bluuebunny/crossref_metadata_2025 huggingface dataset:
A new selective force driving metabolic gene clustering
Authors: Fondi Marco , Pini Francesco , Riccardi Christopher , Gemo Pietro , Brilli Matteo
Published: October 2024

The evolution of operons has puzzled evolutionary biologists since their discovery, and many theories exist to explain their emergence, spreading, and evolutionary conservation. In this work, we suggest that DNA replication introduces a selective force for the clustering of functionally related genes on chromosomes, which we interpret as a preliminary and necessary step in operon formation. Our reasoning starts from the observation that DNA replication produces copy number variations of genomic regions, and we propose that such changes perturb metabolism. The formalization of this effect by exploiting concepts from metabolic control analysis suggests that the minimization of such perturbations during evolution could be achieved through the formation of gene clusters and operons. We support our theoretical derivations with simulations based on a realistic metabolic network, and we confirm that present-day genomes have a degree of compaction of functionally related genes, which is significantly correlated to the proposed perturbations introduced by replication. The formation of clusters of functionally related genes in microbial genomes has puzzled microbiologists since their first discovery. Here, we suggest that replication, and the copy number variations due to the replisome passage, might play a role in the process through a perturbation in metabolite homeostasis. We provide theoretical support to this hypothesis, and we found that both simulations and genomic analysis support our hypothesis.

IMPORTANCE

The formation of clusters of functionally related genes in microbial genomes has puzzled microbiologists since their discovery. Here, we suggest that replication, and the copy number variations due to the replisome passage, might play a role in the process through a perturbation in metabolite homeostasis. We provide theoretical support to this hypothesis, and we found that both simulations and genomic analysis support our hypothesis.
Determination of the Dipole Moment Variation Upon Excitation in the Chromophore of Green Fluorescent Protein From Molecular Dynamic Trajectories with QM/MM Potentials Using Machine Learning Methods
Authors: Zakharova T. M. , Kulakova A. M. , Krinitsky M. A. , Varentsov M. I. , Khrenova M. G.
Published: October 2024

Quantum and molecular mechanics (QM/MM) potentials are used to calculate molecular dynamics trajectories for the EYFP protein of the green fluorescent protein family. Machine learning models are constructed to establish the relationship between the geometric parameters of the chromophore in the frame of its trajectory and the properties of its electronic excitation. It is shown that it is not enough to use only bridging bonds between the phenyl and imidazolidone fragments of the chromophore as a geometric parameter, and at least two more neighboring bonds must be added to the model. The proposed models allow determination of the dipole moment variation upon excitation with an average error of 0.11 a.u.
40Ar/39Ar Dating of Hydrothermal Processes in Large Gold Deposits of the Kochkar Anticlinorium (South Urals, Russia)
Authors: Pritchin M. E. , Kisin A. Yu. , Vikent’eva O. V. , Ozornin D. A. , Travin A. V. , Vikentyev I. V.
Published: October 2024

The age restrictions for productive mineral associations of the two largest gold deposits of the Southern Urals—Svetlinsk and Kochkar, which are located in the East Uralian megazone—are discussed. The 40Ar/39Ar dating method was performed for the first time for potassium-containing hydrothermal minerals (micas and amphiboles) from the ore veins and ore-host alteration, as well as from marbles. The age estimates obtained are in the range of 290–276 Ma; the weighted average value for the Svetlinsk deposit is 276 ± 2 Ma; for the Kochkar field, 284 ± 2 Ma. It is supposed that the studied mineral assemblages of the Svetlinsk and Kochkar deposits were formed in the beginning of the postcollision stage corresponding to the tectonic relaxation regime. Age of hydrothermal mineral formation in the gold fields of the Kochkar anticlinorium are consistent with the time of post-tectonic plutonic activity, which was expressed in the Middle–Southern Urals in large-scale granitization (~300 Ma). The ore-bearing alteration of a femic profile (of the same age for two deposits), which are most likely basificates, are near-synchronous with the granitization.
Supporting a rapid primary care response to emergent communicable disease threats with PACK (Practical Approach to Care Kit) in Florianópolis, Brazil
Authors: Zonta Ronaldo , Zaros Galana Mariela , Zepeda Jorge , Perini Filipe de Barros , Fairall Lara R , Melchior Silva Pinto Fernanda K Karolinne , Pacheco de Andrade Matheus , Manata Eloi Bernardo , da Silveira João Paulo Mello , Siqueira Elizimara Ferreira , Báfica Ana Cristina Magalhães Fernandes , Awotiwon Ajibola , Spiller Pearl Wendy , Wattrus Camilla , Ras Christy Joy , Georgeu-Pepper Daniella , Cornick Ruth Vania
Published: October 2024

Emerging infectious diseases present a significant challenge to healthcare systems with their need for a rapid response and reallocation of resources. This paper explores the implementation of the Practical Approach to Care Kit (PACK) programme in Florianópolis, Brazil as a strategic tool for reinforcing primary healthcare (PHC) responses to emergent communicable diseases. With its focus on enhancing PHC delivery in resource-limited settings, PACK provides a flexible, evidence-based framework that integrates into local health systems. The paper describes experiences adapting PACK to provide rapid responses to outbreaks of Zika, leishmaniasis, COVID-19, Mpox and dengue in primary care between 2014 and 2023. Key features of PACK, including its flexibility to incorporate new clinical content, responsive implementation strategy and health system strengthening approach, are highlighted. The paper emphasises how PACK supported responses to specific disease outbreaks and helped maintain mainstream PHC delivery, preventing the system from becoming condition-centric during crises. We describe the limitations of the PACK approach in an outbreak scenario, the challenges experienced and efforts to tackle these. The lessons learnt from Florianópolis underscore the adaptability and relevance of comprehensive primary care approaches like PACK in supporting PHC professionals and local health systems to navigate emerging health challenges.
Haptoglobin polymorphism, vitamin E and mortality: the Ludwigshafen Risk and Cardiovascular Health Study
Authors: Delgado Graciela E , Kleber Marcus E , Moissl Angela P , Winklhofer-Roob Brigitte M , Krämer Bernhard K , Renner Wilfried , Langsenlehner Tanja , Dschietzig Thomas B , März Winfried , Armbruster Franz P
Published: October 2024

Objective

In humans, haptoglobin (Hp) exists in two allelic forms, Hp1 and Hp2, that differ significantly in their ability to protect the organism from oxidative stress. It has been proposed that in patients with diabetes mellitus carriers of the Hp2-2 genotype may benefit from vitamin E supplementation. Aim of our study was to investigate if there is evidence regarding a potential interaction between the Hp polymorphism and vitamin E with regard to mortality in individuals at medium-to-high cardiovascular risk with and without diabetes mellitus.

Research design and methods

Data from 3176 participants of the Ludwigshafen Risk and Cardiovascular Health study, a monocentric hospital-based study of patients referred for coronary angiography, were analysed using Cox proportional hazard regression.

Results

Participants with the Hp2-2 genotype demonstrated significantly lower Hp levels, while carriers of at least one Hp-2 allele displayed elevated levels of the inflammatory markers high-sensitive C reactive protein and serum amyloid A. No notable differences in comorbidities were observed among the various HP genotype groups. While the HP genotype showed no direct association with mortality, a borderline significant correlation between α-tocopherol plasma concentration and overall mortality was noted. An interaction between vitamin E status and the HP genotype regarding mortality risk was evident, particularly among patients with diabetes mellitus, with a p value of 0.021 for the interaction term. In restricted cubic splice analysis, patients with diabetes mellitus who are carriers of the Hp2-2 genotype seem to benefit from higher γ-tocopherol concentrations whereas for the other genotype groups there was a direct association with mortality risk.

Conclusion

Particularly in patients with diabetes mellitus we could show a significant interaction of γ-tocopherol plasma concentration and HP genotype. Carriers of the Hp2-2 genotype seemed to benefit from higher plasma concentrations of γ-tocopherol. Further research is warranted to elucidate the underlying mechanisms and potential therapeutic implications in cardiovascular disease management.
Right ventricular remodelling and long-term survival after pulmonary endarterectomy versus balloon pulmonary angioplasty in chronic thromboembolic pulmonary hypertension
Authors: Ravnestad Håvard , Murbræch Klaus , Gjønnæss Eyvind , Andersen Rune , Moe Natasha , Birkeland Sigurd , Svalebjørg Morten , Lingaas Per Snorre , Gude Einar , Gullestad Lars , Kvitting John-Peder Escobar , Broch Kaspar , Andreassen Arne K
Published: October 2024

Background

Pulmonary endarterectomy (PEA) is the treatment of choice for chronic thromboembolic pulmonary hypertension (CTEPH), while balloon pulmonary angioplasty (BPA) is an alternative for inoperable patients. We aimed to compare right ventricular (RV) remodelling and late survival after PEA and BPA.

Methods

In this prospective observational cohort study, we performed echocardiography at baseline and follow-up in patients with CTEPH treated with PEA (n=54) or BPA (n=44) between 2011 and 2022.

Results

Follow-up echocardiography was performed at 5 months (IQR 4–7) after PEA and 3 months (IQR 2–4) after the last BPA. Both groups showed significant improvements in left ventricular end-systolic eccentricity index, RV basal diameter and RV fractional area change (RV FAC). Tricuspid regurgitation pressure decreased by 26±18 mm Hg after PEA and 13±21 mm Hg after BPA (p=0.02 for between-group difference). Tricuspid annular systolic excursion (TAPSE) decreased by 4±5 mm after PEA but increased by 1±4 mm after BPA (p<0.001). The TAPSE/systolic pulmonary artery pressure ratio improved similarly in both groups. Five-year survival was 96% (95% CI 86% to 99%) for PEA and 79% (95% CI 61% to 89%) for BPA (p=0.25). Change in RV FAC was an independent predictor of survival (HR 0.9, 95% CI 0.82 to 0.99, p=0.03).

Conclusions

Both PEA and BPA led to significant RV reverse remodelling, with no clear evidence of a difference in survival rates. Improvement in RV function, particularly RV FAC, was associated with better outcomes, highlighting the importance of RV recovery in CTEPH treatment.
Solar neutrinos in cryogenic detectors
Authors: Bento A. , Bertolini A. , Canonica L. , Di Lorenzo S. , Dominsky F. , Iachellini N. Ferreiro , Fuchs D. , Garai A. , Hauff D. , Langenkämper A. , Mancuso M. , Mauri B. , Petricca F. , Pröbst F. , Pucci F. , Stodolsky L.
Published: October 2024

Coherent elastic neutrino-nucleus scattering (CE$$\nu $$
ν
NS) poses an irreducible background in the search for dark matter-nucleus elastic scatterings, which is commonly known as the neutrino floor. As direct dark matter search experiments keep improving their sensitivity into so far unexplored regions, they face the challenge of approaching this neutrino floor. A precise description of the CE$$\nu $$
ν
NS signal is therefore crucial for the description of backgrounds for future DM searches. In this work we discuss the scenario of detecting neutrinos in low-threshold, high-exposure cryogenic solid state experiments optimized for the search of low-mass dark matter. The energy range considered is completely dominated by solar neutrinos. In absence of any dark matter events, we treat solar neutrinos as the main signal of interest. We show that sensitivity to the flux of neutrinos from different production mechanisms can be achieved. In particular we investigate the sensitivity to the flux of pp and $$^{7}$$

7

Be neutrinos, as well as CNO neutrinos. Furthermore, we investigate the sensitivity to dark matter signals in the presence of a solar neutrino background for different experimental scenarios, which are defined by three parameters: the target material, the energy threshold and the exposure. We show that experiments with thresholds of $$\mathcal {O}$$
O
(eV) and exposures of $$\mathcal {O}$$
O
(tonne-years), using $$\hbox {CaWO}_{4}$$

CaWO
4

or $$\hbox {Al}_{2}\hbox {O}_{3}$$

Al
2

O
3

targets, have discovery potential for dark matter interaction cross sections in the neutrino floor.
Recent progress and future plan for STCF collider ring lattice design
Authors: Liu Tao , Zhang Linhao , Li Sangya , Wang Lin , Luo Qing
Published: October 2024

The Super Tau-Charm Facility (STCF) is a proposed dual-ring electron–positron collider in China, designed to operate at a center-of-mass energy (CME) range of 2–7[Formula: see text]GeV with symmetric beam energies. The collider aims for a luminosity exceeding [Formula: see text] at the beam energy of 2.0[Formula: see text]GeV. This work presents the preliminary lattice design for the STCF collider ring, specifically optimized for the 2.0[Formula: see text]GeV beam energy. To improve the nonlinear dynamics performance, the optimization of lattice is carried out by adjusting the strengths of sextupole and octupole magnets following the tuning of phase advances.
Self-Supervised Image Aesthetic Assessment Based on Transformer
Authors: Jia Minrui , Wang Guangao , Wang Zibei , Yang Shuai , Ke Yongzhen , Wang Kai
Published: October 2024

Visual aesthetics has always been an important area of computational vision, and researchers have continued exploring it. To further improve the performance of the image aesthetic evaluation task, we introduce a Transformer into the image aesthetic evaluation task. This paper pioneers a novel self-supervised image aesthetic evaluation model founded upon Transformers. Meanwhile, we expand the pretext task to capture rich visual representations, adding a branch for inpainting the masked images in parallel with the tasks related to aesthetic quality degradation operations. Our model’s refinement employs the innovative uncertainty weighting method, seamlessly amalgamating three distinct losses into a unified objective. On the AVA dataset, our approach surpasses the efficacy of prevailing self-supervised image aesthetic assessment methods. Remarkably, we attain results approaching those of supervised methods, even while operating with a limited dataset. On the AADB dataset, our approach improves the aesthetic binary classification accuracy by roughly 16% compared to other self-supervised image aesthetic assessment methods and improves the prediction of aesthetic attributes.
Path Planning in Payment Channel Networks with Multi-Party Channels
Authors: Corcoran Padraig , Lewis Rhyd
Published: October 2024

Payment Channel Networks (PCNs) provide a means to improve the scaling of cryptocurrency payments by allowing peers to make payments between themselves in an efficient manner. To make a payment between two peers, the task of path planning must first be performed to determine a path in the PCN connecting the peers in question before the payment in question is performed using this path. To date, existing research has focused on the problem of performing path planning in PCNs that contain two-party channels. It has been hypothesised that the scaling of PCNs could be further improved by considering the inclusion of multi-party channels that contain more than two peers. However, the problem of performing path planning in PCNs that contain multi-party channels has not yet been considered.

In this article, we address this gap in the research literature and propose a novel path planning method for PCNs containing multi-party channels. This method involves modelling the PCN with multi-party channels as a hypergraph, a type of graph where edges can contain two or more vertices, and using this model to solve the path planning problem in question. We prove that the proposed method is correct and computationally efficient. Furthermore, assuming path planning is performed using this method, we also present theoretical and experimental analyses that demonstrate the scaling benefits of using multi-party channels.
Structural and Hydrophilic Properties of Nanoporous Aluminium Oxide Film as a Function of Voltage Anodization
Authors: Grayeli A. R. , Balashabadi P. , Mojtahedzadeh M.
Published: October 2024

The impact of voltage on the formation of nanopores through electrochemical anodization of high-purity aluminum was examined. The electrochemical bath was carefully prepared with oxalic acid electrolyte, while a 99.5% pure aluminum electrode served as the cathode and an aluminum template as the anode. The anodization process was conducted at room temperature, with voltage increments ranging from 20 V to 65 V, which was made possible by the in-house electrochemical cell. Notably, each incremental increase in voltage yielded a significant surge in current density, accompanied by a marked expansion in nanopore size, growing from approximately 35 nm to 125 nm. X-ray diffractometry, scanning electron microscopy, energy-dispersive X-ray spectroscopy, and Rutherford backscattering spectrometry were used to characterize the films. A slight phase change was observed in the aluminum substrate’s FCC structure after the anodization process, transitioning to a monoclinic structure at 39° and 45° for all applied potentials. The stoichiometry of the films was determined through RBS analysis. The nano pores’ resulting morphology and phase composition were further examined using SEM and EDS, providing insights into their structural characteristics. Furthermore, the water contact angle of the anodized aluminum oxide samples was measured, revealing a range of approximately 85.16 to 61.01 degrees.
A Compact Circularly Polarized Planar Spiral Antenna With Ultrawide Bandwidth and Directional Radiation Pattern
Authors: Li Junlong , Zhang Yiming , Yu CaiLi , Huang Guogang , Liu Hui
Published: October 2024

A compact circularly polarized (CP) planar spiral antenna with ultrawide bandwidth and directional radiation pattern is proposed for ultra‐wideband (UWB) positioning applications. The proposed antenna consists of a dual‐arm planar spiral with a tapered microstrip line, two L‐shaped metallic shorting stubs, and a square ground plane with four stepped slots. By connecting two L‐shaped metallic stubs to both the ends of the dual‐arm spiral through metal posts, the traveling wave current path is effectively extended, resulting in a significant improvement of the CP bandwidth. Additionally, both impedance bandwidth and circular polarization performance of the proposed antenna can be enhanced by adopting four stepped slots on the square ground plane. Measured results show that the planar spiral antenna features an impedance bandwidth from 3.23 GHz to 7.0 GHz (more than 73.7%), a 3‐dB axial ratio (AR) bandwidth of 62.1% (3.05 GHz–5.8 GHz), and finally achieves an overlapping bandwidth of 56.9% (3.23 GHz–5.8 GHz). On the overlapping bandwidth, this antenna maintains a gain consistently above 6 dBic while the peak gain reaches about 7.4 dBic. The overall size of the antenna is 0.59λg × 0.59λg × 0.17λg (λg is the free‐space wavelength at the lowest frequency, 3.23 GHz). Thanks to the ultrawide CP bandwidth and compact size, the proposed antenna can be a promising candidate for UWB positioning applications.
An Overview of Publications on Extracellular Vesicles in Osteoarthritis from 2012 to 2022: A Bibliometric Analysis
Authors: Wang Rui , Wang Zheng-ming , Xiang Si-cheng , Jin Zhao-kai , Jin Heng-kai , Shi Qi , Xiao Lianbo
Published: October 2024

Background. Extracellular vesicles, particularly those derived from stem cells, have demonstrated promising potential in osteoarthritis in recent years. However, there has been no bibliometric analysis focusing on the relationship between extracellular vesicles and osteoarthritis. This study aimed to investigate trends and hotpots of publications on extracellular vesicles in osteoarthritis. Methods. This study collected publications on extracellular vesicles in osteoarthritis from the Web of Science Core Collection database, focusing on English‐language articles and reviews. Quantitative and visual analysis was performed using Microsoft Excel, R shiny, SCImago Graphica, VOS Viewer, and CiteSpace. The data set comprised information on keywords, authors, institutions, journals, and the country or region of the included literature. Journal impact factors and H‐index values were obtained from the 2021 Journal Citation Reports and SJR‐International Science Ranking. Furthermore, we conducted a frequency analysis of annual publications number and fitting curves of the growth trends in the publications. Moreover, we conducted a citation burst analysis of the top 20 keywords and a related bibliometric analysis (word frequency analysis and cocitation analysis) using CiteSpace. Results. A total of 715 documents were analyzed. The number of publications increased annually from 2012 to 2022. China had the highest number (n = 394, 55.1%) of publications and total citations during the decade, followed by the United States (n = 105, 14.7%). Shanghai JiaoTong University contributed the highest number of publications (n = 28, 3.9%). Wang Y has the highest number of publications (n = 40, 5.6%), and Stem Cell Research & Therapy is the journal with the highest number of publications (n = 64, 9.0%). The hotspots of extracellular vesicle research in recent years are umbilical cord blood, drug delivery, and scaffolds. Conclusion. Our findings indicate an increase in publications on the topic in utilizing extracellular vesicles in the context of osteoarthritis. Extracellular vesicle therapy for cartilage regeneration and repair of bone defects in osteoarthritis holds significant potential. Future research will focus on the development of novel drug delivery systems that utilize extracellular vesicles, the creation of novel biomaterials that incorporate extracellular vesicles, and the potential of extracellular vesicles as early diagnostic markers of disease.
Associations of Vitamin D With GPX4 and Iron Parameters in Chronic Obstructive Pulmonary Disease Patients: A Case–Control Study
Authors: Fei Jun , Liu Ling , Li Jia-Fei , Zhou Qiang , Wei Yu , Zhou Ting-Dong , Fu Lin
Published: October 2024

Background: Vitamin D deficiency elevates the risk of chronic obstructive pulmonary disease (COPD) patients. Iron parameters elevation and glutathione peroxidase 4 (GPX4) reduction are involved in the process of COPD. The goal is to explore the associations of vitamin D with GPX4 and iron parameters in COPD patients through a case–control study.

Methods: COPD patients and control subjects were enrolled. Serum samples and lung tissues were collected. Serum vitamin D and iron levels and pulmonary ferritin and GPX4 expressions were determined. In addition, human pulmonary epithelial cells (BEAS‐2B) were incubated with 1,25(OH)2D3 (100 nM), the active form of vitamin D3. Then, vitamin D receptor (VDR) and nuclear factor (erythroid‐derived 2)‐like 2 (Nrf‐2) signaling were detected.

Results: In patients with COPD, serum 25‐hydroxyvitamin D (25(OH)D) decreased, and iron and ferritin levels in serum and lung tissues increased. Furthermore, pulmonary expression of GPX4 was reduced. Correlative analyzes indicated that lung function was inversely correlated with iron parameters and positively correlated with GPX4. The results showed that serum 25(OH)D deficiency was associated with an elevation in serum iron parameters and a reduction in pulmonary GPX4. In addition, VDR‐ and Nrf‐2‐positive lung nuclei were decreased in COPD patients than in control subjects. In patients with COPD, the results indicated a positive relationship between VDR and Nrf‐2. Further analysis revealed that Nrf‐2‐positive nuclei were negatively correlated with iron parameters. In vitro experiments found that 1,25(OH)2D3 treatment activated VDR signaling and elevated the expression of Nrf‐2 and GPX4 in BEAS‐2B cells.

Conclusions: Vitamin D deficiency is positively associated with GPX4 reduction and iron parameters elevation in COPD patients. It is recommended to explore the role of vitamin D supplementation in the progression of COPD.
New Characterizations of Hyperspheres and Spherical Hypercylinders in Euclidean Space
Authors: Bin Turki Nasser , Deshmukh Sharief , Chen Bang-Yen
Published: October 2024

Let x be an isometric immersion of a Riemannian n‐manifold M into a Euclidean (n + 1)‐space which does not pass through the origin of . Then, the tangential part of the position vector field x of x is called the canonical vector field, and the normal part gives rise to a scalar function called the support function. Using the canonical vector field, support function, and mean curvature, we establish three new characterizations of hyperspheres. In addition, we prove that if the energy function of M satisfies the static perfect fluid equation, then M has at most two distinct principal curvatures. As an application, we prove that a complete noncompact hypersurface M is a spherical hypercylinder if the energy function of M satisfies the static perfect fluid equation, and it has exactly two distinct nonsimple principal curvatures.
The “Visual‐Behavior” Chain and Risk Prediction Model for Sedan Drivers Under the Influence of Container Trucks: A Case Study of Yangshan Port Freight Corridor
Authors: Li Yi , Wang Zhitian , Yang Fengchun , Li Minghui
Published: October 2024

With the development of the Shanghai International Shipping Center, the diversity of vehicle types on the highways and arterial roads near Yangshan port is continually increasing. Within such a container port corridor, large container trucks are primarily utilized for mainline transportation. Their larger size and significant inertia would increase psychological pressure on sedan drivers, and elevate their behavior risk. To investigate the effects of container trucks on drivers’ visual characteristics and driving behavior as well as to predict driving risk, firstly, this research conducted field tests in four scenarios surrounding the port. Visual characteristics and behavior data of sedan drivers were collected. Secondly, a “Visual‐behavior” chain model was established. The relationship between drivers’ visual characteristics, driving behavior, and driving risk was illustrated from the perspective of time‐series behavior patterns. Thirdly, three driving risk prediction models were built with Autoregressive Integrated Moving Average (ARIMA), Long Short‐Term Memory (LSTM), and ARIMA‐LSTM. The results indicate that the ARIMA‐LSTM model shows the most effective prediction performance. This research provides a field‐data comparative analysis of the driving risks influenced by a high proportion of container trucks. The findings contribute to understanding the unique mixed traffic visual environment around large‐scale container ports.
Supplemental Table 2 from Causality between Telomere Length and the Risk of Hematologic Malignancies: A Bidirectional Mendelian Randomization Study
Authors: Jiang Guoyun , Cao LingXiao , Wang Yunshan , Li Li , Wang Zie , Zhao Hui , Qiu Yang , Feng Bin
Published: October 2024

Supplemental Table 2. The reverse MR analysis on telomere length and hematologic malignancies
Supplemental Figure 6 from Causality between Telomere Length and the Risk of Hematologic Malignancies: A Bidirectional Mendelian Randomization Study
Authors: Jiang Guoyun , Cao LingXiao , Wang Yunshan , Li Li , Wang Zie , Zhao Hui , Qiu Yang , Feng Bin
Published: October 2024

Supplemental Figure 6. Scatter plot of single nucleotide polymorphism potential effects on non-Hodgkin lymphoma and TL.
Supplemental Figure 1 from Causality between Telomere Length and the Risk of Hematologic Malignancies: A Bidirectional Mendelian Randomization Study
Authors: Jiang Guoyun , Cao LingXiao , Wang Yunshan , Li Li , Wang Zie , Zhao Hui , Qiu Yang , Feng Bin
Published: October 2024

Supplemental Figure 1. Scatter plot of single nucleotide polymorphism potential effects on TL and hematopoietic malignancies.
Neuroendocrine Tumors and Survival Rates in Multiple Endocrine Neoplasia Type 1 Patients: Impact of Gender Difference
Authors: Modica Roberta , Liccardi Alessia , Minotta Roberto , Benevento Elio , Cannavale Giuseppe , Di Iasi Gianfranco , Colao Annamaria
Published: October 2024

Introduction: Multiple endocrine neoplasia type 1 (MEN-1) is the most common inherited syndrome associated with NET development and gender-specific differences are emerging in neuroendocrine tumors (NETs). This study aimed to analyze gender difference in a single cohort of MEN-1 patients focusing on duodeno-pancreatic (DP)-NET and survival rates. Methods: MEN-1 patients referred to the Endocrinology Unit of the “Federico II” University of Naples, ENETS CoE, were retrospectively evaluated. Results: Among 100 MEN-1 patients enrolled, 59 (59%) were female and 41 (41%) male, and mean age at diagnosis was 39.4 years (range 5–86). No statistically significant association was identified between MEN-1 clinical manifestations and gender (primary hyperparathyroidism [PHPT] p: 1.0, DP-NET p: 0.83, pituitary adenoma [PA] p: 0.84, lung NET p: 0.64, and thymic NET p: 0.10), and similarly, age at diagnosis of MEN-1 and its individual manifestations was similar between genders. Survival analysis revealed no statistically significant difference between genders in DP-NET patients regarding progression disease p: 1.0 and death p: 1.0. Mean progression-free survival (PFS) of patients with DP-NET was 98.6 months (range 3–288), and mean overall survival (OS) was 130.1 months (range 3–444 months), without differences between genders (PFS p: 0.67 and OS p: 0.60). The Kaplan-Meier survival curves for PFS and OS showed no differences between genders (PFS p: 0.92; OS p: 0.87). Conclusion: In this MEN-1 cohort, no gender differences in the occurrence of PHPT, PA, DP-NET, lung NET, and thymic NET, nor in survival outcomes including PFS and OS within the DP-NET subcohort, emerged. Therefore, this study supports similar screening and follow-up for both male and female MEN-1 patients.
Delineating the W Sex Chromosome in the Clam Shrimp, Eulimnadia texana
Authors: Ediriweera Chathumadavi , Weeks Stephen C.
Published: October 2024

Introduction: Sex chromosomes have evolved independently across various lineages, often showing convergent degradation of the sex-limited chromosome. While extensively studied in model organisms with ancient sex chromosomal systems, the evolution of early-stage sex chromosomes remains poorly understood. Eulimnadia texana, a freshwater crustacean with a unique androdioecious breeding system (ZZ, ZW, and viable WW genotypes), provides a rare opportunity to study early sex chromosome evolution. This study examines E. texana’s W chromosome for evidence of a small localized non-recombining region, characterized by a transposable element (TE) “hotspot,” low gene density, and low GC content. Methods: Sex-linked markers were mapped onto the W chromosome (scaffold 1). TEs in the WW genome were identified using RepeatModeler and RepeatMasker. Statistical analyses compared TE distribution between the genome and scaffold 1, which was then divided into 20 equal-sized “bins” for finer-scale statistical analyses. Gene density and GC content were analyzed across these bins. Results: While no significant TE accumulation was found across the entire W chromosome compared to the remaining genome, a specific region (6.6–8.8 Mb, fourth bin) showed significantly higher TE accumulation. This region also exhibited low gene density and low GC content, indicative of reduced recombination. Conclusion: Our findings suggest that E. texana’s W chromosome contains a smaller region of crossover suppression, supporting the hypothesis that it is a proto-sex chromosome in early evolutionary development. This study provides valuable insights into early sex chromosome evolution and establishes E. texana as an ideal model for further investigation of evolutionary processes driving proto-sex chromosome differentiation.
Renal Transplantation with Triple Ureter Implantation into the Urinary Bladder after Dissolving a Bilateral Ureterocutaneostomy for Posterior Urethral Valves
Authors: Jung Jonas , Mandal Subhajit , Groeben Christer , Kortus-Götze Birgit , Hoyer Joachim , Huber Johannes , Flegar Luka
Published: October 2024

Introduction: We report a progressive treatment of a 31-year-old patient with end-stage renal disease secondary to congenital posterior urethral valve and valve bladder syndrome. He underwent a laser ablation of the urethral valve at the age of six, but on continuance of renal function deterioration ultimately a bilateral ureterocutaneostomy (UC) in the left lower abdomen had to be fashioned as a supravesical urinary diversion. Case Presentation: For the management of dialysis dependent end-stage renal disease, an allogenic renal transplantation was planned. When a postmortal organ was available, the patient wished for a complete internalisation of the incontinent diversion if possible. To better delineate the current status of the lower urinary tract, an intraoperative cystoscopy was performed. Besides an elevated bladder neck and a low bladder capacity, there were no distinct pathologies. Therefore, a right iliac allogeneic renal transplantation with simultaneous dissolution of the bilateral UC and an anastomosis of all three ureters to the bladder was performed. Placement of a suprapubic catheter enabled safe urine drainage and a prospective evaluation of the voiding function. Because of obstructive voiding, we performed a transurethral resection of the prostate. This resulted in sufficient spontaneous voiding. Conclusion: After a 19-month observation period, the patient now exhibits good renal function with normal excretion and consistent retention parameters with satisfactory transurethral voiding and quality of life (QoL). This is an encouraging case where it was possible to convert an incontinent urinary diversion to a continent urinary diversion after renal transplantation to improve the patient’s QoL.
Mixed Cardiogenic Shock: A Proposal for Standardized Classification, a Hemodynamic Definition, and Framework for Management
Authors: van Diepen Sean , Pöss Janine , Senaratne Janek M. , Gage Ann , Morrow David A.
Published: October 2024

The classification of cardiogenic shock (CS) has evolved from a singular cold-and wet-hemodynamic profile. Data from registries and clinical trials have contributed to a broader recognition that although all patients with CS have insufficient cardiac output leading to end organ hypoperfusion, there is considerable variability in CS acuity, underlying etiologies, volume status, and systemic vascular resistance. Mixed CS can be broadly categorized as
CS with at least 1 additional shock state
. Mixed CS states are now the second leading cause of shock in contemporary coronary intensive care units, but there is little high-quality evidence to guide routine care, and there are no standardized classification frameworks or well-established hemodynamic definitions. This primer summarizes the current epidemiology and proposes a classification framework and invasive hemodynamic parameters to guide categorization that could be applied to help better phenotype patients captured in registries and trials, as well as guide management of mixed CS states.
Changing Landscape of Randomized Clinical Trials in Stroke: Explaining Contemporary Trial Designs and Methods
Authors: Reeves Mathew J. , Gall Seana , Li Linxin
Published: October 2024

Evidence generated from randomized clinical trials (RCTs) plays an indispensable role in advancing clinical stroke care. Although the number of stroke-related RCTs published every year has grown exponentially over the past 25 years, the execution and completion of RCTs, particularly those conducted in a hyperacute setting, have grown more complicated and challenging over the years. In addition to the practical challenges associated with conducting a clinical trial, like obtaining human subjects approval, identifying clinical sites, training trial personnel, and enrolling the target number of patients within the available funding and timeline, the complexity of contemporary RCT designs and analyses has become much more exacting. It is no longer sufficient to have a decent understanding of the 2-arm, placebo-controlled RCT, combined with a rudimentary grasp of the
P
value; things are now much more complicated. Innovations in trial design and analysis, including adaptive, Bayesian, platform, and noninferiority designs, have occurred to address the problems of poor trial efficiency. However, these advances require the end user to have a much greater level of understanding regarding the rationale, conduct, analysis, and interpretation of each design. While these newer designs seek greater efficiency, there are inevitably tradeoffs that need to be understood.

In this month’s edition of
Stroke
, we introduce a new series designed to help fill in these knowledge gaps. Over the next few months, 4 papers will be published that address major design innovations (adaptive, Bayesian, platform, and noninferiority) with the aim of illustrating how these approaches can make trials more efficient (where efficiency is defined as getting to the right answer, sooner, with a potentially lower sample size). In addition to introducing this series, this current article also reviews traditional hypothesis testing and the common misinterpretations of the
P
value; fortunately, new philosophical schools of inference are beginning to vanquish the overreliance on the
P
value. We are excited about the opportunity to educate the
Stroke
readership about these new trial designs and the profound implications that they bring.
Long-Term Neurologic Outcomes in Pediatric Arterial Ischemic Stroke: The Impact of Age and Lesion Location
Authors: Singh Jaspal , Slim Mahmoud , Moharir Mahendranath , Westmacott Robyn , Krishnan Pradeep , MacGregor Daune , Dlamini Nomazulu , Parthasarathy Sujatha , Musaphir Scherazad , Domi Trish , deVeber Gabrielle
Published: October 2024

BACKGROUND:

The impact of age-at-stroke on outcome following pediatric arterial ischemic stroke remains controversial. We studied the interaction of age-at-stroke and infarct location and extent with long-term neurological outcomes.

METHODS:

We conducted a longitudinal prospective outcome study of children with acute pediatric arterial ischemic stroke diagnosed from 1996 to 2016 at the Hospital for Sick Children, Toronto, Canada. Pediatric Stroke Outcome Measure scores were dichotomized as normal or abnormal (ie, mild, moderate, or severe). Outcomes were analyzed by age-at-stroke (newborn: birth to 28 days; early childhood: 29 days to 5 years; middle/late childhood: >5–18 years), and infarct location, based on each of the following: model 1: circulation (anterior/posterior); model 2: cortical versus subcortical involvement; and model 3: specific arterial territory, including infarct extent (small [<50% arterial territory] or large [≥50%]). Univariable and multivariable logistic regression models were fitted.

RESULTS:

Among 285 children, the outcome at median 6.1 years was 43.5% abnormal. Controlling for infarct location, increasing age-at-stroke was associated with increasing abnormal outcome. Model 1 demonstrated that, compared with neonates, abnormal outcomes were increased in early childhood (adjusted odds ratio [aOR], 2.91 [95% CI, 1.24–7.05]) and more so in middle/late childhood (aOR, 4.46 [95% CI, 1.71–12.13]). Outcomes were worse for combined locations, including anterior+posterior (model 1: aOR, 15.4 [95% CI, 4.49–64.63]) and cortical+subcortical (model 2: aOR, 10.7 [95% CI, 3.88–32.74]). Abnormal outcomes were also increased for anterior circulation (model 1: aOR, 14.91 [95% CI, 5.29–54.21]) and subcortical locations (model 2: aOR, 4.36 [95% CI, 1.37–14.95]). Among individual arterial territories, outcomes were best for superior division middle cerebral artery (100% normal) and worst for lateral lenticulostriate artery infarcts (47.4% abnormal; model 3: aOR, 14.2 [95% CI, 3.5–67.6]).

CONCLUSIONS:

Among survivors of pediatric stroke, abnormal long-term neurological outcome is increased with increasing age-at-stroke, supporting enhanced plasticity after focal injury to the newborn brain compared with older pediatric ages.
Sensitivity of unconstrained quantitative magnetization transfer MRI
to amyloid burden in preclinical Alzheimer’s disease
Authors: Mao Andrew , Flassbeck Sebastian , Marchetto Elisa , Masurkar Arjun V. , Rusinek Henry , Assländer Jakob
Published: October 2024

Magnetization transfer MRI is sensitive to semisolid macromolecules, including amyloid beta, and has previously been used to discriminate Alzheimer’s disease (AD) patients from controls. Here, we fit an unconstrained 2-pool quantitative MT (qMT) model, that is, without constraints on the longitudinal relaxation rate R1s of semisolids, and investigate the sensitivity of the estimated parameters to amyloid accumulation in preclinical participants. We scanned 15 cognitively normal volunteers, of which 9 were amyloid positive by [18F]florbetaben PET. A 12 min hybrid-state qMT scan with an effective resolution of 1.24 mm isotropic and whole-brain coverage was acquired to estimate the unconstrained 2-pool qMT parameters. Group comparisons and correlations with florbetaben PET standardized uptake value ratios were analyzed at the lobar level. We find that the exchange rate and semisolid pool’s R1s were sensitive to the amyloid concentration, while morphometric measures of cortical thickness derived from structural MRI were not. Changes in the exchange rate are consistent with previous reports in clinical AD, while changes in R1s have not been reported previously as its value is typically constrained in the literature. Our results demonstrate that qMT MRI may be a promising surrogate marker of amyloid beta without the need for contrast agents or radiotracers.
Learning from Practice to Teach for Practice: Reflections from a Novel Training Series for International Climate Negotiators Presentation at PON’s 40th Anniversary Symposium
Authors: Dannecker Anselm , Giannone Monica
Published: October 2024

Early career climate negotiators face tough challenges—with little formal authority they must exert influence in a highly formalized negotiation process that produces bad bargaining dynamics. The authors describe the process of devising a training series for such climate negotiators from underrepresented and underresourced countries. They highlight challenges they faced, and distill lessons learned. Specifically, the article explores how negotiation theory can be made useful for people who are granted little authority to negotiate creatively, how to leverage insights from senior practitioners effectively, and how to train and engage an audience online that is scattered around the world, underpaid, overworked, and dials in with bad WiFi.
Cause and Characteristics of Changes in Mesoscale Convective Systems within a Convection-Permitting Regional Climate Model
Authors: Wallace Brendan , Haberlie Alex M. , Gensini Vittorio A. , Ashley Walker S. , Michaelis Allison C.
Published: October 2024

Changes in the frequency and intensity of mesoscale convective systems (MCSs) are assessed using convection-permitting regional climate model simulations. We present a novel classification method that relates MCSs to the magnitude of their large-scale forcing environments to better understand the changing nature of MCSs in a possible future climate scenario. Overall, the annual frequency, intensity, and amount of precipitation associated with MCSs are projected to increase for broad portions of the eastern conterminous United States (CONUS). Furthermore, changes in the characteristics of MCSs show larger, longer-lived, and faster MCSs particularly over the Midwest and Southeast. Seasonal examination of this response reveals a robust intensification of March–May (MAM) MCSs. The higher frequency of MAM MCSs is found to occur in weakly forced synoptic environments. Increased rainfall amounts are explained by an intensification of MCSs due to changing thermodynamics and enhanced lower-tropospheric moisture transport into the central CONUS by the North Atlantic subtropical high. Differences in midlatitude storm tracks are favorable toward the enhanced development of MCSs associated with strong baroclinic forcing within the Midwest and northern plains but are only realized in the presence of strong changes in the lower-tropospheric moisture transport. Overall, these results suggest a shift in the behavior of MAM MCSs that more closely corresponds to the behavior of June–August (JJA) MCSs in the historical climate. The increased occurrence of MCSs in weakly forced environments, particularly in MAM, deserves further investigation.

Significance Statement

Mesoscale convective systems (MCSs) make large contributions to the annual precipitation in the central United States, but we have a limited understanding as to how they may change in a warmer climate. Using a sophisticated tracking algorithm in conjunction with output from a high-resolution regional climate model, we find that MCSs will become more intense overall and occur more frequently in spring in the eastern United States. This frequency increase is strongly supported by a greater occurrence of MCSs in environments lacking support from large-scale weather systems. Instead, simulated changes in persistent large-scale atmospheric features facilitate the climatological transport of warmer and moister air into the eastern United States in spring, supporting an enhanced MCS response despite statistically insignificant changes in the frequency of individual weather systems.
Evaluation of Physical Microphysical Property Retrieval Algorithms during the 2020 IMPACTS Field Campaign
Authors: Nicholls Stephen D. , Heymsfield Andrew , Heymsfield Gerald M. , Yorks John E. , Bansemer Aaron , Aubry Clémantyne , Deng Min , Delanoë Julien
Published: October 2024

The NASA Investigation of Microphysics and Precipitation for Atlantic Coast-Threatening Snowstorms (IMPACTS) field campaign provides high-quality, high-altitude aircraft lidar (532 nm), radar (W band), and in-cloud microphysical aircraft data taken during wintertime storm events impacting the United States. This study evaluates two mass–dimensional relationships [Brown and Francis (BF95); Heymsfield (H14)] and two lidar–radar microphysical retrieval algorithms [CloudSat and CALIPSO Ice Cloud Property Product (2C-ICE); VarPy (a variational method derived from the satellite lidar–radar data community)] to estimate aircraft-retrieved volume extinction coefficient (σ), ice water content (IWC), and effective radius (re) during the 2020 IMPACTS deployment. BF95 and H14 have a close 1:1 correlation (R2 = 0.98) with in situ observations of σ. However, only BF95 displays a linear, consistent, and almost temperature-independent low bias for IWC and re, which likely arises from the environmental conditions used to determine each. Unlike the field-campaign-derived BF95 and H14 relationships, VarPy and 2C-ICE directly ingest the aircraft-based lidar and radar data to simulate σ, IWC, and re. For all three microphysical parameters, VarPy and 2C-ICE retrieval errors became notably more pronounced around the dendritic growth zone (from −15° to −10°C) and near freezing (≥−5°C), which suggests that both algorithms experience difficulty addressing riming and aggregation processes and with larger particles (dendrites and plates) due in part to their simplified ice particle assumptions. However, the mean-melt diameter ice-particle assumption did yield more accurate IWC estimates, which led to slightly better overall results for VarPy.