bluuebunny/crossref_metadata_2025 huggingface dataset:
Structure formation with primordial black holes: collisional dynamics, binaries, and gravitational waves
Authors: Delos M. Sten , Rantala Antti , Young Sam , Schmidt Fabian
Published: December 2024

Primordial black holes (PBHs) could compose the dark matter content of the Universe. We
present the first simulations of cosmological structure formation with PBH dark matter that
consistently include collisional few-body effects, post-Newtonian orbit corrections, orbital decay
due to gravitational wave emission, and black-hole mergers. We carefully construct initial
conditions by considering the evolution during radiation domination as well as early-forming
binary systems. We identify numerous dynamical effects due to the collisional nature of PBH dark
matter, including evolution of the internal structures of PBH halos and the formation of a hot
component of PBHs. We also study the properties of the emergent population of PBH binary systems,
distinguishing those that form at primordial times from those that form during the nonlinear
structure formation process. These results will be crucial to sharpen constraints on the PBH
scenario derived from observational constraints on the gravitational wave background. Even under
conservative assumptions, the gravitational radiation emitted over the course of the simulation
appears to exceed current limits from ground-based experiments, but this depends on the evolution
of the gravitational wave spectrum and PBH merger rate toward lower redshifts.
Low temporal radiation coherence of noise-like pulses
Authors: Kobtsev S , Serebrennikov K
Published: December 2024

It is quite well-known that coherence is an intrinsic property of laser radiation. However, after the advent of noise-like pulses, it turns out that the temporal coherence of their radiation is low and the electromagnetic field oscillations in adjacent noise-like pulses are not correlated. This work experimentally studies for the first time the degree of coherence of electromagnetic field oscillations inside a noise-like pulse. We measure the visibility of interference fringes at the exit from a Michelson interferometer when its optical path difference is scanned around zero up to and exceeding the length of the noise-like pulse. The experimental data indicate close to zero temporal coherence of radiation within noise-like pulses.
Systematic studies of odd-even staggering in isotopic cross sections with new difference formulas*
Authors: Mei 梅 Bo 波 , Guan 关 Yu-Tian 玉田 , Zeng 曾 Ning-Xin 宁馨 , Yu 余 Tian-Jun 天俊 , Tu 涂 Jia-Jun 家骏 , Mai 麦 Zi-Ying 子颖 , Ma 马 Hao-Tian 浩添 , Li 李 Ruo-Ya 若雅 , Pan 潘 Yu-Hao 宇浩
Published: December 2024

Although a 3rd-order difference formula has often been employed to investigate the odd-even staggering (OES) in experimental cross sections, other formulas can also be very useful. In this work, three formulas, the 2nd, 4th, and 5th-order difference formulas, are proposed for systematic OES studies. These new difference formulas with different orders are applied to extract the OES magnitudes in extensive accurate cross sections measured in different fragmentation and spallation reaction systems over a broad energy range. According to comparisons of these (2nd, 4th, and 5th-order) OES magnitudes derived from different reaction systems, they almost do not rely on the projectile-target combinations or the projectile energy. A similar universality was observed for the 3rd-order OES magnitudes obtained from various reaction systems in our previous studies of the 3rd-order OES. The weighted average values of the 2nd, 4th, and 5th-order OES magnitudes extracted from different experimental datasets are recommended as the 2nd, 4th, and 5th-order OES evaluations, respectively. Finally, comparisons of these (new) 2nd, 4th, 5th, and previous 3rd-order OES evaluations support that these OES evaluations with different orders are consistent and that all the difference formulas with different orders are applicable to OES studies.
Impact of nonextensivity on the transport coefficients of strongly interacting QCD matter*
Authors: Singh Dhananjay , Kumar Arvind
Published: December 2024

Tsallis nonextensive statistics is applied to study the transport coefficients of strongly interacting matter within the Polyakov chiral

quark mean field model (PCQMF). Nonextensivity is introduced within the PCQMF model through a dimensionless parameter q to examine the viscous properties, such as shear viscosity (η) and bulk viscosity (

), and conductive properties, such as electrical conductivity (

) and thermal conductivity (κ). Additionally, some key thermodynamic quantities relevant to the transport coefficients, such as the speed of sound (

) and specific heat at constant volume (

), are calculated. The temperature dependence of the transport coefficients is explored through a kinetic theory approach with the relaxation time approximation. The results are compared to those of the extensive case where q approaches 1. The nonextensive q parameter is found to have a significant effect on all transport coefficients. We find that the nonextensive behaviour of the medium enhances specific shear viscosity

, as well as conductive coefficients

and

. In contrast, the normalized bulk viscosity

is found to decrease as the nonextensivity of the medium increases. We also studied the transport coefficients for finite values of chemical potentials. The magnitudes of η,

, and κ increase at lower temperatures, while ζ

b
is found to decrease for systems with non-zero chemical potential.
Experimental results of the pFREYA16 ASIC for x-ray ptychography in continuous wave light sources
Authors: Lazzaroni P. , Hammer M. , Manghisoni M. , Miceli A. , Ratti L. , Re V. , Shi H. , Torilla G.
Published: December 2024

The pFREYA16, prototype Fast Readout for ptYchography Applications with 16 channels, ASIC is a pixellated 8-by-2 readout matrix developed for ptychography experiments based on fourth generation storage ring light sources, also known as diffraction-limited storage rings (DLSR), pushing towards continuous wave operation. The target of the experiment is to obtain a 128-by-128 matrix of pixels, working at a frame rate of 1 MHz with single-photon resolution, as well as low-noise and low-power figures, in a modest-size pixel area of 150 μm × 150 μm. The readout chain is composed of a switch-reset CSA and a semi-Gaussian unipolar RC-CR shaper, and includes signal discrimination, zero-suppression capabilities, and pixel-level analog to digital conversion. The ASIC is also configurable for 5, 9, 18, or 25 keV input photon energy, with a full well capacity of 256 equivalent photons in each mode, and four different peaking times are available for noise optimisation. The paper will focus on the characterisation of the CSA and the shaper stage.
An integrated flux-symmetric spectrometer-magnet system for the SND@LHC experiment upgrade
Authors: Abbaneo D. , Ahmad S. , Albanese R. , Alexandrov A. , Alicante F. , Androsov K. , Anokhina A. , Asada T. , Asawatangtrakuldee C. , Ayala Torres M.A. , Battilana C. , Bay A. , Bertocco A. , Betancourt C. , Bick D. , Biswas R. , Blanco Castro A. , Boccia V. , Bogomilov M. , Bonacorsi D. , Bonivento W.M. , Bordalo P. , Boyarsky A. , Buontempo S. , Campanelli M. , Camporesi T. , Canale V. , Castro A. , Centanni D. , Cerutti F. , Chernyavskiy M. , Choi K.-Y. , Cholak S. , Cindolo F. , Climescu M. , Conaboy A.P. , Dallavalle G.M. , Davino D. , de Bryas P.T. , De Lellis G. , De Magistris M. , De Roeck A. , De Rújula A. , De Simone D. , Di Crescenzo A. , Di Ferdinando D. , Dinc C. , Donà R. , Durhan O. , Fabbri F. , Fedotovs F. , Ferrillo M. , Fiorillo A. , Fresa R. , Funk W. , Garay Walls F.M. , Golovatiuk A. , Golutvin A. , Graverini E. , Guler A.M. , Guliaeva V. , Haefeli G.J. , Hagner C. , Helo Herrera J.C. , van Herwijnen E. , Iengo P. , Ilieva S. , Infantino A. , Iuliano A. , Jacobsson R. , Kamiscioglu C. , Kauniskangas A.M. , Khalikov E. , Kim S.H. , Kim Y.G. , Klioutchnikov G. , Komatsu M. , Konovalova N. , Kuleshov S. , Krzempek L. , Lacker H.M. , Lantwin O. , Lasagni Manghi F. , Lauria A. , Lee K.Y. , Lee K.S. , Lo Meo S. , Loschiavo V.P. , Marcellini S. , Margiotta A. , Mascellani A. , Mei F. , Miano A. , Mikulenko A. , Montesi M.C. , Navarria F.L. , Nuntiyakul W. , Ogawa S. , Okateva N. , Ovchynnikov M. , Paggi G. , Park B.D. , Perrotta A. , Podgrudkov D. , Polukhina N. , Prota A. , Quercia A. , Ramos S. , Reghunath A. , Roganova T. , Ronchetti F. , Rovelli T. , Ruchayskiy O. , Ruf T. , Sabate Gilarte M. , Sadykov Z. , Samoilov M. , Scalera V. , Schmidt-Parzefall W. , Schneider O. , Sekhniaidze G. , Serra N. , Shaposhnikov M. , Shevchenko V. , Shchedrina T. , Shchutska L. , Shibuya H. , Siroli G.P. , Sirri G. , Soares G. , Sohn J.Y. , Soto Sandoval O.J. , Spurio M. , Starkov N. , Steggemann J. , Timiryasov I. , Tioukov V. , Trippl C. , Ursov E. , Ustyuzhanin A. , Vankova-Kirilova G. , Vasquez G. , Verguilov V. , Viegas Guerreiro Leonardo N. , Vilela C. , Visone C. , Wanke R. , Yaman E. , Yang Z. , Yazici C. , Yoon C.S. , Zaffaroni E. , Zamora Saa J. ,   The SND@LHC collaboration
Published: December 2024

The proposed upgrade of the SND@LHC experiment for the High Luminosity phase of the LHC (HL-LHC) will strongly benefit from the presence of a magnetized region, allowing for muon momentum and charge
measurement. In this paper we describe an iron core magnet system that is partly integrated with the calorimeter and that is designed to respect the strict constraints from the available space in the experimental cavern, power consumption, and field requirements.

Semi-analytical tools are introduced to explore the parameter space, in order to define the primary design options. A full 3-D analysis is then performed in order to validate the optimal choice, and to propose a conceptual design, including sizing of the components, detector performances and stray fields. Several technical options are also discussed, anticipating the design phase.
Uncertainty in determining carbon dioxide removal potential of biochar
Authors: Kane Seth , Bin Thaneya Ahmad , Gursel Aysegul Petek , Fan Jin , Bose Baishakhi , Hendrickson Thomas P , Nordahl Sarah L , Scown Corinne D , Miller Sabbie A , Horvath Arpad
Published: December 2024

A quantitative and systematic assessment of uncertainty in life-cycle assessment is critical to informing sustainable development of carbon dioxide removal (CDR) technologies. Biochar is the most commonly sold form of CDR to date and it can be used in applications ranging from concrete to agricultural soil amendments. Previous analyses of biochar rely on modeled or estimated life-cycle data and suggest a cradle-to-gate range of 0.20–1.3 kg CO2 net removal per kg of biomass feedstock, with the range reported driven by differences in energy consumption, pyrolysis temperature, and feedstock sourcing. Herein, we quantify the distribution of CDR possible for biochar production with a compositional life-cycle inventory model paired with scenario-aware Monte Carlo simulation in a ‘best practice’ (incorporating lower transportation distances, high pyrolysis temperatures, high energy efficiency, recapture of energy for drying and pyrolysis energy requirements, and co-generation of heat and electricity) and ‘poor practice’ (higher transportation distances, lower pyrolysis temperatures, low energy efficiency, natural gas for energy requirements, and no energy recovery) scenarios. In the best-practice scenario, cradle-to-gate CDR (which is representative of the upper limit of removal across the entire life cycle) is highly certain, with a median removal of 1.4 kg of CO2e/kg biomass and results in net removal across the entire distribution. In contrast, the poor-practice scenario results in median net emissions of 0.090 kg CO2e/kg biomass. Whether this scenario emits (66% likelihood) or removes (34% likelihood) carbon dioxide is highly uncertain. The emission intensity of energy inputs to the pyrolysis process and whether the bio-oil co-product is used as a chemical feedstock or combusted are critical factors impacting the net carbon dioxide emissions of biochar production, together responsible for 98% of the difference between the best- and poor-practice scenarios.
Photon angular momentum and zero-point oscillations
Authors: Milonni Peter W , Jordan Maclay G
Published: December 2024

Radiation from certain oscillating charge distributions can have angular momentum that cannot be explained in classical electrodynamics. We consider the angular momentum of a single-photon field from an electric dipole oscillator and in particular compare the classical and quantum expressions for the mean-square field angular momentum. We show that differences in these expressions are attributable to zero-point oscillations of unexcited states of the dipole oscillator.
Stabilizing training of affine coupling layers for high-dimensional variational inference
Authors: Andrade Daniel
Published: December 2024

Variational inference with normalizing flows is an increasingly popular alternative to MCMC methods. In particular, normalizing flows based on affine coupling layers (Real NVPs) are frequently used due to their good empirical performance. In theory, increasing the depth of normalizing flows should lead to more accurate posterior approximations. However, in practice, training deep normalizing flows for approximating high-dimensional posterior distributions is often infeasible due to the high variance of the stochastic gradients. In this work, we show that previous methods for stabilizing the variance of stochastic gradient descent can be insufficient to achieve stable training of Real NVPs. As the source of the problem, we identify that, during training, samples often exhibit unusual high values. As a remedy, we propose a combination of two methods: (1) soft-thresholding of the scale in Real NVPs, and (2) a bijective soft log transformation of the samples. We evaluate these and other previously proposed modification on several challenging target distributions, including a high-dimensional horseshoe logistic regression model. Our experiments show that with our modifications, stable training of Real NVPs for posteriors with several thousand dimensions and heavy tails is possible, allowing for more accurate marginal likelihood estimation via importance sampling. Moreover, we evaluate several common training techniques and architecture choices and provide practical advise for training Real NVPs for high-dimensional variational inference. Finally, we also provide new empirical and theoretical justification that optimizing the evidence lower bound of normalizing flows leads to good posterior distribution coverage.
Weak coupling and spectral instability for Neumann Laplacians
Authors: Behrndt Jussi , Gesztesy Fritz , de Snoo Henk
Published: December 2024

We prove an abstract criterion on spectral instability of nonnegative selfadjoint extensions of a symmetric operator and apply this to self-adjoint Neumann Laplacians on bounded Lipschitz domains, intervals, and graphs. Our results can be viewed as variants of the classical weak coupling phenomenon for Schrödinger operators in

L
2

(

R

n

)

L^2(\mathbb {R}^n)

for

n
=
1
,
2

n=1,2

.
A characterization of zero entropy loosely Bernoulli flows via FK-pseudometric
Authors: Trilles Alexandre
Published: December 2024

We introduce the Feldman-Katok pseudometric (FK-pseudometric for short) for flows. We then provide a characterization of zero entropy loosely Bernoulli measures for continuous flows via the FK-pseudometric extending the result known for discrete-time dynamical systems. We also provide a purely topological characterization of uniquely ergodic continuous flows whose unique invariant measure is zero entropy loosely Bernoulli.
The pseudometric topology induced by upper asymptotic density
Authors: Keith Jonathan
Published: December 2024

Upper asymptotic density induces a pseudometric on the power set of the natural numbers, with respect to which

P

(

N

)

{\mathcal {P}}({\mathbb {N}})

is complete. The collection

D

{\mathcal {D}}

of sets with asymptotic density is closed in this pseudometric, and closed subsets of

D

{\mathcal {D}}

are characterised by a generalisation of an additivity property (AP(null)).
Index growth not imputable to topology
Authors: Carlotto Alessandro , Schulz Mario , Wiygul David
Published: December 2024

We employ partitioning methods, in the spirit of Montiel–Ros but here recast for general actions of compact Lie groups, to prove effective lower bounds on the Morse index of certain families of closed minimal hypersurfaces in the round four-dimensional sphere, and of free boundary minimal hypersurfaces in the Euclidean four-dimensional ball. Our analysis reveals, in particular, phenomena of linear index growth for sequences of minimal hypersurfaces of fixed topological type, in strong contrast to the three-dimensional scenario.
Ergodic recurrence and bounded gaps between primes
Authors: Pan Hao
Published: December 2024

Let

(

X

,

B

X

,
μ
,
T
)

(\mathcal {X},\mathscr {B}_\mathcal {X},\mu ,T)

be a measure-preserving probability system with

T
T

is invertible. Suppose that

A
∈

B

X

A\in \mathscr {B}_\mathcal {X}

with

μ
(
A
)
>
0

\mu (A)>0

and

ϵ
>
0

\epsilon >0

. For any

m
≥
1

m\geq 1

, there exist infinitely many primes

p
0

,

p
1

,
…
,

p
m

p_0,p_1,\ldots ,p_m

with

p
0

>
⋯
>

p
m

p_0>\cdots >p_m

such that
<mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" alttext="mu left-parenthesis upper A intersection upper T Superscript minus left-parenthesis p Super Subscript i Superscript minus 1 right-parenthesis Baseline upper A right-parenthesis greater-than-or-equal-to mu left-parenthesis upper A right-parenthesis squared minus epsilon">

μ
(
A
∩

T

−
(

p
i

−
1
)

A
)
≥
μ
(
A

)
2

−
ϵ

\begin{equation*} \mu (A\cap T^{-(p_i-1)}A)\geq \mu (A)^2-\epsilon \end{equation*}

for each

0
≤
i
≤
m

0\leq i\leq m

and

p
m

−

p
0

>

C

m
,
A
,
ϵ

,

\begin{equation*} p_m-p_0>C_{m,A,\epsilon }, \end{equation*}

where

C

m
,
A
,
ϵ

>
0

C_{m,A,\epsilon }>0

is a constant only depending on

m
m

,

A
A

and

ϵ
\epsilon

.
Pointwise convergence of multiple Fourier series over polytopes
Authors: Mastyło Mieczysław , Rodríguez-Piazza Luis
Published: December 2024

For a convex polytope

P
P

in

R

d

\mathbb {R}^d

containing

0
0

in its interior, it is proved an interpolative estimate for the Carleson operator generated by the partial sums of multiple Fourier series over all dilated sets of

P
P

. This result is used to prove that this operator is bounded from the Arias-Reyna space

Q

A
(

T

d

)

Q\!A(\mathbb {T}^d)

to the weak

L

1

L^{1}

-space on the

d
d

-dimensional torus

T

d

\mathbb {T}^d

. As a by-product, it follows that the sums over

λ
P

\lambda P

of the multiple Fourier series of every function in

Q

A
(

T

d

)

Q\!A(\mathbb {T}^d)

converge almost everywhere to the function as

λ
\lambda

tends to

+
∞

+\infty

. It is shown that this statement holds for every function in a Lorentz space

Λ
φ

(

T

d

)

\Lambda _\varphi (\mathbb {T}^d)

, which contains the Orlicz space

L
(
log
⁡
L

)

d

log
⁡
log
⁡
log
⁡
L
(

T

d

)

L(\log L)^{d} \log \log \log L(\mathbb {T}^d)

and so

L
p

(

T

d

)

L^p(\mathbb {T}^d)

for all

p
∈
(
1
,
∞
]

p \in (1, \infty ]

. In particular, this extends Fefferman’s result on the almost everywhere convergence of the of multiple Fourier series over polygon in

R

2

\mathbb {R}^2

of functions in

L
p

(

T

2

)

L^p(\mathbb {T}^2)

.
ET: What should we do?
Authors: Edmunds M G
Published: December 2024

If and when extraterrestrial life is detected, what should we do? Former RAS President Mike G Edmunds suggests that now is a good time to think about it.
Astronomy's noblest problem
Authors: Halyburton A , Kent D
Published: December 2024

Two years of training, with scientific glory in the balance, Lindsay and Gill's shot at the Transit of Venus was the essence of high stakes…
Time to shake out the bullies
Authors: Kanani S
Published: December 2024

The RAS took a long hard look at bullying and harassment in our communities in 2020; the results many nor be not pretty, but they do matter
Panacus: fast and exact pangenome growth and core size estimation
Authors: Parmigiani Luca , Garrison Erik , Stoye Jens , Marschall Tobias , Doerr Daniel
Published: December 2024

Motivation

Using a single linear reference genome poses a limitation to exploring the full genomic diversity of a species. The release of a draft human pangenome underscores the increasing relevance of pangenomics to overcome these limitations. Pangenomes are commonly represented as graphs, which can represent billions of base pairs of sequence. Presently, there is a lack of scalable software able to perform key tasks on pangenomes, such as quantifying universally shared sequence across genomes (the core genome) and measuring the extent of genomic variability as a function of sample size (pangenome growth).

Results

We introduce Panacus (pangenome-abacus), a tool designed to rapidly perform these tasks and visualize the results in interactive plots. Panacus can process GFA files, the accepted standard for pangenome graphs, and is able to analyze a human pangenome graph with 110 million nodes in <1 h.

Availability and implementation

Panacus is implemented in Rust and is published as Open Source software under the MIT license. The source code and documentation are available at https://github.com/marschall-lab/panacus. Panacus can be installed via Bioconda at https://bioconda.github.io/recipes/panacus/README.html.
Extracorporeal membrane oxygenation as a bridge to transplant in severe pulmonary hypertension
Authors: Kruszona Sophie , Aburahma Khalil , Wand Philipp , de Manna Nunzio D , Avsar Murat , Bobylev Dmitry , Müller Carsten , Carlens Julia , Weymann Alexander , Schwerk Nicolaus , Welte Tobias , Liu Bin , Ruhparwar Arjang , Kuehn Christian , Salman Jawad , Greer Mark , Ius Fabio
Published: December 2024

OBJECTIVES

Severe pulmonary hypertension (PH) is the leading indication for a lung transplant in younger patients. Despite the availability of validated risk scores, their influence on lung allocation has been negligible, with continued reliance on decompensation and bridging with extracorporeal membrane oxygenation (ECMO).

This single-centre, retrospective study assessed outcome of ECMO bridging in lung transplant for PH and evaluated short-term predictability of ECMO bridging.

METHODS

Patients with PH listed for a lung transplant between January 2010 and March 2023 were included. Peri- and postoperative courses were compared dependent upon ECMO bridging status. Bridging risk analysis within 90 days of re-evaluation included patients not requiring ECMO at listing, with listing parameters evaluated using a univariate Cox proportional hazard regression.

RESULTS

A total of 114/123 patients listed underwent lung transplant. Twenty-eight required ECMO bridging. No differences in primary graft dysfunction grade 3 at 72 h (30 vs 20%; P = 0.28) or graft survival (1 year: 82 vs 88%; 5 years: 54 vs 59%; P = 0.84) were evident. ECMO bridging resulted in longer intensive care unit stays post-transplant (P = 0.002) and higher rates of both re-thoracotomy (P = 0.049) and vascular complications (P = 0.031). Factors increasing 90-day ECMO risk included N-terminal pro-B-type natriuretic peptide (P < 0.001), 6-min walk distance (P = 0.03) and O2 requirement at rest (P = 0.006).

CONCLUSIONS

Lung transplant survival outcomes are not affected by ECMO bridging in patients with severe PH. It does, however, expose patients to additional risk, and efforts such as easy-to-measure parameters to pre-emptively identify patients requiring bridging to assist with effective allocation should be encouraged.
Contrasting patterns of diversity emerge depending on the initial drivers of speciation during adaptive radiation
Authors: Gillespie Rosemary G
Published: December 2024

I examine the spatial processes that shape species formation in adaptive radiation, and patterns that emerge from the different processes. I first consider situations that set the stage for diversification and conditions under which ecological diversity is maintained in populations without speciation, either due to balancing selection within a population or fluctuating selection between populations; the latter can be a precursor to speciation while the former can not. I then examine how speciation operates within the context of adaptive radiation: while species may diverge without ecological change within an adaptive radiation, I focus on ecological change, emphasizing two key processes through which nascent species may form, with initial divergence being attributed to either: (i) selection due to changes in the environment or substrate on which a species exists leading to ecological speciation; or (ii) geographic isolation leading to ecologically similar species that may subsequently compete and undergo character displacement in syntopy. There is good evidence for both processes in nature, but they lead to different predictions in terms of the production of ephemeral lineages and patterns of accumulation of species diversity. Initial ecological divergence along replicated environmental gradients may lead to predictable sets of allotopic ecomorphs, while initial divergence through geographic isolation may lead to initial supersaturation and predictable sets of syntopic ecomorphs.
Prophylactic cranial irradiation for small cell lung cancer in the era of immunotherapy and molecular subtypes
Authors: Pozonec Veronika , Pozonec Maria Dorothea , Aigner Clemens , Widder Joachim , Boettiger Kristiina , Megyesfalvi Zsolt , Dome Balazs
Published: December 2024

Purpose of review

Small cell lung cancer (SCLC) is an aggressive disease with a poor prognosis, whereas its metastatic capacity carries a predilection for the brain. Although prophylactic cranial irradiation (PCI) has been used to address this problem, upcoming alternatives might necessitate reflection of its application in SCLC treatment.

Recent findings

The addition of immunotherapy to treatment guidelines has provided a new strategy for the management of brain metastases. Complementation of immunotherapy with active MRI surveillance could potentially replace PCI and avoid irradiation-related cognitive side effects. SCLC's molecular profile is heterogeneous, with differential response to treatment modalities between subgroups. Investigation of these variances might be essential to improve therapeutic outcomes in SCLC patients.

The role of PCI in SCLC treatment must be examined in light of immunotherapy. We summarize recent results, bearing SCLC subtypes and therapeutic vulnerabilities in mind, to derive tailored treatment strategies for SCLC patients in future settings.
Therapeutic Drug Monitoring of Nirmatrelvir/Ritonavir (Paxlovid) in Patients Treated for COVID-19: Results from a Prospective Multicenter Observational Study
Authors: Böger Corinna R. , Martens-Lobenhoffer Jens , Worthmann Hans , Stichtenoth Dirk O. , Brod Torben
Published: December 2024

Background:

Paxlovid is a combination of the antiviral agents nirmatrelvir and ritonavir indicated for the oral treatment of high-risk, symptomatic patients with coronavirus disease 2019 (COVID-19). As real-world data on the plasma concentrations of nirmatrelvir/ritonavir (Paxlovid) are limited, the aim of this study was to investigate nirmatrelvir/ritonavir plasma trough levels in a clinical setting using therapeutic drug monitoring.

Methods:

A prospective, noninterventional, multicenter, observational clinical study was conducted in which the plasma trough levels of nirmatrelvir/ritonavir were simultaneously determined by using liquid chromatography tandem mass spectrometry in patients with symptomatic COVID-19. The blood samples were collected on days 1, 3, and 5 after the first full-dose day (day 0), and patient data such as sex, height, weight, renal function, liver enzymes, and concomitant (co-) medications were obtained to describe the plasma levels with respect to potential influencing factors.

Results:

A total of 46 blood samples from 21 patients were analyzed. The geometric mean Cmin was 4997 ng/mL for nirmatrelvir and 529.4 ng/mL for ritonavir. The plasma concentrations covered a wide range, the highest being observed in patients with advanced age and renally excreted comedications. Patients older than 65 years had a significantly higher risk of achieving excessive plasma trough concentrations above 8840 ng/mL for nirmatrelvir and 1440 ng/mL for ritonavir compared with younger patients (odds ratio 11.2, 95% confidence interval 1.04–120.4).

Conclusions:

The plasma trough concentrations of nirmatrelvir and ritonavir in patients treated for symptomatic COVID-19 were higher than the reference values of 2210 ng/mL for nirmatrelvir and 360 ng/mL for ritonavir stated in the product characteristics. Advanced age and renally eliminated comedication were identified as possible influencing factors that warrant further investigation.
Beat-to-beat variability of aortic pulse wave velocity: implications for aortic stiffness measurements
Authors: Giudici Alessandro , Grillo Andrea , Scalise Filippo , Reesink Koen D. , Delhaas Tammo , Salvi Paolo , Spronck Bart , Parati Gianfranco
Published: December 2024

Objectives:

Aortic pulse wave velocity (aPWV) predicts cardiovascular risk. Being the reference method for aortic stiffness evaluation, invasive aPWV is also recommended for validation of noninvasive devices. Because of intrinsic haemodynamic variability and processing issues, aPWV shows beat-to-beat variability. We aimed to quantify this variability and evaluate its implications for the reliability and use of aPWV as reference in validation and clinical application studies.

Methods:

The study included n = 84 patients, in whom two datasets of invasive data were recorded: 1) simultaneous ascending aorta and iliac pressure acquisitions using a dual-tip intra-aortic catheter, and 2) an additional ascending aorta pressure acquisition. By combining the iliac and ascending aorta pressure recordings from the first and second acquisitions, respectively, we evaluated how a sequential acquisition protocol affects variability. We compared three pressure waveform foot identification methods to investigate the effect of data processing on variability. Furthermore, we estimated how averaging over n
beats consecutive heartbeats affects the standard deviation (SD) of such n
beats-averaged estimate of aPWV.

Results:

The simultaneously acquired invasive aPWV showed a 5% beat-to-beat SD (variability), with small but significant differences between foot identification methods. The sequential acquisition protocol doubled aPWV variability compared to simultaneous acquisition. However, because averaging had a much stronger effect on sequentially measured aPWV, the two acquisition protocols yielded comparable variabilities at n
beats = 10 (2% vs. 3%).

Conclusions:

Our study suggests that, independently from the acquisition protocol and data processing, the intrinsic beat-to-beat variability of aPWV becomes manageable when aPWV values of at least ten heartbeats are averaged.
NEOVASCULAR GLAUCOMA AS A PREDICTOR OF RETINOBLASTOMA HIGH-RISK HISTOPATHOLOGY IN AN INTERNATIONAL MULTICENTER STUDY
Authors: Negretti Guy S. , Ushakova Tatiana , Yuri Serov , Vladimir Polyakov , Berry Jesse L. , Pike Sarah , Shields Carol L. , Hubbard G. Baker , Eiger-Moscovich Maya , Pe'er Jacob , Staffieri Sandra E. , Elder James E. , McKenzie John D. , Ahmad Alia , Hussain Mahvish , Casavilca-Zambrano Sandro , Alarcon-Leon Sandra , Yousef Yacoub A. , Mohammad Mona , Tanabe Mika , Arazi Mattan , Fabian Ido Didi , Goldstein Samuel , Kaliki Swathi , Sagoo Mandeep S. , Reddy M. Ashwin
Published: December 2024

Purpose:

To assess histopathology and outcomes after primary enucleation of eyes with retinoblastoma presenting with neovascular glaucoma (NVG).

Methods:

This was an international multicenter case series study across five continents. A retrospective review of patient charts was performed for all patients undergoing primary enucleation for retinoblastoma (n = 1,420) using a standardized data-collection spreadsheet. Clinical features, pathologic grade, and outcomes were compared between NVG patients and those with an American Joint Commission on Cancer eighth edition clinical stage of cT2. High-risk histopathology was defined as American Joint Commission on Cancer eighth edition pathologic stage ≥ pT2b.

Results:

Neovascular glaucoma was seen in 224/1,420 (16%) patients. The mean age at presentation of those with NVG was 30 months (median 25, range 0–120 months), and 131 (58%) patients had high-risk histopathology. The univariate logistic regression odds ratio for NVG predicting high-risk histopathology was 1.73 (95% confidence interval: 1.3–2.31) and from multivariate logistic regression was 1.77 (95% confidence interval: 1.23–2.56). Patients with a longer duration of symptoms (P = 0.03), buphthalmos (P = 0.02), and ectropion uveae (P < 0.01) were more likely to have high-risk histopathology. Patients with NVG were more likely to develop metastasis than cT2 patients (P = 0.04).

Conclusion:

There is a significant association between NVG at presentation, high-risk histopathology, and metastatic risk.
SOMATOSTATIN ANALOGUES VS ACTIVE SURVEILLANCE IN SMALL PANCREATIC NEUROENDOCRINE TUMORS
Authors: Maratta Maria Grazia , Chiloiro Sabrina , Raia Salvatore , Maiorano Brigida A. , Horn Guido , Brizi Maria Gabriella , Rufini Vittoria , Giancipoli Romina Grazia , De Marinis Laura , Bianchi Antonio , Pontecorvi Alfredo , Schinzari Giovanni , Inzani Frediano , Tortora Giampaolo , Rindi Guido
Published: December 2024

Objectives

The best strategy for non-functioning, sporadic, G1-G2 pancreatic neuroendocrine tumors ≤2 cm is unknown. An active surveillance is usually recommended. The PROMID and the CLARINET studies proved the value of somatostatin analogue (SSA) treatment in advanced gastro-entero-pancreatic neuroendocrine tumors. Aim of this study is to assess the value of SSA in PanNET≤2 cm.

Methods

We retrospectively collected data from 72 patients with sporadic non-functioning G1-G2 PanNETs≤2 cm, that were either treated with somatostatin analogues (n = 31) or underwent active surveillance (n = 41) at our Institution.

Results

At a median follow-up of 53.7 months, the median progression free survival was not reached in the treatment group versus an estimated PFS of 85 months in the control group (HR 0.11, p = 0.01), with a rate of progression or death up to 21.9% in the active surveillance group. Additionally, in the group of patients treated with somatostatin analogues the response rate was 16.1% with one complete response.

Conclusions

Our monocentric experience demonstrated a significant antiproliferative activity of somatostatin analogues in patients with sporadic, non-functionating G1-G2 PanNETs ≤2 cm delaying tumor progression and distant spread in small lesions that sometimes may reveal unpredictable aggressiveness.
Phase II randomized controlled trial to evaluate the supportive effect of Koujin (TJ-3020) powder in gemcitabine and nab-paclitaxel-treated unresectable or recurrent pancreatic cancer
Authors: Otsu Tomohisa , Takami Hideki , Yamada Suguru , Nakatochi Masahiro , Fujita Keizo , Tashiro Mitsuru , Hayashi Masamichi , Nakagawa Nobuhiko , Kurimoto Keisuke , Tanaka Haruyoshi , Kinoshita Fumie , Kuwatsuka Yachiyo , Kodera Yasuhiro
Published: December 2024

Objectives

Gemcitabine and nab-paclitaxel combination therapy (GnP) is a standard treatment for unresectable or recurrent pancreatic cancer. However, fatigue and malaise are frequent adverse effects. Recently, Kampo medicine containing ginsenoside has been reported to relieve cancer-related fatigue. Therefore, in this randomized trial, we used red ginseng powder (Koujin, TJ-3020), which contains ginsenoside, to evaluate its effect on unresectable or recurrent pancreatic cancer treatment.

Methods

From December 2017 to December 2020, we enrolled 40 pancreatic cancer patients. The patients underwent two cycles of GnP for unresectable cancer or postoperative recurrence. The patients were randomized into group A (red ginseng powder administration) or group B (no red ginseng). In group A, 0.67 g of red ginseng powder was taken orally three times a day before each meal for 56 days of the planned chemotherapy period. The Cancer Fatigue Scale evaluated physical, mental, cognitive, and comprehensive fatigue over time.

Results

The patients’ backgrounds, including age, sex, pancreatic cancer status, and relative dose intensity of the GnP chemotherapy, did not differ between groups A and B. Cases with abnormal CA19-9 were frequently assigned to group A. None of the Cancer Fatigue Scale fatigue scores differed significantly between the groups. Mental fatigue score was significantly higher in patients aged ≥70 years (odds ratio: 4.57; P = 0.033), and recurrent pancreatic cancer status tended to influence all fatigue scores. However, no other critical factor significantly affected the physical, cognitive, and comprehensive fatigue scores.

Conclusions

In this phase II randomized trial, oral administration of red ginseng powder at 2.0 g per day did not reduce pancreatic cancer patients’ fatigue or malaise induced by GnP combination chemotherapy.
Maternal and Newborn Care for Ornithine Transcarbamylase Deficiency
Authors: Anderson Sharon
Published: December 2024

Ornithine transcarbamylase deficiency is the most common urea cycle disorder. If left untreated, pathogenic variants in the OTC gene can cause hyperammonemia leading to neurotoxicity, coma, and death. A comprehensive overview of ornithine transcarbamylase deficiency is presented including the genetic cause; varied age of onset, clinical presentation, and severity; diagnostic testing; and lifelong and anticipated future treatments. More specifically, there is a focus on the prenatal, natal, and postpartum course and treatment recommendations for genetic heterozygous (carrier) females and hemizygous male newborns with ornithine transcarbamylase deficiency.
Publication Pressure in Nuclear Medicine
Authors: Kwee Thomas C. , Aldub Ali , Kwee Robert M.
Published: December 2024

Purpose

The aims of this study were to determine the publication pressure perceived by nuclear medicine scientists and to identify associated determinants.

Patients and Methods

Corresponding authors who published in Clinical Nuclear Medicine, Journal of Nuclear Medicine, or European Journal of Nuclear Medicine and Molecular Imaging between 2021 and 2023 were invited to participate in this survey study. Publication pressure was assessed using the revised Publication Pressure Questionnaire in the domains of “publication stress” (stress due to perceived pressure to publish), “publication attitude” (attitude regarding current publication culture), and “publication resources” (resources when working on publications or experiencing stress when working on publishing), with 5-point Likert scales.

Results

A total of 181 individuals participated. Median Publication Pressure Questionnaire scores in the domains “publication stress,” “publication attitude,” and “publication resources” were 3.33, 3.33, and 2.17, respectively. None of the researchers’ characteristics were significantly associated with publication stress. Age >65 years was significantly associated with a more positive view on the publication climate (β coefficient of −0.552, P = 0.007). Several variables were significantly associated with a perception of fewer factors available to alleviate publication pressure: age 45–54 years (β coefficient of 0.249, P = 0.030), age 55–64 years (β coefficient of 0.421, P = 0.002), associate professor position (β coefficient of 0.398, P < 0.001), fellow/resident position (β coefficient of 0.355, P = 0.007), <5 years of research experience (β coefficient of 0.410, P = 0.026), and 5–10 years of research experience (β coefficient of 0.361, P = 0.003).

Conclusions

Publication pressure among nuclear medicine scientists is appreciable. Several researcher characteristics appear to be associated with vulnerability to publication pressure.
Tabletop Simulations in Medical Emergencies
Authors: Frégeau Amélie , Vinette Billy , Lapierre Alexandra , Maheu-Cadotte Marc-André , Fontaine Guillaume , Castonguay Véronique , Flores-Soto Rodrigo , Garceau-Tremblay Zoé , Blais Samuel , Vigneault Laura-Philippe , Hansen-Jaumard Delphine , Laramée François , Iseppon Massimiliano , Daoust Raoul , Cossette Sylvie , Buyck Michael , Fleet Richard , Cournoyer Alexis
Published: December 2024

Summary Statement

Tabletop simulations (TTS) are a novel educational modality used in health care education. The objective of this scoping review was to describe the use of TTS in medical emergencies, specifically settings, specialties, participants, formats, and outcomes.

We included 70 studies (33 descriptive studies [47%], 33 cohort studies [47%], and 2 randomized controlled trials [3%]), of which 65 reported positive results regarding reaction and learning educational outcomes (reaction: n = 37, 53%; learning: n = 25, 36%; behavior: n = 7, 10%; result: n = 1, 1%). The scenario for most TTS was a disaster (n = 56; 80%). Most TTS involved participants from several professions (n = 45; 64%). A board game was used in 26 studies (37%).

Most studies on TTS in medical emergencies involved participants from multiple professions addressing disaster scenarios and showed positive results pertaining to reaction or learning educational outcomes.
L-Asparaginase treatment induces reversible immunoregulatory and immunosuppressive effects in non-malignant B cells in a model of T-cell dependent B cell activation
Authors: Hadzic Amar , García-Márquez María Alejandra , Bannasch Pol , Haindl Nina , Frey Katharina , Kirmaier Martin , Funk Maximilian , Tischmacher Anneli , Tu Jingke , Carboniero Adriano , Vona Ludovica , Oganesian Sabine , Schlößer Hans , Schmitz Werner , von Bergwelt Michael , Cordas dos Santos David M. , Theurich Sebastian
Published: December 2024

Metabolic reprogramming is critical for immune cell adaptation upon activation to exert full functionality with amino acids being a key metabolic factor. While L-asparagine is a non- essential amino acid it turns out to be conditionally essential in malignant B cells due to defective asparagine synthetase making L-asparaginase a commonly used chemotherapeutic agent. Off-target enzymatic activity including glutaminolysis impacting crucial immune function. However, its effects on healthy B cells remain unclear, therefore in this study, we explored how L-asparaginase modulates the biology and function of CD40-activated B cells, using an in-vitro model. B cells from healthy donors were treated with increasing L- asparaginase concentrations and analyzed for proliferation, immune phenotype, and metabolic changes. Results showed L-asparaginase reduced B cell proliferation and homotypic clustering without inducing apoptosis, instead impairing metabolic pathways, lowering glycolysis and oxidative phosphorylation, and reducing surface markers associated with antigen-presenting cell (APC) function. Functional assays confirmed that L-asparaginase- treated B cells had diminished ability to activate T cells. Supplementing with asparagine or glutamine restored B cell proliferation and function, with glutamine slightly more effective than asparagine. Interestingly, L-asparaginase induced a regulatory B cell phenotype, marked by CD24+CD38+CD27+ expression and increased interleukin-10 and TGF-beta, suggesting a potential immunosuppressive mechanism. These findings indicate that L-asparaginase not only affects malignant cells but also impacts the function of non-malignant B cells, proposing potential therapeutic applications in B cell-driven autoimmune disorders. Further studies are needed to explore its effects at lower, clinically relevant concentrations.

Abstract Figure
The Regulation of MAGI2 and its Diagnostic Application in Podocytopathies
Authors: Siegerist Florian , Hay Eleonora , Hammer Elke , Iervolino Anna , Weber Claudia , Dikou Juan Saydou , Stamellou Eleni , Butt Linus , Benzing Thomas , Wiech Thorsten , Brinkötter Paul T. , Zimmerman Uwe , Capasso Giovambattista , Chatziantoniou Christos , Chadjichristos Christos , Huber Tobias B. , Völker Uwe , Schindler Maximilian , Endlich Nicole
Published: December 2024

Podocyte dysfunction is central to various glomerular diseases, necessitating reliable biomarkers for early detection and diagnosis. This study investigates the regulatory mechanisms of membrane-associated guanylate kinase inverted 2 (MAGI2) and its potential as a biomarker for podocytopathies. The expression of the gene coding for the scaffolding protein MAGI2 was examined across four species and demonstrated to be conserved within the podocyte filtration slit.In vitroandin vivostudies using isolated glomeruli and mammalian animal models of glomerular disease, including DOCA-salt hypertension, nephrotoxic serum nephritis, and puromycin aminonucleoside nephropathy, demonstrated significant downregulation of MAGI2 in injured podocytes. This downregulation was also conserved in a zebrafish model of focal and segmental glomerulosclerosis (FSGS), and the podocyte-specific MAGI2 ortholog Magi2a was reduced post podocyte injury. CRISPR/Cas9-generated zebrafish mutants formagi2aexhibited marked glomerular filtration barrier defects and downregulation of nephrin, underscoring MAGI2’s critical role in podocyte function.

Human biopsy analyses revealed differential MAGI2 expression: it was increased in minimal change disease (MCD) patients but significantly decreased in primary, but not secondary FSGS cases. As MAGI2 localization did not change in disease states it is an alternative marker for super-resolution microscopy-based morphometry of the filtration slit, correlating with nephrin-based measurements.

These findings highlight the potential of MAGI2 as a sensitive biomarker for podocyte injury and its diagnostic utility in differentiating between primary FSGS and MCD.
A simplified risk model for pretreatment stratification of newly diagnosed acute myeloid leukemia patients treated with venetoclax and azacitidine
Authors: Islam Nazmul , Reuben Jamie S. , Dale Justin L. , Zhang Jingjing , Coates James W. , Sapiah Karan , Markson Frank R. , Wu Lezhou , Kulkarni Ujjwal V. , Boyiadzis Michael , Smith Clayton A.
Published: December 2024

Venetoclax plus azacitidine (ven/aza) is a new standard of care for adult Acute Myeloid Leukemia (AML) patients who are not candidates for intensive therapies. Risk stratification approaches have been proposed to identify patients with favorable, intermediate, and adverse therapeutic outcomes following ven/aza and other lower intensive therapies. However, most have been developed for retrospective data analyses and have limitations in their application to upfront risk stratification of newly diagnosed patients. Here, we describe an AML risk model, termed the Refined Risk Model (RRM), that is specific for ven/aza, addresses important real-world considerations and utilizes pathology features that have the potential to be available relatively quickly-and-broadly following diagnosis. The RRM was developed and internally validated using a single center cohort of 316 AML patients from the University of Colorado treated upfront with ven/aza, and then externally validated on an AML cohort from a nationwide electronic health record-derived de-identified AML database. The RRM effectively stratified patients into Adverse, Intermediate, and Favorable groups across both the internal and external cohorts; it performed well in subsets with or without allogeneic transplant recipients, demonstrated tolerance to missing data, and showed numerical performance comparable to or exceeding the existing alternatives such as the European Leukemia Network (ELN 2022) and molecular prognostic risk signature (mPRS) models. These findings suggest that the RRM may have potential application in defining the prognostic mortality risk for newly diagnosed AML patients, which may help guide clinical trial design and execution as well as other important elements of AML clinical decision support.