bluuebunny/crossref_metadata_2025 huggingface dataset:
The impact of the Large Magellanic Cloud on dark matter direct detection signals
Authors: Smith-Orlik Adam , Ronaghi Nima , Bozorgnia Nassim , Cautun Marius , Fattahi Azadeh , Besla Gurtina , Frenk Carlos S. , Garavito-Camargo Nicolás , Gómez Facundo A. , Grand Robert J.J. , Marinacci Federico , Peter Annika H.G.
Published: October 2023

We study the effect of the Large Magellanic Cloud (LMC) on the dark matter (DM) distribution in the Solar neighborhood, utilizing the Auriga magneto-hydrodynamical simulations of Milky Way (MW) analogues that have an LMC-like system. We extract the local DM velocity distribution at different times during the orbit of the LMC around the MW in the simulations. As found in previous idealized simulations of the MW-LMC system, we find that the DM particles in the Solar neighborhood originating from the LMC analogue dominate the high speed tail of the local DM speed distribution. Furthermore, the native DM particles of the MW in the Solar region are boosted to higher speeds as a result of a response to the LMC's motion.
We simulate the signals expected in near future xenon, germanium, and silicon direct detection experiments, considering DM interactions with target nuclei or electrons. We find that the presence of the LMC causes a considerable shift in the expected direct detection exclusion limits towards smaller cross sections and DM masses, with the effect being more prominent for low mass DM. Hence, our study shows, for the first time, that the LMC's influence on the local DM distribution is significant even in fully cosmological MW analogues.
The impact of cross-covariances between the CMB and reconstructed lensing power
Authors: Trendafilova Cynthia
Published: October 2023

Weak gravitational lensing of the Cosmic Microwave Background (CMB) changes CMB statistics in a nontrivial way, allowing for reconstruction of the lensing potential and the use of these reconstructed maps in determining cosmological parameters that affect the formation of intervening large-scale structures. Although in principle there are correlations between the primary CMB and the reconstructed lensing potential due to the lensing procedure itself, in practice CMB analyses treat these as negligible when combining these band powers in likelihoods. In this paper we quantify explicitly the impact on parameter constraints due to these cross-covariances between the lensed CMB and reconstructed lensing power, and we compare to the effect of including all lensing-induced non-Gaussian covariances, which have previously shown to impact parameter constraints on the order of 10%. We perform our analysis for a range of experimental setups, scanning over instrumental noise levels of 0.5 to 10.0 μK-arcmin in temperature assuming fully polarized detectors, and using a fixed beam size of 1.4 arcmin. When the correlations between the lensed CMB and lensing power are neglected, we find that forecasted constraints shift by at most 3% of the error bar for a 6-parameter ΛCDM model, and for the noise levels considered in this paper. For some of the ΛCDM extensions considered here, however, these correlations have a nontrivial impact, in some cases more than 10% of the error bar, even for current experimental noise levels.
Investigating dark matter-admixed neutron stars with NITR equation of state in light of PSR J0952-0607
Authors: Routaray Pinku , Mohanty Sailesh Ranjan , Das H.C. , Ghosh Sayantan , Kalita P.J. , Parmar Vishal , Kumar Bharat
Published: October 2023

The fastest and heaviest pulsar, PSR J0952-0607, with a mass of M = 2.35±0.17 M
⊙,
has recently been discovered in the disk of the Milky Way Galaxy. In response to this discovery, a
new RMF model, 'NITR' has been developed. The NITR model's naturalness has been confirmed by
assessing its validity for various finite nuclei and nuclear matter properties, including
incompressibility, symmetry energy, and slope parameter values of 225.11, 31.69, and 43.86 MeV,
respectively. These values satisfy the empirical/experimental limits currently available. The
maximum mass and canonical radius of a neutron star (NS) calculated using the NITR model
parameters are 2.355 M
⊙ and 13.13 km, respectively, which fall within the range of PSR
J0952-0607 and the latest NICER limit. This study aims to test the consistency of the NITR model
by applying it to various systems. As a result, its validity is extensively calibrated, and all
the nuclear matter and NS properties of the NITR model are compared with two established models
such as IOPB-I and FSUGarnet. In addition, the NITR model equation of state (EOS) is employed to
obtain the properties of a dark matter admixed NS (DMANS) using two approaches (I) single-fluid
and (II) two-fluid approaches. In both cases, the EOS becomes softer due to DM interactions, which
reduces various macroscopic properties such as maximum mass, radius, tidal deformability, etc. The
various observational data such as NICER and HESS are used to constrain the amount of DM in both
cases. Moreover, we discuss the impact of dark matter (DM) on the nonradial f-mode frequency of
the NS in a single fluid case only and try to constrain the amount of DM using different
theoretical limits available in the literature.
Stochastic gravitational wave background from early dark energy
Authors: Kitajima Naoya , Takahashi Tomo
Published: October 2023

We study the production of stochastic gravitational wave background in early dark energy (EDE) models. It is generated by resonant amplification of scalar field fluctuations, which can easily take place for typical EDE potential based on the string axion or α-attractor model. The resultant spectrum of gravitational wave background is computed by performing 3D lattice simulations. We show that, specifically in some class of a generalized α-attractor EDE model, a significant amount of gravitational waves can be produced via tachyonic instability with a peak around femto-Hz frequency range. Models predicting such gravitational waves can be constrained by cosmic microwave background observations.
Random sequential adsorption of aligned rectangles with two discrete orientations: finite-size scaling effects
Authors: Petrone Luca , Lebovka Nikolai , Cieśla Michał
Published: October 2023

We study saturated packings produced according to the random sequential adsorption (RSA) protocol built of identical rectangles deposited on a flat, continuous plane. An aspect ratio of rectangles is defined as the length-to-width ratio,

f
=
l

/

w

. The rectangles have a fixed unit area (i.e.

l
×
w
=
1

), and therefore, their shape is defined by the value of f (

l
=

f

and

w
=
1

/

f

). The rectangles are allowed to align either vertically or horizontally with equal probability. The particles are deposited on a flat square substrate of side length

L
∈
[
20
,
1000
]

) and periodic boundary conditions are applied along both directions. The finite-size scaling are characterized by a scaled anisotropy defined as

α
=
l

/

L
=

f

/

L

. We showed that the properties of such packings strongly depend on the value of aspect ratio f and the most significant scaling effects are observed for relatively long rectangles when

l
⩾
L

/

2

(i.e.

α
⩾
0.5

). It is especially visible for the mean packing fraction as a function of the scaled anisotropy α. The kinetics of packing growth for low to moderate rectangle anisotropy is to be governed by

ln
t
/
t

law, where t is proportional to the number of RSA iterations, which is the same as in the case of RSA of parallel squares. We also analyzed global orientational ordering in such packings and properties of domains consisting of a set of neighboring rectangles of the same orientation, and the probability that such domain forms a percolation.
On the connection between temperature and volatility in ideal agent systems
Authors: Börner Christoph J , Hoffmann Ingo , Stiebel John H
Published: October 2023

Models for spin systems known from statistical physics are applied by analogy in econometrics in the form of agent-based models. Researchers suggest that the state variable temperature T corresponds to volatility σ in capital market theory problems. To the best of our knowledge, this has not yet been theoretically derived, for example, for an ideal agent system. In the present paper, we derive the exact algebraic relation between T and σ for an ideal agent system and discuss implications and limitations.
Simulation study of the light collection efficiency and the dependency on position resolution in plastic scintillator-based muography detectors
Authors: Wang Z. , Pan Z.W. , Chen Z. , He Z.Y. , Lin Z.B. , Yang T.Y. , Yuan Y. , Wang Y. , Zhang Z.Y. , Xie F. , Liu J.D. , Liu S.B. , Ye B.J.
Published: October 2023

Cosmic-ray muon imaging (muography) has been applied in
various fields in recent years, in which plastic scintillators are
one of the frequently selected detectors internationally. Therefore,
a triangular scintillator strip based muography detection system has
been proposed in the development of the μ Scattering and
Transmission imaging faCility (μSTC). Before the mass production
of detector units, this work studied the impacts of multiple factors
on the light collection efficiency (LCE) and the position resolution
(σ) of plastic scintillators. These factors include
configurations of wavelength shifting (WLS) fibers, fiber grooves on
scintillators, coupling optical glues and silicon photomultiplier
(SiPM) readout mode. According to the simulated results, an
empirical formula was proposed to quantitatively describe the
relation between the LCE and σ, which has seldom been studied
before. In this formula, σ reduces as a power-law function of
the LCE. The SiPM readout mode (single-end or double-end output) and
fiber groove treatments show no significant influence on the
 σ-LCE relation. LCE variations due to different factors lead
to a difference in σ of less than 0.2 mm in the whole range
of LCE. Accordingly, these factors are nearly equivalent in the
improvement of detector position resolution. In comparison, the muon
hit position reconstruction method nearly halves the σ after
using angular and gap corrections. Thus, a better reconstruction
method shows greater importance than the efforts made to increase
LCEs. The simulation study in this work will provide good references
for the construction of plastic scintillators of the μSTC
platform in the near future.
Operating the GridPix detector with helium-isobutane gas mixtures for a high-precision, low-mass Time Projection Chamber
Authors: Cavoto G. , Dutsov C. , Gruber M. , Hildebrandt M. , Hume T.D. , Kaminski J. , Neuhaus F. , Papa A. , Renga F. , Schmidt-Wellenburg P. , Schott M. , Vitali B. , Voena C.
Published: October 2023

High precision experiments with muons and pions often
require tracking charged particles with O(100 μm)
single-hit resolution, possibly with particle identification
capabilities, down to very low momenta (p ≲  
100 MeV/c). In such conditions, the particle trajectories are
strongly affected by the interaction with the detector material, and
the reconstruction of the kinematic observables consequently
deteriorates. A good compromise between resolution and material
budget can be obtained with a Time Projection Chamber (TPC), if very
light gases and a high-granularity readout are used. In this paper,
we present a characterization of the GridPix detector in
helium-isobutane gas mixtures, within a TPC with 9 cm maximum
drift. Measurements of the main electron drift properties for these
gas mixtures are also presented.
Landscape ecological risk assessment of chongming dongtan wetland in shanghai from 1990 to 2020
Authors: Cao Yong , Dong Bin , Xu Haifeng , Xu Zhili , Wei Zhezhu , Lu Zhipeng , Liu Xiao
Published: October 2023

Landscape ecological risk assessment can assess the stability, vulnerability, and anti-interference ability of the ecosystem based on the characteristics, structure, and function of the landscape in order to determine the degree and distribution of landscape ecological risk. In recent years, due to human activities and global climate change, the area and ecological quality of the Chongming Dongtan wetland have been decreasing. As an important wintering habitat and transit point on the ‘East Asia-Australia migration line’, the population and habitat security of wintering migratory birds are also threatened. Therefore, the landscape index method was used to assess the ecological risk of the Chongming Dongtan wetland. Based on transfer analysis and spatial autocorrelation analysis, the spatial and temporal changes of landscape ecological risk were revealed. The findings are as follows: (1) Natural landscapes such as mudflats, grasslands, and waters have been declining, while artificial landscapes such as cultivated land, construction land, and woodland have been gradually expanding, indicating a shift from natural to artificial landscapes. (2) Overall, the landscape ecological risk is showing an increasing trend. Wetlands have moved from being dominated by the lowest and medium ecological risks to being evenly distributed by all ecological risk classes. Notably, there has been a rapid increase in landscape ecological risk in 2000. The highest-risk areas have expanded by 9346.95 hm2, gradually encroaching from the buffer zone into the reclamation area and the nature reserve. Conversely, the lowest ecological risk areas have decreased by 7091.82 hm2, primarily concentrated in nature reserves. (3) The aggregation of landscape ecological risks continues to decrease, indicating a reduced likelihood of dramatic changes in ecological risks.
What would a US green hydrogen energy economy look like?
Authors: Tonon Thomas
Published: October 2023

Detailed description is given for a hypothetical US hydrogen economy with solar and wind energy supplying virtually all current energy needs and with electrolytic hydrogen the energy carrier and storage medium. Fossil fuels provide nonfuel products (plastics, chemicals, cement and asphalt). Only current technologies are considered and hydrogen storage accommodates generation intermittency and variability, using pit storage of high-pressure vessels in open air, yielding daily storage round-trip energy installation costs of 722 and 538 $/kWh for electric and thermal, respectively; and for power, 2351 and 2240 $/kW for electric and thermal, respectively. For long-duration storage, the costs are 94.1 and 23.8 $/kWh and 937 and 845 $/kW, respectively. Increased energy generation 20% over baseline accommodates low-season generation, obviates much required storage and ensures that reserves are topped off; 96% of US 2022 total energy consumption is provided for. In the default scenario (demand energy portions: half photovoltaic, quarter onshore wind and quarter offshore wind), the surface area for the farms (including offshore surface) requires ~4.6% of the US 48-state land area. About 350 pit storage sites provide both daily and long-duration storage, with the latter accounting for complete loss of generation for 4 days over a quarter of the nation. Hydrogen pipelines and a renewed electric grid transmit and distribute energy. The installation cost of the public infrastructure is ~$27.8 trillion for the default scenario. Alternative scenarios show significant infrastructure and cost savings when batteries are used for transportation and/or utility storage, provided current insufficiencies can be overcome. Broadly, cost levels in money, surface and infrastructure are within existing levels already achieved in historical events and modern living.
Inter-brain synchrony during mother–infant interactive parenting in 3–4-month-old infants with and without an elevated likelihood of autism spectrum disorder
Authors: Minagawa Yasuyo , Hata Masahiro , Yamamoto Eriko , Tsuzuki Daisuke , Morimoto Satoshi
Published: October 2023

Maternal bonding for mammalian infants is critical for their survival. Additionally, it is important for human infants’ development into social creatures. However, despite the ample neurobiological evidence of attachment for the mother’s brain, the interplay of this system in infants is poorly understood. We aimed to identify the neural substrates of synchrony in mothers and infants under three interactive conditions and compare the differences between groups with (n = 16) and without (n = 71) an elevated likelihood of autism spectrum disorder by examining the inter-brain synchrony between mothers and their 3–4-month-old infants. Mother–infant hyperscanning with functional near-infrared spectroscopy was performed during breastfeeding and while each of the mother and experimenter was holding the infants. The results showed almost no group differences, with both groups demonstrating the strongest inter-brain coupling for breastfeeding. The cerebral foci underlying these couplings differed between mothers and infants: the ventral prefrontal cortex, focusing on the right orbitofrontal cortex, in the mother and the left temporoparietal junction in the infant were chiefly involved in connecting the two brains. Furthermore, these synchronizations revealed many significant correlations with behavioral measures, including subsequent language development. The maternal reward-motivational system and the infant’s elementary mentalization system seem to underlie mother–infant coupling during breastfeeding.
Prediction of individual brain age using movie and resting-state fMRI
Authors: Bi Suyu , Guan Yun , Tian Lixia
Published: October 2023

Brain age is a promising biomarker for predicting chronological age based on brain imaging data. Although movie and resting-state functional MRI techniques have attracted much research interest for the investigation of brain function, whether the 2 different imaging paradigms show similarities and differences in terms of their capabilities and properties for predicting brain age remains largely unexplored. Here, we used movie and resting-state functional MRI data from 528 participants aged from 18 to 87 years old in the Cambridge Centre for Ageing and Neuroscience data set for functional network construction and further used elastic net for age prediction model building. The connectivity properties of movie and resting-state functional MRI were evaluated based on the connections supporting predictive model building. We found comparable predictive abilities of movie and resting-state connectivity in estimating brain age of individuals, as evidenced by correlation coefficients of 0.868 and 0.862 between actual and predicted age, respectively. Despite some similarities, notable differences in connectivity properties were observed between the predictive models using movie and resting-state functional MRI data, primarily involving components of the default mode network. Our results highlight that both movie and resting-state functional MRI are effective and promising techniques for predicting brain age. Leveraging its data acquisition advantages, such as improved child and patient compliance resulting in reduced motion artifacts, movie functional MRI is emerging as an important paradigm for studying brain function in pediatric and clinical populations.
Enhanced surveillance of hospitalized COVID-19 patients in Europe: an evaluation of the I-MOVE-COVID-19 surveillance network
Authors: Young Johanna J , Mutch Heather , Rose Angela M C , Evans Josie M M ,   the European COVID-19 Hospital Evaluation Writing Group, McMenamin Jim , Murray Josie , Machado Ausenda , Rodrigues Ana Paula , Kislaya Irina , Gefenaite Giedre , Kuliese Monika , Jancoriene Ligita , Kubiliute Ieva , Jonikaitė Indrė , Vaikutytė Roberta , Zablockiene Birute , Mickiene Aukse , Larrauri Amparo , Mazagatos Clara , Demuyser Thomas , Van Nedervelde Els , Seyler Lucie , Lazar Mihaela , Galtier Florence , Vanhems Philippe
Published: October 2023

Background

A pre-existing, well-established European influenza surveillance network known as I-MOVE enabled the rapid implementation of a European multi-country COVID-19 hospital surveillance network for surveillance of hospitalized COVID-19 cases in early 2020. This network included 257 hospitals in 11 surveillance sites across nine countries. We aimed to identify whether the surveillance objectives were relevant to public health actions, whether the surveillance system met its objectives, where and how shortcomings could be improved, and whether the system was sustainable.

Methods

We identified six key attributes (meeting objectives, usefulness, timeliness, data quality, simplicity and sustainability) to assess, using Centers for Disease Control and Prevention’s evaluation framework. We analyzed pooled datasets, held interviews and group discussions with 10 participating and coordinating sites and gathered feedback through web surveys.

Results

There was overall agreement that the surveillance objectives had been met and being involved in a network of European partners had additional important benefits for stakeholders. While the publication of the outputs was not always sufficiently timely, data submission processes were considered straightforward and the key surveillance variables (age, sex, hospital admission and mortality data) were complete. The main challenges were identified as the collection of the large number of variables, limited available human resources and information governance and data protection laws.

Conclusions

I-MOVE-COVID-19 delivered relevant and accurate data supporting the development and implementation of COVID-19 surveillance. Recommendations presented here identify learning opportunities to support preparedness and surveillance response for future pandemics. The applied evaluation framework in this study can be adapted for other European surveillance system evaluations.
The sociodemographic patterning of sick leave and determinants of longer sick leave after mild and severe COVID-19: a nationwide register-based study in Sweden
Authors: Spetz Malin , Natt och Dag Yvonne , Li Huiqi , Nwaru Chioma , Santosa Ailiana , Nyberg Fredrik , Rosvall Maria
Published: October 2023

Background

Studies on sociodemographic differences in sick leave after coronavirus disease 2019 (COVID-19) are limited and research on COVID-19 long-term health consequences has mainly addressed hospitalized individuals. The aim of this study was to investigate the social patterning of sick leave and determinants of longer sick leave after COVID-19 among mild and severe cases.

Methods

The study population, from the Swedish multi-register observational study SCIFI-PEARL, included individuals aged 18–64 years in the Swedish population, gainfully employed, with a first positive polymerase chain reaction (PCR) test for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) from 1 January 2020 until 31 August 2021 (n = 661 780). Using logistic regression models, analyses were adjusted for sociodemographic factors, vaccination, prior sick leave, comorbidities and stratified by hospitalization.

Results

In total, 37 420 (5.7%) individuals were on sick leave due to COVID-19 in connection with their first positive COVID-19 test. Individuals on sick leave were more often women, older, had lower income and/or were born outside Sweden. These differences were similar across COVID-19 pandemic phases. The highest proportion of sick leave was seen in the oldest age group (10.3%) with an odds ratio of 4.32 (95% confidence interval 4.18–4.47) compared with the youngest individuals. Among individuals hospitalized due to COVID-19, the sociodemographic pattern was less pronounced, and in some models, even reversed. The intersectional analysis revealed considerable variability in sick leave between sociodemographic groups (range: 1.5–17.0%).

Conclusion

In the entire Swedish population of gainfully employed individuals, our findings demonstrated evident sociodemographic differences in sick leave due to COVID-19. In the hospitalized group, the social patterning was different and less pronounced.
Unfit to Bounce Back: On the Martial Politics of Resilience in WWI-Weimar Germany and Austerity Britain
Authors: Jung Laura
Published: October 2023

Resilience discourse, with its implicit assumption of a return to health and productivity following a crisis, is often mobilized to target disabled people. Yet while resilience scholarship has rapidly expanded and become prevalent in various fields over recent decades, it has largely failed to analyze the multiple connections between resilience, disability, and eugenics. This article argues that resilience discourse is a form of martial politics, wielded against disabled people to protect the health and prosperity of the political community. A martial politics of resilience works through three registers, responsibilizing disabled subjects by withdrawing state support, dehumanizing them as unproductive and a burden, and exposing these subjects to abandonment/death through medical and policy interventions. I use the lens of martial politics to think through relationships between resilience, disability, and security in Germany and Britain in the early twentieth and twenty-first centuries, respectively, focusing on psychiatric treatment of trauma in the former and the implementation of austerity policies in the latter. The article thus expands our understanding of relationships between resilience, subjectivity, and security by highlighting the ableist and lethal contours of resilient subjects, polities, and economies.
Phenotypic alteration by dengue virus serotype 2 delays neutrophil apoptosis and stimulates the release of prosurvival secretome with immunomodulatory functions
Authors: Rawat Surender , Kumar Shubham , Duggal Shweta , Banerjee Arup
Published: October 2023

Neutrophils are the most abundant granuloytes, are phenotypically heterogeneous, and exert detrimental or protective roles during antiviral response. Dengue virus has been reported to activate neutrophils. However, the effect of the dengue virus on the neutrophil phenotypes, survival, and release of inflammatory secretome is yet to be understood. Herein, we investigated the effect of dengue virus serotype 2 (DV-2) on effector functions of naïve neutrophils and studied the impact of its secretome on different immune cells. We found that DV-2 activates purified human neutrophils and causes a significant shift toward the CD16bright/CD62Ldim subtype in a multiplicity of infection and time-dependent manner. These phenotypically altered neutrophils show delayed apoptosis through nuclear factor κB and PI3K pathways and have decreased phagocytic capacity. Treatment of neutrophils with myeloperoxidase and PAD4 inhibitor before DV-2 incubation significantly reduced DV-2–induced double-stranded DNA release, suggesting that myeloperoxidase and PAD4 were involved at early stages for the neutrophil activation and double-stranded DNA release. We also report that DV-2–stimulated neutrophil secretome had a significant effect on viral infection, platelet activation, and naïve neutrophil survival via binding of tumor necrosis factor α to tumor necrosis factor receptor 1/2 receptors. Furthermore, incubation of endothelial cells with the DV-2–stimulated neutrophil secretome potentially inhibits proliferation and wound healing capacity and induces endothelial cell death, which can contribute to endothelial barrier dysfunction. In conclusion, the neutrophil–DV-2 interaction modulates the phenotype of neutrophils and the release of prosurvival and antiviral secretome that may act as a double-edged sword during dengue pathogenesis.
Cardioprotection of Eucommiae Folium: the extract and pharmaceutically active compounds attenuate hyperglycemia, mitochondrial dysfunction, calcium dyshomeostasis, insulin resistance, and oxidative stress in diabetic cardiomyopathy db/db mice
Authors: Zhang Shuai-nan , Liu Qi , Li Xu-zhao , Yang Wu-de , Zhou Ying
Published: October 2023

Objectives

A biolabel research based on multi-omics, informatics, molecular docking, and experimental verification was used to investigate the cardioprotective effect and pharmaceutically active compounds of Eucommiae Folium (EF).

Key findings

Based on the biolabel research pattern, metabonomics, proteomics, and bioinformatics indicated that EF has a therapeutic potential for a variety of heart diseases, especially cardiomyopathy, and the most critical mechanism involved is the diabetic cardiomyopathy pathway. Bioinformatics, cheminformatics, and molecular docking showed that 24 EF compounds may play a therapeutic role in diabetic cardiomyopathy via this pathway. Among which, four compounds (kaempferol, esculetin, (+)-catechin, and astragalin) showed appropriate pharmacokinetic parameters and formed stable binding with biolabels in the pathway. In diabetic cardiomyopathy db/db mice, histopathological analysis, mitochondrial swelling and membrane potential assay, ELISA, and biochemical analysis demonstrated that EF and four active compounds had obvious hypoglycemic effects and attenuated myocardial damage and related pathological processes, such as mitochondrial dysfunction, calcium dyshomeostasis, insulin resistance, and oxidative stress.

Conclusions

This study provides new evidence and insights into the effect, mechanism, and material basis of EF in treating diabetic cardiomyopathy.
SLKB: synthetic lethality knowledge base
Authors: Gökbağ Birkan , Tang Shan , Fan Kunjie , Cheng Lijun , Yu Lianbo , Zhao Yue , Li Lang
Published: October 2023

Emerging CRISPR–Cas9 technology permits synthetic lethality (SL) screening of large number of gene pairs from gene combination double knockout (CDKO) experiments. However, the poor integration and annotation of CDKO SL data in current SL databases limit their utility, and diverse methods of calculating SL scores prohibit their comparison. To overcome these shortcomings, we have developed SL knowledge base (SLKB) that incorporates data of 11 CDKO experiments in 22 cell lines, 16,059 SL gene pairs and 264,424 non-SL gene pairs. Additionally, within SLKB, we have implemented five SL calculation methods: median score with and without background control normalization (Median-B/NB), sgRNA-derived score (sgRNA-B/NB), Horlbeck score, GEMINI score and MAGeCK score. The five scores have demonstrated a mere 1.21% overlap among their top 10% SL gene pairs, reflecting high diversity. Users can browse SL networks and assess the impact of scoring methods using Venn diagrams. The SL network generated from all data in SLKB shows a greater likelihood of SL gene pair connectivity with other SL gene pairs than non-SL pairs. Comparison of SL networks between two cell lines demonstrated greater likelihood to share SL hub genes than SL gene pairs. SLKB website and pipeline can be freely accessed at https://slkb.osubmi.org and https://slkb.docs.osubmi.org/, respectively.
CDS-DB, an omnibus for patient-derived gene expression signatures induced by cancer treatment
Authors: Liu Zhongyang , Chen Ruzhen , Yang Lele , Jiang Jianzhou , Ma Shurui , Chen Lanhui , He Mengqi , Mao Yichao , Guo Congcong , Kong Xiangya , Zhang Xinlei , Qi Yaning , Liu Fengsong , He Fuchu , Li Dong
Published: October 2023

Patient-derived gene expression signatures induced by cancer treatment, obtained from paired pre- and post-treatment clinical transcriptomes, can help reveal drug mechanisms of action (MOAs) in cancer patients and understand the molecular response mechanism of tumor sensitivity or resistance. Their integration and reuse may bring new insights. Paired pre- and post-treatment clinical transcriptomic data are rapidly accumulating. However, a lack of systematic collection makes data access, integration, and reuse challenging. We therefore present the Cancer Drug-induced gene expression Signature DataBase (CDS-DB). CDS-DB has collected 78 patient-derived, paired pre- and post-treatment transcriptomic source datasets with uniformly reprocessed expression profiles and manually curated metadata such as drug administration dosage, sampling time and location, and intrinsic drug response status. From these source datasets, 2012 patient-level gene perturbation signatures were obtained, covering 85 therapeutic regimens, 39 cancer subtypes and 3628 patient samples. Besides data browsing, download and search, CDS-DB also supports single signature analysis (including differential gene expression, functional enrichment, tumor microenvironment and correlation analyses), signature comparative analysis and signature connectivity analysis. This provides insights into drug MOA and its heterogeneity in patients, drug resistance mechanisms, drug repositioning and drug (combination) discovery, etc. CDS-DB is available at http://cdsdb.ncpsb.org.cn/.
Design and deep learning of synthetic B-cell-specific promoters
Authors: Fu Zong-Heng , He Si-Zhe , Wu Yi , Zhao Guang-Rong
Published: October 2023

Synthetic biology and deep learning synergistically revolutionize our ability for decoding and recoding DNA regulatory grammar. The B-cell-specific transcriptional regulation is intricate, and unlock the potential of B-cell-specific promoters as synthetic elements is important for B-cell engineering. Here, we designed and pooled synthesized 23 640 B-cell-specific promoters that exhibit larger sequence space, B-cell-specific expression, and enable diverse transcriptional patterns in B-cells. By MPRA (Massively parallel reporter assays), we deciphered the sequence features that regulate promoter transcriptional, including motifs and motif syntax (their combination and distance). Finally, we built and trained a deep learning model capable of predicting the transcriptional strength of the immunoglobulin V gene promoter directly from sequence. Prediction of thousands of promoter variants identified in the global human population shows that polymorphisms in promoters influence the transcription of immunoglobulin V genes, which may contribute to individual differences in adaptive humoral immune responses. Our work helps to decipher the transcription mechanism in immunoglobulin genes and offers thousands of non-similar promoters for B-cell engineering.
Switch to generic formulation of temozolomide results in statistically significant increase in grade 3 and 4 bone marrow toxicity in glioma patients in the province of Alberta
Authors: Omene Egiroh , Abdel-Rahman Omar , Batuyong Eugene , Patel Samir , Coppens Roland , Easaw Jacob , Young Kelvin
Published: October 2023

Background

Temozolomide (TMZ) is an oral, systemic chemotherapy used chiefly for treating high-grade glioma. Due to the rising costs of systemic chemotherapy, many jurisdictions have replaced brand name with generic formulations. The aim of this study was to determine whether or not there was difference in the incidence of grade 3 or 4 bone marrow toxicity and median overall survival in patients treated with brand name versus generic TMZ in the province of Alberta, Canada. The province suspended the use of generic TMZ based on preliminary data pointing to excess toxicity.

Methods

This multicenter, retrospective study included data from patients with newly diagnosed high-grade glioma that received treatment with TMZ in Alberta. Multivariate logistic regression analysis was performed to determine the association between grade 3 or 4 toxicity to generic versus brand name TMZ exposure, ECOG score, and age. Kaplan–Meier survival estimates and log-rank testing were used to determine differences in overall survival between the brand name and generic TMZ cohorts, as well as the cytopenic versus non-cytopenic patients. Furthermore, a screening analysis for grade 3 or 4 bone marrow toxicity was conducted on all de novo glioma patients treated with brand name TMZ after Alberta preemptively stopped generic TMZ.

Results

Grade 3 or 4 neutropenia and thrombocytopenia were observed in 15% and 19% of patients treated with generic TMZ (n = 156) as compared to 3% and 5% of patients (n = 100) treated with brand name TMZ-treated patients; P= .003 and .001. A trend toward increased median overall survival in glioblastoma patients treated with generic TMZ (13.7 months) versus brand name (15.8 months, P = .178.) was also observed through meeting statistical significance. Based on these results, the province stopped the use of generic TMZ and reverted to the Merck TMZ. An initial review of all new glioma patients (n = 89) treated with Merck TMZ since the province stopped the generic drug demonstrated 3.4% and 10.1% grade 3 or 4 neutropenia, respectively.

Conclusions

The statistically significant difference in toxicity profile has prompted the province of Alberta to replace generic TMZ with brand name TMZ in high-grade glioma patients pending more detailed analysis. Our study provides evidence supporting the importance of conducting prospective studies on long-term safety for generic chemotherapies.
Magnetic-field structure of the Crab pulsar wind nebula revealed with IXPE
Authors: Mizuno Tsunefumi , Ohno Hiroshi , Watanabe Eri , Bucciantini Niccolò , Gunji Shuichi , Shibata Sinpei , Slane Patrick , Weisskopf Martin C
Published: October 2023

We report a detailed study of the magnetic-field structure of the Crab pulsar wind nebula, using the X-ray polarization data in 2–8 keV obtained with the Imaging X-ray Polarimetry Explorer. Contamination of the data for the nebula region by the pulsar emission was removed through application of a stringent pulsation phase cut, extracting a phase range of 0.7–1.0 only. We found that the electric-field vector polarization angle (PA) was about 130○ from north to east with a polarization degree (PD) of about 25% at the pulsar position, indicating that the direction of the toroidal magnetic field is perpendicular to the pulsar spin axis in the region close to the termination shock. The PA gradually deviated from the angle as an increasing function of the distance from the pulsar. There was a region of low PD to the west of the X-ray torus. Although such a region is expected to be located at the torus edge, where geometrical depolarization due to a steep spatial variation of the PA is expected, the observed low-PD region positionally deviated from the edge. We found that the region of low PD positionally coincided with a dense filament seen in the optical band, and conjecture that the low-PD region may be produced through deflection of the pulsar wind. By comparing the values of the PD at the pulsar position between the data and a model, in which toroidal and turbulent magnetic fields were considered, we estimated the fractional energy of the turbulent magnetic field to be about 2$/$3 of the total. We also evaluated the potential polarization of the northern jet in the nebula and derived the PD and PA to be about 30% and 120○, respectively.
AstroYOLO: A hybrid CNN–Transformer deep-learning object-detection model for blue horizontal-branch stars
Authors: He Yuchen , Wu Jingjing , Wang Wenyu , Jiang Bin , Zhang Yanxia
Published: October 2023

Blue horizontal-branch stars (BHBs) are ideal tracers for studying the Milky Way (MW) due to their bright and nearly constant magnitude. However, an incomplete screen of BHBs from a survey would result in bias of estimation of the structure or mass of the MW. With surveys of large sky telescopes like the Sloan Digital Sky Survey (SDSS), it is possible to obtain a complete sample. Thus, detecting BHBs from massive photometric images quickly and effectually is necessary. The current acquisition methods of BHBs are mainly based on manual or semi-automatic modes. Therefore, novel approaches are required to replace manual or traditional machine-learning detection. The mainstream deep-learning-based object-detection methods are often vanilla convolutional neural networks whose ability to extract global features is limited by the receptive field of the convolution operator. Recently, a new Transformer-based method has benefited from the global receptive field advantage brought by the self-attention mechanism, exceeded the vanilla convolution model in many tasks, and achieved excellent results. Therefore, this paper proposes a hybrid convolution and Transformer model called AstroYOLO to take advantage of the convolution in local feature representation and Transformer’s easier discovery of long-distance feature dependences. We conduct a comparative experiment on the 4799 SDSS DR16 photometric image dataset. The experimental results show that our model achieves 99.25% AP@50, 93.79% AP@75, and 64.45% AP@95 on the test dataset, outperforming the YOLOv3 and YOLOv4 object-detection models. In addition, we test on larger cutout images based on the same resolution. Our model can reach 99.02% AP@50, 92.00% AP@75, and 61.96% AP@95 respectively, still better than YOLOv3 and YOLOv4. These results also suggest that an appropriate size for cutout images is necessary for the performance and computation of object detection. Compared with the previous models, our model has achieved satisfactory object-detection results and can effectively improve the accuracy of BHB detection.
Vascularization ability of glioma stem cells in different three-dimensional microenvironments
Authors: Wang Xuanzhi , Xu Tao , Niu Chaoshi
Published: October 2023

Glioblastoma (GBM) is among the most common and aggressive adult central nervous system tumors. One prominent characteristic of GBM is the presence of abnormal microvessels. A significant correlation between angiogenesis and prognosis has been observed. Accurately reconstructing this neovascularization and tumor microenvironment through personalized in vitro disease models presents a significant challenge. However, it is crucial to develop new anti-angiogenic therapies for GBM. In this study, 3D bioprinted glioma stem cell (GSC)-laden hydrogel scaffolds, hybrid GSC hydrogels and cell-free hydrogel scaffolds were manufactured to investigate the vascularization ability of GSCs in varying 3D microenvironments. Our results demonstrated that the bioactivity of GSCs in the 3D bioprinted GSC-laden hydrogel scaffold was preferable and stable, and the amounts of vascular endothelial growth factor A and basic fibroblast growth factor were the highest in the microenvironment. When the three different models were co-cultured with human umbilical vein endothelial cells, the expression of angiogenesis-related markers was the most abundant in the bioprinted GSC-laden hydrogel scaffold. Additionally, xenograft tumors formed by bioprinted GSC-laden hydrogel scaffolds more closely resembled human gliomas regarding color, texture and vascularization. Notably, in xenograft tumors derived from 3D bioprinted GSC-laden hydrogel scaffolds, the number of human CD105+ cells was significantly higher, and human endothelial vascular lumen-like structures were observed. This indicates that the 3D bioprinted GSC-laden hydrogel scaffold is a suitable model for mimicking the glioma microenvironment and studying tumor angiogenesis.
Glycolysis: A fork in the path of normal and pathological pregnancy
Authors: Gou Rui , Zhang Xiaohong
Published: October 2023

Glucose metabolism is vital to the survival of living organisms. Since the discovery of the Warburg effect in the 1920s, glycolysis has become a major research area in the field of metabolism. Glycolysis has been extensively studied in the field of cancer and is considered as a promising therapeutic target. However, research on the role of glycolysis in pregnancy is limited. Recent evidence suggests that blastocysts, trophoblasts, decidua, and tumors all acquire metabolic energy at specific stages in a highly similar manner. Glycolysis, carefully controlled throughout pregnancy, maintains a dynamic and coordinated state, so as to maintain the homeostasis of the maternal–fetal interface and ensure normal gestation. In the present review, we investigate metabolic remodeling and the selective propensity of the embryo and placenta for glycolysis. We then address dysregulated glycolysis that occurs in the cellular interactive network at the maternal–fetal interface in miscarriage, preeclampsia, fetal growth restriction, and gestational diabetes mellitus. We provide new insights into the field of maternal–fetal medicine from a metabolic perspective, thus revealing the mystery of human pregnancy.
Single-cell transcriptome analysis reveals the key genes associated with macrophage polarization in liver cancer
Authors: Ding Zhenghua , Deng Zhongming , Li Hengping
Published: October 2023

Background:

The aim of this study was to reveal the key genes associated with macrophage polarization in liver cancer.

Methods:

Data were downloaded from the Gene Expression Omnibus (GEO) and the Cancer Genome Atlas databases (TCGA). R package Seurat 4.0 was used to preprocess the downloaded single-cell sequencing data, principal component analysis, and clustering. R package SingleR was used to annotate cell types and calculate macrophage polarization scores. Spearman correlation analysis was performed to obtain key genes highly correlated with macrophage polarization in liver cancer. The Tumor IMmune Estimation Resource algorithm was used to analyze the correlation between genes and the infiltration level of macrophages. Finally, the prognostic model was constructed based on 6 macrophage polarization-related genes by multivariate Cox regression analysis. Kaplan-Meier curves and receiver operating characteristic curves validated the prognostic value of the prognostic model.

Results:

Two thousand highly variable genes were obtained after the normalization of single-cell profiles. In all, 16 principal components and 15 cell clusters were obtained. Monocytes and macrophages were the main immune cells in the microenvironment of liver cancer tissues. Macrophage polarization scores showed that cluster 5 had the highest degree of polarization. Spearman analysis yielded that a total of 6 key genes associated with macrophage polarization (CD53, TGFBI, S100A4, pyruvate kinase M, LSP1, SPP1), and Tumor IMmune Estimation Resource analysis showed that 6 key genes were significantly positively correlated with macrophage infiltration levels. The model constructed by 6 key genes could effectively evaluate the prognosis of patients with liver cancer.

Conclusions:

The key genes associated with macrophage polarization, namely CD53, TGFBI, S100A4, pyruvate kinase M, LSP1, and SPP1, may be potential therapeutic targets for liver cancer.
Main Mechanisms of Remote Monitoring Programs for Cardiac Rehabilitation and Secondary Prevention
Authors: Clark Alexander M. , Sousa Bailey J. , Ski Chantal F. , Redfern Julie , Neubeck Lis , Allana Saleema , Peart Annette , MacDougall Danielle , Thompson David R.
Published: October 2023

Purpose:

The objective of this report was to identify the main mechanisms of home-based remote monitoring programs for cardiac rehabilitation (RM CR) and examine how these mechanisms vary by context.

Methods:

This was a systematic review using realist synthesis. To be included, articles had to be published in English between 2010 and November 2020 and contain specific data related to mechanisms of effect of programs. MEDLINE All (1946-) via Ovid, Embase (1974-) via Ovid, APA PsycINFO (1806-), CINAHL via EBSCO, Scopus databases, and gray literature were searched.

Results:

From 13 747 citations, 91 focused on cardiac conditions, with 23 reports including patients in CR. Effective RM CR programs more successfully adapted to different patient home settings and broader lives, incorporated individualized patient health data, and had content designed specifically for patients in cardiac rehabilitation. Relatively minor but common technical issues could significantly reduce perceived benefits. Patients and families were highly receptive to the programs and viewed themselves as fortunate to receive such services. The RM CR programs could be improved via incorporating more connectivity to other patients. No clear negative effects on perceived utility or outcomes occurred by patient age, ethnicity, or sex. Overall, the programs were seen to best suit highly motivated patients and consolidated rather than harmed existing relationships with health care professionals and teams.

Conclusions:

Remote monitoring CR programs are perceived by patients to be beneficial and attractive. Future RM CR programs should consider adaptability to different home settings, incorporate individualized health data, and contain content specific to patient needs.