bluuebunny/crossref_metadata_2025 huggingface dataset:
Optimizing the light output of a plastic scintillator and SiPM based detector through optical characterization and simulation: a case study for POLAR-2
Authors: De Angelis Nicolas , Cadoux Franck , Husi Coralie , Kole Merlin , Mianowski Sławomir
Published: February 2025

The combination of plastic scintillators with Silicon
Photo-Multipliers (SiPMs) is widely used for detecting radiation in
high-energy astrophysics, particle physics, neutrino physics, or
medical physics. An example of application for this kind of
detectors are Compton polarimeters such as
POLAR-2 [1,2,3]
or LEAP [4,5,6] for which a
low-Z material is needed for the Compton effect to be dominant
down to as low energy as possible. Such detectors aim to measure low
energy Compton depositions in organic scintillators which produce
small amounts of optical light because of the low energy deposited
and the low scintillation efficiency, and for which optimizing the
instrumental optical properties consequently imperative.

The light collection efficiency of such a device was studied with a
focus on the POLAR-2 Gamma-Ray Burst polarimeter. POLAR-2 consists
of a segmented array of 6400 elongated plastic scintillators divided
into 100 modules, all read out by SiPMs. The conversion of incoming
γ-rays into readable signal goes through the production and
collection of optical light, which has been optimized both through
measurements and simulations. The optical elements of the POLAR-2
polarimeter prototype module were optically characterized and an
optical simulation based on Geant4 was developed to fully model its
optical performances. The results from simulations were used to
optimize the design and finally to verify its performance. The study
resulted in a detector capable of measuring energy depositions of
several keV. In addition, an important finding of this work is the
impact of the plastic scintillator surface roughness on the light
collection. It was found that a plastic scintillator with a higher
scintillation efficiency but made of a softer material, hence with a
rougher surface, was not necessarily the best option to optimize the
light collection. Furthermore, in order to optimize the optical
crosstalk between different channels, a production technique for
very thin (∼150 μm) and reusable silicone-based optical
coupling pads was developed. This method can be adapted to produce
either standalone pads or to directly mold a layer on any SiPM to be
later coupled to the scintillators.

After an introductory discussion describing the need of a large
scale GRB polarimeter like POLAR-2, the optical design and
characterization of the polarimeter modules that compose its
sensitive part are described. The Geant4-based optical simulations
of the POLAR-2 modules and the impact of the optical properties of
its various elements on the light collection efficiency of the
instrument are later presented. The work is finally summarized and
an outlook is given on the potential applications of the POLAR-2
optical characterization and simulation work to other experiments
employing similar elements.
The spectrometric practical voltage: determination of X-ray tube voltage up to 300 kV by in-beam X-ray spectrometry with a cadmium telluride detector
Authors: Šolc Jaroslav , Pojtinger Stefan , Šmoldasová Jana , Sochor Vladimír , Rusňák Jan
Published: February 2025

This paper describes a method for determining the energy of
the X-ray spectrum end-point (E
end) by means of X-ray
spectrometry performed with a CdTe detector. Designated the
spectrometric practical end-point (SPE) method, this technique is
based on the comparison of the high-energy part of the measured
detector spectrum with a detector spectrum obtained using Monte
Carlo calculations. It combines findings and results from a detector
characterization previously done for the purpose of unfolding the
X-ray fluence spectra. Here, the influences of tube current, tube
voltage ripple, detector count rate, and the choice of calibration
radionuclide sources were studied. The findings for the latter two
parameters led to the modification of a procedure for energy
calibration of the detector as well as to updated parameters of the
charge carrier transport (CCT) and Gaussian energy broadening (GEB)
models valid for high-count-rate measurements. Additionally, the
influence of improper energy calibration and of neglecting the CCT
and GEB effects on the main characteristics of the unfolded X-ray
fluence spectra was analyzed to provide an overview of systematic
errors. A quantity obtained with the SPE method, the spectrometric
practical voltage (SPV), is introduced. It is demonstrated that the
SPV agrees with the practical peak voltage within 0.03% when the
voltage ripple of a high-voltage generator is below 2%. A
comparison done at PTB, Germany, of the SPV to voltage divider
readings showed relative and absolute differences between the
reading and the SPV of between 0.1% and 0.8% (0.15 keV to
1.16 keV) in the 20 to 300 kV tube voltage range. Its combined
uncertainty varied between 0.13 and 0.33 keV for continuous beam
N-series qualities ranging from 10 to 300 kV. The SPE method was
then used to determine E
end of N-series qualities
realized at Czech Metrology Institute. Also, the difference between
E
end as obtained with the SPE method and that found with
a simple linear fit of the straight high-energy part of the detector
spectra was evaluated, revealing a difference of between -0.2 and
+1.5 keV for N-series qualities up to 300 kV. The SPE method is
suitable for users who have already implemented an in-beam X-ray
spectrometry technique and seek to determine the tube voltage but do
not possess a voltage divider.
Biomedical applications of Bombyx mori silk in skin regeneration and cutaneous wound healing
Authors: Khosropanah Mohammad Hossein , Ghofrani Alireza , Vaghasloo Mahdi Alizadeh , Zahir Mazyar , Bahrami Afshin , Azimzadeh Ashkan , Hassannejad Zahra , Majidi Zolbin Masoumeh
Published: February 2025

A mere glance at the foundation of the sericulture industry to produce silk and the consequent establishment of the Silk Road to transport it; elucidates the significant role that this material has played in human history. Owing to its exceptional robustness, silk was introduced into medicine as a surgical suture approximately two millennia ago. During the last decades, silk has garnered attention as a possible source of biological-based materials that can be effectively used in regenerative medicine. Silk’s unique characteristics, like its low immunogenicity, suitable adhesive properties, exceptional tensile strength, perfect hemostatic properties, adequate permeability to oxygen and water, resistance to microbial colonization, and most importantly, excellent biodegradability; make it an outstanding choice for biomedical applications. Although there are many different types of silk in nature, Bombyx mori (B. mori) silk accounts for about 90% of global production and is the most thoroughly investigated and the most commonly used. Silk fibroin (SF) and silk sericin (SS) are the two main protein constituents of silk. SF has been manufactured in various morphologic forms (e.g. hydrogels, sponges, films, etc) and has been widely used in the biomedical field, especially as a scaffold in tissue engineering. Similarly, SS has demonstrated a vast potential as a suitable biomaterial in tissue engineering and regenerative medicine. Initial studies on SF and SS as wound dressings have shown encouraging results. This review aims to comprehensively discuss the potential role of silk proteins in refining wound healing and skin regeneration.
Thiolated gellan gum/polyethylene glycol diacrylate hydrogels containing timolol maleate-loaded chitosan nanoparticles for ophthalmic delivery
Authors: Shajari Golnaz , Erfan-Niya Hamid , Fathi Marziyeh , Amiryaghoubi Nazanin
Published: February 2025

The combination of hydrogels with nanoformulations can significantly enhance the delivery and effectiveness of drugs in ophthalmic drug delivery systems. In the current study, the polyethylene glycol diacrylate (PEGDA)/thiolated gellan gum (GGSH) hydrogels based on GGSH and PEGDA were prepared via thiol-ene reaction using Irgacure 2959 as a photoinitiator. To this end, the modification of GG was achieved by esterification of the hydroxyl groups of GG with the carboxyl group of mercaptopropionic acid with a free thiol amount of 95.5 μmol g−1. To provide sustained release, chitosan nanoparticles (CSNPs) containing timolol maleate (TM) with 56.4% entrapment efficiency were synthesized by the desolvation method and encapsulated in the developed hydrogel. The values of zeta potential and particle size of CSNPs were +26.0 mV and 182.4 nm, respectively. The physico/chemical properties of the hydrogels were investigated via texture analyzer, FT-IR, XRD, and SEM. The in vitro degradation, swelling behavior, rheological assessments, cell viability testing, and porosity determination were evaluated. With the increase in PEGDA concentration, the mechanical properties were increased. While the rate of swelling, degradation, and drug release were decreased. The in vitro biocompatibility of hydrogels was confirmed using the MTT test. According to an ex vivo study, ocular drug delivery using the obtained transparent hydrogels is promising due to improved drug permeation and sustained release of TM via CSNPs.
Variability of marine heatwaves and atmospheric cyclones in the Mediterranean Sea during the last four decades
Authors: Androulidakis Yannis , Pytharoulis Ioannis
Published: February 2025

The Mediterranean Sea has been recognized as a hotspot for marine heatwaves (MHWs) and climate change impacts. Cyclogenesis and the occurrence of tropical-like cyclones (also known as Medicanes) in the Mediterranean appear to have intensified during the last decades. This study investigates the relationship between increased sea surface temperature (SST) levels and low-pressure systems in the Mediterranean Sea over four recent decades (1982–2020), highlighting a strong spatial variability in regions affected by MHWs. Key areas, such as the Ligurian, Tyrrhenian, Ionian, Aegean, and Northern Levantine Seas, demonstrate a notable interaction between MHWs and cyclogenesis. Stronger relations are identified at the west of Cyprus (Northern Levantine), in the northern Ionian Sea, and in the Gulf of Genoa (Ligurian Sea). Conversely, weaker interactions are observed in the southern Mediterranean, where both MHWs and cyclonic activity are weaker. The sea level pressure (SLP) in the Mediterranean and the intensity of the surface MHW revealed decreasing and increasing trends, respectively, during the 39 year period. A marked negative trend in SLP and an increase in SSTs in the northern Aegean point to heightened cyclone activity in this region. MHWs may ampilfy atmospheric systems that increase coastal hazards like flooding, strong winds and heavy precipitation. The study also highlights that periods of intense cyclonic activity often coincide with intense MHW formations, with both phenomena peaking in 2018. The cumulative intensity of the MHWs, measured by their duration and magnitude, correlates with the intensification of low-pressure systems in most of the Mediterranean sub-regions. These findings suggest that monitoring MHWs could improve the understanding and forecasting of cyclogenesis, benefiting both short-term weather predictions and long-term climate assessments.
Re-examining urban rainfall enhancement over North America
Authors: Pryor Sara C , Barthelmie Rebecca J , Zhou Xin , Huffman George J
Published: February 2025

Quantifying intensification/suppression of precipitation over urban areas relative to their rural surroundings can inform efforts to reduce urban flooding. Few studies have systematically addressed whether urban areas exhibit a higher/lower probability of precipitation and/or higher/lower annual total precipitation and/or intensification/weakening of intense precipitation events relative to nearby rural areas across a range of hydroclimatic conditions and urban contexts. Here we address this literature gap using the IMERG V07 data set and analyses of rural and urban samples drawn from 47 conurbations across North America. Specifically, we quantify whether/how precipitation regimes over the urban grid cells differ from those in rural grid cells located 100–250 km from the city center and at a similar elevation. As in previous research, there is evidence that both the probability of precipitation and annual total precipitation are typically higher in the urban grid cells. However, most conurbations have lower upper percentile precipitation rates in the urban sample and lower median precipitation rates above the 95th percentile than are present in samples drawn from rural grid cells. Thus, these conurbations are not, on average, intensifying high-magnitude precipitation events over urban grid cells. Further, the total volume of water accumulated at the surface during events of equivalent duration is not systematically higher over the urban areas, and 20 year return period values of 30 min and wettest pentad precipitation are also not systematically higher over the urban areas. The nature of urban modification of precipitation is a strong function of the prevailing hydroclimate. For example, the heaviest rainfall periods are enhanced over urban grid cells within regional hydroclimates where the overall probability of precipitation and annual total precipitation are low. Conversely, there is evidence for urban suppression of the highest percentile precipitation rates in wetter hydroclimates.
Mechanical properties and microscopic mechanisms of carbon curing-alkali activation modified iron tailings
Authors: Wei Pengfei , Wang Wei , Yu Yanfei , Hu Xingchen , Wang Biao , Li Na , Jiang Ping
Published: February 2025

Seeking ways to effectively utilise iron tailings within the green building sector is a pressing issue at present. In this study, using iron tailings as the main raw material and cement as the auxiliary cementitious material, the effects of sodium silicate (SS) content and carbonation curing on the compressive strength, stiffness, microstructure and mineral composition of cemented iron tailings (SSCIT) were investigated. The results showed that a certain amount of SS could increase the strength and stiffness of SSCIT. By adding 6% SS, the strength and stiffness of SSCIT reached the maximum value. The addition of SS promoted the dissolution of silicate minerals, and the generated geopolymerised gel binder filled the pores of specimens, enhanced the bonding force between the interfaces of soil particles, and improved the specimen compactness. However, carbonation curing adversely affected the strength of SSCIT. Carbonation caused the hydration products of SSCIT to change, and the decalcification and decomposition of the C-S-H gel increased the porosity of SSCIT, leading to a decrease in strength. In addition, using iron tailings for road base materials is an efficient and feasible method of utilisation.
Impact of Majorana fermions on the Kondo state in the carbon nanotube quantum dot
Authors: Krychowski D
Published: February 2025

We have studied the quantum conductance of the Kondo state in the carbon nanotube quantum dot (CNTQD) with side-attached multi-Majorana fermion states in topological superconductors (TSCs). The zero-energy Majorana fermions interfere with the fourfold degenerate states of the CNTQD in the spin-orbital Kondo regime. Using the extended Kotliar-Ruckenstein slave-boson mean-field approach, we have analyzed the symmetry reduction of the SU(4) Kondo effect to the SU⋆(3) Kondo state with a fractional charge in the system by increasing the tunneling strength to a single Majorana fermion (TSC). We observed the fractional quantum conductance, the enhancement of the thermoelectric power with two compensation points, the fractional linear and nonlinear Fano factor (F

K
), and the spin polarization of the conductance. Two Majoranas (2TSC) in conjunction with the CNTQD have reduced the spin-orbital Kondo effect to the SU⋆(2) Kondo state with 2e in the system. The F

K
contains information about the effective charge and the interaction between the quasiparticles, two- and three-body correlators and identifies the broken symmetry of the Kondo state. Furthermore, we have shown that the device coupled with three Majorana fermions (3TSC) achieves a quantized conductance 5/2(e
2/h), preserves the U⋆(1) charge symmetry at the electron-hole symmetry point and manifests the increase in nonlinear current and shot noise due to the entanglement in octuplets with opposite charge-leaking states.
Defect modeling in semiconductors: the role of first principles simulations and machine learning
Authors: Rahman Md Habibur , Mannodi-Kanakkithodi Arun
Published: February 2025

Point defects in semiconductors dictate their electronic and optical properties. Vacancies, interstitials, substitutional defects, and defect complexes can form in the semiconductor lattice and significantly impact its performance in applications such as solar absorption, light emission, electronics, and catalysis. Understanding the nature and energetics of point defects is essential for the design and optimization of next-generation semiconductor technologies. Here, we provide a comprehensive overview of the current state of research on point defects in semiconductors, focusing on the application of density functional theory (DFT) and machine learning (ML) in accelerating the prediction and understanding of defect properties. DFT has been instrumental in accurately calculating defect formation energies, charge transition levels, and other defect-related properties such as carrier recombination rates and lifetimes, and ion migration barriers. ML techniques, particularly neural networks, have emerged as powerful tools for enabling rapid prediction of defect properties at DFT-accuracy in order to overcome the expense of using large supercells and advanced functionals. We begin this article with a discussion of different types of point defects and complexes, their impact on semiconductor properties, and the experimental and DFT approaches typically used for their characterization. Through multiple case studies, we explore how DFT has been successfully applied to understand defect behavior across a variety of semiconductors, and how ML approaches integrated with DFT can efficiently predict defect properties and facilitate the discovery of new materials with tailored defect behavior. Overall, the advent of ‘DFT+ML’ promises to drive advancements in semiconductor technology, catalysis, and renewable energy applications, paving the way for the development of high-performance semiconductors which are defect-tolerant or have desirable dopability.
Independence of Centromeric and Pericentromeric Chromatin Stability on CCAN Components
Authors: Biggs Ronald J. , Sundararajan Kousik , Sun Mingxuan , Hendrix Eline , Straight Aaron F. , Marko John F.
Published: February 2025

The chromatin of the centromere provides the assembly site for the mitotic kinetochore that couples microtubule attachment and force production to chromosome movement in mitosis. The chromatin of the centromere is specified by nucleosomes containing the histone H3 variant CENP-A. The constitutive centromeric-associated network (CCAN) and kinetochore are assembled on CENP-A chromatin to enable chromosome separation. CENP-A chromatin is surrounded by pericentromeric heterochromatin and bound by the sequence specific binding protein CENP-B. We performed mechanical experiments on mitotic chromosomes while tracking CENP-A and CENP-B to observe the centromere's stiffness and the role of the CCAN. We degraded CENP-C and CENP-N using auxin-inducible degrons, which we verified compromises the CCAN via observation of CENP-T loss. Chromosome stretching revealed that the CENP-A domain does not visibly stretch, even in the absence of CENP-C and/or CENP-N. Pericentromeric chromatin deforms upon force application, stretching approximately 3-fold less than the entire chromosome. CENP-C and/or CENP-N loss has no impact on pericentromere stretching. Chromosome-disconnecting nuclease treatments showed no structural effects on CENP-A. Our experiments show that the core-centromeric chromatin is more resilient and likely mechanically disconnected from the underlying pericentromeric chromatin, while the pericentric chromatin is deformable yet stiffer than the chromosome arms.
The Archaeology of the Ark and Iron Age Religion
Authors: McGeough Kevin M
Published: February 2025

Chapter 2 addresses what archaeology can and cannot tell us about the Ark of the Covenant. It provides an introduction to one of the major controversies in the archaeology of ancient Israel: whether there was an historical kingdom of Saul, David, and Solomon. It explores the difficulties of integrating historical narratives and archaeological data but illustrates some of the positive ways that archaeology can inform our understanding of the Bible. While acknowledging that archaeologists do not ever expect to find the Ark of the Covenant, this chapter explores some of the possible analogues to the Ark that can be identified in Egyptian and Mesopotamian contexts. The chapter also describes ancient Near Eastern religious and temple practices, suggesting some of the functions that the Ark may have had based on those contexts.
Medieval Theology
Authors: McGeough Kevin M
Published: February 2025

How the Ark was understood in medieval European thought is the subject of Chapter 4. It explores how medieval theologians treated the Ark as metaphor in various ways, in some cases taking the Virgin Mary as a “new Ark” because she bore Christ in her womb or treating various wise scholars as “Arks” of Christian knowledge. The Ark was often depicted in the art of the era, reflecting these theologies, but often considerable liberties were taken with the biblical descriptions of its physicality. Jewish theologies of the era also understood the Ark through metaphor, as was the case with Kabbalah, the mystical system that emerged at this time. Relatedly, early modern scholars and scientists were very much interested in Solomon’s Temple and its metaphorical meanings, and the Ark’s association with the Temple inspired their studies. The chapter ends with a discussion of early Christian pilgrimage to the Holy Land.
Welcome (In)attention
Authors: Weaver Erica
Published: February 2025

My final chapter traces the creation of a broader, multimedia literature of (in)attention. I argue that, in their efforts to focus on the elusive or illusory, distraction paradoxically helped medieval devotees to recapture central theological concepts—such as resurrection, or damnation—that risked exceeding attention altogether. Here, I turn to the disappearance of Christ at the heart of the Easter drama known as the Visitatio sepulchri in order to locate the rise of what is traditionally known as “liturgical drama” in precisely the same decades and spaces in Æthelwold’s Winchester. Yet, I also interrogate the desire to capture the inconceivable manifested by the Visitatio, situating it not only alongside the schoolroom texts of my fourth chapter and the sensory overload of Wulfstan Cantor’s preface to his Narratio metrica de S. Swithuno but also alongside the mysterious addition of two conjurors to a catalogue known as The Wonders of the East.
Motion and Turn: Water’s Ways
Authors: Stewart Susan
Published: February 2025

This chapter extends the previous chapter’s concern with the cyclical to consider water as a resource for poets thinking through questions of cycles, recurrence, and the possibilities of poetic form. The waterfall is both a form and a process: a fall of water that remains as a constant (to humans) geological feature, while also changing the landscape around it. The water cycle both changes and stays the same. Like water, poems both change and recur through formal features of rhythm, refrain, and lineation. The chapter takes up several poetic representations of motion and considers questions of force, influence, and causality.
The causal association between polyunsaturated fatty acids and acne: A two-sample Mendelian randomization study
Authors: Kim Bo Ri , Kim Gahyun , Jin Seon-Pil , Choi Chong Won , Kim Jinho , Park Hyunsun
Published: February 2025

Background

Observational studies have demonstrated a close association between polyunsaturated fatty acids (PUFAs) and acne. However, the findings of clinical trials have been inconsistent, leaving the causal relationship between PUFAs and acne unclear.

Objectives

To investigate the causal association between genetically proxied PUFAs and acne risk

Methods

Mendelian randomization (MR) was performed using single-nucleotide polymorphisms associated with PUFAs as instrumental variables. The causal associations between PUFAs and acne were estimated among 115,006 UK biobank participants and 363,927 participants of Finnish descent.

Results

Genetically predicted docosahexaenoic acid (DHA) levels (Beta= -0.303; 95% CI: –0.480 to –0.126; p = 7.74E-04) and its percentage to total fatty acids (Beta= -0.402; 95% CI: –0.651 to –0.258; p = 5.91E-06) showed a significant causal association with a decreased risk of acne. Conversely, genetically predicted percentages of linoleic acid (LA) in total fatty acids (Beta=0.768; 95% CI: 0.411–0.126; p = 2.87E-04) and omega-6: omega-3 (Beta=0.373; 95% CI: 0.142–0.604; p = 4.48E-03) were robustly associated with an increased risk of acne. These effects were attenuated after excluding a genetic variant of rs174528 located upstream of fatty acid desaturase 1 (FADS1), highlighting the biological link between FADS1 and delta-5 desaturase activity. Multivariable MR analysis indicated that PUFAs were causally associated with acne, independent of body mass index.

Conclusions

Our study indicates that high DHA levels and their ratios to total fatty acids have causal protective effects against acne, while high LA levels and omega-6: omega-3 ratio are associated with increased acne risk. This association was largely attributable to the influence of genetic variants related to FADS1.
Investigating The Effect on Backscatter Factor When Measuring Entrance Surface Dose Using the Raysafe X2 Solid State Radiography and Fluoroscopy Detector
Authors: Lordinot Vadim , Koller Chris
Published: February 2025

Objectives

Assessment of patient dose is a critical quality assurance check towards ensuring it is kept as low as reasonably practicable. One metric used to evaluate this is Entrance Surface Dose (ESD)- the summed magnitudes of the incident radiation and Compton scatter resulting from photon interactions within tissue. ESD can be directly measured using a dosemeter that is sensitive to backscattered radiation. However, the increasing use of solid-state detectors such as the tin backed RaySafe X2 R/F detector, means that ESD cannot be directly measured. The IAEA Technical Report No.457, recommends using backscatter factors (BSF) as calculated by Petoussi-Henss et al in1998 via Monte Carlo methods when measuring ESD using such dosemeters. This research seeks to practically determine a reliable method of calculating the BSF using a PMMA patient-equivalent phantom.

Methods

A comparison between the solid-state detector and an ionisation chamber capable of detecting backscatter was conducted. Special attention was given to BSF variation with both radiation field size and beam quality by varying additional copper and aluminium filtration to mimic the behaviour of patient-dose reducing techniques on modern fluoroscopy systems.

Results

Results have shown significant correspondence with those of Petoussi-Henss et al using the simulated water and ICRU tissue equivalent phantoms.

Conclusions

Given the results consistency, BSFs from this study have been proposed for use when measuring ESD using the RaySafe solid state detector with a PMMA patient-equivalent phantom for quality assurance purposes.

Advances in Knowledge

This research provides the opportunity to obtain more accurate patient dose data during quality assurance testing with modern solid-state dosemeters.
Roles of dendritic epidermal T cells in steady and different pathological states
Authors: Hao Jiaqi , Zhang Jie , Liu Yan
Published: February 2025

The epidermis is the outermost layer of the skin and acts as the primary barrier to protect the body. Dendritic epidermal T cells (DETCs), which are specifically distributed in epidermal tissues, play a crucial role in skin immune surveillance and wound healing. DETCs are one of the most important components of the epidermis and exert a steady-state monitoring function, facilitating wound healing and tissue regeneration after skin injury. Skin wounds are often linked to other pathological conditions such as ageing, ultraviolet radiation, and metabolic diseases such as diabetes mellitus and obesity. Therefore, it is crucial to investigate how DETCs regulate themselves and the external environment during these pathological states. DETCs interact closely with keratinocytes in the epidermis, and this intercellular interaction may be essential for maintaining health and integrity. In this review, we focus on the characteristics and underlying mechanisms of DETCs in maintaining epidermal homeostasis and re-epithelialization in different pathological states.
The effect of diabetes on long-term outcomes in patients following coronary artery bypass grafting
Authors: Barili Fabio , Vitale Nicolò , D’Errigo Paola , Porcedda Francesco , Pollari Francesco , Baglio Giovanni , Daprati Andrea , Badoni Gabriella , Duranti Giorgia , Donatelli Francesco , Parolari Alessandro , Rosato Stefano
Published: February 2025

OBJECTIVES

Diabetes mellitus is a risk factor for coronary artery disease, but its role following coronary artery bypass grafting (CABG) is still unclear and few data on long-term outcomes are available. This study aimed to evaluate the impact of diabetes on long-term outcomes after CABG.

METHODS

The PRIORITY (PRedictIng long-term Outcomes afteR Isolated coronary arTery bypass surgerY) project is an observational cohort study merging 2 prospective multicentre studies on isolated CABG. Follow-up information was obtained through administrative databases and was truncated 10 years after the intervention. Baseline differences between patients with and without diabetes were balanced with inverse probability of treatment weighting.

RESULTS

The cohort consisted of 10 989 patients with complete follow-up information who underwent isolated CABG (diabetes 32.3%). Diabetes did not affect short-term mortality [odds ratio (OR) 0.90, 95% confidence interval (CI) 0.73–1.10] and repeat revascularization (OR 0.79, 95% CI 0.42–1.49), while it is related to lower incidence of 30-day major adverse cardiac and cerebrovascular events (OR 0.67, 95% CI 0.60–0.76), acute myocardial infarction (OR 0.60, 95% CI 0.51–0.70) and stroke (OR 0.47, 95% CI 0.28–0.77). Diabetic patients had a higher long-term risk for major adverse cardiac and cerebrovascular event [weighted hazard ratio (HR) 1.31, 95% CI 1.26–1.37], mortality (HR 1.45, 95% CI 1.37–1.53), as well as stroke (HR 1.38, 95% CI 1.25–1.53) and myocardial infarction (HR 1.39, 95% CI 1.26–1. 53). Diabetes had not been associated with an increased incidence of repeated revascularization up to 10 years (HR 1.04, 95% CI 0.96–1.12).

CONCLUSIONS

Diabetic patients had worse long-term outcomes. Diabetes may have a greater negative impact on micro-vasculopathy than grafts, as evidenced by the increased long-term incidence of myocardial infarction without affecting myocardial revascularization.
PREDICTING DEPRESSED AND ELEVATED MOOD SYMPTOMATOLOGY IN BIPOLAR DISORDER USING BRAIN FUNCTIONAL CONNECTOMES
Authors: Sankar *Anjali , Shen Xilin , Colic Lejla , Goldman Danielle A , Villa Luca M , Kim Jihoon A , Pittman Brian , Scheinost Dustin , Constable R Todd , Blumberg Hilary P
Published: February 2025

Background

Depressed and elevated mood symptom severity underlie the suffering associated with bipolar disorder and are among the strongest clinical predictors of functional impairment and disability in the disorder. Furthermore, mood symptoms contribute to the high risk for suicide in the disorder.

Elucidation of the brain functional disturbances that contribute to mood symptoms in individuals with bipolar disorder could advance our understanding of the pathophysiology of the disorder and enable the development of more targeted therapeutic approaches.

Aims and Objectives

The study is aimed to identify brain functional connectomes predictive of depressed and elevated mood symptomatology in individuals with bipolar disorder using the machine learning approach Connectome-based Predictive Modeling (CPM).

Methods

Functional magnetic resonance imaging data were obtained from 81 adults with bipolar disorder while they performed an emotion processing task. CPM with 5000 permutations of leave-one- out cross-validation was applied to identify functional connectomes predictive of depressed and elevated mood symptom scores on the Hamilton Depression and Young Mania rating scales. The predictive ability of the identified connectomes was tested in an independent sample of 43 adults with bipolar disorder.

Results

CPM predicted the severity of depressed [concordance between actual and predicted values (r = 0.23, pperm (permutation test) = 0.031) and elevated (r = 0.27, pperm = 0.01) mood. Functional connectivity of left dorsolateral prefrontal cortex and supplementary motor area nodes, with inter- and intra-hemispheric connections to other anterior and posterior cortical, limbic, motor, and cerebellar regions, predicted depressed mood severity. Connectivity of left fusiform and right visual association area nodes with inter- and intra-hemispheric connections to the motor, insular, limbic, and posterior cortices predicted elevated mood severity. These networks were predictive of mood symptomatology in the independent sample (r = 0.45, p = 0.002).

Discussion and Conclusion

This study identified distributed functional connectomes predictive of depressed and elevated mood severity in bipolar disorder. Connectomes subserving emotional, cognitive, and psychomotor control predicted depressed mood severity, while those subserving emotional and social perceptual functions predicted elevated mood severity. Identification of these connectome networks may help inform the development of targeted treatments for mood symptoms.
“IMMUNOSUPPRESSIVE” CANNABINOID CB2 RECEPTORS TAKE “IMMUNOACTIVE” ROLE IN HIGH-FAT DIET EVOKED SYSTEMIC INFLAMMATORY RESPONSE
Authors: Nozaki *Chihiro , Hosoki Haruka , Zimmer Andreas
Published: February 2025

Background

It is widely known that cannabinoid type 2 (CB2) receptor deficiency enhances inflammatory response and further symptoms in various animal models of inflammation, allergy, or cancer. As CB2 receptors are inhibitory Gi/Go G-protein coupled receptors and as major expression site of CB2 receptors are immune cells, it is no wonder that lack of CB2 receptor might lead the exacerbated inflammation.

Aims & Objectives

Number of study shows high fat diet (HFD) induce peripheral inflammation, however contribution of CB2 receptor has not been studied yet. We therefore exposed HFD to CB2 deficient mice (CB2-KOs), and evaluated the development of peripheral hypersensitivity and neuroinflammation as well as modification of splenic immune cell population.

Method

6-weeks-old male CB2-KOs and their wild-type (WT) controls are used. All animals are single housed, and exposed to either HFD (60kcal% fat, 5.24 kcal/g) or SFD (Standard fat diet, 10kcal% fat, 3.85kcal/g). At 5th week of exposure, animals are subjected to von-Frey test to evaluate the tactile sensitivity, then sacrificed to collect the sciatic nerve and dorsal root ganglia for further immunohistochemistry, and spleen for flow cytometric analysis.

Results

Surprisingly, CB2-KOs showed the significant resistance to the HFD-induced neuroinflammation. Namely, 5-week feeding of HFD induced substantial hypersensitivity in WT mice, while tactile sensitivity of HFD- fed CB2-KO remained intact. In the same animals, we further found the robust upregulation of infiltrated macrophages, chemokine receptor CXCR4 expression and modified differentiation of splenic myeloid-derived suppressor cells (MDSCs) in HFD-fed WT animals, but not in either HFD-fed CB2 knockout mice or SFD-fed CB2-KO animals (Fig 1).

Discussion & Conclusion

Based on these results, we will propose that CB2 receptors might have the bipolar regulatory role to chemokine receptor-mediated inflammatory response through the modulation of splenic MDSC differentiation, which in the end might enhance or inhibit the development of neuroinflammation depending on its cause. Present results also suggests that modulation of CB2 signaling might be able to modify the physiological change lead by metabolism change (e.g. HFD exposure), however further study using other models e.g. diabetic or inflammatory model animal is required to prove this upcoming hypothesis.
CHRONIC POST-COVID NEUROPSYCHIATRIC SYMPTOM CLUSTERS DO NOT SHARE THE SAME RISK FACTORS IN A COHORT INFECTED BY THE OMICRON VARIANT
Authors: Chau *Steven Wai Ho , Chue Timothy Mitchell , Lai Yee Lok , Tsui Ling , Lam Tsz Ching , Chan Rachel Ngai Yin
Published: February 2025

Background

It is suggested that post-COVID neuropsychiatric symptoms are not a unified syndrome, but a heterogeneous entity consisting of distinct symptom clusters (Chau et al., 2023). In a cohort infected by pre-Omicron strain, we showed that the symptoms could be clustered into a cognitive dysfunction- fatigue cluster and an anxiety-depression cluster, which do not share the same predictors.

Aims & Objectives

We aim to test whether we can discover the same symptom structure in a larger cohort infected by the Omicron variant of SARS-CoV-2 virus, and whether the symptom clusters have different risk factors as well. Method:We recruited 508 adult subjects who were infected by the Omicron variant, but not the pre-Omicron variants of SARS-CoV-2 for the first time more than one year ago from the community.

They completed a COVID symptom checklist, questionnaires on the demographics, socioeconomic status and health status and self-reported symptom scales on mood, anxiety, insomnia, and PTSD symptoms via a mobile app.

Results

The mean age of the subjects is 38.2 years. 68% of them are female and 5.1% had known psychiatric illness prior to COVID. 74% of them suffered from asymptomatic to mild acute COVID, and none of them required oxygen therapy. Partial correlation network analysis discovered two symptom clusters: one features cognitive complaints and another one features anxiety-depression (Figure 1). Multiple regression model showed that, while the number of pre-COVID medical conditions and existence of pre- COVID mental illness predicts the number of symptoms from either cluster, level of pre-COVID material deprivation only predicts number of symptoms from the anxiety depression cluster, and the severity of the index infection only predicts number of symptoms from the cognitive complaints cluster.

Discussion & Conclusion

Our result from the Omicron cohort replicated our previous findings from the pre-Omicron cohort by demonstrating that cognitive complaints and anxiety-depression symptoms are distinct sub-syndromes with overlapping yet distinct risk factors. This replication suggests that the characteristics of chronic post-COVID neuropsychiatric symptoms from the pre-Omicron and Omicron strains infection are similar. This replication also strengthens the argument that the two symptom clusters should not be considered a unified entity.

References

Chau, S.W.H, et al. 'Chronic post-COVID neuropsychiatric symptoms persisting beyond one year from infection: a case-control study and network analysis’. Under review.
STIMULATING THE PREFRONTAL CORTEX TO REDUCE HYPERREACTIVITY TO STRESS IN PEOPLE AT RISK OF SCHIZOPHRENIA
Authors: Brunelin *Jerome , Adam Ondine , Mondino Marine
Published: February 2025

Background

According to the vulnerability stress model of schizophrenia, an abnormal hyperreactivity to stress is incriminated in the transition from at risk stages to full-blown psychotic episodes.

Aims & Objectives

We proposed that stimulating the dorsolateral prefrontal cortex (DLPFC) with transcranial direct current stimulation (tDCS) during acute stress exposure would lead to modulation of hypothalamo-pituitary-adrenal (HPA) axis responsiveness in people at risk for schizophrenia.

Method

In a randomized sham-controlled 2-arm study (http://clinicaltrials.gov, NCT03217357, 05/07/2017), 30 unaffected siblings of patients with schizophrenia were randomly allocated to receive either active (n=15) or sham tDCS (n=15) while exposed to an acute stress situation combining physical and psychological stress (the Maastricht Acute Stress Test). The stress exposure started 5 minutes after the start of the tDCS session and lasted 10 minutes. Active stimulation consisted of delivering 2 mA of DC current for 30 min with the anode placed over the left DLPFC and the cathode over the right DLPFC. Sham stimulation consisted of 30 s of ramp up/down and 1 min of active stimulation followed by no stimulation for the remaining 30 min of the stimulation period. Our primary outcome was the concentration of salivary cortisol. A saliva sample was taken every 10 min (every 5 min during stress exposure) for a total of 10 samples. A general linear model with group (active, sham) and time (10 saliva samples) followed by FDR corrected contrasts was performed to examine the effect of tDCS on HPA axis reactivity.

Results

The two groups did not differ at baseline in any sociodemographic characteristics, nor in baseline cortisol concentration (4.69 nmol/L (± 2.53) in the sham group versus 3.54 nmol/L (± SD 1.99) in the active group; W = 78.00; p = 0.25). The GLM revealed a significant association between the group and the time (X2 = 41.16; p <0.001), with the difference between groups being significant at 5 and 10 minutes after the end of the stress exposure. In the sham group, the mean increase in cortisol release was +291% from baseline, whereas the cortisol increase in the active group was +259%.

Discussion & Conclusion

Bifrontal tDCS can prevent stress-induced cortisol release in people at genetic risk of schizophrenia. These results are consistent with our previous studies in healthy participants and suggest that tDCS, which shows promise in treating patients with treatment-resistant symptoms of schizophrenia, may also be of interest in the early stages of the disease to reduce biological hyperreactivity to stress.
ERGOGENIC WORDS: HOW PLACEBOS CHANGE OUR BRAIN
Authors: Carlino *Elisa , Persiani Francesca , Campaci Francesco , Lanzo Gianluca , Volpino Valeria , Piedimonte Alessandro
Published: February 2025

Background

The placebo effect is an illustrative example of the mind-brain-body interaction whereby a positive physical outcome follows the administration of an inert treatment that is expected to be effective. The two main psychological determinants of the placebo effect are conscious expectations, induced through verbal suggestion, and learning, induced through classical conditioning. Accumulating behavioral data suggested that positive expectations of motor improvement result in better motor control for several motor functions in athletes, non-athletes, and patients with motor deficits. These effects have been related to changes in brain areas involved in motor planning and execution, although a deep understanding of the precise neural network underlying this complex psychobiological phenomenon is still missing.

Aims and Objectives

The aim of this study was to tackle the role of frontal cortical regions after placebo manipulations using, for the first time, fNIRS (functional near infrared spectroscopy). The fNIRS is a non-invasive technique used to investigate changes in the concentration of blood oxygen levels induced by brain activity, hence, oxygenated hemoglobin (HbO) and deoxygenated hemoglobin (HbR), at the level of cortical microcirculation blood vessels. Although not having the same spatial resolution as the fMRI, fNIRS has often been compared to fMRI due to both following the same kind of signal and recording the same activity from the cortex.

Methods

For this study, 30 healthy volunteers have been recruited from the student population of the University of Turin. Participants were asked to perform a force motor task and were randomly assigned to two different groups. Participants in the Placebo Group (P group) were informed that the application of 2 electrodes (actually sham) would have improved their motor performance. Participants in the Control Group (C group) performed the motor task without positive verbal information about the effectiveness of the sham electrodes.

Results

From a behavioral point of view, results showed that participants in the P group improved their motor performance compared with the C group (p< 0.05). Moreover, differences in HbO have been observed in the P group in different brain regions, including the left dorsolateral prefrontal cortex (DLPFC).

Discussion

These findings bring new evidence on the neural underpinnings of the motor placebo effect, by showing that the left DLPFC may undermine the expectation-induced enhancement of motor performance in participants that expected a positive motor improvement.
CAUSAL RELATIONSHIPS BETWEEN STRUCTURAL BRAIN IMAGING MARKERS IN ADOLESCENCE AND PSYCHIATRIC DISORDERS IN ADULTHOOD
Authors: Lin *Yen-Feng , Lin Shu-Chin
Published: February 2025

Background

Adolescent brain imaging markers have been identified as potential predictors of adult psychiatric disorders, but it remains unclear whether brain development during childhood and adolescence causally results in psychiatric disorders.

Aims & Objectives

The goal of our research is to better understand the causal relationship between youth’ s cerebral cortex and three primary psychiatric disorders: bipolar disorder (BIP), major depressive disorder (MDD), and schizophrenia (SCZ).

Method

We implemented a two-sample Mendelian randomization (MR) approach to estimate the causal effects of adolescent cortical thickness (CT) and cortical surface area (SA) of 34 regions of interest (ROIs) on the three mental disorders. We integrated imaging and genotypic data from the Adolescent Brain Cognitive Development (ABCD) Study and the summary results of genome-wide association studies (GWAS) from the ENIGMA consortium (N=33,992) and the Psychiatric Genomics Consortium (BIP: 41,917 cases and 371,549 controls; MDD: 170,756 cases and 329,443 controls; SCZ:74,776 cases and 101,023 controls) to conduct the causal analysis. We computed the genetic correlations (rg) between the cortical measures and mental disorders. We employed MR to investigate the causal relationship between ROIs that are genetically associated with the mental disorders.

Results

The global measure of SA was positively correlated with BIP (rg: 0.068 and P-value: 0.037) and inversely correlated with MDD (rg: -0.080 and P-value: 0.009). We identified significant genetic correlations between SA of seven ROIs and BIP, and SA of twelve ROIs and MDD. We identified that SA of the superior frontal as a potential causal region for BIP (OR: 1.22 and 95% CI: 1.10-1.36) based on MR causal analysis. Other ROIs with nominally significant causal effects (P <0.05) included SA of the caudal middle frontal on BIP, and the SA of the four regions (medial orbitofrontal, lateral orbitofrontal, inferior temporal and lateral occipital) on MDD.

Discussion & Conclusion

Our findings suggest that larger SA in early adolescence may causally increase the risk of BIP, with superior frontal being the potential causal ROI. Additionally, we identified potential ROIs such as medial and lateral orbitofrontal regions, which are negatively associated with MDD.