bluuebunny/crossref_metadata_2025 huggingface dataset:
Inactivation of CaV1 and CaV2 channels
Authors: Limpitikul Worawan B. , Dick Ivy E.
Published: January 2025

Voltage-gated Ca2+ channels (VGCCs) are highly expressed throughout numerous biological systems and play critical roles in synaptic transmission, cardiac excitation, and muscle contraction. To perform these various functions, VGCCs are highly regulated. Inactivation comprises a critical mechanism controlling the entry of Ca2+ through these channels and constitutes an important means to regulate cellular excitability, shape action potentials, control intracellular Ca2+ levels, and contribute to long-term potentiation and depression. For CaV1 and CaV2 channel families, inactivation proceeds via two distinct processes. Voltage-dependent inactivation (VDI) reduces Ca2+ entry through the channel in response to sustained or repetitive depolarization, while Ca2+-dependent inactivation (CDI) occurs in response to elevations in intracellular Ca2+ levels. These processes are critical for physiological function and undergo exquisite fine-tuning through multiple mechanisms. Here, we review known determinants and modulatory features of these two critical forms of channel regulation and their role in normal physiology and pathophysiology.
Momentum dependent potentials from a parity doubling CMF model in UrQMD: results on flow and particle production
Authors: Steinheimer Jan , Reichert Tom , Nara Yasushi , Bleicher Marcus
Published: January 2025

The quantum molecular dynamics (QMD) part of the UrQMD model is extended to allow implementation of momentum dependent potentials from a parity doubling chiral mean field (CMF) model. Important aspects like energy conservation and effects on particle production and flow are discussed. It is shown, that this new implementation reproduces qualitatively and quantitatively available data over a wide range of beam energies and improves the description of observables without exception. In particular the description of hyperon and pion production at SIS18 energies is improved. From a comparison with HADES data one could conclude that the present parametrization of the CMF model leads to a slightly too weak momentum dependence. However, a more firm conclusion will require a systematic comparison with flow and multiplicity data over a range of beam energies and system sizes. Our work serves as an important step towards such future studies where the properties of dense QCD matter, through parameters of the CMF model, can be constraint using a comparison of the UrQMD model with high precision heavy ion data, finally also allowing direct comparisons with neutron star and neutron star merger observables.
Universal underwater camera calibration method based on a forward multilayer refractive model
Authors: Wang Yukun , Ye Fan , Chen Xiaobo , Xi Juntong
Published: January 2025

Multiple refractions between different media lead to camera refractive distortions, thereby making it difficult to ensure underwater measurement accuracy. Consequently, precise modeling and calibration of underwater multilayer imaging systems is essential to address these distortions. In this paper, employing a perspective projection scale factor along the light propagation direction, a universal forward multilayer refractive model is presented. On this basis, the refractive model incorporates a general rotation matrix, which not only enriches application diversity but also enhances solution precision. Allowing for direct underwater camera calibration without prior calibration in air, the model simplifies the calibration process and enhances its suitability for practical applications. Through underwater calibration experiments, the refractive model enhances solution efficiency, improves identification precision and distributes evenly and mediately in terms of reprojection error. In addition, it increases the number of identifiable parameters, demonstrating its robustness and superiority in complex parameter identification scenarios. Finally, underwater measurement experiments indicate that the absolute accuracy calibrated and measured by the refractive model is better than 0.25 mm. Overall, combining all the benefits of forward and backward compensation methods, the forward refractive model offers versatility in handling multiple refractions without limited refractive layers.
Relativistic effects on properties of halogen group elements/ions
Authors: Kahil Mohamed , Joudieh Nabil , Chamoun Nidal
Published: January 2025

This study investigates the influence of relativistic effects on some atomic properties of the halogen group and gold atoms, including their ions (±1). The analysis covers radii, orbital’s energy, first and second ionization energies, electron affinity, and polarizability. The study confirms that the p1/2 orbitals contract under relativistic effects, whereas for the p3/2 orbitals, the mass-velocity and spin–orbit effects do not appear to cancel each other out completely. This may indicate that the spin–orbit effect grows, when increasing the atomic number, slightly faster than the mass-velocity effect. In addition, expansion of the np3/2 orbitals may lead to dilation of the bond length in the related molecules. We found that the non-relativistic Hartree–Fock method gave, for atoms from fluorine to iodine, first ionization energy values with smaller deviations from their experimental ones than other methods involving relativistic and correlation effects. In particular, the method accurately, up to three significative digits, predicts the experimental value for chlorine, and thus can be adopted, discarding other sophisticated methods considering the huge computational effort required by them while not improving much on the agreement with experiment, when evaluating physical/chemical properties of large systems containing light halogen elements. It also predicts an electron affinity of 2.4 eV for the tennessine atom, where it shows also that the relativistic effects play a more important role than in gold atoms.
Stochastic parabolic system: homogenization in time-dependent potential and random fluctuations
Authors: Li Wanyun , Ma Feiyao , Wo Weifeng
Published: January 2025

We study the convergence of the solution to the parabolic system with time-dependent, zero-mean Gaussian potential. Depending on the decorrelation properties of the Gaussian potential, the spatial dimension, and the order of the elliptic operator, we prove that the solution to the parabolic system strongly converges to the deterministic solution of the homogenized system. Additionally, we also getthat the random fluctuation converges in distribution, after a certain scaling transformation, to the solution of the stochastic partial differential system with additive noise. Unlike the error term, the random fluctuation can asymptotically capture the stochasticity in the solution.
Viral load inference of high dynamic range signals using non-adaptive pooled testing
Authors: Sheikh Mansoor , Saad David
Published: January 2025

Medical diagnostic testing can be made significantly more efficient using pooled testing protocols. These typically require a sparse infection signal and use either binary or real-valued entries of

O
(
1
)

. However, existing methods do not allow for inferring viral loads which span many orders of magnitude. We develop a message passing algorithm coupled with a PCR (Polymerase Chain Reaction) specific noise function to allow accurate inference of realistic viral load signals. A version of the Combinatorial Orthogonal Matching Pursuit algorithm is employed to compare the obtained inference results with those of our probabilistic message passing. This work is in the non-adaptive setting and could open the possibility of efficient screening where viral load determination is clinically important.
Enhancement of optoelectronic performance by plasmonic effect in TiO2-rGO/Ag-TiO2 based on UV detectors
Authors: Zhumabekov Аlmar , Dossanov Talgat , Kassanova Assia , Ispulov Nurlybek , Iskakova Anargul , Temirbayeva Dilara , Daniyarova Zhanat
Published: January 2025

This paper investigates the plasmonic effect in ultraviolet (UV) detectors based on titanium dioxide (TiO2) and reduced graphene oxide (rGO). Studies have shown that a TiO2-rGO nanocomposite material is obtained by hydrothermal synthesis. Adding silver nanoparticles (NPs) and Ag-TiO2 ‘core-shell’ nanostructures (NSs) leads to the plasmonic effect and an increase in the optoelectronic parameters. The TiO2-rGO images were obtained with the help of SEM and Raman spectroscopy, and the ratio ID/IG was found. Hydrothermal synthesis results in a long-term reduction of rGO, i.e., the amount of oxygen-containing groups decreases. Raman spectroscopy shows the presence of peaks characteristic of the starting materials. The absorption properties when adding plasmonic nanoparticles to the films show changes in the absorption spectrum in the visible light region due to the transparency of rGO. The current-voltage characteristics show that the presence of plasmonic particles in the nanocomposite material leads to an increase in the photoinduced current of about 94 μA, which is almost 3.0 times greater. When irradiated, the multicomponent nanocomposite material with plasmonic nanoparticles responds to light three times faster than TiO2- rGO. The results can be used to develop new light-sensitive devices for optoelectronic and photocatalytic applications.
Scale–free localization: the role of semi-edges
Authors: Yuce Cem
Published: January 2025

In a one-dimensional lattice, a semi-edge refers to a boundary region where one direction of coupling between lattice sites is absent, while the coupling in the opposite direction remains intact. This creates a transitional regime where the lattice does not exhibit a complete edge with zero couplings in both directions, but rather shows partial edge-like characteristics due to the absence of coupling in one direction. In this region, certain properties or behaviors associated with edges appear. We consider a one-dimensional non-Hermitian lattice and explore skin localization in the presence of a coupling impurity that acts as a semi-edge. Our findings reveal the emergence of scale-free localized (SFL) modes when an impurity significantly reduces coupling in one direction.
Detection of Emission Line Galaxies in the Slitless Spectra of HST and CSST
Authors: Chen Kaiyuan , Zhu Shuairu , Jiang Linhua , Zheng Zhenya
Published: January 2025

Slitless spectroscopy onboard space telescopes is a powerful tool to detect emission-line objects such as emission-line galaxies (ELGs) and quasars. In this work, we present a study of ELGs observed with slitless spectroscopy by the Hubble Space Telescope (HST) in a deep field of ​​​​​​∼44 arcmin2. This is one of the deepest HST fields with a wealth of imaging and spectral data. In particular, previous VLT/MUSE observations have covered this field and identified a large number of ELGs. We reduce the HST spectra using the latest pipeline with a forward modeling algorithm and construct a sample of ELGs. By comparing with the MUSE spectra, we characterize our ELG detection in the HST spectra, including the impact of the line flux, line width, signal-to-noise ratio, etc. We find that the morphological broadening may affect the detection of ELGs, such that more compact sources are easier to be detected in slitless spectra. We discuss its implications to future slitless spectroscopic surveys that will be carried out by the China Space Station Telescope (CSST) and find that the CSST slitless spectroscopy has a capability comparable to that of HST in terms of the detection of emission lines.
Modelling the brittle failure of graphite induced by the controlled impact of runaway electrons in DIII-D
Authors: Ratynskaia S. , Tolias P. , Rizzi T. , Paschalidis K. , Kulachenko A. , Hollmann E. , Beidler M. , Liu Y. , Rudakov D. , Bykov I. , Pitts R.A.
Published: January 2025

The thermo-mechanical response of an ATJ graphite sample to controlled runaway electron (RE) dissipation, realized in DIII-D, is modelled with a novel work-flow that features the RE orbit code KORC, the Monte Carlo particle transport code Geant4 and the finite element multiphysics software COMSOL. KORC provides the RE striking positions and momenta, Geant4 calculates the volumetric energy deposition and COMSOL simulates the thermoelastic response. Brittle failure is predicted according to the maximum normal stress criterion, which is suitable for ATJ graphite owing to its linear elastic behavior up to fracture and its isotropic mechanical properties. Measurements of the conducted energy, damage topology, explosion timing and blown-off material volume, impose a number of empirical constraints that suffice to distinguish between different RE impact scenarios and to identify RE parameters which provide the best match to the observations.
Understanding the formation of a low-pressure pedestal in the presence of a strong internal transport barrier in DIII-D high βp plasmas
Authors: Zhang X.R. , Jian X. , Zhu Y.R. , Zou Y.P. , Li Z.Y. , Zhou Y.J. , Liu L.Z. , Zheng S. , Wang Z.X. , Chen W. , Ding S.Y. , Garofalo A.M. , Chan V.S. , Li G.Q.
Published: January 2025

As a promising scenario for fusion reactors, the high poloidal-beta (

β

P

) scenario is characterized by a strong large radius internal transport barrier (ITB), which significantly enhances the overall confinement quality and the bootstrap current fraction for fully non-inductive operation. It is frequently observed that in the presence of a strong ITB, the pedestal height is lower and is accompanied by small edge localized modes (ELMs), which further improves the compatibility of a high performance core with an edge solution. A mechanism for the formation of the low pedestal is proposed in this paper. It is found that the strong ITB creates an off-axis bootstrap current to clamp the local safety factor q, and thus the magnetic shear in the outer core/pedestal region is increased. Gyrokinetic simulations with the CGYRO code show that the higher magnetic shear brings the experimental profiles into the range where the growth rate of drift-wave instabilities and thus transport is higher, and therefore a lower pedestal gradient is expected. The combination of low pedestal and high magnetic shear further enhances the turbulent transport across the whole pedestal, consistent with power balance analysis. Such a positive feedback mechanism ultimately results in a lower pressure pedestal as observed in experiments. Under such a low pedestal, linear simulations with BOUT++ predict the growth rates of peeling–ballooning modes to be lower across the whole toroidal mode number spectra, and the nonlinear BOUT++ simulation exhibits lower saturated fluctuation intensity as well, consistent with the experimentally observed lower ELM size.
Mapping the social-ecological suitability of agroforestry in the US Midwest
Authors: Castle Sarah E , Miller Daniel C , Wardropper Chloe B
Published: January 2025

Agroforestry practices offer the potential to increase agricultural sustainability, but their adoption remains limited, especially in some of the world’s most highly productive regions like the United States (US) Midwest. Integrated assessment of the environmental, social, and economic factors that determine agroforestry’s potential benefits and social acceptability is needed to effectively target agroforestry expansion. To meet this need, we used geospatial multi-criteria decision analysis to map agroforestry’s suitability across the US Midwest. We mapped priority areas where agroforestry is expected to reduce the risk of environmental degradation, provide productive tree growth, and be socially and economically viable. We show that integrating social and economic factors dramatically shifted priorities compared to an environmental-only suitability assessment. Using COMET-Planner, we estimated that expanding agroforestry to the top 5% most suitable land from our analysis (totaling 18.3 million acres) has the potential to store 43 [29–58] Mt of CO2e per year over the business-as-usual scenario. Our integrated approach can help stakeholders identify target areas for agroforestry and provides a theoretical foundation for interdisciplinary suitability mapping that can be adapted for use in other global regions.
The Dirac equation near centenary: a contemporary introduction to the Dirac equation consideration
Authors: Simulik V M
Published: January 2025

More then 35 approaches to the Dirac equation derivation are presented. Various physical principles and mathematical methods are used. A review of well-known and not enough known contributions to the problem is given, unexpected and unconventional derivations are presented as well. Three original approaches to the problem suggested by the author are considered: (i) generalization of H. Sallhofer derivation, (ii) obtaining of massless Dirac equation from the Maxwell equations in a maximally symmetrical form, (iii) derivation of the Dirac equation with nonzero mass from relativistic canonical quantum mechanics of the fermion-antifermion spin s = 1/2 doublet. Today we are able to demonstrate new features of our derivations given in original papers. In some sense the important role of the Dirac equation in contemporary theoretical physics is demonstrated. A criterion for the usefulness of one or another derivation of the Dirac equation is established.
Volumetric bioprinting of the osteoid niche
Authors: Duquesne Jessie , Parmentier Laurens , Vermeersch Edward , Lemaire Flora , Seo Jung Won , Dmitriev Ruslan I , Vlierberghe Sandra Van
Published: January 2025

Volumetric bioprinting has revolutionized the field of biofabrication by enabling the creation of cubic centimeter-scale living constructs at faster printing times (in the order of seconds). However, a key challenge remains: developing a wider variety of available osteogenic bioinks that allow osteogenic maturation of the encapsulated cells within the construct. Herein, the bioink exploiting a step-growth mechanism (norbornene–norbornene functionalized gelatin in combination with thiolated gelatin—GelNBNBSH) outperformed the bioink exploiting a chain-growth mechanism (gelatin methacryloyl—GelMA), as the necessary photo-initiator concentration was three times lower combined with a more than 50% reduction in required light exposure dose resulting in an improved positive and negative resolution. To mimic the substrate elasticity of the osteoid, two concentrations of the photo-initiator Li-TPO-L (1 and 10 mg ml−1) were compared for post-curing whereby the lowest concentration was selected since it resulted in attaining the osteogenic substrate elasticity combined with excellent biocompatibility with HT1080 cells (>95%). Further physico-chemical testing revealed that the volumetric printing (VP) process affected the degradation time of the constructs with volumetric constructs degrading slower than the control sheets which could be due to the introduced fibrillar structure inherent to the VP process. Moreover, GelNBNBSH volumetric constructs significantly outperformed the GelMA volumetric constructs in terms of a 2-fold increase in photo-crosslinkable moiety conversion and a 3-fold increase in bulk stiffness of the construct. Finally, a 21-day osteogenic cell study was performed with highly viable dental pulp-derived stem cells (>95%) encapsulated within the volumetric printed constructs. Osteogenesis was greatly favored for the GelNBNBSH constructs through enhanced early (alkaline phosphatase activity) and late maturation (calcium production) osteogenic markers. After 21 d, a secretome analysis revealed a more mature osteogenic phenotype within GelNBNBSH constructs as compared to their chain-growth counterpart in terms of osteogenic, immunological and angiogenic signaling.
Plasmonic waveguide-mode based aluminum nanogratings for enhanced chemical and biological sensing in the UV regime
Authors: Ahmed K , Agrawal A K , Kaushik S , Dhawan A
Published: January 2025

We have designed and modeled one dimensional narrow-gap aluminum nanogratings for plasmonic sensing of bulk and localized changes in the refractive index in the UV spectral region. The proposed configuration of the plasmonic sensors based on narrow-gap nanogratings allows normally light to be directly coupled into plasmonic waveguide modes in the gaps between the nanogratings, thereby alleviating the problem of employing bulky prism coupling mechanisms. The rigorous coupled wave analysis (RCWA) simulations were performed to optimize all the narrow-gap nanograting parameters such as the periodicity ‘P’, the gap between the nanograting walls ‘W’, and height ‘H’ of the nanogratings such that the plasmonic sensors based on these nanogratings operated in the UV spectral region and had the highest values of sensing performance characteristics. The plasmon resonance related dips in the reflectance spectra of these narrow-groove nanogratings can be tuned in the far-UV and deep-UV wavelength ranges by varying the different structural parameters of these nanogratings. Furthermore, we have defined other performance parameters like FOM
bulk
* and FOM
localized
* to account for the depth of the plasmonic resonance dip along with the sensitivity (S) and figure of merit (FOM). These narrow-gap nanogratings have localized regions of high electromagnetic fields inside the gaps between the nanogratings, which results in enhanced sensitivity of the proposed structures. We have calculated the maximum bulk sensitivity (S) of 190 nm RIU−1 with the figure of merit (FOM
bulk
*) of 2.567 RIU−1 in the UV region. Similarly, the highest localized sensitivity (S
s) of 18.2 nm nm−1 and a figure of merit (FOM
localized
*) of 0.15356 nm−1 was obtained for the narrow-gap aluminum nanograting based plasmonic sensor. The high sensitivity achieved in localized and bulk sensing enables this configuration to be developed into a compact and highly robust sensor for chemical and bio-sensing applications.
Determining event-related desynchronization onset latency of foot dorsiflexion in people with multiple sclerosis using the cluster depth tests
Authors: Carrere L Carolina , Furios Julián , Biurrun Manresa José A , Ballario Carlos H , Tabernig Carolina B
Published: January 2025

Multiple sclerosis (MS) is a disorder in which the body’s immune system attacks structures of the central nervous system, resulting in lesions that can occur throughout the brain and spinal cord. Cortical lesions, in particular, can contribute to motor dysfunction. Walking disability is reported as the main impairment by people with MS (pwMS), often due to limited ankle movement. This study explored the event-related desynchronization (ERD) onset latency of the sensorimotor rhythms during foot dorsiflexion in pwMS computed using an objective and independent of human criterion method, as an electroencephalogram (EEG) based biomarker. EEG signals were recorded in eight persons with neither neurological condition nor motor dysfunction and eight pwMS with relapsing-remitting, primary progressive or secondary progressive MS. Recordings were divided into three groups: control, more affected lower limb and less affected lower limb. The ERD-onset latency was determined using a method based on the percent of ERD time course and the cluster depth tests. The median and interquartile range of the ERD-onset latency were 1186.0 (1100.0, 1250.0) ms; 1064.0 (1031.0, 1127.0) ms for the more and less affected groups respectively, whereas the median and interquartile range for the control group was 656.0 (472.2, 950.0) ms. There was a significant delay in the ERD-onset latencies of the pwMS groups compared to the control group (p<0.001 for both comparisons). These findings suggest that the ERD-onset latency computed using the proposed method could be used as an EEG biomarker to evaluate disease progression or therapeutic interventions in pwMS.
Robustness of diabatic enhancement in quantum annealing
Authors: Feinstein Natasha , Shalashilin Ivan , Bose Sougato , Warburton P A
Published: January 2025

In adiabatic quantum annealing, the speed with which an anneal can be run, while still achieving a high final ground state (GS) fidelity, is dictated by the size of the minimum gap that appears between the ground and first excited state in the annealing spectrum. To avoid the exponential slowdown associated with exponentially closing gaps, diabatic transitions to higher energy levels may be exploited in such a way that the system returns to the GS before the end of the anneal. In certain cases, this is facilitated by the original annealing spectrum. However, there are also examples where careful manipulation of the annealing Hamiltonian has been used to alter the spectrum to create a diabatic path to the GS. Since diabatic transitions depend on the evolution rate and the gap sizes in the spectrum, it is important to consider the sensitivity of any potential enhancement to changes in the anneal time as well as any parameters involved in the manipulation of the spectrum. We explore this sensitivity using annealing spectra containing an exponentially closing gap and an additional, tuneable, small gap created by a catalyst. We find that there is a trade-off between the precision needed in the catalyst strength and the anneal time in order to maintain the enhancement to the final GS fidelity.
Nanosecond pulsed current source for light emitting diode (LED) driven photoacoustic signal acquisition systems
Authors: Das Avishek , Pramanik Manojit
Published: January 2025

Photoacoustic imaging (PAI) is gaining attention for its non-invasive diagnostic capabilities. Traditionally, bulky and expensive laser systems have been used as excitation light sources in PAI, posing challenges for translation and remote applications. High-power light emitting diodes (LEDs) can be an alternative light source. However, the necessary driver circuitry has not been extensively studied for driving the nanoseconds pulsed LEDs. This study develops and demonstrate for the first time the full circuit, performance, optimization and operating procedures of a nanosecond pulsed current source (NSPCS) to drive a high-power, high-speed LED array for PAI. The NSPCS driver can deliver tunable pulsed LED currents between 0 and 20 A, pulse widths of 50–100 ns, and trigger pulse repetition rates up to 20 kHz, achieving a driver efficiency of 58.27%. It can drive an array of 37 high-power LEDs (850 nm wavelength) with an electrical-to-optical efficiency of 24.8%. Illumination with this LED array produced a photoacoustic signal (after 79 dB amplification with low-noise amplifier) of 3.92 V (peak-to-peak) and a signal-to-noise ratio of 79.36 dB. The NSPCS circuit has demonstrated effective generation of tunable high-current pulses for LED-based PAI applications.
Barriers and drivers of near-term climate change mitigation: a Canadian case study
Authors: Sauer Jeffrey , Posen I Daniel , Saxe Shoshanna
Published: January 2025

This work investigates, through semi-structured interviews, the prospects for rapid transitions towards low-carbon civil infrastructure systems. Rapid greenhouse gas (GHG) mitigation is critical to facilitate the near-term (i.e. within five years) reductions needed to limit global temperature rise to 2 °C. In addition, ongoing delays in climate action in many countries and sectors mean that rapid interventions will be needed in the 2030s and 2040s as climate change evolves and the need to mitigate becomes more urgent. This work examines, among twenty decisionmakers involved in developing, operating, or using Canadian infrastructure: (1) ongoing and expected near-term GHG mitigation actions (2) barriers constraining faster change, and (3) mitigation goals and expectations of the near future. Interviews were coded to identify common perspectives. Results indicate that organizations prioritize enabling deep change in a more distant future over executing rapid change, that detailed roadmaps for meeting near-term (e.g. 2030) goals were rare, and that participants view government policy certainty as crucial to near-term action. This work identifies deficits in action on the near-term scale and aids policymakers and decisionmakers by describing planned near-term mitigation actions and assessing barriers to going faster.
The Ethics of Public Health Paternalism
Authors: Wilkinson T M
Published: January 2025

The Ethics of Public Health Paternalism is about policies that try to stop people damaging their own health. From the point of view of public health advocates, if people did not smoke, or drank less alcohol, or kept off junk food and sugary liquids, they would tend to be healthier. Hence such tactics as taxing tobacco, restricting the sale of alcohol, and limiting the density of fast-food outlets. These tactics are often pejoratively described as the actions of a ‘nanny state’ that overvalues health and wrongly infringes on the autonomy of adults. But many of us want to be healthy rather than ill, and alive rather than dead. Does a state really nanny us when it uses its power to make us healthier? If it does, should it stop? Some public health policies might reduce inequities of health, or save costs in medical treatment, or correct market failures. But, as this book shows, many would not. The best case for many public health interventions is paternalistic, aiming to steer people away from making unhealthy choices against their own interests. But even though it is the best case, it often fails. It advocates overvalue health and undervalue autonomy. They exaggerate the influence of addiction and the marketing of unhealthy products. Except for smoking, we do not have the evidence needed to show that unhealthy choices are so mistaken as to justify the interventions. Many public health interventions probably make their targets worse off and infringe on their autonomy without having compensating benefits to other people.
Public Health and the Nanny State
Authors: Wilkinson T M
Published: January 2025

One aim of public health is to stop people damaging their own health, and this aim invites the nanny state objection. Contrary to what some in public health say, this objection should be taken seriously. One can object to the overreach of public health without being a doctrinaire neoliberal or a cynical defender of corporate interests. The objection has three parts: that public health interventions overvalue health (the ‘healthism’ objection), that they infringe on autonomy (the autonomy objection), and that they do not work (scepticism). The chapter gives examples where exercises of public health power have failed or been abused, but points out that some interventions have succeeded in their own terms. The book then works through healthism and autonomy.
The Limited and Variable Value of Health
Authors: Wilkinson T M
Published: January 2025

Because health is not so overwhelmingly important in our lives that we should never give it up, a public health policy could make people worse off even when it succeeds in making them healthier. And because people vary in how they would trade off health against other benefits, a public health policy could be good for some people but bad for others. These two points seem obvious, but they are often overlooked by public health advocates when they argue for their policies. It is an open question whether even successful public health policies would be ethically justifiable.
The Value of Health and a Challenge to Public Health
Authors: Wilkinson T M
Published: January 2025

The value of a health benefit depends upon the extent to which it fulfils ultimate preferences. While people’s unhealthy behaviour could be against their interests if they make factual mistakes or are not motivated to do what they themselves think best, it could not be against their interests just because they valued other things more than health. This chapter defends that claim against those who might say that values are objective or preferences are adaptive. It qualifies the claim after considering anorexia nervosa. We then come to a challenge: how could public health interventions that reduce people’s options make them better off? This challenge cannot be avoided by saying that unhealthy behaviour is due to poverty, or manipulation, or addiction.
Applications
Authors: Wilkinson T M
Published: January 2025

Smoking is probably against most smokers’ interests but drinking alcohol and consuming junk food and sugary drinks are probably not against the interests of most drinkers and eaters. This chapter considers evidence about regrets, addictions, and attempts to quit or otherwise reverse unhealthy behaviour. The evidence gives strong support for thinking that paternalistically regulating smoking can, in principle, make people better off. But the evidence is much weaker when it comes to alcohol and fattening food and drink. In part, the reason is an absence of evidence. Although researchers have studied the effects of regulations on behaviour and the effects of behaviour on health, they have not done much to connect people’s health to their ultimate preferences. Insofar as we have evidence, it implies that only relatively few eaters and drinkers (whether of alcohol or sugary drinks) make mistakes about their interests. Even if this observation is correct, the paternalistic case for regulation is not lost. But it is in trouble.
Health Equity and Distributive Ethics
Authors: Wilkinson T M
Published: January 2025

Public health interventions would often be inequitable unless the worse off were mistaken in pursuing their interests; and we often have no good reason to think they are mistaken. The chapter argues as follows: reducing the well-being of the worst off is inequitable; public health interventions often reduce choice; when they do, they would tend to make the worst off worse off, not better off, except when choosing unhealthy options is a mistake. Since reducing choice to stop people making mistakes is paternalistic, the equity case for preventive regulations presupposes paternalism. Moreover, advocates make unsupported claims about the choosing abilities of the worst off and, contrary to their claims, public health interventions may well be inequitable. The chapter concludes by considering an argument for burdening the majority to save a minority from alcoholism. This argument has difficulties but cannot be dismissed.
What Is Left for Public Health?
Authors: Wilkinson T M
Published: January 2025

Public health taxes, bans, and other restrictive regulations will tend to make their targets worse off even if they end up healthier. The main exceptions are interventions to reduce smoking. And restrictive interventions infringe on autonomy. They thus seem wrong. These conclusions leave plenty of space for public health interventions, and redistributive social and economic policies; just not ones justified by paternalistic arguments. The chapter concludes with a checklist of questions to ask about the ethics of public health interventions, emphasizing the importance of remembering that people can be made healthier but worse off.
Effect of microemulsion system on water dispersibility and bioavailability of γ-oryzanol
Authors: Ito Junya , Kumagai Naoko , Suzuki Ayaka , Shoji Naoki , Parida Isabella Supardi , Takahashi Mamoru , Nakagawa Kiyotaka
Published: January 2025

This study developed water-dispersible γ-oryzanol (WD-OZ) using a microemulsion system and assessed their absorption in rats. While OZ itself is hardly soluble in water, WD-OZ exhibited high water dispersibility, and OZ, along with its metabolites, was detected in rat plasma. These findings provide a solid basis for future application of the microemulsion-based approach to enhance the bioavailability of OZ in food.
FRPR-1, a G protein-coupled receptor in the FMRFamide-related peptide receptor family, modulates larval development as a receptor candidate of the FMRFamide-like peptide FLP-1 in Caenorhabditis elegans
Authors: Une Risako , Uegaki Riko , Maega Sho , Ono Masahiro , Bito Tomohiro , Iwasaki Takashi , Shiraishi Akira , Satake Honoo , Kawano Tsuyoshi
Published: January 2025

FMRFamide-like peptides (FLPs) and their receptors, FMRFamide-related peptide receptors (FRPRs) are widely conserved in free-living and parasitic nematodes. Herein, we identified FRPR-1 as an FLP-1 receptor candidate involved in larval development and diapause in the model nematode Caenorhabditis elegans. Our molecular genetic study, supported by in silico research, revealed the following: (1) frpr-1 loss-of-function completely suppresses the promotion of larval diapause caused by flp-1 overexpression; (2) AlphaFold2 analysis revealed the binding of FLP-1 to FRPR-1; (3) FRPR-1 as well as FLP-1 modulates the production and secretion of the predominant insulin-like peptide DAF-28, which is produced in ASI neurons; and (4) the suppression of larval diapause by frpr-1 loss-of-function is completely suppressed by a daf-28 defect. Thus, FRPR-1 regulates larval development and diapause by modulating DAF-28 production and secretion. This study may provide new insights into the development of novel nematicides targeting parasitic nematodes using FRPR-1 inhibitors.
Multi-source biological knowledge-guided hypergraph spatiotemporal subnetwork embedding for protein complex identification
Authors: Wang Shilong , Cui Hai , Qu Yanchen , Zhang Yijia
Published: January 2025

Identifying biologically significant protein complexes from protein–protein interaction (PPI) networks and understanding their roles are essential for elucidating protein functions, life processes, and disease mechanisms. Current methods typically rely on static PPI networks and model PPI data as pairwise relationships, which presents several limitations. Firstly, static PPI networks do not adequately represent the scopes and temporal dynamics of protein interactions. Secondly, a large amount of available biological resources have not been fully integrated. Moreover, PPIs in biological systems are not merely one-to-one relationships but involve higher order non-pairwise interactions. To alleviate these issues, we propose HGST, a multi-source biological knowledge-guided hypergraph spatiotemporal subnetwork (subnet) embedding method for identifying biologically significant protein complexes from PPI networks. HGST initially constructs spatiotemporal PPI subnets using the scopes and temporal dynamics of proteins derived from multi-source biological knowledge, treating them as dynamic networks through fine-grained spatiotemporal partitioning. The spatiotemporal subnets are then transformed into hypergraphs, which model higher order non-pairwise relationships via hypergraph embedding. Simultaneously, fine-grained amino acid sequence features and coarse-grained gene ontology attributes are introduced for multi-dimensional feature fusion. Finally, protein complexes are identified from the reweighted subnets based on fused feature representations using the core-attachment strategy. Evaluations on four real PPI datasets demonstrate that HGST achieves competitive performance. Furthermore, a series of biological analyses confirm the high biological significance of the complexes identified by HGST. The source code is available at https://github.com/qifen37/HGST.
Seizures and premature death in mice with targeted Kv1.1 deficiency in corticolimbic circuits
Authors: Paulhus Kelsey , Glasscock Edward
Published: January 2025

Sudden unexpected death in epilepsy (SUDEP) is the leading cause of epilepsy-related death, likely stemming from seizure activity disrupting vital brain centres controlling heart and breathing function. However, understanding of SUDEP's anatomical basis and mechanisms remains limited, hampering risk evaluation and prevention strategies. Prior studies using a neuron-specific Kcna1 conditional knockout mouse model of SUDEP identified the primary importance of brain-driven mechanisms contributing to sudden death and cardiorespiratory dysregulation; yet, the underlying neurocircuits have not been identified. Using the Emx1-Cre driver, we generated a new conditional knockout mouse model lacking Kcna1 in excitatory neurons of the cortex, hippocampus, amygdala and select vagal afferents. To test whether the absence of Kv1.1 in forebrain corticolimbic circuits is sufficient to induce spontaneous seizures, premature mortality and cardiorespiratory dysfunction, we performed survival studies and EEG, ECG, and plethysmography (EEG-ECG-Pleth) recordings. We demonstrate premature death and epilepsy in corticolimbic conditional knockout mice. During monitoring, we fortuitously captured one SUDEP event, which showed a generalized tonic-clonic seizure that initiated respiratory dysfunction culminating in cardiorespiratory failure. In addition, we observed that cardiorespiratory abnormalities are common during non-fatal seizures in conditional knockout mice, but mostly absent during interictal periods, implying ictal, not interictal, cardiorespiratory impairment as a more reliable indicator of SUDEP risk. These results point to corticolimbic excitatory neurons as critical neural substrates in SUDEP and affirm seizure-related respiratory and cardiac failure as a likely cause of death.
Clinical characteristics and biomarker profile in early- and late-onset Alzheimer’s disease: the Shanghai Memory Study
Authors: Wu Jie , Wang Jing , Xiao Zhenxu , Lu Jiaying , Ma Xiaoxi , Zhou Xiaowen , Wu Yuhan , Liang Xiaoniu , Zheng Li , Ding Ding , Zhang Huiwei , Guan Yihui , Zuo Chuantao , Zhao Qianhua ,   the Shanghai Memory Study, Zhao Qianhua , Zuo Chuantao , Ding Ding , Guan Yihui , Zhang Huiwei , Lu Jiaying , Bao Weiqi , Zheng Li , Liang Xiaoniu , Wang Jing , Xiao Zhenxu , Ma Xiaoxi , Wu Jie , Wang Jie , Zhou Xiaowen
Published: January 2025

Early-onset Alzheimer’s disease constitutes ∼5–10% of Alzheimer’s disease. Its clinical characteristics and biomarker profiles are not well documented. To compare the characteristics covering clinical, neuropsychological and biomarker profiles between patients with early- and late-onset Alzheimer’s disease, we enrolled 203 patients (late-onset Alzheimer’s disease = 99; early-onset Alzheimer’s disease = 104) from a Chinese hospital-based cohort, the Shanghai Memory Study. A full panel of plasma biomarkers under the amyloid/tau/neurodegeneration framework including plasma amyloid beta 40, amyloid beta 42, total-tau, neurofilament light chain and phosphorylated tau 181 were assayed using ultra-sensitive Simoa technology. Seventy-five patients underwent an amyloid molecular positron emission tomography scan whereas 43 received comprehensive amyloid, Tau deposition and hypometabolism analysis. Clinical features, plasma and imaging biomarkers were compared cross-sectionally. Compared to those with late-onset Alzheimer’s disease, patients with early-onset Alzheimer’s disease presented more severe impairment in language function, lower frequency of APOE ɛ4 and lower levels of plasma neurofilament light chain (all P < 0.05). The plasma phosphorylated tau 181 concentration and phosphorylated tau 181/amyloid beta 42 ratios were higher in early-onset Alzheimer’s disease than in late-onset Alzheimer’s disease (all P < 0.05). More severe Tau deposition as indicated by 18F-florzolotau binding in the precuneus, posterior cingulate cortex and angular gyrus was observed in the early-onset Alzheimer’s disease group. Plasma phosphorylated tau 181 was associated with earlier age at onset and domain-specific cognitive impairment, especially in patients with early-onset Alzheimer’s disease. We concluded that patients with early-onset Alzheimer’s disease differed from late-onset Alzheimer’s disease in cognitive performance and biomarker profile. A higher burden of pathological tau was observed in early-onset Alzheimer’s disease and was associated with earlier age at onset and more profound cognitive impairment.
Microstructure of the residual corticofugal projection from primary motor cortex in chronic stroke
Authors: Bikmal Saket , Liu Fang , Moon Chan Hong , Urbin Michael A
Published: January 2025

Movement dysfunction after stroke is largely due to the inability of cortical motor neurons to activate spinal motor neurons via transmission of descending motor commands along the corticofugal projection from the primary motor cortex. Pathophysiological processes that ensue following injury have mostly resolved and white matter volume within the remodelled tract has mostly stabilized by the chronic stage many months to years after symptom onset. Where along the cranial course of the residual corticofugal projection white matter microstructure explains potential to activate muscles weakened by stroke at this stage is still not well understood. Here, diffusion spectrum imaging was used to reconstruct the descending corticofugal projection and quantify its microstructure in stroke survivors (n = 25) with longstanding hand impairment (7.7 ± 6.5 years). Portions of the residual tract overlapping with abnormalities on structural images were defined as the ‘Overlap’ compartment, and portions above and below this compartment were defined as ‘Rostral’ and ‘Caudal’ compartments, respectively. Maximal precision grip force and size of motor-evoked potentials elicited by transcranial magnetic stimulation were used to quantify activation of paretic hand muscles. Coherence of fibre anisotropy and directional diffusivities between tracts in either cerebral hemisphere was reduced in stroke survivors relative to neurologically-intact controls, with most abnormal asymmetries observed in the ‘Overlap’ compartment. While differences in fibre anisotropy and diffusivity between residual and intact tracts were detected most prominently in the ‘Overlap’ compartment, the overall magnitude of unrestricted diffusion within the ‘Caudal’ compartment was most closely linked to paretic muscle activation. The ability of cortical motor neurons to access spinal motor neuron pools long after stroke onset is therefore associated with microstructural integrity in portions of the residual corticofugal projection subject to secondary degeneration. These findings expand knowledge on white matter adaptation in response to neurological injury and may inform applications that seek to reverse brain pathology long after stroke onset when movement dysfunction tends to persist.
Disseminated polymorphic mucocutaneous lesions in an immunocompetent 65-year-old man
Authors: Vageshappa Rashmi K , Verma Neeharika , Bains Anupama , Aggarwal Divya
Published: January 2025

A 65-year-old man presented with recurrent episodes of asymptomatic erythematous papular and nodular lesions over the trunk and extremities for 6 years. Over the previous month, he had developed painful oral ulcers associated with lip oedema and sudden-onset hoarseness of voice.