bluuebunny/crossref_metadata_2025 huggingface dataset:
High erosion and re-deposition rates of tungsten in the highly collisional plasmas of Magnum-PSI
Authors: Cornelissen Mark J.H. , Tyburska-Pueschel Beata , Rasinski Marcin , Brons Serge , Zoethout Erwin , Dorow-Gerspach Daniel , Brezinsek Sebastijan , Wirtz Marius , Pintsuk Gerald , Beckers Job , Morgan Thomas W.
Published: November 2024

Prompt re-deposition strongly reduces the migration of eroded material in current fusion devices, thus lowering core dilution and extending the lifetime of the plasma-facing components. However, under the high-density (

n

e

>
2
×

10

20

m−3), low-temperature (

T

e

<
5

eV) divertor plasma conditions anticipated for future fusion devices like ITER, Coulomb collisions become highly efficient. These collisions not only prevent the ions from completing their Larmor orbits but also strongly couple the sputtered impurities to the plasma, leading to impurity entrainment. Entrainment drags impurities with the plasma flow to the surface, leading to enhanced impurity impact energies as discussed in the companion paper (Cornelissen M.J.H. et al 2025 Nucl. Fusion
65 026009), and the re-deposition of sputtered particles. This entrained re-deposition was studied with the linear plasma generator Magnum-PSI, whose linear geometry allowed for a clear distinction between entrained and prompt re-deposition. Five W targets were exposed to high-density (

n

e

≈
5
×

10

20

m−3), low-temperature (

T

e

≈
1.2

eV) argon (Ar) plasmas. The deposition pattern of tungsten (W) on molybdenum (Mo) witness plates was determined using ion beam analysis and electron scanning microscopy. As the ion-impact energy of Ar+ increased from

E

i

≈

43 eV to

E

i

≈

94 eV, the local re-deposition rate decreased from

R
≈

93% to

R
≈

68%. Entrained re-deposition became evident from an up-downstream asymmetry in the re-deposition profile and was dominant over prompt re-deposition for the exposures investigated. Although the ionization length was long, high re-deposition rates were found, revealing that neutral-ion interactions were important. Thus, entrainment will be a crucial ingredient in the erosion and re-deposition studies of future fusion reactors.
The impact of helium on plasma-driven hydrogen permeation and implications for direct internal recycling in the fusion fuel cycle
Authors: Li Chao , Way J. Douglas , Fuerst Thomas F. , Wolden Colin A.
Published: November 2024

Metal foil pumps (MFPs) are the leading technology for direct internal recycling (DIR) of hydrogen isotopes from the plasma exhaust in future fusion plants. MFPs rely on the concept of superpermeation, where superthermal H atoms directly absorb into the metal foil, rapidly diffuse, and desorb downstream. To date, studies of superpermeation have predominantly employed either pure hydrogen or in some cases trace levels of impurities. The plasma exhaust is expected to contain just ∼1% helium, but in DIR the source gas would be enriched in helium as hydrogen isotopes are extracted. In this work, we explore the impact of helium on hydrogen superpermeation at low temperature (75 °C–200 °C) using Pd-based foils. To first order, the flux scaled linearly with the hydrogen mole fraction. Stable permeation was observed until the helium fraction reached ∼80%, where the flux began to decline slowly with time. In addition, short term (1–5 min) exposure to pure helium plasma significantly attenuated subsequent hydrogen plasma permeation, and the degree was more dramatic at elevated temperature. This attenuation was correlated with He retention in the foils, which was detected by time-of-flight secondary ion mass spectrometry at low levels (<0.1 at. %) and limited to the near surface (<10 nm). Similar trends were observed among all alloys (Pd, PdAg, PdCu), and the foils were restored to full performance with an Ar+ sputter clean. The potential for helium plasma exposure to impact MFP performance under these conditions has not been previously reported, and these findings have significant implications to the design and implementation of practical DIR systems.
A study of particle detectors based on single crystal diamond substrate
Authors: Zaťko Bohumír , Varga Marian , Kováčová Eva , Šagátová Andrea
Published: November 2024

The diamond radiation detector was prepared using a high-quality monocrystalline substrate. A square contact of 3.6 × 3.6 mm2 was fabricated on one side of the substrate, while the other side has a full area metallized contact. The current-voltage characteristics were measured up to 1 kV in both directions. The fabricated diamond detector shows very low current below 2 pA in whole voltage ranges. The detector was then used for alpha particle detection. The triple radiation source was used with different monoenergetic particles with energies varying from 5.1 MeV to 5.8 MeV. The range of alpha particles used was no more than 15 μm according to SRIM simulations. The diamond detector shows a high resolution for alpha particle spectroscopy below 0.43% at 5.5 MeV energy.
Characterization of TlBr gamma detector based on electrical charge and Cherenkov light analysis
Authors: Hamdan M. , Feng B. , Shimazoe K. , Nogami M. , Hitomi K. , Takahashi H. , Uenomachi M. , Toyokawa H.
Published: November 2024

Thallium Bromide (TlBr) semiconductors have been extensively studied for their potential as room-temperature gamma-ray detectors, owing to their advantageous material properties. Recent advancements have demonstrated that timing performance in TlBr detectors can be enhanced by incorporating Cherenkov photon detection during gamma-ray interactions. In this study, TlBr detector (5 × 5 × 5 mm3) was investigated through a combined analysis of electrical charge and Cherenkov light signals. The depth of interaction (DoI) correction applied to the trapezoidal filter output yielded significant improvements in energy resolution, reducing it from 5.6% to as low as 2.51% FWHM at 511 keV and from 4.6% to as low as 1.94% FWHM at 662 keV, within specific C/A ratio ranges. The drift time, ranging from 2 to 30 μs, was found to be proportional to the C/A ratio, covering 4 to 9 photoelectrons. Furthermore, a time resolution of 511 ps was achieved at 6 photoelectrons, based on the FWHM of the time difference distribution in coincidence measurements at 511 keV using a 22Na source. These results highlight the potential of TlBr detectors for achieving high energy and timing resolution in gamma detection, particularly for Compton-PET systems.
Quantifying food security and mitigation risks consequential to climate change impacts on crop yields
Authors: Luchtenbelt Hermen , Doelman Jonathan , Bos Astrid , Daioglou Vassilis , Jägermeyr Jonas , Müller Christoph , Stehfest Elke , van Vuuren Detlef
Published: November 2024

Climate change is expected to impact crop yields globally, with some regions benefiting from favorable conditions and CO2 fertilization, while others face adverse effects from altered precipitation and higher temperatures. Changes in crop yields can destabilize the global food system and pose challenges to food security. Moreover, crop production is crucial, as biofuels are becoming increasingly important contributors to climate change mitigation measures aimed at limiting global warming. This study uses the Integrated Model to Assess the Global Environment integrated assessment model framework to analyze different indicators related to food security and climate change mitigation under varying climate change impacts on crop yields. Twelve spatially explicit crop productivity projections were taken from the full archive of the Global Gridded Crop Model Intercomparison of 120 climate-crop model combinations, forced by CMIP6-based climate scenarios. The selection includes two average-performing climate-crop model combinations, two pessimistic combinations that perform one standard deviation below the mean, and two optimistic model combinations that perform one standard deviation above the mean. To single out the effect of climate change on productivity changes, we drew samples from two representative concentration pathways (RCP2.6 and RCP8.5). These productivity projections were applied within an otherwise uniform scenario (SSP2) and analyzed for their effect on total calorie demand, crop prices, and number of people at risk of undernourishment to quantify food security. Risks to climate change mitigation targets were explored by modeling the total bioenergy supply, emissions, and global mean temperature. The results revealed significant differences in the risk of food security and mitigation potential between different regions and climate change scenarios. Across scenarios, the crop area extent can vary up to 2 million km2 due to changing crop yields. The projected change in global hunger ranges from 60 to 160 million undernourished people, indicating uncertainty between climate and crop model combinations. Low-income regions are especially impacted because of their high sensitivity to changes in food prices. Global climate change mitigation ambitions can also deviate by the latter part of the 21st century, as changes in yields will impact biofuel production as well as agriculture, forestry and other land use emissions. The quantitative insights generated by this study highlight the need for global policy efforts to make the agricultural system more adaptive to climate change to handle potential negative impacts.
Replica bound for Ising spin glass models in one dimension
Authors: Okuyama Manaka , Ohzeki Masayuki
Published: November 2024

The interpolation method is a powerful tool for rigorous analysis of mean-field spin glass models, both with and without dilution. In this study, we show that the interpolation method can be applied to Ising spin glass models in one dimension, such as a one-dimensional chain and a two-leg ladder. In one dimension, the replica symmetric (RS) cavity method is naturally expected to be rigorous for Ising spin glass models. Using the interpolation method, we rigorously prove that the RS cavity method provides lower bounds on the quenched free energies of Ising spin glass models in one dimension at any finite temperature in the thermodynamic limit.
Nano-optics of transition metal dichalcogenides and their van der Waals heterostructures with electron spectroscopies
Authors: Woo Steffi Y , Tizei Luiz H G
Published: November 2024

The outstanding properties of transition metal dichalcogenide (TMD) monolayers and their van der Waals (vdW) heterostructures, arising from their structure and the modified electron–hole Coulomb interaction in 2D, make them promising candidates for potential electro-optical devices. However, the production of reproducible devices remains challenging, partly due to variability at the nanometer to atomic scales. Thus, access to chemical, structural, and optical characterization at these length scales is essential. While electron microscopy and spectroscopy can provide chemical and structural data, accessing the optical response at the nanoscale through electron spectroscopies has been hindered until recently. This review focuses on the application of two electron spectroscopies in scanning (transmission) electron microscopes, namely cathodoluminescence and electron energy-loss spectroscopy, to study the nano-optics of TMD atomic layers and their vdW heterostructures. How technological advancements can improve these spectroscopies, many of which are already underway, that will make them ideal for studying the physics of vdW heterostructures at the nanoscale will also be discussed.
Residual Pix2Pix networks: streamlining PET/CT imaging process by eliminating CT energy conversion
Authors: Ghanbari S , Sadremomtaz A
Published: November 2024

Attenuation correction of PET data is commonly conducted through the utilization of a secondary imaging technique to produce attenuation maps. The customary approach to attenuation correction, which entails the employment of CT images, necessitates energy conversion. However, the present study introduces a novel deep learning-based method that obviates the requirement for CT images and energy conversion. This study employs a residual Pix2Pix network to generate attenuation-corrected PET images using the 4033 2D PET images of 37 healthy adult brains for train and test. The model, implemented in TensorFlow and Keras, was evaluated by comparing image similarity, intensity correlation, and distribution against CT-AC images using metrics such as PSNR and SSIM for image similarity, while a 2D histogram plotted pixel intensities. Differences in standardized uptake values (SUV) demonstrated the model’s efficiency compared to the CTAC method. The residual Pix2Pix demonstrated strong agreement with the CT-based attenuation correction, the proposed network yielding MAE, MSE, PSNR, and MS-SSIM values of 3 × 10−3, 2 × 10−4, 38.859, and 0.99, respectively. The residual Pix2Pix model’s results showed a negligible mean SUV difference of 8 × 10−4 (P-value = 0.10), indicating its accuracy in PET image correction. The residual Pix2Pix model exhibits high precision with a strong correlation coefficient of R2 = 0.99 to CT-based methods. The findings indicate that this approach surpasses the conventional method in terms of precision and efficacy. The proposed residual Pix2Pix framework enables accurate and feasible attenuation correction of brain F-FDG PET without CT. However, clinical trials are required to evaluate its clinical performance. The PET images reconstructed by the framework have low errors compared to the accepted test reliability of PET/CT, indicating high quantitative similarity.
Measurements of neurite extension and nucleokinesis in an iPSC-derived model system following microtubule perturbation
Authors: Sébastien Muriel , Paquette Alexandra L. , Ferotin Lilian , Hendricks Adam G. , Brouhard Gary J.
Published: November 2024

In neurons, patterns of different microtubule types are essential for neurite extension and nucleokinesis. Cellular model systems such as rodent primary cultures and induced pluripotent stem cells (iPSC)-derived neurons have provided key insights into how these patterns are created and maintained through the action of microtubule-associated proteins, motor proteins, and regulatory enzymes. iPSC-derived models show tremendous promise but lack benchmarking and validation relative to rodent primary cultures. Here we have characterized a recent iPSC-derived model, in which doxycycline-induced expression of Neurogenin-2 drives consistent transdifferentiation into the neuronal state (EBiSC-NEUR1 neurons, referred to as NGN2 neurons below). We developed a suite of open-access, semiautomated methods to measure neurite extension and nucleokinesis of NGN2 neurons, which compare favorably to published data from other models. Then, we challenged NGN2 neurons with a panel of drugs that perturb microtubule physiology. NGN2 neurons extension and nucleokinesis were significantly perturbed by two microtubule-targeting drugs, namely a taxane (paclitaxel) and a vinca alkaloid (DZ-2384). In contrast, inhibition of microtubule severing (spastazoline) or of deacetylation (trichostatin A) had a limited effect on nucleokinesis only. Our results support the primary importance of microtubule dynamics in neuronal development and demonstrate the power of NGN2 neurons as a model system.
Salmonella-induced cholesterol accumulation in infected macrophages suppresses autophagy via mTORC1 activation
Authors: Torsilieri Holly M. , Upchurch Clint M. , Leitinger Norbert , Casanova James E.
Published: November 2024

Salmonella enterica serovar Typhimurium is a Gram-negative bacillus that infects the host intestinal epithelium and resident macrophages. Many intracellular pathogens induce an autophagic response in host cells but have evolved mechanisms to subvert that response. Autophagy is closely linked to cellular cholesterol levels; mTORC1 senses increased cholesterol in lysosomal membranes, leading to its hyperactivity and suppression of autophagy. Previous studies indicate that Salmonella infection induces dramatic accumulation of cholesterol in macrophages, a fraction of which localizes to Salmonella containing vacuoles (SCVs). We previously reported that the bacterial effector protein SseJ triggers cholesterol accumulation through a signaling cascade involving focal adhesion kinase (FAK) and Akt. Here we show that mTORC1 is recruited to SCVs and is hyperactivated in a cholesterol-dependent manner. If cholesterol accumulation is prevented pharmacologically or through mutation of sseJ, autophagy is induced and bacterial survival is attenuated. Notably, the host lipid transfer protein OSBP (oxysterol binding protein 1) is also recruited to SCVs and its activity is necessary for both cholesterol transfer to SCVs and mTORC1 activation during infection. Finally, lipidomic analysis of Salmonella-infected macrophages revealed new insights into how Salmonella may manipulate lipid homeostasis to benefit its survival. We propose that S. Typhimurium induces cholesterol accumulation through SseJ to activate mTORC1, preventing autophagic clearance of bacteria.
GpsB interacts with FtsZ in multiple species and may serve as an accessory Z-ring anchor
Authors: Bhattacharya Dipanwita , King Asher , McKnight Lily , Horigian Pilar , Eswara Prahathees J.
Published: November 2024

Bacterial cytokinesis commences when a tubulin-like GTPase, FtsZ, forms a Z-ring to mark the division site. Synchronized movement of Z-ring filaments and peptidoglycan synthesis along the axis of division generates a division septum to separate the daughter cells. Thus, FtsZ needs to be linked to the peptidoglycan synthesis machinery. GpsB is a highly conserved protein among species of the Firmicutes phylum known to regulate peptidoglycan synthesis. Previously, we showed that Staphylococcus aureus GpsB directly binds to FtsZ by recognizing a signature sequence in its C-terminal tail (CTT) region. As the GpsB recognition sequence is also present in Bacillus subtilis, we speculated that GpsB may interact with FtsZ in this organism. Earlier reports revealed that disruption of gpsB and ftsA or gpsB and ezrA is deleterious. Given that both FtsA and EzrA also target the CTT of FtsZ for interaction, we hypothesized that in the absence of other FtsZ partners, GpsB-FtsZ interaction may become apparent. Our data confirm that is the case, and reveal that GpsB interacts with FtsZ in multiple species and stimulates the GTPase activity of the latter. Moreover, it appears that GpsB may serve as an accessory Z-ring anchor such as when FtsA, one of the main anchors, is absent.
TSC2-mTORC1 axis regulates morphogenesis and neurological function of Gli1+ adult-born dentate granule cells
Authors: Kowalczyk Max , Lee Yu-Ju , Huang Wei-Hsiang
Published: November 2024

Aberrant adult hippocampal neurogenesis is implicated in neurological and mood disorders associated with dysregulation of the mechanistic target of rapamycin (mTOR). Understanding how the mTOR pathway shapes the functional development of different subpopulations of adult-born hippocampal neural stem cells will enable insight into potential therapeutic pathways for these disorders. Here we study how loss of TSC2, a regulator of mTOR pathway and a causal gene for tuberous sclerosis complex (TSC), affects dentate gyrus granule cell morphogenesis and hippocampal-dependent function. We found that Tsc2KO mice with TSC2 specifically ablated from Gli1+ adult-born neural stem cells showed neuronal hypertrophy, reduced NEUN expression, increased dendritic arborization, premature cellular senescence, and hypervascularization of the dentate gyrus. Neurologically, Tsc2KO mice showed altered exploratory behavior, impaired spatial learning, abnormal contextual recall, and hypersensitivity to kainic acid–induced seizures. Importantly, genetic reduction of Raptor, essential for mTORC1 signaling, rebalanced mTORC1 signaling and mitigated molecular, cellular, and neurological deficits in Tsc2KO mice. This study uncovered functions of TSC2 in Gli1+ adult-born neural stem cells and highlights RAPTOR as a potential therapeutic target for reversing disease features associated with TSC2 mutations.
CARMIL1-AA selectively inhibits macropinocytosis while sparing autophagy
Authors: Lim Rebecca M. , Lu Alexa , Chuang Brennan M. , Anaraki Cecily , Chu Brandon , Halbrook Christopher J. , Edinger Aimee L.
Published: November 2024

Macropinocytosis is reported to fuel tumor growth and drug resistance by allowing cancer cells to scavenge extracellular macromolecules. However, accurately defining the role of macropinocytosis in cancer depends on our ability to selectively block this process. 5-(N-ethyl-N-isopropyl)-amiloride (EIPA) is widely used to inhibit macropinocytosis but affects multiple Na+/H+ exchangers (NHE) that regulate cytoplasmic and organellar pH. Consistent with this, we report that EIPA slows proliferation to a greater extent than can be accounted for by macropinocytosis inhibition and triggers conjugation of ATG8 to single membranes (CASM). Knocking down only NHE1 would not avoid macropinocytosis-independent effects on pH. Moreover, contrary to published reports, NHE1 loss did not block macropinocytosis in multiple cell lines. Knocking down CARMIL1 with CRISPR-Cas9 editing limited macropinocytosis, but only by 50%. In contrast, expressing the CARMIL1-AA mutant inhibits macropinocytosis induced by a wide range of macropinocytic stimuli to a similar extent as EIPA. CARMIL1-AA expression did not inhibit proliferation, highlighting the shortcomings of EIPA as a macropinocytosis inhibitor. Importantly, autophagy, another actin dependent, nutrient-producing process, was not affected by CARMIL1-AA expression. In sum, constitutive or inducible CARMIL1-AA expression reduced macropinocytosis without affecting proliferation, RAC activation, or autophagy, other processes that drive tumor initiation and progression.
Adverse events caused by cannabinoids in middle aged and older adults for all indications: a meta-analysis of incidence rate difference
Authors: Velayudhan Latha , Pisani Sara , Dugonjic Marta , McGoohan Katie , Bhattacharyya Sagnik
Published: November 2024

Background

Cannabinoid-based medicines (CBMs) are being used widely in older people. However, information on the incidence of adverse events (AEs) is limited.

Objective

To quantify the incidence rate difference (IRD) of AEs in middle aged and older adults of age ≥50 years receiving CBMs and also examine associations with weekly doses.

Design

Systematic review and meta-analysis.

Data sources

MEDLINE, PubMed, EMBASE, CINAHL, PsychInfo, Cochrane Library and ClinicalTrials.gov (1st Jan 1990–12th June 2023).

Methods

We included randomised clinical trials (RCTs) using CBMs with mean participant age ≥50 years for medicinal purposes for all clinical indications. Paired reviewers independently screened studies, extracted data and appraised risk of bias. We estimated pooled effect-sizes IRD under the random-effects model.

Results

Data from 58 RCTs (37 moderate-high quality studies, pooled n = 6611, mean age range 50–87 years, 50% male, n = 3450 receiving CBMs) showed that compared with controls, the incidence of all-cause and treatment-related AEs attributable to delta-9-tetrahydrocannabinol (THC)-containing CBMs were: THC alone [IRD:18.83(95% Confidence Interval [CI], 1.47–55.79) and 16.35(95% CI, 1.25–48.56)] respectively; THC:cannabidiol (CBD) combination [IRD:19.37(95% CI, 4.24–45.47) and 11.36(95% CI, 2.55–26.48)] respectively. IRDs of serious AEs, withdrawals and deaths were not significantly greater for CBMs containing THC with or without CBD. THC dose-dependently increased the incidence of dry mouth, dizziness/lightheadedness, mobility/balance/coordination difficulties, dissociative/thinking/perception problems and somnolence/drowsiness. The interaction of weekly THC:CBD doses played a role in mostly neurological, psychiatric and cardiac side-effects.

Conclusions

Although CBMs in general are safe and acceptable in middle aged and older adults, one needs to be mindful of certain common dose-dependent side-effects of THC-containing CBMs.
Pectoralis Major Muscle 3D Volumetric Reconstruction in the Tuberous Breast: Anatomical and Radiomics Differences With Potential Surgical Impact
Authors: Vaccari Stefano , Lusi Stefano , Klinger Marco Ettore Attilio , Provini Francesca , Furlan Simone , Bandi Valeria , Di Giuli Riccardo , Bernardi Daniela , Klinger Francesco Maria , Vinci Valeriano
Published: November 2024

Background

Tuberous breast (TB) is a congenital anomaly characterized by morphological, structural, and breast region alterations. The pectoralis major muscle (PMM) is crucial for correction when placing breast implants. Alterations at this level have received little attention in the literature.

Objectives

In this study we aimed to define the anatomical characteristics of the PMM in TB patients with radiomics data extracted from MRI sequences.

Methods

The PMMs of 30 TB patients and 30 controls were analyzed by manual segmentation with 3D-Slicer v.5.4.0 software and radiomics techniques. A total of 46 features were extracted, both first-order statistical features and shape features (eg, median, mean, standard deviation, volume, area, centroid, number of voxels, flatness, roundness, elongation, principal axis length x, y, z, diameter).

Results

A statistically significant difference was found in favor of the TB group for PMM roundness; PMM elongation was greater in the TB group. Principal axes 1, 2, and 3 were analyzed in the 3 planes x, y, and z. In the TB group, principal x axis 3 was lower than in the control group. Also, between the axes, principal z axis 2 was on average higher in the TB group than in the non-TB group.

Conclusions

These results provide the first quantitative evidence of alterations affecting the PMM in TB patients. These differences were found in different planes and volumetric shape features, with potential surgical implications.

Level of Evidence: 4

(Therapeutic)
Aging and environment affect female more than male color in a mutually ornamented bird
Authors: Gomes Ana Cristina R , Guerra Soraia , Romero-Diaz Cristina , Silva Paulo A , Trigo Sandra , Cardoso Gonçalo C
Published: November 2024

Color ornamentation is often sexually selected as a signal of condition, which may be affected by the environment and senescence, but long-term studies in mutually ornamented species are rare, limiting our understanding of sex-specific senescence. We measured color ornamentation of 60 common waxbills (Estrilda astrild) after capture from the wild and in 4 autumns in a large open-air mesocosm. We found longitudinal decreases in the size of the red mask and redness of plumage and bill color, consistent with senescence. Bill color decreased more in females. In males, there was a longitudinal increase in the size of the red breast patch. We also found increased color ornamentation, especially in females, when moving from the wild to the mesocosm, likely due to environmental effects. Monitoring waxbills in bird cages suggested that bill and plumage redness peak in the breeding season. Stronger senescence and environmental effects in females indicate cautious investment in ornamentation, while weaker senescence in males could be due to stronger sexual selection. Overall, although similarly ornamented, the sexes differ in their temporal investment in ornamentation, in line with their life histories.
Toward molecular diagnosis of major depressive disorder by plasma peptides using a deep learning approach
Authors: Wang Jiaqi , Xi Ronggang , Wang Yi , Gao Huiyuan , Gao Ming , Zhang Xiaozhe , Zhang Lihua , Zhang Yukui
Published: November 2024

Major depressive disorder (MDD) is a severe psychiatric disorder that currently lacks any objective diagnostic markers. Here, we develop a deep learning approach to discover the mass spectrometric features that can discriminate MDD patients from health controls. Using plasma peptides, the neural network, termed as CMS-Net, can perform diagnosis and prediction with an accuracy of 0.9441. The sensitivity and specificity reached 0.9352 and 0.9517 respectively, and the area under the curve was enhanced to 0.9634. Using the gradient-based feature importance method to interpret crucial features, we identify 28 differential peptide sequences from 14 precursor proteins (e.g. hemoglobin, immunoglobulin, albumin, etc.). This work highlights the possibility of molecular diagnosis of MDD with the aid of chemical and computer science.
The improved de Bruijn graph for multitask learning: predicting functions, subcellular localization, and interactions of noncoding RNAs
Authors: Wei Yuxiao , Zhang Qi , Liu Liwei
Published: November 2024

Noncoding RNA refers to RNA that does not encode proteins. The lncRNA and miRNA it contains play crucial regulatory roles in organisms, and their aberrant expression is closely related to various diseases. Traditional experimental methods for validating the interactions of these RNAs have limitations, and existing prediction models exhibit relatively limited functionality, relying on isolated feature extraction and performing poorly in handling various types of small sample tasks. This paper proposes an improved de Bruijn graph that can inject RNA structural information into the graph while preserving sequence information. Furthermore, the improved de Bruijn graph enables graph neural networks to learn broader dependencies and correlations among data by introducing richer edge relationships. Meanwhile, the multitask learning model, DVMnet, proposed in this paper can handle multiple related tasks, and we optimize model parameters by integrating the total loss of three tasks. This enables multitask prediction of RNA interactions, disease associations, and subcellular localization. Compared with the best existing models in this field, DVMnet has achieved the best performance with a 3% improvement in the area under the curve value and demonstrates robust results in predicting diseases and subcellular localization. The improved de Bruijn graph is also applicable to various scenarios and can unify the sequence and structural information of various nucleic acids into a single graph.
Protomix: a Python package for 1H-NMR metabolomics data preprocessing
Authors: Zniber Mohammed , Fatihi Youssef , Huynh Tan-Phat
Published: November 2024

Motivation

NMR-based metabolomics is a field driven by technological advancements, necessitating the use of advanced preprocessing tools. Despite this need, there is a remarkable scarcity of comprehensive and user-friendly preprocessing tools in Python. To bridge this gap, we have developed Protomix—a Python package designed for metabolomics research. Protomix offers a set of automated, efficient, and user-friendly signal-preprocessing steps, tailored to streamline and enhance the preprocessing phase in metabolomics studies.

Results

This package presents a comprehensive preprocessing pipeline compatible with various data analysis tools. It encompasses a suite of functionalities for data extraction, preprocessing, and interactive visualization. Additionally, it includes a tutorial in the form of a Python Jupyter notebook, specifically designed for the analysis of 1D 1H-NMR metabolomics data related to prostate cancer and benign prostatic hyperplasia.

Availability and implementation

Protomix can be accessed at https://github.com/mzniber/protomix and https://protomix.readthedocs.io/en/latest/index.html.
Phylogeography and palaeoecological modelling shed light on the diversification history of a montane New Guinea passerine, Peneothello cyanus (Petroicidae)
Authors: Benz Brett W
Published: November 2024

Tropical montane ecosystems have undergone recurrent elevational shifts in distribution owing to climatic cycling in the Quaternary, yet the extent to which these events have influenced patterns of diversification and endemism within highland bird communities remains poorly understood. Here, I examine the phylogeographical structure and palaeoecology of a montane New Guinea passerine (Peneothello cyanus) to assess how climate change and topography have shaped its evolutionary history. Mitochondrial sequence data were collected from 169 individuals across 31 localities, and the resulting spatial assessments of genetic variation were integrated with contemporary and Last Glacial Maximum ecological niche reconstructions to test hypotheses of climate-mediated diversification. Three primary lineages of mid-Pleistocene origin were recovered within P. cyanus, revealing a previously unrecognized contact zone in the Star Mountains. Population genetic structure was largely consistent with the distribution of contemporary sky islands and an isolation-by-distance effect, as indicated by hierarchical analyses of molecular variance and Mantel tests, respectively. Although global cooling during the Last Glacial Maximum is likely to have enhanced population connectivity within the central cordillera of New Guinea, persistence of genetic diversity and population structure across multiple climate cycles suggests that dispersal ability and constraints on admixture associated with the linear distribution of these montane environments have played a larger role in shaping regional genetic structure.
The role of Q10 engineering mesenchymal stem cell-derived exosomes in inhibiting ferroptosis for diabetic wound healing
Authors: Yang Ronghua , Zhou Sitong , Huang Jie , Kang Deni , Chen Yao , Wang Xinyi , Shi Yan , Wang Zhengguang
Published: November 2024

Background

Ferroptosis plays an essential role in the development of diabetes and its complications, suggesting its potential as a therapeutic target. Stem cell-derived extracellular vesicles (EVs) are increasingly being developed as nano-scale drug carriers. The aim of this study was to determine the role of ferroptosis in the pathogenesis of diabetic wound healing and evaluate the therapeutic effects of coenzyme Q10 (Q10)-stimulated exosmes derived from mesenchymal stem cells (MSCs).

Methods

Human keratinocytes (HaCaTs) were exposed to high glucose (HG) conditions in vitro to mimic diabetic conditions, and the ferroptosis markers and expression level of acyl-coenzyme A synthase long-chain family member 4 (ACSL4) were determined. Exosomes were isolated from control and Q10-primed umbilical cord mesenchymal stem cells (huMSCs) and characterized by tramsmission electron microscopy and immunofluorescence staining. The HG-treated HaCaTs were cultured in the presence of exosomes derived from Q10-treated huMSCs (Q10-Exo) and their in vitro migratory capacity was analyzed.

Results

Q10-Exo significantly improved keratinocyte viability and inhibited ferroptosis in vitro. miR-548ai and miR-660 were upregulated in the Q10-Exo and taken up by HaCaT cells. Furthermore, miR-548ai and miR-660 mimics downregulated ACSL4-inhibited ferroptosis in the HG-treated HaCaT cells and enhanced their proliferation and migration. However, simultaneous upregulation of ACSL4 reversed their effects. Q10-Exo also accelerated diabetic wound healing in a mouse model by inhibiting ACSL4-induced ferroptosis.

Conclusions

Q10-Exo promoted the proliferation and migration of keratinocytes and inhibited ferroptosis under hyperglycemic conditions by delivering miR-548ai and miR-660. Q10-Exo also enhanced cutaneous wound healing in diabetic mice by repressing ACSL4-mediated ferroptosis.
Genome-wide identification of SSR markers from coding regions for endangered Argania spinosa L. skeels and construction of SSR database: AsSSRdb
Authors: Rabeh Karim , Mghazli Najoua , Gaboun Fatima , Filali-Maltouf Abdelkarim , Sbabou Laila , Belkadi Bouchra
Published: November 2024

Microsatellites [simple sequence repeats (SSRs)] are one of the most widely used sources of genetic markers, particularly prevalent in plants. Despite their importance in various applications, a comprehensive genome-wide identification of coding sequence (CDS)-associated SSR markers in the Argania spinosa L. genome has yet to be conducted. In this study, 66 280 CDSs containing 5351 SSRs within 4535 A. spinosa L. CDSs were identified. Among these, tri-nucleotide motifs (58.96%) were the most common, followed by hexa-nucleotide (15.71%) and di-nucleotide motifs (13.32%). The predominant SSR motif in the tri-nucleotide category was AAG (24.4%), while AG (94.1%) was the most abundant among di-nucleotide repeats. Furthermore, the extracted CDSs containing SSRs were subjected to functional annotation; 3396 CDSs (74.88%) exhibited homology with known proteins, 3341 CDSs (73.7%) were assigned Gene Ontology terms, 1004 CDSs were annotated with Enzyme Commission numbers, and 832 (18.3%) were annotated with KEGG pathways. A total of 3475 primer pairs were designed, out of which 3264 were successfully validated in silico against the A. spinosa L. genome, with 99.6% representing high-resolution markers yielding no more than three products. Additionally, the SSR markers demonstrated a low rate of transferability through in-silico verification in two species within the Sapotaceae family. Furthermore, we developed an online database, the “Argania spinosa L. SSR database: https://as-fmmdb.shinyapps.io/asssrdb/” (AsSSRdb) to provide access to the CDS-associated SSRs identified in this study. Overall, this research provides valuable marker resources for DNA fingerprinting, genetic studies, and molecular breeding in argan and related species.

Database URL: https://as-fmmdb.shinyapps.io/asssrdb/
The transaxillary concept for minimally invasive isolated aortic valve replacement: results of 1000 consecutive patients
Authors: Wilbring Manuel , Arzt Sebastian , Taghizadeh-Waghefi Ali , Petrov Asen , Di Eusanio Marco , Matschke Klaus , Alexiou Konstantin , Kappert Utz
Published: November 2024

OBJECTIVES

The transaxillary concept for minimally invasive cardiac surgery-aortic valve replacement is a new and versatile approach with nearly no visible scars. Due to its novelty, available data in literature are scarce. This study reports clinical outcomes of 1000 consecutive patients.

METHODS

Between 2019 and 2023, 4394 patients underwent elective isolated aortic valve procedures, with 2958 (67.5%) transcatheter aortic valve implantation’s and 1436 patients surgical aortic valve replacement’s (32.5%). Within this period, 1st consecutive 1000 transaxillary isolated minimally invasive cardiac surgery-aortic valve replacement were enrolled. Endocarditis, redo’s or combined procedures were excluded. Mean age was 67.9 ± 8.3 years, STS-PROM 1.39 ± 2.89% and EuroScore II 1.65 ± 1.12%.

RESULTS

Use of the transaxillary access increased from 18.7% (2019) to 97.8% (2023). Mean procedure time was 127 ± 31 min, and average cross-clamp time was 43 ± 14 min. Used prostheses were rapid deployment (81.1%), sutured biologic (14.5%) or sutured mechanical valves (4.1%). Conversion rate was 1.9%. No patient died intraoperatively. Thirty-day major adverse cardiac and cerebrovascular event was 1.9% including 0.9% mortality, 0.8% perioperative stroke and 0.6% myocardial infarction. Multivariate factors for major adverse cardiac and cerebrovascular event are intraoperative conversion [OR 1.08 (1.00–1.16); P = 0.04], intraoperative transfusions [OR 1.21 (1.07–1.38); P < 0.01] and respiratory failure [OR 1.39 (1.30–1.49); P < 0.01]. Corresponding factors for mortality are diabetes on insulin [OR 1.02 (1.00–1.04); P = 0.03], pure aortic regurgitation for primary indication [OR 1.03 (1.01–1.05); P < 0.01], intraoperative conversion [OR 1.11 (1.07–1.16); P < 0.01], renal failure [OR 1.08 (1.05–1.10); P < 0.01] and respiratory failure [OR 1.22 (1.17–1.26); P < 0.01].

CONCLUSIONS

Transaxillary minimally invasive cardiac surgery-aortic valve replacement is a safe, effective and cosmetically convincing method for surgical aortic valve replacement, having the potential for >95.0% minimally invasive cardiac surgery rate in selected patients.
Serum and urinary 5-hydroxyindolacetic acid, serotonin, chromogranin A, and NT-proBNP for the detection of carcinoid heart disease
Authors: Lecoeur Antoine , Sfeir Rita-Maria , Gerard Laura , Souifi Myriam , Damour Johanna , Lombard-Bohas Catherine , Francois Laurent , Fort Justine , Delsart Daphne , Forestier Julien , Walter Thomas , Durand Alice , Chardon Laurence
Published: November 2024

Objective

The aim of this study was to evaluate the performance of different biomarkers for the detection of carcinoid heart disease (CHD) in neuroendocrine tumours (NETs), in particular serum 5-HIAA (s5HIAA).

Design

An explorative ancillary study of the French CrusoeNET cohort.

Methods

Patients managed in the Lyon-EURACAN Center of Excellence (CoE) were included when they were aged of at least 18 years, treated and followed for an advanced/metastatic ileum or lung NET, a NET irrespective of the primary location or from unknown primary location but with clinical CS, and/or elevation of urinary 5-HIAA (u5HIAA) twice greater than the upper limit of normal. All patients included had 1 available serum stored within the local biobank between January 2021 and April 2022. Echocardiography was performed by 1 of the 3 expert cardiologists of the Lyon-EURACAN-CoE.

Results

We included 138 patients with NETs, mainly of the small intestine and lung, and 19 of them had a CHD. Analysis showed that s5HIAA was well correlated with u5HIAA (ρ = 0.824 [0.76-0.88], P < .0001) and was a good biomarker for CHD detection (receiver operating characteristic curve = 0.85 [0.75-0.94], P < .0001). Using a threshold value of 757 nmol/L, the sensitivity and specificity for the detection of CHD were 84% and 80%, respectively.

Conclusions

s5HIAA is highly sensitive and specific for CHD detection. It could be used as a pre-screening tool in centres where systematic and regular echocardiography by an expert cardiologist is not performed in this population.
Reporting of participant race and ethnicity from COVID-19 randomized controlled drug and biologicals trials: a scoping review
Authors: Pranić Shelly Melissa , Estevão Maria Dulce , Vasanthan Lenny T , Pérez-Neri Iván , Pulumati Anika , de Lima Junior Fábio Antonio Serra , Malih Narges , Mishra Vinayak , Thompson Jacqueline , Nnate Daniel
Published: November 2024

Racial and ethnic minorities have been disproportionally burdened by hospitalization and death due to COVID-19. Participation of individuals of diverse races and ethnicities in clinical trials, according to study-level characteristics of randomized controlled trials (RCTs) that test effectiveness of COVID-19 drugs, could be insightful for future researchers. Our objective for this scoping review was to describe the frequency of race and ethnicity reported as demographic variables and specific reporting of race and ethnicity according to COVID-19 RCT characteristics. We conducted comprehensive searches in PubMed, ProQuest, World Health Organization Database, and Cochrane Central Register of Controlled Trials, and gray literature via preprint servers from January 1, 2020, to May 4, 2022. We included RCTs on emergency- or conditionally approved COVID-19 drug interventions (remdesivir, baricitinib, and molnupiravir) with or without comparators. Self-reported race as American Indian/Pacific Islander, Asian, Black/African American, or White, ethnicity as Hispanic/Latinx, study design characteristics, and participant-relevant data were collected. In total, 17 RCTs with 17 935 participants were included. Most (n = 13; 76%) reported at least 1 race and ethnicity and were US-based, industry-funded RCTs. Asian, Black, Latinx, and White participants were mostly enrolled in RCTs that studied remdesivir. Native American and Hawaiian participants were mostly assessed for progression to high-flow oxygen/noninvasive ventilation. Time to recovery was assessed predominantly in Black and White participants, whereas hospitalization or death was mostly assessed in Asian, Latinx, and multirace participants. Trialists should be aware of RCT-level factors and characteristics that may be associated with low participation of racial and ethnic minorities, which could inform evidence-based interventions to increase minority participation.
Percutaneous vs. surgical revascularization of non-ST-segment elevation myocardial infarction with multivessel disease: the SWEDEHEART registry
Authors: Omerovic Elmir , Råmunddal Truls , Petursson Petur , Angerås Oskar , Rawshani Araz , Jha Sandeep , Skoglund Kristofer , Mohammad Moman A , Persson Jonas , Alfredsson Joakim , Hofmann Robin , Jernberg Tomas , Fröbert Ole , Jeppsson Anders , Hansson Emma C , Dellgren Göran , Erlinge David , Redfors Björn
Published: November 2024

Background and Aims

The long-term outcomes of percutaneous coronary intervention (PCI) vs. coronary artery bypass grafting (CABG) in patients with non-ST-segment elevation myocardial infarction (NSTEMI) and multivessel disease remain debated.

Methods

The Swedish Web-system for Enhancement and Development of Evidence-based care in Heart disease Evaluated According to Recommended Therapies registry was used to analyse 57 097 revascularized patients with NSTEMI with multivessel disease in Sweden from January 2005 to June 2022. The primary endpoint was all-cause mortality, encompassing both in-hospital and long-term mortality; the secondary endpoints included myocardial infarction (MI), stroke, new revascularization, and heart failure. Multilevel logistic regression with follow-up time as a log-transformed offset variable and double-robust adjustment with the instrumental variable method were applied to control for known and unknown confounders.

Results

Percutaneous coronary intervention was the primary therapy in 42 190 (73.9%) patients, while 14 907 (26.1%) received CABG. Percutaneous coronary intervention patients were generally older with more prior cardiovascular events, whereas CABG patients had higher incidences of diabetes, hypertension, left main and three-vessel disease, and reduced ejection fraction. Over a median follow-up of 7.1 years, PCI was associated with higher risks of death [adjusted odds ratio (aOR) 1.67; 95% confidence interval (CI) 1.54–1.81] and MI (aOR 1.51; 95% CI 1.41–1.62) but there was no significant difference in stroke. Repeat revascularization was three times more likely to PCI (aOR 3.01; 95% CI 2.57–3.51), while heart failure risk was 15% higher (aOR 1.15; 95% CI 1.07–1.25). Coronary artery bypass grafting provided longer survival within 15 years, especially in patients under 70 years of age, with left main disease or left ventricular dysfunction, though this benefit diminished over shorter time horizons.

Conclusions

Coronary artery bypass grafting is associated with lower risks of mortality, MI, repeat revascularization, and heart failure in patients with NSTEMI, particularly in high-risk subgroups. However, its survival benefit lessens with shorter life expectancy.