bluuebunny/crossref_metadata_2025 huggingface dataset:
A new spin on color quantization
Authors: Lakhal Samy , Darmon Alexandre , Benzaquen Michael
Published: March 2023

We address the problem of image color quantization using a maximum entropy based approach. Focusing on pixel mapping we argue that adding thermal noise to the system yields better visual impressions than that obtained from a simple energy minimization. To quantify this observation, we introduce the coarse-grained quantization error, and seek the optimal temperature which minimizes this new observable. By comparing images with different structural properties, we show that the optimal temperature is a good proxy for complexity at different scales. Noting that the convoluted error is a key observable, we directly minimize it using a Monte Carlo algorithm to generate a new series of quantized images. Adopting an original approach based on the informativity of finite size samples, we are able to determine the optimal convolution parameter leading to the best visuals. Finally, we test the robustness of our method against changes in image type, color palette and convolution kernel.
Null recurrence and transience for a binomial catastrophe model in random environment
Authors: Renato Fontes Luiz , Machado Fabio P , Schinazi Rinaldo B
Published: March 2023

We consider a discrete time population model for which each individual alive at time n survives independently of everybody else at time n + 1 with probability β

n
. The sequence

(

β
n

)

is i.i.d. and constitutes our random environment. Moreover, at every time n we add Z

n
individuals to the population. The sequence

(

Z
n

)

is also i.i.d. We find sufficient conditions for null recurrence and transience (positive recurrence has been addressed by Neuts 1994 J. Appl. Probab.
31 48–58). We apply our results to a particular

(

Z
n

)

distribution and deterministic β. This particular case shows a rather unusual phase transition in β in the sense that the Markov chain goes from transience to null recurrence without ever reaching positive recurrence.
Hardware design and testing of the generic rear transition module for the global trigger subsystem of ATLAS Phase-II Upgrade
Authors: Bonini F. , Tang S.
Published: March 2023

In the framework of the ATLAS experiment’s Phase-II Upgrade at the High-Luminosity Large Hadron Collider (HL-LHC), new and improved trigger hardware and algorithms will be implemented onto a single-level, 10 μs-latency architecture. The Global Trigger is a new subsystem which will bring event-filter capabilities by performing offline-like algorithms on full-granularity calorimeter data. The implementation of the functionality is firmware-focused and composed of several processing nodes, which are hosted on identical hardware, made up of an Advanced Telecommunications Computing Architecture (ATCA) front board, called Global Common Module (GCM), and a rear transition module (RTM), called Generic RTM (GRM). The GRM, which was developed to mitigate the risks deriving from the complex design and power management of the GCM, features an advanced Xilinx Versal Prime system-on-chip and can handle communication with the GCM and Front-End Link eXchange (FELIX) subsystem and trigger processors through 124 25.8 Gb/s transceiver links, for readout and control. Additionally, the GRM mounts a Low-Power GigaBit Transceiver (lpGBT) chip which enables emulation of the detector front-ends for integration tests. This paper presents the GRM hardware design and its testing.
Design and development of the core software for STCF offline data processing
Authors: Huang W.H. , Li H. , Zhou H. , Li T. , Li Q.Y. , Huang X.T.
Published: March 2023

The Super Tau Charm Facility (STCF) is a proposed
electron-positron collider working at √s = 2 ∼ 7 GeV, and
the peak luminosity is designed to be above
0.5 × 1035 cm-2s-1. The huge amount
of scientific data brings great challenges to the offline data
processing software, including the Monte Carlo simulation,
calibration, reconstruction as well as the data analysis. To
facilitate efficient offline data processing, the offline software
of Super Tau Charm Facility (OSCAR) is developed based on SNiPER, a
lightweight framework designed for HEP experiments, as well as a few
state-of-art software in the HEP community, such as podio and
DD4hep.

This paper describes the design and implementation of the core
software of OSCAR, which provides the foundation for the
development of complex algorithms to be applied on the large data
sets produced by STCF, particularly the way to integrate the common
HEP software toolkits, such as Geant4, DD4hep and podio, into
SNiPER. The software framework also provides a potential solution
for other lightweight HEP experiments as well.
Investigating high methane emissions from urban areas detected by TROPOMI and their association with untreated wastewater
Authors: de Foy Benjamin , Schauer James J , Lorente Alba , Borsdorff Tobias
Published: March 2023

Even though methane concentrations have contributed an estimated 23% of climate forcing, part of the recent increases in the global methane background concentrations remain unexplained. Satellite remote sensing has been used extensively to constrain emission inventories, for example with the TROPOspheric Monitoring Instrument which has been measuring methane since November 2017. We have identified enhancements of methane over 61 urban areas around the world and estimate their emissions using a two-dimensional Gaussian model. We show that methane emissions from urban areas may be underestimated by a factor of 3–4 in the Emissions Database for Global Atmospheric Research (EDGAR) greenhouse gas emission inventory. Scaling our results to the 385 urban areas with more than 2 million inhabitants suggests that they could account for up to 22% of global methane emissions. The emission estimates of the 61 urban areas do not correlate with the total or sectoral EDGAR emission inventory. They do however correlate with estimated rates of untreated wastewater, varying from 33 kg person−1 year−1 for cities with zero untreated wastewater to 138 kg person−1 year−1 for the cities with the most untreated wastewater. If this relationship were confirmed by higher resolution remote sensing or in situ monitoring, we estimate that reducing discharges of untreated wastewater could reduce global methane emissions by up to 5%–10% while at the same time yielding significant ecological and human co-benefits.
A measure of dissimilarity between diffusive processes on networks
Authors: Riascos Alejandro P , Hernández Padilla Francisco
Published: March 2023

In this paper, we present a framework to compare the differences in the occupation probabilities of two random walk processes, which can be generated by modifications of the network or the transition probabilities between the nodes of the same network. We explore a dissimilarity measure defined in terms of the eigenvalues and eigenvectors of the normalized Laplacian of each process. This formalism is implemented to examine differences in the diffusive dynamics described by circulant matrices, the effect of new edges, and the rewiring in networks as well as to evaluate divergences in the transport in degree-biased random walks and random walks with stochastic reset. Our results provide a general tool to compare dynamical processes on networks considering the evolution of states and capturing the complexity of these structures.
Dynamics of mixed quantum–classical spin systems
*
Authors: Gay-Balmaz François , Tronci Cesare
Published: March 2023

Mixed quantum–classical spin systems have been proposed in spin chain theory and, more recently, in magnon spintronics. However, current models of quantum–classical dynamics beyond mean-field approximations typically suffer from long-standing consistency issues, and, in some cases, invalidate Heisenberg’s uncertainty principle. Here, we present a fully Hamiltonian theory of quantum–classical spin dynamics that appears to be the first to ensure an entire series of consistency properties, including positivity of both the classical and the quantum density, so that Heisenberg’s principle is satisfied at all times. We show how this theory may connect to recent energy-balance considerations in measurement theory and we present its Poisson bracket structure explicitly. After focusing on the simpler case of a classical Bloch vector interacting with a quantum spin observable, we illustrate the extension of the model to systems with several spins, and restore the presence of orbital degrees of freedom.
A critical survey of twisted spectral triples beyond the Standard Model
Authors: Filaci Manuele , Martinetti Pierre
Published: March 2023

We review the applications of twisted spectral triples to the Standard Model. The initial motivation was to generate a scalar field, required to stabilise the electroweak vacuum and fit the Higgs mass, while respecting the first-order condition. Ultimately, it turns out that the truest interest of the twist lies in a new—and unexpected—field of 1-forms, which is related to the transition from Euclidean to Lorentzian signature.
Bioremediation of heavy metals using a novel species of ciliate Paramecium multimicronucleatum isolated from industrial wastewater
Authors: Zahra Itrat , Liaqat Ayesha , Betenbaugh Michael , Ramzan Uzma , Elmnasri Khaled , Hedfi Amor , Ben Ali Manel , Albogami Bander , Shakoori Farah R , Shakoori Abdul R
Published: March 2023

The introduction of heavy metals by industries in the aquatic ecosystem is a threatening alarm for living organisms. Bioremediation is an eco-friendly and inexpensive technique as an alternative to chemical methods for wastewater treatment. Wastewater samples were collected from ponds receiving effluents from the Kot Lakhpat Industrial zone, Lahore (Pakistan). Heavy metal-resistant ciliate, Paramecium multimicronucleatum was isolated and characterized with the help of 18SrRNA biomarker. The ciliate showed optimum growth at 25 °C ± 1 °C and pH 7. Growth patterns of P. multimicronucleatum were observed with and without metal stress in wheat grain medium. The minimum inhibitory concentration of cadmium, copper, zinc, and lead was 60, 70, 110, and 160 μg ml−1, respectively. The maximum uptake by Paramecia for Cd, Cu, and Zn was recorded as 90%, 82%, and 93% respectively after 96 h of exposure in each case. While 90% of lead ions were absorbed by Paramecium cells after 48 h of exposure. The order of uptake ability by Paramecium sp. was Zn2+ > Cd2+ > Cu2+ > Pb2+. This preliminary study of exploring bioremediation ability of this ciliate would be helpful for investigating it further using advanced molecular techniques.
Molecular simulation study of the adhesion characteristics of β-phosphogypsum product surface to mold biomolecules
Authors: Wanshuang Liu , Longjiang Li , Xiaotian Zhou
Published: March 2023

The adhesion of β-phosphogypsum product (M-β-PG) to mold is one of the factors affecting its mildew, and the possible structure and mechanism of the interaction between mold adsorbed on M-β-PG surface remain unclear. From the point of view of the interaction between the main biomolecular (Z) on the surface of mold cell wall and the main component of M-β-PG gypsum (G), the adsorption characteristics and interaction mechanism of Z on G surface were studied by means of molecular simulation and experiment. Using x-ray diffraction, gypsum phase composition analysis, x-ray fluorescence spectroscopy, scanning electron microscopy, microbial diversity detection and other tests, the object of molecular simulation modeling was determined. By analyzing the fourier infrared spectroscopy (FTIR) functional group test, the geometric optimization, the band structure and the density of states calculated by quantum mechanics; the adsorption heat, interaction energy, adsorption isotherm, adsorption bond length and mean square displacement calculated by molecular mechanics, the interaction mechanism between G and Z is studied. The results showed that the adsorption occurred primarily between the hydroxyl and carboxyl O atoms and amino N atoms of Z and Ca, S and H atoms in G. The forms of interaction were hydrogen bonding and van der Waals force interaction, which belonged to physical adsorption. On the surface of G, the most and least adsorbed were β-glucan and galactosamine, respectively, whereas the strongest and weakest adsorbed were galactomannan and galactosamine, respectively. This study provides some indication for the interaction mechanism between mold and phosphogypsum surface.
Dielectric barrier discharge plasma synthesis of Ag/γ-Al2O3 catalysts for catalytic oxidation of CO
Authors: TAO Yunming , XU Yuebing , CHANG Kuan , CHEN Meiling , STAROSTIN Sergey A , XU Hujun , LIN Liangliang
Published: March 2023

In this study, Ag/γ-Al2O3 catalysts were synthesized by an Ar dielectric barrier discharge plasma using silver nitrate as the Ag source and γ-alumina (γ-Al2O3) as the support. It is revealed that plasma can reduce silver ions to generate crystalline silver nanoparticles (AgNPs) of good dispersion and uniformity on the alumina surface, leading to the formation of Ag/γ-Al2O3 catalysts in a green manner without traditional chemical reductants. Ag/γ-Al2O3 exhibited good catalytic activity and stability in CO oxidation reactions, and the activity increased with increase in the Ag content. For catalysts with more than 2 wt% Ag, 100% CO conversion can be achieved at 300 °C. The catalytic activity of the Ag/γ-Al2O3 catalysts is also closely related to the size of the γ-alumina, where Ag/nano-γ-Al2O3 catalysts demonstrate better performance than Ag/micro-γ-Al2O3 catalysts with the same Ag content. In addition, the catalytic properties of plasma-generated Ag/nano-γ-Al2O3 (Ag/γ-Al2O3-P) catalysts were compared with those of Ag/nano-γ-Al2O3 catalysts prepared by the traditional calcination approach (Ag/γ-Al2O3-C), with the plasma-generated samples demonstrating better overall performance. This simple, rapid and green plasma process is considered to be applicable for the synthesis of diverse noble metal-based catalysts.
The issuance and enforcement of interim measures in international arbitration under Chinese law
Authors: Wu Jian’an , Qin Shicong , Wang Xuetong
Published: March 2023

The issuance and enforcement of interim measures in international arbitration play a critical role for the parties to resolve the dispute and realize the final arbitral award. For arbitration seated in China, the power to issue interim measures traditionally vests exclusively in the Chinese Courts under the current Arbitration Law and Civil Procedure Law of PRC, except for limited types of arbitration. Aiming to align the Chinese arbitration law with international practices, the Ministry of Justice of China introduced the Arbitration Law of the People’s Republic of China (Amendment) (Draft for Comments) in July 2021 which for the first time empowers the arbitral institutions at the legislative level to issue interim measures. This paper provides a comprehensive overview of the current as well as the newly introduced legal framework in China for the issuance and enforcement of interim measures in foreign-related arbitrations. Although the Amendment recognises the power of arbitral tribunals to issue interim measures in arbitrations seated in China, whether measures issued in arbitrations seated outside of China could be enforced in China remains unclear and the existing Civil Procedure Law of PRC would need to be further clarified to synchronise with the latest reform in Arbitration law.
NMDA-receptor-Fc-fusion constructs neutralize anti-NMDA receptor antibodies
Authors: Steinke Stephan , Kirmann Toni , Loi Eleonora A , Nerlich Jana , Weichard Iron , Kuhn Philipp , Bullmann Torsten , Ritzau-Jost Andreas , Rizalar Filiz Sila , Prüss Harald , Haucke Volker , Geis Christian , Hust Michael , Hallermann Stefan
Published: March 2023

N-methyl-D-aspartate receptor (NMDAR) encephalitis is the most common subtype of autoimmune encephalitis characterized by a complex neuropsychiatric syndrome usually including memory impairment. Patients develop an intrathecal immune response against NMDARs with antibodies that presumably bind to the amino-terminal domain of the GluN1 subunit. The therapeutic response to immunotherapy is often delayed. Therefore, new therapeutic approaches for fast neutralization of NMDAR antibodies are needed. Here, we developed fusion constructs consisting of the Fc part of immunoglobulin G and the amino-terminal domains of either GluN1 or combinations of GluN1 with GluN2A or GluN2B. Surprisingly, both GluN1 and GluN2 subunits were required to generate high-affinity epitopes. The construct with both subunits efficiently prevented NMDAR binding of patient-derived monoclonal antibodies and of patient CSF containing high-titre NMDAR antibodies. Furthermore, it inhibited the internalization of NMDARs in rodent dissociated neurons and human induced pluripotent stem cell-derived neurons. Finally, the construct stabilized NMDAR currents recorded in rodent neurons and rescued memory defects in passive-transfer mouse models using intrahippocampal injections. Our results demonstrate that both GluN1 and GluN2B subunits contribute to the main immunogenic region of the NMDAR and provide a promising strategy for fast and specific treatment of NMDAR encephalitis, which could complement immunotherapy.
Brain-derived neurotrophic factor released from blood platelets prevents dendritic atrophy of lesioned adult central nervous system neurons
Authors: Want Andrew , Nan Xinsheng , Kokkali Eirini , Barde Yves-Alain , Morgan James E
Published: March 2023

In humans and other primates, blood platelets contain high concentrations of brain-derived neurotrophic factor due to the expression of the BDNF gene in megakaryocytes. By contrast, mice, typically used to investigate the impact of CNS lesions, have no demonstrable levels of brain-derived neurotrophic factor in platelets, and their megakaryocytes do not transcribe significant levels of the Bdnf gene. Here, we explore potential contributions of platelet brain-derived neurotrophic factor with two well-established CNS lesion models, using ‘humanized’ mice engineered to express the Bdnf gene under the control of a megakaryocyte-specific promoter. Retinal explants prepared from mice containing brain-derived neurotrophic factor in platelets were labelled using DiOlistics and the dendritic integrity of retinal ganglion cells assessed after 3 days by Sholl analysis. The results were compared with retinas of wild-type animals and with wild-type explants supplemented with saturating concentrations of brain-derived neurotrophic factor or the tropomyosin kinase B antibody agonist, ZEB85. An optic nerve crush was also performed, and the dendrites of retinal ganglion cells similarly assessed 7-day post-injury, comparing the results of mice containing brain-derived neurotrophic factor in platelets with wild-type animals. In mice engineered to contain brain-derived neurotrophic factor in platelets, the mean serum brain-derived neurotrophic factor levels were 25.74 ± 11.36 ng/mL for homozygous and 17.02 ± 6.44 ng/mL for heterozygous mice, close to those determined in primates. Retinal explants from these animals showed robust preservation of dendrite complexity, similar to that seen with wild-type explants incubated with medium supplemented with brain-derived neurotrophic factor or the tropomyosin receptor kinase B antibody agonist, ZEB85. The Sholl areas under curve were 1811 ± 258, 1776 ± 435 and 1763 ± 256 versus 1406 ± 315 in the wild-type control group (P ≤ 0.001). Retinal ganglion cell survival based on cell counts was similar in all four groups, showing ∼15% loss. A robust neuroprotective effect was also observed following optic nerve crush when assessing the dendrites of the retinal ganglion cells in the transgenic mouse, with Sholl area under the curve significantly higher compared to wild-type (2667 ± 690 and 1921 ± 392, P = 0.026), with no significant difference in the contralateral eye controls. Repeat experiments found no difference in cell survival, with both showing ∼50% loss. These results indicate that platelet brain-derived neurotrophic factor has a strong neuroprotective effect on the dendrite complexity of retinal ganglion cells in both an ex vivo and in vivo model, suggesting that platelet brain-derived neurotrophic factor is likely to be a significant neuroprotective factor in primates.
Left atrial intramural haematoma: a fatal complication of cardiac amyloidosis—a case report
Authors: Terashima Rika , Nakagawa Takashi , Hara Hisao , Hiroi Yukio
Published: March 2023

Background

Spontaneous left atrial intramural hematoma (LAIH) is extremely rare and there are only two cases of spontaneous LAIH involving cardiac amyloidosis (CA) reported in literature. In both cases, LAIH rapidly compromised hemodynamic stability proving to be a rare yet fatal complication.

Case summary

An 83-year-old man presented with cardiogenic shock. Electrocardiogram showed complete atrioventricular block, and echocardiogram revealed severe hypokinesis and left ventricular hypertrophy. Coronary angiography revealed no significant coronary stenosis and tissue biopsy was taken from the left ventricle. The patient was intubated, placed on extracorporeal membrane oxygenation with intra-aortic balloon pump and temporary pacemaker, and admitted to ICU. Day 6 of admission, he became hemodynamically unstable, and presented with atrial fibrillation. Transesophageal echocardiography showed a newly formed large mass in the left atrium. Day 11 of admission, the patient passed away. Autopsy revealed cardiac amyloidosis and showed the mass to be a left atrial intramural hematoma. Diffuse amyloid deposits were found in the myocardium as well as the blood vessel walls of the region surrounding the LAIH.

Conclusion

LAIH is a rare yet fatal complication of CA. Autopsy revealed diffuse amyloid deposits within the left atrium may lead to left atrial fragility and contribute to development of LAIH. LAIH should be considered as an important differential diagnosis in the setting of a rapidly growing left atrial mass, and in hemodynamic instability in patients with CA.
Hyperlipidaemia elicits an atypical, T helper 1–like CD4+ T-cell response: a key role for very low-density lipoprotein
Authors: van Os Bram W , Vos Winnie G , Bosmans Laura A , van Tiel Claudia M , Lith Sanne C , den Toom Myrthe S , Beckers Linda , Levels Johannes H M , van Wouw Suzanne A E , Zelcer Noam , Zaal Esther A , Berkers Celia R , van der Lest Chris H A , Helms J Bernd , Weber Christian , Atzler Dorothee , de Winther Menno P J , Baardman Jeroen , Lutgens Esther
Published: March 2023

Aims

Hyperlipidemia and T cell driven inflammation are important drivers of atherosclerosis, the main underlying cause of cardiovascular disease. Here, we detailed the effects of hyperlipidemia on T cells.

Methods and results

In vitro, exposure of human and murine CD4+ T cells to very low-density lipoprotein (VLDL), but not to low-density lipoprotein (LDL) resulted in upregulation of Th1 associated pathways. VLDL was taken up via a CD36-dependent pathway and resulted in membrane stiffening and a reduction in lipid rafts. To further detail this response in vivo, T cells of mice lacking the LDL receptor (LDLr), which develop a strong increase in VLDL cholesterol and triglyceride levels upon high cholesterol feeding were investigated. CD4+ T cells of hyperlipidemic Ldlr-/- mice exhibited an increased expression of the C-X-C-chemokine receptor 3 (CXCR3) and produced more interferon-γ (IFN-γ). Gene set enrichment analysis identified IFN-γ-mediated signaling as the most upregulated pathway in hyperlipidemic T cells. However, the classical Th1 associated transcription factor profile with strong upregulation of Tbet and Il12rb2 was not observed. Hyperlipidemia did not affect levels of the CD4+ T cell's metabolites involved in glycolysis or other canonical metabolic pathways but enhanced amino acids levels. However, CD4+ T cells of hyperlipidemic mice showed increased cholesterol accumulation and an increased arachidonic acid (AA) to docosahexaenoic acid (DHA) ratio, which was associated with inflammatory T cell activation.

Conclusions

Hyperlipidemia, and especially its VLDL component induces an atypical Th1 response in CD4+ T cells. Underlying mechanisms include CD36 mediated uptake of VLDL, and an altered AA/DHA ratio.
A fast 3-D inversion for airborne EM data using pre-conditioned stochastic gradient descent
Authors: Ren Xiuyan , Lai Mingquan , Wang Luyuan , Yin Changchun , Liu Yunhe , Su Yang , Zhang Bo , Ben Fang , Huang Wei
Published: March 2023

Airborne electromagnetic (AEM) exploration produces large amounts of data due to its high sampling rate, so that the 3-D inversions take extremely big computation and time consumption. We present a fast 3-D inversion framework for large-scale AEM explorations using a pre-conditioned stochastic gradient descent combined with Gauss–Newton (PSG-GN) method. We adopt a compressed sensing (CS) in the 3-D forward modelling, in which a random undersampling is used to reduce the calculation, while the responses for all survey stations are obtained via a reconstruction technique. For our 3-D AEM inversions, a method of combining the stochastic gradient descent with Gauss–Newton (SG-GN) that requires only a small data set in each iteration instead of the conventional full-batch data (complete original data) inversion have been investigated. To further speed up the 3-D inversion, we develop a pre-conditioner considering the random sampling rate and gradient noise to achieve a fast convergence. We use two synthetic models to test the accuracy, convergence and efficiency of our algorithm. The results show that the conventional inversion with full-batch data and the PSG-GN method can both converge quickly, but our method can enhance the inversion efficiency up to 78 per cent. Finally, we invert a field data set acquired from a massive sulfide deposit in Ireland and obtain the results that agree well with the known geologies.
Seasonal and diel habitat use of blue marlin Makaira nigricans in the North Atlantic Ocean
Authors: Andrzejaczek Samantha , Mikles Chloe S , Dale Jonathan J , Castleton Michael , Block Barbara A
Published: March 2023

Knowledge of blue marlin, Makaira nigricans, movement patterns across a range of spatiotemporal scales is important for understanding the ecology of this epipelagic fish, informing responsible management strategies, and understanding the potential impacts of a changing ocean climate to the species. To gain insight into movement patterns, we analyzed data from 66 blue marlin satellite-tagged between 2001 and 2021 throughout the North Atlantic. We recorded migrations connecting west and east Atlantic tagging locations, as well as long-term residency within small sub-regions. Blue marlin showed a pattern of latitudinal migration, occupying lower latitudes during cooler months and higher latitudes in warmer months. Diving data indicate blue marlin primarily inhabited a shallow vertical habitat with deeper diving associated with higher sea surface temperatures and dissolved oxygen content. Consistent patterns in diel vertical habitat use support the hypothesis that these fish are visual hunters, diving deeper during the day, as well as dawn, dusk, and full moon periods. The wide-ranging movements of blue marlin indicate that traditional spatial management measures, such as static marine reserves, are unlikely to be effective in reducing the fishing mortality of this species. Longer tag deployment durations are required to delineate its annual and multi-annual migratory cycle.
Healthcare professionals’ perspectives of deprescribing in older patients at the end of life in hospice care: a qualitative study using the Theoretical Domains Framework
Authors: Alwidyan Tahani , McCorry Noleen K , Parsons Carole
Published: March 2023

Objectives

This study aimed to investigate healthcare professionals’ barriers to and enablers of deprescribing in older hospice patients at the end of life and prioritise relevant theoretical domains for behaviour change to be incorporated into future interventions to facilitate deprescribing.

Methods

Twenty doctors, nurses and pharmacists from four hospices in Northern Ireland participated in qualitative semistructured interviews using Theoretical Domains Framework (TDF)-based topic guides. Data were recorded, transcribed verbatim and analysed inductively using thematic analysis. Deprescribing determinants were mapped to the TDF enabling the prioritisation of domains for behaviour change.

Key findings

Four prioritised TDF domains represented key barriers to deprescribing implementation; lack of formal documentation of deprescribing outcomes (Behavioural regulation), challenges in communication with patients and families (Skills), lack of implementation of deprescribing tools in practice (Environmental context/resources) and patient and caregiver perceptions of medication (Social influences). Access to information was identified as a key enabler (Environmental context/resources). Perceived risks versus benefits of deprescribing were identified as a key barrier or enabler (Beliefs about consequences).

Conclusions

This study highlights that further guidance on deprescribing in the context of end-of-life is required to address the growing problems of inappropriate prescribing, Guidance should consider factors such as the adoption of deprescribing tools, monitoring and documentation of deprescribing outcomes and how best to discuss prognostic uncertainty.
In vitro gas production kinetics are influenced by grain processing, flake density, starch retrogradation, andAspergillus oryzaefermentation extract containing α-amylase activity
Authors: Schiff Amanda P , Trotta Ronald J , Holder Vaughn , Kreikemeier Kelly K , Harmon David L
Published: March 2023

Grain processing such as particle size, flake density, or starch retrogradation can influence ruminal degradability characteristics; however, it is unclear how exogenous α-amylase supplementation interacts with different processed grains. Four experiments were conducted to compare the effects of Aspergillus oryzae fermentation extract (Amaize; Alltech Biotechnology Inc., Nicholasville, KY) supplementation on in vitro gas production kinetics of grain substrates with different processing methods that are common in the feedlot industry. In experiment 1, corn processing (dry-rolled, high-moisture, steam-flaked) and Amaize supplementation (0 or 15 U α-amylase activity/100 mL) were evaluated in a 3 × 2 factorial arrangement of treatments. The rate of gas production for dry-rolled corn was higher (P < 0.001) with Amaize supplementation. In experiment 2, flake density (296, 322, 348, 373, and 399 g/L) and starch retrogradation (storage in heat-sealed foil bags for 3 d at 23 or 55°C) were evaluated in a 5 × 2 factorial arrangement of treatments. There was a flake density × starch retrogradation interaction (P < 0.01) for the rate of gas production because the decrease in the rate of gas production with starch retrogradation was greater at lighter flake densities compared with heavier flake densities. In experiment 3, Amaize supplementation was evaluated across flake densities of nonretrograded steam-flaked corn (stored at 23°C) used in experiment 2. There was a flake density × Amaize interaction (P < 0.01) for the rate of gas production where Amaize supplementation resulted in a lower rate of gas production at lighter flake densities (296, 322, and 348 g/L) but a higher rate of gas production at heavier flake densities (373 and 399 g/L). In experiment 4, Amaize supplementation was evaluated across flake densities of retrograded steam-flaked corn (stored at 55°C) used in experiment 2. Gas production was lower after 24 h with Amaize supplementation for retrograded flakes produced to a density of 322 and 399 g/L while Amaize supplementation did not influence gas production at 24 h at other flake densities. There was a flake density × Amaize interaction for the rate of gas production because Amaize supplementation resulted in a faster (P < 0.01) rate of gas production for all flake densities except retrograded flakes produced to a density of 296 g/L. Enzymatic starch availability was positively correlated with the rate of gas production. These data demonstrate that supplementation of 15 U/100 mL of Amaize resulted in greater rates of gas production for dry-rolled corn, corn steam-flaked to heavier densities, and retrograded steam-flaked corn.
Exendin-4 attenuates atherosclerosis progression via controlling hematopoietic stem/progenitor cell proliferation
Authors: Yan Cen , Ma Xiaojuan , Lam Sin Man , Zhang Yuejie , Cao Yu , Dong Yuan , Su Li , Shui Guanghou , Feng Yingmei
Published: March 2023

Beyond glycemic control, applications of glucagon-like peptide-1 receptor (GLP-1r) agonists (GLP-1 RAs) inhibit inflammation and plaque development in murine atherosclerotic models. However, whether they modulate hematopoietic stem/progenitor cells (HSPCs) to prohibit skewed myelopoiesis in hypercholesteremia remains unknown. In this study, GLP-1r expression in fluorescence-activated cell sorting (FACS)-sorted wild-type HSPCs was determined by capillary western blotting. Bone marrow cells (BMCs) of wild-type or GLP-1r−/− mice were transplanted into lethally irradiated low-density lipoprotein receptor deficient (LDLr−/−) recipients followed by high-fat diet (HFD) for chimerism analysis by FACS. In parallel, LDLr−/− mice were placed on HFD for 6 weeks and then treated with saline or Exendin-4 (Ex-4) for another 6 weeks. HSPC frequency and cell cycle were analyzed by FACS, and intracellular metabolite levels were assessed by targeted metabolomics. The results demonstrated that HSPCs expressed GLP-1r and transplantation of GLP-1r−/− BMCs resulted in skewed myelopoiesis in hypercholesterolemic LDLr−/− recipients. In vitro, Ex-4 treatment of FACS-purified HSPCs suppressed cell expansion and granulocyte production induced by LDL. In vivo, Ex-4 treatment inhibited plaque progression, suppressed HSPC proliferation, and modified glycolytic and lipid metabolism in HSPCs of hypercholesteremic LDLr−/− mice. In conclusion, Ex-4 could directly inhibit HSPC proliferation induced by hypercholesteremia.
Outside the fiber: Endomysial stromal and capillary pathology in skeletal muscle may impede infusion therapy in infantile-onset Pompe disease
Authors: Buckley Anne F , Desai Ankit K , Ha Christine I , Petersen Maureen A , Estrada Januario C , Waterﬁeld Justin R , Bossen Edward H , Kishnani Priya S
Published: March 2023

The survival of infantile-onset Pompe disease (IOPD) patients has improved dramatically since the introduction of enzyme replacement therapy (ERT) with a1glucosidase alfa. However, long-term IOPD survivors on ERT demonstrate motor deficits indicating that current therapy cannot completely prevent disease progression in skeletal muscle. We hypothesized that in IOPD, skeletal muscle endomysial stroma and capillaries would show consistent changes that could impede the movement of infused ERT from blood to muscle fibers. We retrospectively examined 9 skeletal muscle biopsies from 6 treated IOPD patients using light and electron microscopy. We found consistent ultrastructural endomysial stromal and capillary changes. The endomysial interstitium was expanded by lysosomal material, glycosomes/glycogen, cellular debris, and organelles, some exocytosed by viable muscle fibers and some released on fiber lysis. Endomysial scavenger cells phagocytosed this material. Mature fibrillary collagen was seen in the endomysium, and both muscle fibers and endomysial capillaries showed basal laminar reduplication and/or expansion. Capillary endothelial cells showed hypertrophy and degeneration, with narrowing of the vascular lumen. Ultrastructurally defined stromal and vascular changes likely constitute obstacles to movement of infused ERT from capillary lumen to muscle fiber sarcolemma, contributing to the incomplete efficacy of infused ERT in skeletal muscle. Our observations can inform approaches to overcoming these barriers to therapy.
Sensitivity of strong lensing observations to dark matter substructure: a case study with Euclid
Authors: O’Riordan Conor M , Despali Giulia , Vegetti Simona , Lovell Mark R , Moliné Ángeles
Published: March 2023

We introduce a machine learning method for estimating the sensitivity of strong lens observations to dark matter subhaloes in the lens. Our training data include elliptical power-law lenses, Hubble Deep Field sources, external shear, and noise and PSF for the Euclid VIS instrument. We set the concentration of the subhaloes using a vmax–rmax relation. We then estimate the dark matter subhalo sensitivity in 16 000 simulated strong lens observations with depth and resolution resembling Euclid VIS images. We find that with a 3σ detection threshold, 2.35 per cent of pixels inside twice the Einstein radius are sensitive to subhaloes with a mass Mmax ≤ 1010 M⊙, 0.03 per cent are sensitive to Mmax ≤ 109 M⊙, and the limit of sensitivity is found to be Mmax = 108.8 ± 0.2 M⊙. Using our sensitivity maps and assuming CDM, we estimate that Euclid-like lenses will yield $1.43^{+0.14}_{-0.11}[f_\mathrm{sub}^{-1}]$ detectable subhaloes per lens in the entire sample, but this increases to $35.6^{+0.9}_{-0.9}[f_\mathrm{sub}^{-1}]$ per lens in the most sensitive lenses. Estimates are given in units of the inverse of the substructure mass fraction $f_\mathrm{sub}^{-1}$. Assuming fsub = 0.01, one in every 70 lenses in general should yield a detection, or one in every ∼ three lenses in the most sensitive sample. From 170 000 new strong lenses detected by Euclid, we expect ∼2500 new subhalo detections. We find that the expected number of detectable subhaloes in warm dark matter models only changes relative to cold dark matter for models which have already been ruled out, i.e. those with half-mode masses Mhm > 108 M⊙.
Growing the first galaxies’ merger trees
Authors: Nadler Ethan O , Benson Andrew , Driskell Trey , Du Xiaolong , Gluscevic Vera
Published: March 2023

Modelling the growth histories of specific galaxies often involves generating the entire population of objects that arise in a given cosmology and selecting systems with appropriate properties. This approach is highly inefficient when targeting rare systems such as the extremely luminous high-redshift galaxy candidates detected by JWST. Here, we present a novel framework for generating merger trees with branches that are guaranteed to achieve a desired halo mass at a chosen redshift. This method augments extended Press Schechter theory solutions with constrained random processes known as Brownian bridges and is implemented in the open-source semi-analytic model galacticus. We generate ensembles of constrained merger trees to predict the growth histories of seven high-redshift JWST galaxy candidates, finding that these systems most likely merge ≈2 Gyr after the observation epoch and occupy haloes of mass ≳1014 M⊙ today. These calculations are thousands of times more efficient than existing methods, are analytically controlled, and provide physical insights into the evolution of haloes with rapid early growth. Our constrained merger tree implementation is publicly available at https://github.com/galacticusorg/galacticus.
Extremely powerful flare phenomenon of H2O maser in W49N near −40 km s−1
Authors: Volvach A E , Volvach L N , Larionov M G
Published: March 2023

As a result of detailed observations of the water vapour maser at the 22-m Simeiz radio telescope from 2017 June to 2019 December, two powerful flares were recorded in the Galactic source W49N, which occurred near the high-velocity feature −40 km s−1. The extremely powerful flare had an ultrashort duration of about 2 d and reached a flux density of 110 kJy. An ultrashort flare occurred at the top of a less powerful, but ten times longer one. To our knowledge, a flare of a water maser with such extreme characteristics has never been reported before. A correlation between the exponential increase and decrease in the flare flux density and decrease in line widths with increasing flux density, which is characteristic of an unsaturated maser, is found. The maser of the third flare was in a saturated state and provided a large input flux density 9.5 kJy for the occurrence of two powerful flares, the masers of which were in an unsaturated state. New data have been obtained concerning the physical characteristics of the water maser phenomenon during powerful flares.
Recombination Variation Shapes Phylogeny and Introgression in Wild Diploid Strawberries
Authors: Feng Chao , Wang Jing , Liston Aaron , Kang Ming
Published: March 2023

Introgressive hybridization is widespread in wild plants and has important consequences. However, frequent hybridization between species makes the estimation of the species’ phylogeny challenging, and little is known about the genomic landscape of introgression as it results from complex interactions of multiple evolutionary processes. Here, we reconstructed the phylogeny of ten wild diploid strawberries with whole genome resequencing data and then investigated the influence of recombination rate variation on phylogeny and introgression. We found that genomic regions with low recombination showed reduced levels of incomplete lineage sorting and introgression, and concentrated phylogenetic signals, thus contributing to the most likely species tree of wild diploid strawberries. We revealed complex and widespread introgression across the genus Fragaria, with an average proportion of approximately 4.1% of the extant genome. Introgression tends to be retained in the regions with high recombination rates and low gene density. Furthermore, we identified four SLF genes under selective sweeps that may play potential roles in the possible regain of self-incompatibility by ancient introgression. Altogether, our study yielded novel insights into the evolutionary history and genomic characteristics of introgression in wild diploid strawberries and provides evidence for the role of introgression in plant mating system transitions.
Filament assembly underpins the double-stranded DNA specificity of AIM2-like receptors
Authors: Garg Archit , Stallings Christina M , Sohn Jungsan
Published: March 2023

Upon sensing cytosolic- and/or viral double-stranded (ds)DNA, absent-in-melanoma-2 (AIM2)-like-receptors (ALRs) assemble into filamentous signaling platforms to initiate inflammatory responses. The versatile yet critical roles of ALRs in host innate defense are increasingly appreciated; however, the mechanisms by which AIM2 and its related IFI16 specifically recognize dsDNA over other nucleic acids remain poorly understood (i.e. single-stranded (ss)DNA, dsRNA, ssRNA and DNA:RNA hybrid). Here, we find that although AIM2 can interact with various nucleic acids, it preferentially binds to and assembles filaments faster on dsDNA in a duplex length-dependent manner. Moreover, AIM2 oligomers assembled on nucleic acids other than dsDNA not only display less ordered filamentous structures, but also fail to induce the polymerization of downstream ASC. Likewise, although showing broader nucleic acid selectivity than AIM2, IFI16 binds to and oligomerizes most readily on dsDNA in a duplex length-dependent manner. Nevertheless, IFI16 fails to form filaments on single-stranded nucleic acids and does not accelerate the polymerization of ASC regardless of bound nucleic acids. Together, we reveal that filament assembly is integral to nucleic acid distinction by ALRs.
Endogenous retrovirus-derived enhancers confer the transcriptional regulation of human trophoblast syncytialization
Authors: Yu Miao , Hu Xiaoqian , Pan Zihang , Du Cui , Jiang Jing , Zheng Wanshan , Cai Han , Wang Yinan , Deng Wenbo , Wang Haibin , Lu Jinhua , Sun Ming-an , Cao Bin
Published: March 2023

Endogenous retroviruses (ERVs) have been proposed as a driving force for the evolution of the mammalian placenta, however, the contribution of ERVs to placental development and the underlying regulatory mechanism remain largely elusive. A key process of placental development is the formation of multinucleated syncytiotrophoblasts (STBs) in direct contact with maternal blood, through which constitutes the maternal-fetal interface critical for nutrient allocation, hormone production and immunological modulation during pregnancy. We delineate that ERVs profoundly rewire the transcriptional program of trophoblast syncytialization. Here, we first determined the dynamic landscape of bivalent ERV-derived enhancers with dual occupancy of H3K27ac and H3K9me3 in human trophoblast stem cells (hTSCs). We further demonstrated that enhancers overlapping several ERV families tend to exhibit increased H3K27ac and reduced H3K9me3 occupancy in STBs relative to hTSCs. Particularly, bivalent enhancers derived from the Simiiformes-specific MER50 transposons were linked to a cluster of genes important for STB formation. Importantly, deletions of MER50 elements adjacent to several STB genes, including MFSD2A and TNFAIP2, significantly attenuated their expression concomitant to compromised syncytium formation. Together, we propose that ERV-derived enhancers, MER50 specifically, fine-tune the transcriptional networks accounting for human trophoblast syncytialization, which sheds light on a novel ERV-mediated regulatory mechanism underlying placental development.
BACH1 deficiency prevents neointima formation and maintains the differentiated phenotype of vascular smooth muscle cells by regulating chromatin accessibility
Authors: Guo Jieyu , Qiu Jingjing , Jia Mengping , Li Qinhan , Wei Xiangxiang , Li Liliang , Pan Qi , Jin Jiayu , Ge Fei , Ma Siyu , He Yunquan , Lin Jiayi , Li Yongbo , Ma Jinghua , Jiang Nan , Zhi Xiuling , Jiang Lindi , Zhang Jianyi , Osto Elena , Jing Qing , Wang Xinhong , Meng Dan
Published: March 2023

The transcription factor BTB and CNC homology 1(BACH1) has been linked to coronary artery disease risk by human genome-wide association studies, but little is known about the role of BACH1 in vascular smooth muscle cell (VSMC) phenotype switching and neointima formation following vascular injury. Therefore, this study aims to explore the role of BACH1 in vascular remodeling and its underlying mechanisms. BACH1 was highly expressed in human atherosclerotic plaques and has high transcriptional factor activity in VSMCs of human atherosclerotic arteries. VSMC-specific loss of Bach1 in mice inhibited the transformation of VSMC from contractile to synthetic phenotype and VSMC proliferation and attenuated the neointimal hyperplasia induced by wire injury. Mechanistically, BACH1 suppressed chromatin accessibility at the promoters of VSMC marker genes via recruiting histone methyltransferase G9a and cofactor YAP and maintaining the H3K9me2 state, thereby repressing VSMC marker genes expression in human aortic smooth muscle cells (HASMCs). BACH1-induced repression of VSMC marker genes was abolished by the silencing of G9a or YAP. Thus, these findings demonstrate a crucial regulatory role of BACH1 in VSMC phenotypic transition and vascular homeostasis and shed light on potential future protective vascular disease intervention via manipulation of BACH1.