bluuebunny/crossref_metadata_2025 huggingface dataset:
Monte Carlo simulations of cell survival in proton SOBP
Authors: Sebastián Salgado Maldonado , Alejandro Carabe , Ignacio Espinoza , Sophia Galvez , Pía Valenzuela María , Andrea Russomando
Published: September 2023

Objective. The objective of this study is to develop a multi-scale modeling approach that accurately predicts radiation-induced DNA damage and survival fraction in specific cell lines. Approach. A Monte Carlo based simulation framework was employed to make the predictions. The FLUKA Monte Carlo code was utilized to estimate absorbed doses and fluence energy spectra, which were then used in the Monte Carlo Damage Simulation code to compute DNA damage yields in Chinese hamster V79 cell lines. The outputs were converted into cell survival fractions using a previously published theoretical model. To reduce the uncertainties of the predictions, new values for the parameters of the theoretical model were computed, expanding the database of experimental points considered in the previous estimation. Simulated results were validated against experimental data, confirming the applicability of the framework for proton beams up to 230 MeV. Additionally, the impact of secondary particles on cell survival was estimated. Main results. The simulated survival fraction versus depth in a glycerol phantom is reported for eighteen different configurations. Two proton spread out Bragg peaks at several doses were simulated and compared with experimental data. In all cases, the simulations follow the experimental trends, demonstrating the accuracy of the predictions up to 230 MeV. Significance. This study holds significant importance as it contributes to the advancement of models for predicting biological responses to radiation, ultimately contributing to more effective cancer treatment in proton therapy.
Potential limitations of measuring ambulatory activity of part-time wheelchair users: a comparative study of two research grade activity monitors
Authors: Stevens Wilshaw , Harlett Fernanda , Wimberly Robert L , Tulchin-Francis Kirsten
Published: September 2023

Objective. Research grade activity monitors such as the StepWatch Activity Monitor (SAM) and Actigraph have been shown to be highly accurate for the assessment of ambulatory activity, but some individuals function in the community using a combination of both walking and wheelchair activity. The purpose of this study was to assess the accuracy of the SAM and Actigraph at not detecting ambulatory activity, during wheelchair activities at two intensity levels. Approach. Two independent cohorts were tested while simultaneously wearing a SAM and Actigraph on the ankle. Group 1 consisted of twelve adults performing a six-minute push test (6MPT). Group 2 were eighteen members of an adolescent wheelchair basketball team tested during a scrimmage/practice and regional tournament. Visual observation was used to confirm the number of ambulatory steps taken during testing was zero. Main results. The average number of ‘steps’ detected during a 6MPT was 19 ± 25 (range: 0–85) with the Actigraph. No ‘steps’ were detected using the SAM in Group 1. In Group 2, the average ‘step’ count during basketball practice was 1421 ± 750 (range: 612–2798) using the Actigraph and 1363 ± 1238 (range: 84–3462) using the SAM, and correlated with playing time, despite the leg/ankle being strapped down. Similar findings were observed during the wheelchair basketball regional tournament. Significance. Caution should be heeded when utilizing these activity monitors in individuals with disabilities who participate in wheelchair sports. Additional written activity logs should be used to exclude periods of time during which high acceleration wheelchair sporting activity occurs, or study participants should be fully educated in removing the activity monitors during non-ambulatory wheelchair sports.
Mechanical behavior of a torsional shear thickening fluid damper
Authors: Lin Kun , Wei Minghai , Qi Jiapeng
Published: September 2023

This study utilizes a fatigue testing machine to examine the damping moment response of the torsional shear thickened fluid (STF) damper (T-STF-D) under various loading velocities. In the first stage, three STF samples were prepared using nano-silica and polyethylene glycol, and their shear thickening properties were verified using a rheometer. Next, the theoretical model of the T-STF-D was established based on the parallel plate theory, and its validity was confirmed through experimental data. Afterward, a prototype of the T-STF-D was designed and fabricated, and its dynamic response was tested at different velocities over both short- and long-term periods. The findings reveal that the T-STF-D exhibits favorable damping performance as the loading velocity increases, and the initial damping moment rises with the augmentation of loading velocity. However, the damping moment decays exponentially with time during loading. Given this behavior, a phenomenal model is subsequently proposed in this study to forecast the damping moment, and the experimental data provide evidence for the accuracy and effectiveness of this model.
Characterization of flux pump-charging of high-temperature superconducting coils using coupled numerical models
Authors: Zhou Pengbo , Ghabeli Asef , Ainslie Mark , Grilli Francesco
Published: September 2023

Flux pumps provide a promising solution for contactless charging of high-temperature superconducting (HTS) coils, eliminating the need for bulk current leads and reducing the heat burden for the cryogenic system. Characterizing the nonlinear effects of an HTS coil charged by a flux pump and understanding the dynamics of the charging process is essential for promoting the practical application of flux pumps. Numerical models provide a fast and cost-effective way of achieving this. In this study, we propose a methodology for coupling HTS coil and flux pump models using an electrical circuit, resulting in reduced computation costs. We validate the effectiveness of our approach against the experimental results of an HTS coil charged by a dynamo-type flux pump. Specifically, we obtain the voltage produced by the HTS dynamo using a 3D model based on the minimum electromagnetic entropy production method and apply this voltage to the load HTS coil using a

T

−

A

formulation finite-element method model coupled via an electrical circuit. The simulated charging current shows good agreement with experimental observations, validating our modeling strategy. The results demonstrate that the flux flow state in the HTS coil is the primary factor limiting the charging performance of the HTS dynamo as the charging current approaches the coil’s critical current. Furthermore, based on the simulation, we demonstrate that, when using flux pumps, it is advisable to leave a margin between the operating current and the critical current of the coil. Overall, our approach has the potential to be applied to HTS coils charged by any device.
Design optimization of a stepped HTS magnet for electrodynamic suspension train
Authors: Li Songlin , Liu Boqiang , Zhou Pengbo , Wang Ruichen , Wu Xinyu , Gong Tianyong , Ma Guangtong
Published: September 2023

High-temperature superconducting (HTS) magnets are promising candidates for transportation and power systems, such as the electrodynamic suspension (EDS) train, ultra-high field magnet and magnetic resonance imaging, because of their large current-carrying capacity and low power loss. The critical current depending on magnetic flux density is an essential factor in assessing the application performance of HTS magnets. As usual, the existing HTS magnet is wound with rectangular cross-section, which results in magnetic field concentration inside winding. In this paper, we propose a novel HTS magnet structure with stepped cross-section to alleviate the magnetic field concentration, and resultantly improve the critical current. From this point, this paper aims to design and optimize a stepped HTS magnet with the critical current maximized. Firstly, the structure design of the stepped HTS magnet is performed with a consideration of the application scenario of EDS train. Then, the critical current of the HTS magnet is estimated with a homogenized self-consistent model. Afterwards, an HTS magnet with stepped cross-section is optimized, fabricated and finally tested. The critical current was experimentally measured to verify the simulation results, followed by the electromagnetic investigations of the stepped HTS magnet in the EDS train.
A 220 GHz superconducting titanium transition edge sensor array developed for cosmic microwave background experiments
Authors: Luo Qianghui , Zhong Jiaqiang , Miao Wei , Li Feiming , Wang Qingcheng , Ding Jiangqiao , Wu Feng , Wang Zheng , Zhou Kangmin , Ren Yuan , Zhang Wen , Li Jing , Shi Shengcai
Published: September 2023

In this paper, we report on the design, fabrication, and characterization of a 220 GHz superconducting transition edge sensor (TES) array developed for ground-based cosmic microwave background (CMB) experiments. Unlike conventional TES arrays adopting thermometers made of bilayer superconducting films, the TES array has thermometers made of simpler single-layer titanium (Ti) film deposited on a suspended silicon nitride (SiN
x
) membrane. The thermal weak link is realized by releasing the TES’s thermal island including the Ti thermometer by dry etching with xenon difluoride (XeF2), giving a typical thermal conductance of 25 pW K−1. Its thermal-conductance mechanism is further studied by fitting the measured TES’s complex impedance with a three-block thermal model. The dark and optical noise equivalent power (NEP) of a superconducting TES are both measured. Despite existing lens reflection and dielectric loss in the superconducting microstrip line, its typical optical NEP reaches 100 aW Hz−0.5, which meets the sensitivity requirement for ground-based CMB experiments.
Dynamical aspects of excitonic Floquet states generated by a phase-locked mid-infrared pulse in a one-dimensional Mott insulator
Authors: Yamakawa Takashi , Miyamoto Tatsuya , Sakai Daiki , Okamoto Hiroshi
Published: September 2023

A periodic electric field of light applied on a solid is predicted to generate coupled states of the light electric fields and electronic system called photon-dressed Floquet states. Previous studies of those Floquet states have focused on time-averaged energy-level structures. Here, we report time-dependent responses of Floquet states of excitons generated by a mid-infrared (MIR) pulse excitation in a prototypical one-dimensional (1D) Mott insulator, a chlorine-bridged nickel-chain compound, [Ni(chxn)2Cl](NO3)2 (chxn = cyclohexanediamine). Sub-cycle reflection spectroscopy on this compound using a phase-locked MIR pump pulse and an ultrashort visible probe pulse with the temporal width of ∼7 fs revealed that large and ultrafast reflectivity changes occur along the electric field of the MIR pulse; the reflectivity change reached approximately 50% of the original value around the exciton absorption peak. It comprised a high-frequency oscillation at twice the frequency of the MIR pulse and a low-frequency component following the intensity envelope of the MIR pulse, which showed different probe-energy dependences. Simulations considering one-photon-allowed and one-photon-forbidden excitons reproduced the temporal and spectral characteristics of both the high-frequency oscillation and low-frequency component. These simulations demonstrated that all responses originated from the quantum interferences of the linear reflection process and nonlinear light-scattering processes owing to the excitonic Floquet states characteristic of 1D Mott insulators. The present results lead to the developments of Floquet engineering, and demonstrate the possibility of rapidly controlling the intensity of visible or near-IR pulse by varying the phase of MIR electric fields, which will be utilized for ultrafast optical switching devices.
Optical deceleration of atomic hydrogen
Authors: Cooper S F , Rasor C , Bullis R G , Brandt A D , Yost D C
Published: September 2023

We demonstrate control over the motional degrees of freedom of a cryogenic hydrogen atomic beam using an accelerating optical lattice. For our method, we load metastable atoms from a cryogenic beam into a moving optical lattice, decelerate the lattice, and observe a commensurate deceleration of the atoms. For this demonstration, hydrogen atoms are decelerated by about 20 m s−1 in a 40 ns slowing cycle, with a peak acceleration of ≈4

×

10
8

m s−2. Since the optical lattice is governed by standard optoelectronics, this technique represents a robust platform for the motional control of hydrogen.
Privacy protection of quantum BP neural network based on game theory
Authors: Lin Yusheng , Chang Yan , Huang Siwei , Zhang Shibin
Published: September 2023

How to ensure privacy security and improve computing efficiency is a research hotspot in the field of machine learning. Among them, how to balance the interests of users, cloud servers and attackers on the premise of ensuring user privacy is a difficult problem in the field of machine learning privacy protection. The development of quantum computing breaks through the computational bottleneck of classical machine learning and has derived the research direction of quantum machine learning. At present, hybrid quantum–classical machine learning in NISQ era has become a research hotspot, but researchers rarely pay attention to the privacy protection in quantum machine learning. Therefore, this paper is the first to apply game theory to the privacy protection in quantum machine learning and proposes the privacy game model of user - server - attacker in Hybrid Classical Quantum BP Neural Network (HCQBPNN). Different from previous studies, this paper sets game strategies based on users’ privacy requirements in practical applications, and aims to maximize the interests of attackers, cloud servers and users. The experiment proves that users can use the privacy game model proposed in this paper to get the optimal privacy combination strategy, and at the same time make the cloud server and the attacker can obtain positive income.
Supersymmetric quantum mechanics, multiphoton algebras and coherent states
Authors: García-Muñoz Juan D , Fernández C David J , Vergara-Méndez F
Published: September 2023

The multiphoton algebras for one-dimensional Hamiltonians with infinite discrete spectrum, and for their associated kth-order SUSY partners are studied. In both cases, such an algebra is generated by the multiphoton annihilation and creation operators, as well as by Hamiltonians which are functions of an appropriate number operator. The algebras obtained turn out to be polynomial deformations of the corresponding single-photon algebra previously studied in literature. The Barut-Girardello coherent states, which are eigenstates of the annihilation operator, are obtained and their uncertainty relations are explored by means of the associated quadratures.
Study of microwave quantum electrometric sensors via electromagnetically induced transparency in thermal Rydberg atoms
Authors: Iqbal Dar Zubair , Kaur Amanjot , Arora Bindiya , Kaur Paramjit
Published: September 2023

Quantum electrometric sensing properties of a four-level system are theoretically investigated for microwave (MW) field measurement in thermal Rydberg atoms. In the considered system, the phenomenon of electromagnetically induced transparency (EIT) is invoked to study the impact of microwave (MW) field strength on its optical response. The amplitude of the MW electric field is obtained directly by measuring the height and frequency of EIT peaks. Further, for MW frequency measurement, the probe spectra are examined for red and blue MW detuned cases. It is found that the responsiveness of 133Cs for MW electric field as well as frequency is relatively higher than 87Rb. The overall sensitivity of both these atoms can be enhanced by the convenient setting of the system and field parameters.
Coherence monotones of quantum channels based on two generalized quantum relative entropies
Authors: Fan Jiaorui , Wu Zhaoqi , Fei Shao-Ming
Published: September 2023

By using the Choi–Jamiołkowski isomorphism, we propose two classes of coherence monotones of quantum channels based on the unified (r, s)-relative entropy and the sandwiched Rényi relative entropy. Elegant properties of the coherence monotones for quantum channels are explored. Moreover, we present the upper bounds of the coherence monotones and derive the explicit formulas of the coherence monotones for qubit unitary channels.
Directional-to-random transition of cell cluster migration
Authors: Zeng 曾 Yang 阳 , Che 车 Bingchen 丙晨 , Sun 孙 Dan 聃 , Zhang 张 Ce 策 , Jing 经 Guangyin 光银
Published: September 2023

Efficient cell migration is crucial for the functioning of biological processes, e.g., morphogenesis, wound healing, and cancer metastasis. In this study, we monitor the migratory behavior of the 3D fibroblast clusters using live cell microscopy, and find that crowded environment affects cell migration, i.e., crowding leads to directional migration at the cluster’s periphery. The number of cell layers being stacked during seeding determines the directional-to-random transition. Intriguingly, the migratory behavior of cell clusters resembles the dispersion dynamics of clouds of passive particles, indicating that the biological process is driven by physical effects (e.g., entropy) rather than cell communication. Our findings highlight the role of intrinsic physical characteristics, such as crowding, in regulating biological behavior, and suggest new therapeutic approaches targeting at cancer metastasis.
Application of linear electron Bernstein current drive models in reactor-relevant spherical tokamaks
Authors: Biswas Bodhi , Speirs David , Freethy Simon , Vann Roddy
Published: September 2023

Electron Bernstein current drive (EBCD) systems in spherical tokamaks are sensitive to plasma and launch conditions, and therefore require large parametric scans to optimise their design. One particular bottleneck in the simulation workflow is quasilinear modelling of current drive efficiency. Linear adjoint models are an attractive alternative, offering a

∼

10

3

 
×

speed-up compared to quasilinear codes. While linear models are well-tested and commonly used for electron cyclotron current drive (ECCD), they have seen little use in EBCD modelling. In this work, variants of the linear model are applied to EBCD and compared to quasilinear results in a reactor-relevant plasma, i.e. Spherical Tokamak for Energy Production (STEP). This comparison reveals it is important to accurately model the collision operator and finite Larmor radius effects in the linear model. When done properly, good agreement is found with quasilinear calculations, at least for normalised minor radii ρ < 0.7 and at low power densities. The power density threshold for quasilinear effects during EBCD is found to be significantly lower than that of ECCD. This is attributed to the much lower group velocity of the electron Bernstein wave (EBW). Thus, the linear model is only valid for EBCD modelling at low power densities (e.g.

≲

1 MW launched EBW power in STEP). This may be satisfied in present-day experimental devices, but certainly not in reactors targeting non-inductive operation.
Effects of stepwise tidal flat reclamation on tidal evolution in the East China and Yellow Sea
Authors: Lim Byoung-Jun , Chang You-Soon , Cho Yang-Ki
Published: September 2023

Because many coastal developments have been continuously occurred in the Yellow and the East China Sea, it is necessary to analyze the effect of persistent topographic change. This study simulated the tidal change in response to stepwise tidal flat reclamation in East China and the Yellow Sea using the MOdelo HIDrodinâmico (MOHID) ocean model. Based on previous studies and historical coastal information maps, we conducted several numerical experiments with reliable coastal topography changes around two areas (Jiangsu Shoalwater and Gyeonggi Bay) from 1990 to 1994 when the most active development took place. The results show that, unlike other components (S2, O1, and K1), the simulated amplitude of the M2 constituent significantly increased with the disappearance of the tidal flat in the Yellow Sea. At the same time, it decreased in the East China Sea. These results are consistent with the quantile regression analysis using observational data. We also found an accumulating effect of tidal energy flux when the reclamation continued, which does not appear in the previous studies. These results indicate persistent man-made tidal flat reclamation in a specific area can cause more remarkable regional tidal changes through tidal energy redistribution and modification.
A Lehmer-type height lower bound for abelian surfaces over function fields
Authors: Looper Nicole , Silverman Joseph
Published: September 2023

Let

K
K

be an 1-dimensional function field over an algebraically closed field of characteristic

0
0

, and let

A

/

K

A/K

be an abelian surface. Under mild assumptions, we prove a Lehmer-type lower bound for points in 

A
(

K
¯

)

A(\overline {K})

. More precisely, we prove that there are constants

C
1

,

C
2

>
0

C_1,C_2>0

such that the normalized Bernoulli-part of the canonical height is bounded below by
\[
<mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" alttext="ModifyingAbove h With caret Subscript upper A Superscript double-struck upper B Baseline left-parenthesis upper P right-parenthesis greater-than-or-equal-to upper C 1 left-bracket upper K left-parenthesis upper P right-parenthesis colon upper K right-bracket Superscript negative 2">

h
^

A

B

(
P
)
≥

C
1

[

K
(
P
)
:
K

]

−
2

\hat {h}_A^{\mathbb {B}}(P) \ge C_1\bigl [K(P):K\bigr ]^{-2}

\]
for all points 

P
∈

A
(

K
¯

)

P\in {A(\overline {K})}

whose height satisfies 

0
>

h
^

A

(
P
)
≤

C
2

0>\hat {h}_A(P)\le {C_2}

.
Logarithmic Pandharipande–Thomas spaces and the secondary polytope
Authors: Kennedy–Hunt Patrick
Published: September 2023

Maulik and Ranganathan have recently introduced moduli spaces of logarithmic stable pairs. In the case of toric surfaces we recast this theory using three ingredients: Gelfand, Kapranov and Zelevinsky secondary polytopes, Hilbert schemes of points, and tautological vector bundles. In particular, logarithmic stable pairs spaces are expressed as the zero set of an explicit section of a vector bundle on a logarithmically smooth space, thus providing an explicit description of their virtual fundamental class. A key feature of our construction is that moduli spaces are completely canonical, unlike the existing construction, which is only well-defined up to logarithmic modifications. We calculate the Euler–Satake characteristics of our moduli spaces in a number of basic examples. These computations indicate the complexity of the spaces we construct.
Hyperbolic manifolds with a large number of systoles
Authors: Dória Cayo , Freire Emanoel , Murillo Plinio
Published: September 2023

In this article, for any

n
≥
4

n\geq 4

we construct a sequence of compact hyperbolic

n
n

-manifolds

{

M
i

}

\{M_i\}

with number of systoles at least as

v
o
l

(

M
i

)

1
+

1

3
n
(
n
+
1
)

−
ϵ

\mathrm {vol}(M_i)^{1+\frac {1}{3n(n+1)}-\epsilon }

for any

ϵ
>
0

\epsilon >0

. In dimension 3, the bound is improved to

v
o
l

(

M
i

)

4
3

−
ϵ

\mathrm {vol}(M_i)^{\frac {4}{3}-\epsilon }

. These results generalize previous work of Schmutz for

n
=
2

n=2

, and Dória-Murillo for

n
=
3

n=3

to higher dimensions.
Using the Behavior Change Wheel to Identify and Understand Key Facilitators and Barriers for Lifestyle Care for Postmenopausal Breast Cancer Survivors: A Delphi-Study
Authors: van Cappellen-van Maldegem Sandra J M , Mols Floortje , Seidell Jacob C , de Kruif Anja , van de Poll-Franse Lonneke V , Hoedjes Meeke
Published: September 2023

Background

Optimal approaches to promote sustained adherence to lifestyle and bodyweight recommendations in postmenopausal breast cancer (PMBC) survivors are lacking.

Purpose

This Delphi-study aims to identify and understand expert-opinion on potential barriers and facilitators for promoting adherence to these lifestyle and bodyweight recommendations in (clinical) care for PMBC survivors, and to determine potential effective intervention strategies.

Methods

The expert panel consisted of oncology Health Care Professionals (HCPs) (N = 57), patient advocates (N = 5), and PMBC survivors (N = 38). They completed three questionnaires: Q1—idea generation; Q2—validation and prioritization; Q3—ranking. The Behavior Change Wheel was used as theoretical framework for analysis. Thematic analysis was applied to identify key overarching themes based on the top-ranked facilitators and barriers. Potential Behavior Change Techniques (BCTs) and intervention strategies were identified using the Behavior Change Technique Taxonomy version 1 and the Behavior Change Wheel.

Results

Eleven core categories of key barriers/facilitators for the promotion of adherence to recommendations for lifestyle and bodyweight among PMBC survivors were identified. For each core category, relevant BCTs and practical potential intervention strategies were selected based on suggestions from the expert panel. These included: increasing knowledge about the link between lifestyle and cancer; enabling self-monitoring of lifestyle behaviors followed by evaluation; offering group lifestyle counseling for PMBC survivors, enhancing social support for favorable lifestyle behaviors; and stimulating multidisciplinary collaboration among HCPs.

Conclusions

Findings provide valuable insight for the development of interventions changing behavior of PMBC survivors and HCPs toward increased healthy lifestyle (support) behavior.
Female state and condition-dependent chemical signaling revealed by male choice of silk trails
Authors: Beyer Michelle , Uludağ Kardelen Özgün , Tuni Cristina
Published: September 2023

Male mate choice is predicted in systems with high costs of mating, as for those with male nuptial gifts and/or sexual cannibalism. We ask whether males of the nuptial gift-giving spider Pisaura mirabilis exert preferences for mates varying in their reproductive potential based on chemical information during mate search. Males were presented with binary trails consisting of silk lines and substrate-borne chemicals deposited while females were walking, from females varying in 1) body condition (high vs. low), 2) developmental state (subadult vs. adult), and 3) mating state (unmated vs. mated). If female chemical signaling co-varies with individual state, we expect males to choose trails of females that are 1) in higher body condition, indicating higher fecundity, 2) adults, which can successfully reproduce, and 3) unmated, to avoid sperm competition. We show that female signaling is condition-dependent, with males being more likely to follow trails of higher body condition females, but not dependent on female mating state. Males also tended to prefer trails of adults over subadults. Choice did not depend on male individual body condition. Our findings suggest costs to chemical signaling in nutritionally deprived females, often considered negligible, and their potential as reliable indicators of individual quality. Selection may favor male preferences for more fecund partners given the energetic investment nuptial gifts entail. Nutritional and reproductive benefits of multiple mating to females and high share of paternity for males, may instead select against signaling of female mating state, and/or male discrimination and choice.
A scan of all coding region variants of the human genome, identifies 13q12.2-rs9579139 and 15q24.1-rs2277598 as novel risk loci for pancreatic ductal adenocarcinoma
Authors: Giaccherini Matteo , Gori Leonardo , Gentiluomo Manuel , Farinella Riccardo , Cervena Klara , Skieceviciene Jurgita , Dijk Frederike , Capurso Gabriele , Vezakis Antonis , Archibugi Livia , Chammas Roger , Hussein Tamás , Tavano Francesca , Hegyi Péter , Lovecek Martin , Izbicki Jakob R , Brenner Hermann , Mohelnikova-Duchonova Beatrice , Dell’Anna Giuseppe , Kupcinskas Juozas , Ermini Stefano , Aoki Mateus Nóbrega , Neoptolemos John P , Gazouli Maria , Pasquali Claudio , Pezzilli Raffaele , Talar-Wojnarowska Renata , Oliverius Martin , Al-Saeedi Mohammed , Lucchesi Maurizio , Furbetta Niccolò , Carrara Silvia , van Eijck Casper H J , Maleckas Almantas , Milanetto Anna Caterina , Lawlor Rita T , Schöttker Ben , Boggi Ugo , Morelli Luca , Ginocchi Laura , Ponz de Leon Pisani Ruggero , Sperti Cosimo , Zerbi Alessandro , Arcidiacono Paolo Giorgio , Uzunoglu Faik G , Bunduc Stefania , Holleczek Bernd , Gioffreda Domenica , Małecka-Wojciesko Ewa , Kiudelis Mindaugas , Szentesi Andrea , van Laarhoven Hanneke W M , Soucek Pavel , Götz Mara , Erőss Bálint , Cavestro Giulia Martina , Basso Daniela , Perri Francesco , Landi Stefano , Canzian Federico , Campa Daniele
Published: September 2023

Coding sequence variants comprise a small fraction of the germline genetic variability of the human genome. However, they often cause deleterious change in protein function and are therefore associated with pathogenic phenotypes. To identify novel pancreatic ductal adenocarcinoma (PDAC) risk loci, we carried out a complete scan of all common missense and synonymous SNPs and analysed them in a case–control study comprising four different populations, for a total of 14 538 PDAC cases and 190 657 controls. We observed a statistically significant association between 13q12.2-rs9581957-T and PDAC risk (P = 2.46 × 10−9), that is in linkage disequilibrium (LD) with a deleterious missense variant (rs9579139) of the URAD gene. Recent findings suggest that this gene is active in peroxisomes. Considering that peroxisomes have a key role as molecular scavengers, especially in eliminating reactive oxygen species, a malfunctioning URAD protein might expose the cell to a higher load of potentially DNA damaging molecules and therefore increase PDAC risk. The association was observed in individuals of European and Asian ethnicity. We also observed the association of the missense variant 15q24.1-rs2277598-T, that belongs to BBS4 gene, with increased PDAC risk (P = 1.53 × 10−6). rs2277598 is associated with body mass index and is in LD with diabetes susceptibility loci. In conclusion, we identified two missense variants associated with the risk of developing PDAC independently from the ethnicity highlighting the importance of conducting reanalysis of genome-wide association studies (GWASs) in light of functional data.
Mussel mass mortality in the Clinch River, USA: metabolomics detects affected pathways and biomarkers of stress
Authors: Putnam Joel G , Steiner John N , Richard Jordan C , Leis Eric , Goldberg Tony L , Dunn Christopher D , Agbalog Rose , Knowles Susan , Waller Diane L
Published: September 2023

Biologists monitoring freshwater mussel (order Unionida) populations rely on behavioral, often subjective, signs to identify moribund (“sick”) or stressed mussels, such as gaping valves and slow response to probing, and they lack clinical indicators to support a diagnosis. As part of a multi-year study to investigate causes of reoccurring mortality of pheasantshell (Ortmanniana pectorosa; synonym Actinonaias pectorosa) in the Clinch River, Virginia and Tennessee, USA, we analyzed the hemolymph metabolome of a subset of mussels from the 2018 sampling period. Mussels at the mortality sites were diagnosed in the field as affected (case) or unaffected (control) based on behavioral and physical signs. Hemolymph was collected in the field by non-lethal methods from the anterior adductor muscle for analysis. We used ultra-high-performance liquid chromatography with quadrupole time-of-flight mass spectroscopy to detect targeted and untargeted metabolites in hemolymph and compared metabolomic profiles by field assessment of clinical status. Targeted biomarker analysis found 13 metabolites associated with field assessments of clinical status. Of these, increased gamma-linolenic acid and N-methyl-l-alanine were most indicative of case mussels, while adenine and inosine were the best indicators of control mussels. Five pathways in the targeted analysis differed by clinical status; two of these, purine metabolism and glycerophospholipid metabolism, were also indicated in the untargeted analysis. In the untargeted nalysis, 22 metabolic pathways were associated with clinical status. Many of the impacted pathways in the case group were catabolic processes, such as degradation of amino acids and fatty acids. Hierarchical clustering analysis matched clinical status in 72% (18 of 25) of mussels, with control mussels more frequently (5 of 16) not matching clinical status. Our study demonstrated that metabolomic analysis of hemolymph is suitable for assessing mussel condition and complements field-based indicators of health.
Non-invasive myocardial work in aortic stenosis: validation and improvement in left ventricular pressure estimation
Authors: Ribic Darijan , Remme Espen W , Smiseth Otto A , Massey Richard J , Eek Christian H , Kvitting John-Peder Escobar , Gullestad Lars , Broch Kaspar , Russell Kristoffer
Published: September 2023

Aims

The non-invasive myocardial work index (MWI) has been validated in patients without aortic stenosis (AS). A thorough assessment of methodological limitations is warranted before this index can be applied to patients with AS.

Methods and results

We simultaneously measured left ventricular pressure (LVP) by using a micromanometer-tipped catheter and obtained echocardiograms in 20 patients with severe AS. We estimated LVP curves and calculated pressure–strain loops using three different models: (i) the model validated in patients without AS; (ii) the same model, but with pressure at the aortic valve opening (AVO) adjusted to diastolic cuff pressure; and (iii) a new model based on the invasive measurements from patients with AS. Valvular events were determined by echocardiography. Peak LVP was estimated as the sum of the mean aortic transvalvular gradient and systolic cuff pressure. In same-beat comparisons between invasive and estimated LVP curves, Model 1 significantly overestimated early systolic pressure by 61 ± 5 mmHg at AVO compared with Models 2 and 3. However, the average correlation coefficients between estimated and invasive LVP traces were excellent for all models, and the overestimation had limited influence on MWI, with excellent correlation (r = 0.98, P < 0.001) and good agreement between the MWI calculated with estimated (all models) and invasive LVP.

Conclusion

This study confirms the validity of the non-invasive MWI in patients with AS. The accuracy of estimated LVP curves improved when matching AVO to the diastolic pressure in the original model, mirroring that of the AS-specific model. This may sequentially enhance the accuracy of regional MWI assessment.
Gender-affirming treatment and mental health diagnoses in Danish transgender persons: a nationwide register-based cohort study
Authors: Glintborg Dorte , Møller Jens-Jakob Kjer , Rubin Katrine Hass , Lidegaard Øjvind , T’Sjoen Guy , Larsen Mie-Louise Julie Ørsted , Hilden Malene , Andersen Marianne Skovsager
Published: September 2023

Importance

Gender affirming treatment aims to improve mental health.

Objective

To investigate longitudinal mental health outcomes in Danish transgender persons.

Design

National register-based cohort study in Danish transgender persons with diagnosis code of “gender identity disorder” during the period 2000-2021.

Participants

Five age-matched controls of the same sex at birth and five age-matched controls of the other sex at birth were included for each transgender person.

Main outcomes

Diagnosis codes of mental and behavioral disorders and/or prescription of psychopharmacological agents until June 2022.

Results

The cohort included 3812 transgender persons with median age (interquartile range) 19 (15; 24) years for persons assigned female at birth (AFAB, N = 1993) and 23 (19; 33) years for persons assigned male at birth (AMAB, N = 1819) and 38 120 controls. Follow up duration was up to 10 years with mean (standard deviation) 4.5 (4.3) years. In transgender persons AFAB compared to control women, the odds ratio (OR) (95% confidence interval) for mental and behavioral disorders was 6.7 (5.5; 8.1) before the index date, 9.9 (8.4; 11.7) at 1 year, 5.8 (4.4; 7.7) at 5 years, and 3.4 (2.1; 7.5) at 8 years follow up. In transgender persons AMAB compared to control men, corresponding ORs were 5.0 (4.0; 6.4), 11.3 (9.3; 13.7), 4.8 (3.5; 6.5), and 6.6 (4.2; 10.3) at 8 years follow up (all P < .001).

Conclusion

The OR for mental health disorders was higher in transgender persons compared to controls and remained elevated throughout follow up, especially in transgender persons AMAB.
Situated socio-material assemblages: assemmethodology in the making
Authors: Due Brian L
Published: September 2023

This article proposes the concept of assemmethodology, which combines assemblage theory and ethnomethodology. Relating to the ongoing studies in sociomateriality, this article advances our understanding of the details of social conduct and the consequentiality of materials. By explicating the role of the situation and its processual becoming, which is inherent in ethnomethodology, and by replacing the unit of analysis from the individual to the assemblage made up of heterogenous elements, this article contributes to communication research that seeks to advance our understanding of the ways in which humans are entangled with the material world. As a perspicuous case for the study of assemmethodology, this article explores situations in which screens are assembled with humans and other materials in social situations. The article uses these examples to highlight the necessity of maintaining a focus on the situated emergence of socio-material orders as a property of the activity.
Genes positively regulated by Mef2c in cortical neurons are enriched for common genetic variation associated with IQ and educational attainment
Authors: Fahey Laura , Ali Deema , Donohoe Gary , Ó Broin Pilib , Morris Derek W
Published: September 2023

The myocyte enhancer factor 2 C (MEF2C) gene encodes a transcription factor important for neurogenesis and synapse development and contains common variants associated with intelligence (IQ) and educational attainment (EA). Here, we took gene expression data from the mouse cortex of a Mef2c mouse model with a heterozygous DNA binding-deficient mutation of Mef2c (Mef2c-het) and combined these data with MEF2C ChIP-seq data from cortical neurons and single-cell data from the mouse brain. This enabled us to create a set of genes that were differentially regulated in Mef2c-het mice, represented direct target genes of MEF2C and had elevated in expression in cortical neurons. We found this gene-set to be enriched for genes containing common genetic variation associated with IQ and EA. Genes within this gene-set that were down-regulated, i.e. have reduced expression in Mef2c-het mice versus controls, were specifically significantly enriched for both EA and IQ associated genes. These down-regulated genes were enriched for functionality in the adenylyl cyclase signalling system, which is known to positively regulate synaptic transmission and has been linked to learning and memory. Within the adenylyl cyclase signalling system, three genes regulated by MEF2C, CRHR1, RGS6, and GABRG3, are associated at genome-wide significant levels with IQ and/or EA. Our results indicate that genetic variation in MEF2C and its direct target genes within cortical neurons contribute to variance in cognition within the general population, and the molecular mechanisms involved include the adenylyl cyclase signalling system’s role in synaptic function.
Software Application Profile:dynamicLM—a tool for performing dynamic risk prediction using a landmark supermodel for survival data under competing risks
Authors: Fries Anya H , Choi Eunji , Wu Julie T , Lee Justin H , Ding Victoria Y , Huang Robert J , Liang Su-Ying , Wakelee Heather A , Wilkens Lynne R , Cheng Iona , Han Summer S
Published: September 2023

Motivation

Providing a dynamic assessment of prognosis is essential for improved personalized medicine. The landmark model for survival data provides a potentially powerful solution to the dynamic prediction of disease progression. However, a general framework and a flexible implementation of the model that incorporates various outcomes, such as competing events, have been lacking. We present an R package, dynamicLM, a user-friendly tool for the landmark model for the dynamic prediction of survival data under competing risks, which includes various functions for data preparation, model development, prediction and evaluation of predictive performance.

Implementation

dynamicLM as an R package.

General features

The package includes options for incorporating time-varying covariates, capturing time-dependent effects of predictors and fitting a cause-specific landmark model for time-to-event data with or without competing risks. Tools for evaluating the prediction performance include time-dependent area under the ROC curve, Brier Score and calibration.

Availability

Available on GitHub [https://github.com/thehanlab/dynamicLM].
The promotion strategies of heat metering and charging in China’s heating region based on complex network evolutionary game model
Authors: Hu Wei , Yuan Hongwen , Chen Xi , Ding Qin
Published: September 2023

Heat metering and charging can help raise residents’ awareness of energy conservation and save heat consumption in buildings. The heat metering and charging in China, however, was promoted insignificantly. To explore the behavior mechanism of heat-supply enterprises implementing heat metering and charging under the background of complex network in China’s heating region, and put forward the promotion strategies of heat metering and charging, this paper uses the heat-supply enterprises as the sample, improves the utility function of heat-supply enterprises by considering their difference aversion preference and altruistic preference at the same time based on the Difference Averse Surplus Maximizer Model. Then, we establish a complex network evolutionary game model among different heat-supply enterprises, and an empirical analysis is conducted to examine the impact of different factor on heat-supply enterprises in China’s heating region to implement heat metering and charging. The conclusions are as follows: (1) With the current heating cost and income, even if the government subsidizes all environmental benefit generated by heat metering and charging to heat-supply enterprises, the heat metering and charging could not be promoted in different scales of networks. (2) Increasing metering heat price, government fine, environmental protection tax and carbon emission trading price have positive effects on the promotion of heat metering and charging in different scales of networks. (3) The value of metering heat price, government fine, environmental protection tax and carbon emission trading price have no significant impacts on the evolutionary speeds of different scales of networks.
Impact of the COVID-19 pandemic on community antibiotic consumption in the EU/European Economic Area: a changepoint analysis
Authors: Vermeulen Helene , Hens Niel , Catteau Lucy , Catry Boudewijn , Coenen Samuel
Published: September 2023

Objectives

A decrease in community antibiotic consumption in Europe has been observed during the COVID-19 pandemic. The magnitude of this decrease, how fast after the outbreak it occurred, whether it was sustained during the pandemic and whether the seasonal variation in antibiotic consumption was affected, have not yet been evaluated in detail.

Methods

Data on community antibiotic consumption were available from the European Surveillance of Antimicrobial Consumption Network for 28 EU/European Economic Area (EEA) countries between 2010 and 2021. Antibiotic consumption was expressed as DDDs per 1000 inhabitants per day (DID). The impact of the pandemic on antibiotic consumption was investigated using descriptive statistics and non-linear mixed changepoint models for quarterly and yearly data.

Results

The decrease in overall antibiotic consumption between 2019 and 2020 (−3.4 DID; −18.6%) was mainly due to a decrease in the consumption of penicillins [Anatomical Therapeutic Chemical (ATC) code J01C] (−1.9 DID; −23.0%), other β-lactam antibacterials (J01D) (−0.6 DID; −25.8%) and macrolides, lincosamides and streptogramins (J01F) (−0.5 DID; −17.4%) and was sustained during 2021. The changepoint analysis of yearly data (28 countries) estimated a decrease of 3.3 DID in overall antibiotic consumption (J01) between 2019 and 2020. The analysis of quarterly data (16 countries) estimated a decrease in overall antibiotic consumption (J01) of 4.0 DID and a decrease in seasonal variation of 1.2 DID between the first and second quarters of 2020.

Conclusions

The changepoint analysis indicated a significant, sudden and steep decrease in community antibiotic consumption in the EU/EEA immediately after the start of the COVID-19 outbreak in Europe, as well as a decrease in its seasonal variation.
A hydrophilic polyimidazolium antibiotic targeting the membranes of Gram-negative bacteria
Authors: Chen Yahua , Yong Melvin , Li Ming , Si Zhangyong , Koh Chong Hui , Lau Pearlyn , Chang Yi Wei , Teo Jeanette , Chan-Park Mary B , Gan Yunn-Hwen
Published: September 2023

Objectives

The rise of MDR Gram-negative bacteria (GNB), especially those resistant to last-resort drugs such as carbapenems and colistin, is a global health risk and calls for increased efforts to discover new antimicrobial compounds. We previously reported that polyimidazolium (PIM) compounds exhibited significant antimicrobial activity and minimal mammalian cytotoxicity. However, their mechanism of action is relatively unknown. We examined the efficacy and mechanism of action of a hydrophilic PIM (PIM5) against colistin- and meropenem-resistant clinical isolates.

Methods

MIC and time–kill testing was performed for drug-resistant Escherichia coli and Klebsiella pneumoniae clinical isolates. N-phenyl-1-naphthylamine and propidium iodide dyes were employed to determine membrane permeabilization. Spontaneous resistant mutants and single deletion mutants were generated to understand potential resistance mechanisms to the drug.

Results

PIM5 had the same effectiveness against colistin- and meropenem-resistant strains as susceptible strains of GNB. PIM5 exhibited a rapid bactericidal effect independent of bacterial growth phase and was especially effective in water. The polymer disrupts both the outer and cytoplasmic membranes. PIM5 binds and intercalates into bacterial genomic DNA upon entry of cells. GNB do not develop high resistance to PIM5. However, the susceptibility and uptake of the polymer is moderately affected by mutations in the two-component histidine kinase sensor BaeS. PIM5 has negligible cytotoxicity on human cells at bacterial-killing concentrations, comparable to the commercial antibiotics polymyxin B and colistin.

Conclusions

PIM5 is a potent broad-spectrum antibiotic targeting GNB resistant to last-resort antibiotics.