFTs) of patients with (n = 10) and without (n = 14) prior PCP at a median of 18 weeks after ART initiation.

Results

After 96 weeks of ART, PWH with prior PCP showed no significant differences in laboratory measurements, including CD4 count, when compared with those without prior PCP. Survival rates following ART initiation were similar. However, PWH with prior PCP had increased evidence of restrictive lung pathology and diffusion impairment in PFTs. Furthermore, on chest imaging, 13% of patients had bronchiectasis and 11% had subpleural cysts. Treatment with corticosteroids was associated with an increased incidence of cytomegalovirus disease (odds ratio, 2.62; P = .014).

Conclusions

PCP remains an important opportunistic infection in the ART era. While it did not negatively affect CD4 reconstitution, it could pose an increased risk for incident cytomegalovirus disease with corticosteroid treatment and may cause residual pulmonary sequelae. These findings suggest that PCP and its treatment may contribute to long-term morbidity in PWH, even in the ART era.
Plasma diagnostics and Alfvén wave heating of solar prominences by multiwavelength observations
Authors: Hashimoto Yuki , Ichimoto Kiyoshi , Huang Yuwei
Published: July 2023

Solar prominences are cool and dense plasma supported by the magnetic field in the solar corona. They are composed of fine-scale structures called threads. Prominences are heated by the incident radiation from the solar atmosphere, but previous studies have shown that additional heating is necessary to maintain the temperature of prominences of about 104 K. This study aims to investigate quantitatively the mechanical heating of the prominences from observations. We performed spectroscopic observations of prominences in Hα (6563 Å), Hβ (4861 Å), and Ca ii IR (8542 Å) with the Domeless Solar Telescope at Hida observatory. The plasma parameters of the prominences are estimated by fittings of line profiles using the single-slab model and by solving the statistical equilibrium equation. By assuming that the turbulent motion is the manifestation of propagating Alfvén waves, net radiative losses and Alfvén wave energy flux in the prominences are estimated from these parameters. As a result, it was found that the energy flux by Alfvén waves is sufficient to compensate for the net radiative losses in most regions of the central part of the prominences. On the other hand, Alfvén wave energy flux tends to be insufficient at the outer part of prominences. In such regions, another heating mechanism such as enthalpy flux of mixing with coronal plasma needs to be considered.
Health as Complete Well-Being: The WHO Definition and Beyond
Authors: Schramme Thomas
Published: July 2023

The paper defends the World Health Organisation (WHO) definition of health against widespread criticism. The common objections are due to a possible misinterpretation of the word complete in the descriptor of health as ‘complete physical, mental and social well-being’. Complete here does not necessarily refer to perfect well-being but can alternatively mean exhaustive well-being, that is, containing all its constitutive features. In line with the alternative reading, I argue that the WHO definition puts forward a holistic account, not a notion of perfect health. I use historical and analytical evidence to defend this interpretation. In the second part of the paper, I further investigate the two different notions of health (holistic health and perfect health). I argue that both ideas are relevant but that the holistic interpretation is more adept for political aims.
Titrating CD47 by mismatch CRISPR-interference reveals incomplete repression can eliminate IgG-opsonized tumors but limits induction of antitumor IgG
Authors: Hayes Brandon H , Zhu Hui , Andrechak Jason C , Dooling Lawrence J , Discher Dennis E
Published: July 2023

Phagocytic elimination of solid tumors by innate immune cells seems attractive for immunotherapy, particularly because of the possibilities for acquired immunity. However, the approach remains challenging, with blockade of the macrophage checkpoint CD47 working in immunodeficient mice and against highly immunogenic tumors but not in the clinic where tumors are poorly immunogenic. Even when mouse tumors of poorly immunogenic B16F10 melanoma are opsonized to drive engulfment with a suitable monoclonal antibody (mAb), anti-CD47 blockade remains insufficient. Using both in vitro immuno-tumoroids and in vivo mouse models, we show with CRISPR interference (CRISPRi) that a relatively uniform minimum repression of CD47 by 80% is needed for phagocytosis to dominate net growth when combined with an otherwise ineffective mAb (anti-Tyrp1). Heterogeneity enriches for CD47-high cells, but mice that eliminate tumors generate prophagocytic IgGs that increase in titer with CD47 repression and with tumor accumulation of macrophages, although deeper repression does not improve survival. Given well-known limitations of antibody permeation into solid tumors, our studies clarify benchmarks for CD47 disruption that should be more clinically feasible and safer but just as effective as complete ablation. Additionally, safe but ineffective opsonization in human melanoma trials suggests that combinations with deep repression of CD47 could prove effective and initiate durable immunity.
Effects for global agriculture of country-specific climate policy regimes with a focus on methane
Authors: Mittenzwei Klaus , Hristov Jordan , Pérez-Domínguez Ignacio , Witzke Peter
Published: July 2023

While countries have agreed in the Paris-agreement on common rules to report greenhouse gas emissions, the design of domestic climate policy regimes remains in the national domain. This may cause different carbon prices for climate gasses across countries, between a country's emission sectors, and within the same sector. Our focus is on methane, which is a major emitter from agriculture, but also linked to livestock farming which is a core activity in agriculture worldwide. We analyse the potential effects of domestic carbon pricing regimes for agriculture in a non-cooperative game theoretic setting using a global agricultural sector model. Our results indicate no ‘race to the bottom’ to apply carbon pricing regimes that result in lowest implicit carbon prices for methane. Enforcing a uniform regime can reduce additional global warming with up to 0.02 °C, but runs the risk of agreeing to lower emission cuts than a nationally determined choice would suggest.
Legal Nurse Consulting
Authors: McCullum Marilyn E.
Published: July 2023

These nurses bridge the gap between the legal and medical realms.
Implementation Facilitation Increases Intimate Partner Screening
Authors: Rosenberg Karen
Published: July 2023

According to this study:
A Helping Hand: A School Nurse Offers a Desperate Young Mother Compassion
Authors: Brooks Andrea Nicole
Published: July 2023

An NP remembers how compassion kept her hope alive.
Primary central nervous system lymphoma (PCNSL) in older patients
Authors: Bertucci Alexandre , Harlay Vincent , Chinot Olivier , Tabouret Emeline
Published: July 2023

Introduction

Primary central nervous system lymphoma (PCNSL) is a rare, chemo and radio-sensitive tumor limited to the central nervous system. The incidence of PCSNL increases notably in the elderly population which represented approximately half of the patients. The limit of ‘elderly’ population remained debated and nonuniform, including 60 years as a cutoff for brain radiotherapy, 65 years for autologous stem-cell transplantation, and 70 years for the last clinical trials. Current therapeutic options include first line treatment based on high-dose methotrexate based polychemotherapy, consolidation chemotherapy, and adapted autologous stem cell transplantation for highly selected patients. At relapse, single agent targeted therapies or salvage chemotherapy followed by intensive consolidation are promising therapeutic options. Nevertheless, improving management of elderly patients is an urgent medical need that currently remains unresolved.

Objective

We will focus on elderly patients with PCNSL and their specificities including clinical presentations, available therapeutic options and adaptations to be made.

Conclusion

To improve survival, it will be necessary to personalized and adapt the treatments, to each patient and his comorbidities, to increase their effectiveness and limit their toxicity in this frail population. Finally, inclusion of these patients in clinical trials is one of the major challenges to significantly change PCNSL elderly patient prognosis.