bluuebunny/crossref_metadata_2025 huggingface dataset:
Resetting of the Human Circadian Melatonin Rhythm by Ambient Hypoxia
Authors: Post Titiaan E. , De Gioannis Riccardo , Schmitz Jan , Wittkowski Martin , Schäper Tina Martin , Wrobeln Anna , Fandrey Joachim , Schmitz Marie‐Therese , Takahashi Joseph S. , Jordan Jens , Elmenhorst Eva‐Maria , Aeschbach Daniel
Published: January 2025

Circadian clocks in the body drive daily cycles in physiology and behavior. A master clock in the brain maintains synchrony with the environmental day–night cycle and uses internal signals to keep clocks in other tissues aligned. Work in cell cultures uncovered cyclic changes in tissue oxygenation that may serve to reset and synchronize circadian clocks. Here we show in healthy humans, following a randomized controlled single‐blind counterbalanced crossover study design, that one‐time exposure to moderate ambient hypoxia (FiO2 ~15%, normobaric) for ~6.5 h during the early night advances the dim‐light onset of melatonin secretion by 9 min (95% CI: 1–16 min). Exposure to moderate hypoxia may thus be strong enough to entrain circadian clocks to a 24‐h cycle in the absence of other entraining cues. Together, the results provide direct evidence for an interaction between the body's hypoxia‐sensing pathway and circadian clocks. The finding offers a mechanism through which behaviors that change tissue oxygenation (e.g., exercise and fasting/eating) can affect circadian timing and through which hypoxia‐related diseases (e.g., obstructive sleep apnea and chronic obstructive pulmonary disease) can result in circadian misalignment and associated pathologies.

Trial Registration: Registration number: DRKS00023387; German Clinical Trials Register: http://www.drks.de
Genotype–Phenotype Correlation in Progressive External Ophthalmoplegia: Insights From a Retrospective Analysis
Authors: Wang Jiayin , Lin Yan , Zhuang Xingyu , Zhao Dandan , Li Busu , Zhao Ying , Xu Zhe , Liu Fuchen , Dai Tingjun , Li Wei , Jiang Min , Yan Chuanzhu , Zhao Yuying , Ji Kunqian
Published: January 2025

Background

Progressive external ophthalmoplegia (PEO) is a classic manifestation of mitochondrial disease. However, the link between its genetic characteristics and clinical presentations remains poorly investigated.

Methods

We analysed the clinical, pathological and genetic characteristics of a large cohort of patients with PEO, based on the type of their mtDNA variations. Eighty‐two PEO patients were enrolled and grouped into three categories: mtDNA single large‐scale deletions (SLDs), multiple deletions (MulDs) and the m.3243A > G point variant. Patients in the SLD category were further divided into ‘common deletion’ and ‘noncommon deletion’ groups based on the presence or absence of a 4977‐bp deletion. The mutational load of deleted mtDNA of these patients was comprehensively detected by real‐time polymerase chain reaction (RT‐PCR).

Results

SLD Patients showed the highest proportion of cytochrome C oxidase‐negative (COX‐n) fibres on muscle biopsy. The mutational load of deleted mtDNA exhibited an inverse relationship with deletion length and a direct relationship with the COX‐n fibre ratio. Compared with patients having noncommon deletions, those with common deletions tend to have other muscle involvement, lower body mass index (BMI) scores (17 ± 3 vs. 22 ± 4 kg/m2), higher mutational load in muscle (63% ± 22% vs. 46% ± 24%), more COX‐n fibres (26% vs. 9%, interquartile range [IQR]: 15%–32% vs. 6%–26%) and higher growth and differentiation factor 15 (GDF15) levels (2583 vs. 1472, IQR: 1746–4081 vs. 924–2155 pg/mL). MulDs patients displayed milder symptoms, especially compared to patients with m.3243A > G variant, as indicated by their later age of onset (31 vs. 13, IQR: 27–49 vs. 6–29 years), higher BMI scores (24.0 ± 4 vs. 16.5 ± 3.4 kg/m2), lower lactate (1.6 ± 1.1 vs. 6.3 ± 6.0 mmol/L) levels and lower proportion of ragged‐blue fibres (RBFs) (3 vs. 16, IQR: 1%–9% vs. 7%–27%).

Conclusion

The m.3243A > G variant group exhibits more severe symptoms compared to other subgroups, particularly MulDs patients. In the SLD group, those with common deletions experience more severe clinical and pathological manifestations. These findings enhance our understanding of PEO, facilitating its diagnosis, prognosis and genetic counselling.
Insights into the subdaily variations in methane, nitrous oxide and carbon dioxide fluxes from upland tropical tree stems
Authors: Bréchet Laëtitia M. , Salomόn Roberto L. , Machacova Katerina , Stahl Clément , Burban Benoît , Goret Jean‐Yves , Steppe Kathy , Bonal Damien , Janssens Ivan A.
Published: January 2025

Recent studies have shown that stem fluxes, although highly variable among trees, can alter the strength of the methane (CH4) sink or nitrous oxide (N2O) source in some forests, but the patterns and magnitudes of these fluxes remain unclear. This study investigated the drivers of subdaily and seasonal variations in stem and soil CH4, N2O and carbon dioxide (CO2) fluxes.

CH4, N2O and CO2 fluxes were measured continuously for 19 months in individual stems of two tree species, Eperua falcata (Aubl.) and Lecythis poiteaui (O. Berg), and surrounding soils using an automated chamber system in an upland tropical forest. Subdaily variations in these fluxes were related to environmental and stem physiological (sap flow and stem diameter variations) measurements under contrasting soil water conditions.

The results showed that physiological and climatic drivers only partially explained the subdaily flux variations. Stem CH4 and CO2 emissions and N2O uptake varied with soil water content, time of day and between individuals. Stem fluxes decoupled from soil fluxes.

Our study contributes to understanding the regulation of stem greenhouse gas fluxes. It suggests that additional variables (e.g. internal gas concentrations, wood‐colonising microorganisms, wood density and anatomy) may account for the remaining unexplained variability in stem fluxes, highlighting the need for further studies.
Two reductases complete steroidal glycoalkaloids biosynthesis in potato
Authors: Akiyama Ryota , Terami Daiki , Noda Aozora , Watanabe Bunta , Umemoto Naoyuki , Muranaka Toshiya , Saito Kazuki , Sugimoto Yukihiro , Mizutani Masaharu
Published: January 2025

Steroidal glycoalkaloids (SGAs) are specialized metabolites primarily produced by Solanaceae plants such as potatoes and tomatoes. Notably, α‐solanine and α‐chaconine are recognized as toxic substances in potatoes. While the biosynthetic pathways of SGAs are largely understood, the final steps of α‐solanine and α‐chaconine biosynthesis remained elusive.

In this study, we discovered that two reductase‐encoding genes, reductase for potato glycoalkaloid biosynthesis 1 (RPG1) and RPG2, complete SGA biosynthesis in potato. Knockout of both RPG1 and RPG2 in potato hairy roots halted α‐solanine production, leading to the accumulation of zwittersolanine.

We analyzed the catalytic function of recombinant enzymes and conducted structural determination of the reaction products by nuclear magnetic resonance. As a result, RPG1 converted zwittersolanine to 16‐iminiumsolanine, and RPG2 further converted it to α‐solanine. RPG2 also transformed zwittersolanine to 22‐iminiumsolanine, which RPG1 then converted to α‐solanine. Similar processes were observed for α‐chaconine synthesis from zwitterchaconine. Due to differences in enzymatic reaction efficiency, the biosynthetic pathway via 16‐iminiumsolanine/16‐iminiumchaconine was suggested to be predominant in potato.

Our results could pave the way for tailoring SGA structures within Solanum plants, enabling the development of Solanum crop varieties with reduced toxicity or enhanced resistance to diseases and pests.
Sphingolipid long chain bases as mediators of cell death in olive fruit abscission
Authors: Briegas Beatriz , Camarero Maria C. , Corbacho Jorge , Labrador Juana , Sanchez‐Vera Victoria , Gavilanes‐Ruiz Marina , Saucedo‐García Mariana , Gomez‐Jimenez Maria C.
Published: January 2025

Plant sphingolipids are lipophilic membrane components essential for different cellular functions but they also act as signaling molecules in various aspects of plant development. However, the interaction between plant sphingolipids and abscission remains largely uncharacterized. Here, the possible role of sphingolipids in regulating fruit abscission was examined in the abscission zone (AZ) of olive fruit. To this end, sphingolipid levels were manipulated through the application of exogenous sphingolipid long‐chain bases (LCBs) or biosynthesis inhibitors, and their effects on fruit abscission as well as sphingolipid LCB/gene expression, hormones, reactive oxygen species (ROS) and cell death levels were examined in the AZ of olive fruit. Our data indicated that exogenous sphinganine (d18:0) induced fruit abscission, whereas the application of sphingosine (d18:1) or phytosphingosine (t18:0) or their phosphorylated derivatives did not have an effect on fruit abscission. Moreover, inhibition of LCB kinase or ceramide synthase, which increases sphingolipid LCB levels in the AZ, reduced fruit break strength. This induction of fruit abscission is associated with elevated ROS levels and cell death in the AZ enriched in salicylic acid (SA) and jasmonic acid (JA). Along the same line, programmed cell death (PCD) was particularly evident on the distal side of the AZ. These data suggest that endogenous d18:0 plays a key cellular role as signaling molecule functioning upstream of the SA/JA signaling pathway in mediating PCD spatially regulated in the AZ during fruit abscission. Overall, the findings reported here provide insight into the complex connection between PCD and plant sphingolipid LCBs, uncovering their interaction in the abscission process.
Hydrous Asthenosphere Underneath the Northern Pannonian Basin
Authors: Patkó Levente , Kővágó Ákos , Huraiová Monika , Kövér Szilvia , Gergely Szilveszter , Konečný Patrik , Hurai Vratislav
Published: January 2025

This study reveals the structural hydroxyl content in clinopyroxenes of three cumulate xenoliths from the Nógrád‐Gömör/Novohrad‐Gemer Volcanic Field (northern Pannonian Basin), with values ranging from 275 to 384 ppm. Based on these data, the water content of the equilibrium parental alkali basaltic melt was estimated to be between 1.5 and 2.1 wt.%, which aligns well with values for alkali basalts worldwide. The mantle source water content was also calculated, yielding values between 510 and 700 ppm for batch melting and 400–550 ppm for fractional melting models. These findings point to a hydrous asthenospheric source, likely linked to Mesozoic‐Paleogene subduction events of the Penninic Ocean, which introduced significant water into sub‐lithospheric depths. Our results suggest that intraplate basaltic melt generation can be influenced by long‐lived water‐rich zones preserved in the upper mantle.
Resilience of Developing Economies to External Shocks: Empirical Evidence from CEMAC Countries
Authors: Foabeh Peter Ajonghakoh , Aumeboonsuke Vesarach
Published: January 2025

This study explores the effects of the 1994 CFA currency depreciation, the 2008 Global Financial Crisis (GFC), and instances of political coups on the relationships between FDI inflow, economic growth, and governance in the Central African Economic and Monetary Community (CEMAC) countries. By examining the impact of these events on FDI, growth, and governance, this paper provides important details of CEMAC economies in response to external shocks and internal political disruptions. We employ a panel VAR analysis with data from 1990 to 2019 to explore the dynamic relationships among these variables. The results show that growth and governance are not determining factors for attracting FDI in the CEMAC sub-region. Governance, on the other hand, stands as a determining factor for growth. Our findings also suggest that the 1994 CFA currency depreciation, 2008 GFC, and coups had no significantly impact on FDI inflows, growth, and governance in CEMAC countries. Although the effects of these events may expose the vulnerability of these countries to external shocks, influencing the dynamics of FDI, economic growth, and governance, their impact did not seem to be evident. However, political instability, evidenced by coups, emerges as a crucial factor shaping the interactions between FDI, economic growth, and governance in the region. Our analysis was conducted using the EViews software package.
EntrepreEntrepreneurship Knowledge, Challenges, and Sustainable Entrepreneurship Framework for Retirees: A Systematic Reviewneurship Knowledge, Challenges, and Sustainable Entrepreneurship Framework for Retirees: A Systematic Review
Authors: Ogundele Sakiru , Abdul Kohar Umar Haiyat
Published: January 2025

AbstractThis study conducts a comprehensive literature review to clarify knowledge dynamics, obstacles, and the need for a customized sustainable entrepreneurship framework for retirees in response to the notable increase in post-retirement engagement in entrepreneurship. Using the PRISMA procedure, 24 academic publications in the field of retirees and entrepreneurship were examined. Important conclusions highlight finance as the most common knowledge area and the biggest obstacle retirees encounter while pursuing company endeavours. Aside from taking risks and adapting to them, other essential knowledge areas include innovation, managerial proficiency, creative thinking, competitive analysis, and market insight. Retirees face obstacles beyond money, such as health issues, age-related biases, government regulations, disparities in technical proficiency, and risk comprehension. The study also explores five models and frameworks that are now in use for successful retiree entrepreneurship, pointing out elements like networking, cultural orientation, entrepreneur competency, resource prioritizing, awareness, and technical orientation. The study offers a new conceptual model by combining insights from these models and frameworks with the recognized knowledge areas. This model is a useful tool for retirees who are starting their own businesses or who are already in the process of starting one. It also adds to the body of knowledge in academia and has applications for educators and policymakers who want to encourage and promote entrepreneurship after retirement.
Prostaglandin D2 delays CD8+ T-cell responses and respiratory syncytial virus clearance in geriatric cotton rats
Authors: Miller Jonathan L. , Leedale Cameron , Kang Danyue , Lilue Jingtao , Harder Olivia E. , Niewiesk Stefan
Published: January 2025

Respiratory syncytial virus (RSV) infection is associated with increased rates of severe disease, hospitalization, and death in elderly individuals. Clearance of RSV is frequently delayed within this demographic, contributing to the more severe disease course. Geriatric cotton rats mimic this prolonged clearance kinetic and serve as a useful animal model for studying age-associated immunological deficits during RSV infection. Treatment with the cyclooxygenase (COX) inhibitor ibuprofen restores RSV clearance, indicating that inflammation contributes to impaired clearance in geriatric cotton rats. Here, we further characterize a compromised immune response in geriatric cotton rats and identify an inflammatory pathway that contributes to this deficiency. Dendritic cell (DC) activation and migration to mediastinal lymph nodes are decreased during early infection in geriatric cotton rats, resulting in delayed generation of cytotoxic T cells and virus clearance. Prostaglandin D
2
(PGD2), which reduces DC migration through the elevation of D-type prostanoid 1 receptor (DP1 receptor), is elevated in the airways of infected geriatric cotton rats. Reducing PGD2 production by inhibiting COX-2 or PGD2 synthase improves RSV clearance kinetics through DC activation and RSV-specific CD8+ T-cell responses in geriatric cotton rats, whereas activation of DP1 receptor through an agonist resulted in delayed viral clearance in adult cotton rats. These results indicate that PGD2 contributes to delayed antigen presentation and CD8+ T-cell responses to RSV in geriatric cotton rats. Inhibiting PGD2 generation or signaling may be a useful mechanism of therapeutic intervention in elderly individuals.

IMPORTANCE

Elderly adults are at increased risk of severe disease resulting from infection with respiratory syncytial virus (RSV), characterized in part by delayed clearance (removal of the virus from airways). Understanding the immunological factors that lead to this delayed clearance may allow for the development of therapies to improve disease outcomes in elderly individuals infected with RSV and other respiratory viruses. Here, we describe an inflammatory pathway in geriatric cotton rats, the preferred small animal laboratory model for RSV, that impairs the generation of an effective immune response. We show that inhibiting this inflammatory pathway in geriatric cotton rats improves immune parameters and speeds clearance of RSV. These results contribute to our understanding of delayed RSV clearance in elderly individuals with possible applications for improving immune responses to RSV in clinical settings.
AAC Walker Canada Western Red Spring Wheat
Authors: Kumar S. , Nilsen K.T. , Green D. , McCallum B. , Menzies J. , Aboukhaddour R. , Henriquez M.-A.
Published: January 2025

AAC Walker (BW1116) is a hollow-stemmed, awned, and high yielding Canada Western Red Spring (CWRS) wheat cultivar suited to the growing conditions of western Canada. AAC Walker was 7% higher yielding than AAC Brandon and 5% higher yielding than AAC Viewfield in the Central Bread Wheat Cooperative (CBWC) registration trials (2020–2022). AAC Walker had maturity, height, and lodging similar to Carberry. It was 11 cm shorter than Unity. The test weight of AAC Walker was similar to AAC Brandon and 1000-kernel weight similar to AAC Viewfield. The grain protein content of AAC Walker was 0.6 units lower than AAC Brandon. AAC Walker expressed moderately resistant reaction to Fusarium head blight ( Fusarium spp.) and common bunt ( Tilletia caries (DC) Tul. & C. Tul.). AAC Walker was resistant to prevalent races of leaf rust ( Puccinia triticina Erikss.), stem rust ( Puccinia graminis Pers. f. sp. tritici Eriks. & E. Henn), and stripe rust ( Puccinia striiformis Westend) prevalent in western Canada. AAC Walker was resistant to orange wheat blossom midge ( Sitodiplosis mosellana Géhin). AAC Walker was deemed to fit the CWRS wheat class by the Canadian Grain Commission (CGC) and registered with Canadian Food Inspection Agency (CFIA).
Addendum — Vector invariants of permutation groups in characteristic zero
Authors: Reimers Fabian , Sezer Müfit
Published: January 2025

This note proves that rings of vector invariants of permutation groups acting on an [Formula: see text]-dimensional vector space in characteristic zero are generated by its invariants of degree less than or equal to [Formula: see text]. This improves our previous result [F. Reimers and M. Sezer, Vector invariants of permutation groups in characteristic zero, Internat. J. Math. 35(3) (2024) 2350111] and fully extends Göbel’s theorem [M. Göbel, Computing bases for rings of permutation-invariant polynomials, J. Symbolic Comput. 19(4) (1995) 285–291] to the case of vector invariants.
Global existence of a classical solution for the isentropic nozzle flow
Authors: Chou Shih-Wei , Huang Bo-Chih , Lu Yun-Guang , Tsuge Naoki
Published: January 2025

Our goal in this paper is to prove the global existence of a classical solution for the isentropic nozzle flow. Regarding this problem, there exist some global existence theorems of weak solutions. However, those of classical solutions did not have much attention until now. When we consider the present problem, the main difficulty is to obtain the uniform bound of solutions and their derivatives. To solve this, we introduce an invariant region depending on the space variable and a functional satisfying the Riccati equation along the characteristic lines.
Epidemiology of Congenital Hand Anomalies at a Single Center in Mainland China: An Analysis of 1,415 Cases
Authors: GUO Yang , SUN Liying , ZHAO Zongxuan , SHENG Chao , DING Yunyun , TIAN Wen
Published: January 2025

Background: Currently, large-sample epidemiological studies on congenital upper limb differences (CULD) in China are relatively rare. This report presents our centre’s experience on the spectrum of diseases and related factors.

Methods: Information was collected from patients with CULD who underwent surgical treatment at our centre from September 2018 to October 2023. Data collection included patient name, gender, age, clinical features and diagnosis, family history, parents’ age, parents’ medical history, pregnancy history and family income. Bivariate relationships between these variables were examined.

Results: The average age of the patients was 4 years; 1,398 patients (99%) were aged 9 months to 18 years, and 17 patients (1%) were adults. There were 848 males (60%) and 567 females (40%), with a statistically significant gender distribution (p < 0.05). The most common differences were polydactyly and syndactyly, accounting for 47% and 14%, respectively. Syndromic patients accounted for 14%, and cardiac conditions were the most prevalent non-musculoskeletal issue (55%). First-born patients accounted for 54% of patients, and the average age of parents for first-born patients was 30 ± 5 years for fathers and 29 ± 2 years for mothers. For non-first-born patients, the average age of parents was 33 ± 6 years for fathers and 32 ± 5 years for mothers, with a statistically significant difference between the two groups (p < 0.001).

Conclusions: In China, congenital limb differences are still dominated by polydactyly and syndactyly. Heart conditions occur most frequently in patients with syndromes.

Level of Evidence: Level IV (Epidemiological)
Deformation Field Fusion for Medical Image Registration
Authors: Zhao Haifeng , Zhang Chi , Liu Deyin , Wu Lin
Published: January 2025

Deformable medical image registration is to find a series of non-linear spatial transformations to align a pair of fixed and moving voxel images. Deep learning based registration models are effective in learning differences between such image pair to obtain the deformation field which is specialized in describing non-rigid deformations in the 3D voxel context. However, existing models tend to learn either one single deformation field only or multi-stage(multi-level) deformation fields progressively arriving at a final optimal field. Actually, deformation fields resulting from different architectures or losses are capable of capturing diverse types of deformations, complementing to each other. In this paper, we propose a novel framework of fusing different deformation fields to acquire an overall field to describe all-round deformations, in which multiple complementary cues regarding deformable 3D voxels can be strategically leveraged to improve the alignment of the given image pair. The key to the effect of deformation field fusion for registration lies in two aspects: the fusion network architecture and the loss function. Thus, we develop a well-designed fusion block using ingenious operations based on different types of pooling, convolution, and concatenation. Moreover, since calculating the deformation field using a conventional similarity loss cannot describe the
contextual variations
which are inter-dependent in each pair of fixed and moving images, we propose a novel Contrast-Structural loss to enhance the motion displacement between the image pair by calculating the similarity of pixels in density values, while being ranged in their spatial proximity. Extensive experimental results demonstrate that our proposed method achieves state-of-the-art performance on currently mainstream benchmark datasets.
PRest-Net: Multi-domain Probability Estimation Network for Robust Image Forgery Detection
Authors: Chen Jiaxin , Liao Xin , Qian Zhenxing , Qin Zheng
Published: January 2025

As an important carrier of information transmission in online social networks (OSNs), the authenticity protection of images is of great significance. However, the abuse of image processing technology makes its security questionable. Meantime, lossy operations adopted by OSNs will change the forgery artifacts, which brings challenges to robust image forgery detection. To address this issue, considering the suppression of lossy noise caused by transmission, a novel multi-domain probability estimation network (PRest-Net) is proposed. Firstly, we design a multi-domain probability estimation method to capture the most differentiated regional information from the spatial, residual, and wavelet domains. Since the wavelet coefficient of semantic information is larger than that of lossy noise, and the edge texture can be highlighted in the residual image, the negative effect of lossy noise would be reduced and semantic forgery traces can be exposed more easily. We further design a forgery detector composed of low-level feature extraction, high-level feature extraction, and regional edge difference learning module, which can adaptively learn rich forgery clues. Extensive experimental results are provided to validate the superiority of PRest-Net compared with existing state-of-the-art detectors in the scenarios of detecting forged images transmitted over various OSNs.
Contextual Interaction via Primitive-based Adversarial Training for Compositional Zero-shot Learning
Authors: Li Suyi , Jiang Chenyi , Wang Shidong , Long Yang , Zhang Zheng , Zhang Haofeng
Published: January 2025

Compositional Zero-shot Learning (CZSL) aims to identify novel compositions via known attribute-object pairs. The primary challenge in CZSL tasks lies in the significant discrepancies introduced by the complex interaction between the visual primitives of attribute and object, consequently decreasing the classification performance towards novel compositions. Previous remarkable works primarily addressed this issue by focusing on disentangling strategy or utilizing object-based conditional probabilities to constrain the selection space of attributes. Unfortunately, few studies have explored the problem from the perspective of modeling the mechanism of visual primitive interactions. Inspired by the success of vanilla adversarial learning in Cross-Domain Few-Shot Learning, we take a step further and devise a model-agnostic and
P
rimitive-
B
ased
Adv
ersarial training (PBadv) method to deal with this problem. Besides, the latest studies highlight the weakness of the perception of hard compositions even under data-balanced conditions. To this end, we propose a novel over-sampling strategy with object-similarity guidance to augment target compositional training data. We performed detailed quantitative analysis and retrieval experiments on well-established datasets, such as UT-Zappos50K, MIT-States, and C-GQA, to validate the effectiveness of our proposed method, and the state-of-the-art (SOTA) performance demonstrates the superiority of our approach. The code is available at
https://github.com/lisuyi/PBadv_czsl
.
Oxide Barrier Thinning in 1050, 2024 and 6062 Aluminum Alloys Using Linear Ramp at the End of Sulfuric Anodizing
Authors: Daval J. , Brunol E. , Rouge N. , Moutarlier V. , Viennet R. , Ricq L. , Hihn J.-Y.
Published: January 2025

A simple method for thinning barrier layers in various aluminum alloys was proposed, involving a linear voltage decrease at the end of sulfuric anodizing. Two techniques were used for barrier layer thickness assessment: direct measurement with field-emission gun scanning electron microscopy and indirect determination using electrochemical impedance spectroscopy. The linear thinning process was successfully tested on 1050 aluminum and on higher alloy element contents used for structural parts in aeronautics: 6062 and 2024 alloys. In our operating conditions, the linear thinning process reduces the barrier oxide at pore bottoms without modification of anodic layer porosity. The relationship for controlling barrier layer thickness (DBL) was established as DBL = U - a x Δt, with U (applied voltage) at 20 V, and Δt (ramp time) at 0 s, 30 s, 45 s, 60 s, and 90 s, with a constant rate (a) of 0.11 nm s−1 for all alloys. However, longer ramp times led to degradation at the pore bottoms, indicating that barrier layer morphology depends on the rate of voltage decrease. Shorter ramp times are preferable. The linear thinning process has potential applications in improving metal electrodeposition into the anodic layer by enhancing electrical accessibility to pore bottoms. Thinning the barrier layer effectively facilitates the electro-coloring process.
Ribosomal s6 kinase is a mediator of aquaporin-2 S256 phosphorylation and membrane accumulation after EGFR inhibition with erlotinib
Authors: Babicz Richard S. E. , Baylor Noah , Terlouw Abby , Faber Daphne A. , Fukushima Kazuhiko , Biondi Ricardo M. , Bouley Richard , Brown Dennis
Published: January 2025

Epidermal growth factor receptor (EGFR) inhibition with erlotinib induces aquaporin-2 (AQP2) membrane accumulation with a phosphorylation pattern similar to vasopressin (VP). Here, we identify the ribosomal s6 kinase (RSK) as a major mediator phosphorylating AQP2 in this novel, erlotinib-induced pathway. In addition, we show that phosphoinositide-dependent kinase-1 (PDK1), a known activator of RSK, is implicated in this pathway: PDK1 inhibition blocks erlotinib-induced AQP2 S256 phosphorylation and membrane accumulation.
Oxidative stress suppresses internal carotid artery dilation to hypercapnia in healthy older adults
Authors: Freeberg Kaitlin A. , McCarty Narissa P. , Chonchol Michel , Seals Douglas R. , Craighead Daniel H.
Published: January 2025

This study is the first to report oxidative stress-mediated suppression of cerebrovascular reactivity to hypercapnia in the internal carotid artery in older compared with young adults. Overall, these in vivo findings identify oxidative stress as an important pathophysiological contributor to cerebrovascular aging in humans, highlighting the need to identify novel interventions that can reduce oxidative stress in the aging population.
Without visual feedback voluntary torque is overestimated during muscle potentiation despite similar motor unit firing rate and perception of exertion
Authors: Zero Alexander M. , Rice Charles L.
Published: January 2025

Without visual feedback of torque, no modification in motor unit output occurred despite peripheral muscle potentiation. Therefore, reduced voluntary drive lowered firing rates so that torque did not exceed the task demand, rather than peripheral muscle afferent feedback. During muscle potentiation, the motoneuron is not sensitive to acute enhanced changes in the active state of the muscle unit per se, but rather compensatory adjustments in neuromuscular output are due to perceptual reductions in descending input.
An Exosome-Based Liquid Biopsy Predicts Depth of Response and Survival Outcomes to Cetuximab and Panitumumab in Metastatic Colorectal Cancer: The EXONERATE Study
Authors: Xu Caiming , Mannucci Alessandro , Esposito Francis , Oliveres Helena , Alonso-Orduña Vicente , Yubero Alfonso , Fernández-Martos Carlos , Salud Antonieta , Gallego Javier , Martín-Richard Marta , Fernández-Plana Julen , Guillot Mónica , Aparicio Jorge , Fakih Marwan , Kopetz Scott , Feliu Jaime , Maurel Joan , Goel Ajay
Published: January 2025

Purpose:

The EXOsome and cell-free miRNAs of anti-EGFR ResistAnce (EXONERATE) study was an open-label, biomarker interventional study designed to develop, test, and validate a liquid biopsy predictive of progression-free survival (PFS), overall survival (OS), and objective response rate (ORR) for first-line EGFR inhibitors in metastatic colorectal cancer (mCRC).

Patients and Methods:

Patients with newly diagnosed RAS wild-type, chemotherapy-naïve mCRC, both right- and left-sided, were enrolled in two nationwide trials to receive cetuximab or panitumumab along with chemotherapy. The primary endpoint was 12-month PFS, which was hierarchically tested in left- and right-sided mCRCs to predict PFS, OS, and ORR.

Results:

Genome-wide small RNA sequencing identified 12 cell-free and 14 exosomal candidates that were differentially expressed in both plasma and tumor tissue of good versus poor responders (based on PFS <12 months). The 8 and 9 best performing candidates, respectively, were used to generate the EXONERATE assay. In left-sided mCRC, 65% were EXONERATE-high, correlating with shorter median PFS (9.5 vs. 18.5 months; P < 0.001). In the independent right-sided mCRC cohort, 80.8% were EXONERATE-high and experienced a similarly shorter median PFS (8.6 vs. 41.2 months; P = 0.0004). In the right-sided group, EXONERATE predicted PFS ≥12 months with 100% sensitivity. A linear relationship existed between EXONERATE values and response depth. Multivariate analysis revealed that EXONERATE predicts PFS and OS independently of tumor sidedness.

Conclusions:

The EXONERATE assay robustly predicted PFS and OS outcomes in patients with mCRC, both right- and left-sided, before they received either panitumumab or cetuximab. It stratified PFS, OS, and ORR better than a right versus left approach.
Consortium Author List from Cancer Research in the Age of Spatial Omics: Lessons from IMAXT
Authors: Bressan Dario , Walton Nicholas , Hannon Gregory J. , Al Sa’d Mohammad , Albuquerque Bruno , Ali Hamid Raza , Alini Martina , Aparicio Samuel , Ashmore Heather , Ashmore Thomas , Au Vinci , Balasubramanian Shankar , Baril Caroline , Battistoni Giorgia , Beatty Sean , Becker Robby , Bodenmiller Bernd , Bollhagen Alina , Boquetale Carla , Boyden Edward S. , Bressan Dario , Bruna Alejandra , Burger Marcel , Caldas Carlos , Callari Maurizio , Cannell Ian Gordon , Casbolt Hannah , Chornay Nick , Coutts Nikki , Dariush Ali , Deighton Lauren , Dinh Khanh N. , Duncan Natalie , Eyal-Lubling Yaniv , Falciatori Ilaria , Fan Jean , Fatemi Atefeh , Ghosh Debarati , González-Fernández Carlos , González-Solares Eduardo A. , Greenwood Wendy , Grimaldi Flaminia , Hannon Gregory J. , Harris Owen , Harris Suvi , Hemmer Nicole , Hua Kui , Irfan Melis , Jauset Cristina , Joyce Johanna A. , Kovačević Tatjana , Kuett Laura , Kunes Russell , Yoldaş Aybüke Küpcü , Lai Daniel , Laks Emma , Lee Hsuan , Lee Max , Lerda Giulia , Li Yangguang , Lovell Jack , Lu Yangning , Marioni John , McPherson Andrew , Millar Neil , Molaeinezhad Alireza , Mulvey Claire M. , Narayanan Natasha , Nogueira João C.F. , Nugent Fiona , O’Flanagan Ciara H. , Ribes Marta Paez , Pearsall Isabella , Pearsall Sarah , Pryor Brett , Qosaj Fatime , Rebbeck Clare , Roth Andrew , Rueda Oscar M. , Ruiz Teresa , Sawicka Kirsty , Sepúlveda Leonardo A. , Shah Sohrab P. , Shea Abigail , Sinha Anubhav , Smith Austin , Smith Leigh , Tavaré Simon , Vázquez-García Ignacio , Vogl Sara Lisa , Walton Nicholas A. , Watson Spencer S. , Weselak Joanna , Whitmarsh Tristan , Wild Sophia A. , Williams Elena , Windhager Jonas , Xia Chenglong , Sia Chee Ying , Zhang Chi , Zhang Ruihan , Zheng Pu , Zhuang Xiaowei
Published: January 2025

IMAXT Consortium Author List
Figure S6 from RNA-encoded Interleukin 2 with Extended Bioavailability Amplifies RNA Vaccine–Induced Antitumor T-cell Immunity
Authors: Peters Daniel , Kranz Lena M. , Eisel David , Diken Mustafa , Kreiter Sebastian , Türeci Özlem , Sahin Ugur , Vormehr Mathias
Published: January 2025

Gating strategy for antigen-specific CD8+ T cells in the spleen.
New Progress in the Study of Pathogenesis of Alcoholic Pancreatitis
Authors: Li Hanhui , Tan Xiaoping , Li Jie , Zhang Qing
Published: January 2025

Background: Alcoholic pancreatitis is a progressive condition characterized by susceptibility to recurrence, progression to chronic pancreatitis, complications, and high morbidity. Summary: The main causes include long-term alcoholism, excessive drinking, the toxic effects of alcohol metabolites, interactions with biliary diseases, and genetic factors. Alcohol is the second leading cause of acute pancreatitis (AP) in the USA, accounting for one-third of all AP cases. A follow-up study on readmission revealed that the readmission rate of alcoholic acute pancreatitis (AAP) patients within 11 months was 43.1%, of which men dominated the admissions and readmissions of AAP. Among this population, 82.3% have alcohol use disorder, over half have tobacco use disorders, 6.7% have tobacco use disorder, 4.5% have opioid use disorder, and 18.5% of patients exhibit signs of potential alcoholic chronic pancreatitis. Numerous animal and clinical studies suggest that alcohol alone does not cause pancreatitis; rather, additional factors such as smoking, endotoxin lipopolysaccharide (LPS), genetic mutations, or other genetic predispositions – are necessary for the disease’s progression. Key Messages: Given the high rates of admission and readmission for alcoholic pancreatitis, it is essential to further investigate its pathogenesis and pathological processes to develop more effective treatment strategies. Therefore, this paper summarizes the current understanding of the pathogenesis and treatment status of alcoholic pancreatitis, drawing on recently published literature and data to provide insights and references for future research and treatment efforts.
Exercise in the prevention of age related fragility fractures (narrative review)
Authors: Kerschan-Schindl Katharina , Hasenoehrl Timothy
Published: January 2025

Background: Loss of bone integrity and the age-associated decrease of the neuromuscular function make elderly subjects prone to fragility fractures.
Summary: Exercise is a strategy to counteract these age-associated changes and impairments. Because of the tight relationship between muscle and bone – anatomically, functionally, and biochemically – physical activities and targeted exercises, which induce muscle contraction and sufficient mechanical stress, influence bone metabolism. Exercise proved to have a positive effect on bone mineral density. The young skeleton is especially susceptible to impact and strenuous stimuli. This also applies to the neuromuscular system in the case of balance training. Therefore, the best time to start preventing fragility fractures is at young age. Despite the lower responsiveness in older age, targeted training is also very important at an advanced age. Lowering the modeling threshold, osteoanabolic treatment seems to increase the responsiveness to mechanical loading. In case of antiresorptive treatment, a more intensive training may be necessary.
Key Message: A multiple component exercise intervention reduces the risk of age-associated fragility fractures. Depending on the mode of exercise, it mainly affects bone integrity or the neuromuscular system. The effect of exercising also depends on age and bone-specific medications influencing the sensitivity of these structures. However, despite a lower sensitivity to exercise at higher age, targeted training is especially important when getting older to decrease the risk of fragility fractures. In case of prevalent fragility fractures, patients should exercise as well; the training stimulus simply needs to be adapted.
Adaption and validation of the Greek version of Addenbrooke's Cognitive Examination III scale as a screening tool for perioperative cognitive impairment detection
Authors: Tsaousi Georgia , Zouka Maria , Chatsiou Eleni , Nikopoulou Anastasia , Palaska Eleftheria , Birba Vasiliki , Papazisis Georgios , Tsimtsiou Zoi
Published: January 2025

Introduction: Postoperative cognitive dysfunction constitutes an extremely prevalent implication in individuals subjected to cardiac or non-cardiac surgery. This study aims to assess the validity and reliability of a culturally adapted Greek version of the Addenbrooke’s Cognitive Examination III (ACE-III) scale as a screening tool for perioperative neurocognitive status determination in elderly surgical patients.
Methods: A cross-cultural adaptation and validation of instruments throughout the
a cross-sectional study was conducted. The study sample consisted of 128 individuals over 55 years old scheduled for surgical intervention. All participants were screened twice; at the preadmission clinic and the day before surgery using the already established MoCA scale and the culturally adapted Greek version of the ACE-III scale. Subjects with a MoCA score of < 26 constituted the cognitively impaired group.
Results: Regarding construct validity, ACE-III’s performance in detecting cognitive impairment was excellent (AUC =0.942; 95%CI 0.899-0.971). Convergent validity between ACE-III and MoCA scales was excellent (r= 0.876; 95%CI 0.839-0.905). Known group validity was confirmed since advanced age and lower educational attainment adversely impacted ACE-III’s total score (p<0.001). Additionally, specialists suggested face validity (mean 8.7 out of 10, SD 1.1). In terms of reliability, ACE-III demonstrated good internal consistency (Cronbach's alpha 0.786) and high inter-rater (ICC=0.936 [95%CI 0.921-0.941]) and test-retest reliability (ICC=0.972 (95%CI 0.958-0.981).
Conclusion: The Greek version of ACE-III is a valid, and reliable screening tool that could be routinely employed perioperatively as a valid alternative to the MoCA test to distinguish the mild cognitively impaired from healthy elderly candidates for surgical interventions.
Dynamic arterial lactate values are associated with 30-day mortality in patients with acute myocardial infarction and cardiogenic shock on intra-aortic balloon pump circulatory support
Authors: Solomonean Aurelia Georgeta , Dregoesc Mihaela Ioana , Istrate Mihnea , Buiga Victor Ștefan , Bindea Dan Ion , Stef Adrian , Botiș Cătălin , Iancu Adrian Corneliu
Published: January 2025

Introduction: In patients with acute myocardial infarction and cardiogenic shock (AMICS), the intra-aortic balloon pump (IABP) remains the most commonly used form of mechanical circulatory support (MCS). However, information on the characteristics of non-responders is limited. This study evaluated the risk factors associated with 30-day mortality in a cohort of patients with AMICS, on IABP support.
Methods: The medical records of patients admitted for AMICS, who underwent IABP insertion over a period of five years, were extracted from the electronic database of a tertiary cardiovascular disease center. The primary end-point was 30-day all-cause mortality.
Results: A cohort of 62 patients was included in the analysis. Mechanical complications were diagnosed in 54.8% of the patients. At 30 days follow-up, mortality reached 69.3%. High arterial lactate at the time of IABP insertion (OR 1.04; 95%CI 1.01–1.09; p=0.04), high arterial lactate after 24h of circulatory support (OR 1.07; 95%CI 1.02–1.17; p=0.03), and low lactate clearance at 24h (OR 0.51; 95%CI 0.22–0.83; p=0.03) were associated with 30-day mortality independent of infarct type, mechanical complications, baseline SCAI stage, creatinine, and bicarbonate value at the time of support initiation. Lactate at the time of IABP insertion and lactate at 24h predicted 30-day mortality at a cutoff value >50mg/dl and >27mg/dl, respectively.
Conclusion: In a cohort of patients with AMICS who underwent IABP therapy, dynamic arterial lactate values both pre- and post-IABP insertion were independently associated with increased 30-day all-cause mortality. The dynamic changes in arterial lactate could help establish the optimal timing of circulatory support initiation and guide treatment escalation in patients at risk for adverse outcomes.
Comparative effectiveness of the exact versus estimated angle of head position in the Epley maneuver: a randomized controlled trial
Authors: Chowsilpa Sanathorn , Chawachat Jakarin , Hansudewechakul Nicha , Isaradisaikul Suwicha Kaewsiri , Hanprasertpong Charuk
Published: January 2025

Introduction
The Epley maneuver is the recommended treatment for benign paroxysmal positional vertigo of the posterior semicircular canal (PC-BPPV). Traditionally, the angle of the patient’s head in each position during the Epley maneuver is not monitored and subjectively estimated by physicians. As a result, deviations of head angles from the standard may affect the treatment result. This study aimed to compare the outcome of the Epley maneuver between the group of exact head angles and the group of subjectively estimated angles (traditional Epley maneuver).

Methods
A single-blind randomized controlled trial was conducted at the Department of Otolaryngology, Chiang Mai University Hospital. PC-BPPV patients were attached with the head angle measuring device and randomized into 2 groups: Group I – the exact angle group, physicians performed the Epley maneuver with accurate head angle in each step; and Group II – the estimated angle group, physicians performed the Epley maneuver by estimating the head angle (traditional Epley maneuver). The treatment outcomes were measured at 1 week in the aspects of negative Dix Hallpike results and severity of dizziness.

Results
Thirty-one PC-BPPV patients were recruited and randomized into Group I (15 participants) and Group II (16 participants). Both groups showed clinical improvement. Although significant deviations of head angles were observed in group II, there was no significant difference in outcomes between the two groups in terms of negative Dix Hallpike and severity of dizziness at the 1-week follow-up.

Conclusion
Although significant variations of head angles were observed during the traditional Epley maneuver by experienced physicians, these deviations were slight (less than 15°) and did not significantly affect the successful treatment outcome at 1 week, in terms of negative Dix Hallpike and severity of dizziness, when compared to the group with accurate head angle during the Epley maneuver.
A rare case of dichorionic twins concordant for arterial tortuosity syndrome: case report and review of the literature
Authors: Ponziani Ilaria , Checcucci Carlotta , Masini Giulia , Pasquini Lucia
Published: January 2025

Introduction: Arterial Tortuosity Syndrome (ATS) is a rare congenital disorder characterized by elongation and tortuosity of the aorta and mid-sized arteries. Additional features typical of connective tissue disorders are usually present, but the clinical presentation of the syndrome can extensively change. The cardiovascular implications are the major source of morbidity and mortality and can be present even during neonatal period, therefore a correct neonatal management is extremely important. However, only few cases of ATS have been suspected or diagnosed prenatally.
Case Presentation: In our study we present a rare case of dichorionic twins both affect by ATS, in which the syndrome was suspected antenatally. Moreover, we performed a review of the literature and summarized the main findings identified at prenatal ultrasounds and postnatal examination, in order to help clinicians with the management of this rare diagnosis.
Conclusion: The most suspicious ultrasound prenatal finding of ATS is the elongation and tortuosity of great arteries. When ATS is suspected prenatally, the newborn should be referred immediately after birth to a high specialized center for proper neonatal care. In case of confirmed ATS parents should be counseled regarding the recurrence risk in other pregnancies.