bluuebunny/crossref_metadata_2025_split huggingface dataset:
THG-1/TSC22D4 Promotes IL-1 Signaling through Stabilization of TRAF6 in Squamous Cell Carcinoma
Authors: Okano Yasuhito , Suzuki Hiroyuki , Watanabe Yukihide , Abdelaziz Mohammed , Manevich Lev , Kawanishi Kunio , Ozaki Haruka , Ishii Ryota , Matsumoto Shin , Goto Nohara , Zheng Ling , Okita Yukari , Hwang Jongchan , Nakayama Masahiro , Shima Yoshihide , Sakamoto Noriaki , Noguchi Masayuki , Tabuchi Keiji , Kato Mitsuyasu 
Published: January 2025

Abstract
Malignant neoplasms arise within a region of chronic inflammation, which is a key factor in all aspects of tumorigenesis including initiation, proliferation, invasion, angiogenesis, and metastasis. IL-1 plays critical functions in tumor development by influencing the tumor microenvironment and promoting cancer progression. However, the mechanism of continuous activation of the IL-1–mediated inflammatory pathway in tumors has not been fully elucidated. This study provides a novel mechanism of the autocrine activation of IL-1 signaling in squamous cell carcinoma (SCC) through a novel oncoprotein, TSC-22 homologous gene-1 (THG-1, also known as TSC22D4). The RNA sequencing analysis revealed that THG-1 overexpression enhances the transcription of NF-κB targets including IL1A, IL1B, TNFA, and IL8. Furthermore, THG-1 knockdown reduced the responsiveness to IL-1 through the suppression of NF-κB nuclear translocation. To elucidate the mechanism, we focused on a THG-1 interacting protein, NRBP1. We found that NRBP1 facilitates the degradation of TNF receptor–associated factor 6 (TRAF6) through its E3 ubiquitin ligase activity. THG-1 bound to NRBP1 and suppressed the degradation of TRAF6. Furthermore, THG-1 knockdown reduced TRAF6 abundance and NF-κB activity in SCC cells. Public database analyses of head and neck SCC revealed that high expression of THG-1 is associated with the activation of the IL-1 and TNF pathways, which share TRAF6 in the signal transductions. Finally, THG-1 abundance in laryngeal SCC specimens is elevated in patients with recurrence. These results indicated that THG-1 drives the self-sufficiency of IL-1–mediated inflammatory pathway, which could contribute to the future diagnosis and immunotherapy of SCCs.
Implications: An oncoprotein, THG-1/TSC22D4 activates the IL-1–mediated inflammatory pathway through the suppression of TRAF6 degradation, which mediates the continuous inflammation in tumors.
Association Between Liver Fibrosis and Risk of Incident Stroke and Mortality: A Large Prospective Cohort Study
Authors: Wang Zijie , Gong Zhitao , Wen Jianshang , Zhang Shanyu , Hu Xiao , Guo Wenliang , Tian Yanghua , Li Qi 
Published: January 2025

Background
There is a well‐established relationship between liver conditions and cardiovascular diseases. However, uncertainty persists regarding the contribution of liver fibrosis to major stroke types including ischemic stroke, intracerebral hemorrhage, and subarachnoid hemorrhage at the population level.

Methods
In this large prospective cohort study, participants without previous stroke or coronary heart disease at baseline from the UK Biobank were included. We identified participants at high probability of advanced liver fibrosis using the Fibrosis‐4 index >2.67 or aspartate aminotransferase to platelet ratio index ≥1.0. Multivariable Cox proportional hazard regression analyses were conducted to estimate hazard ratios (HRs) for liver fibrosis with the incidence of major stroke types, stroke‐related death, and all‐cause death.

Results
Among 379 953 participants (mean age, 56.2 [SD, 8.1] years; 44.6% men), 7396 (1.9%) had a Fibrosis‐4 index >2.67 at baseline. During a median follow‐up of 12.75 (interquartile range, 12.03–13.48) years, 7143 (1.9%) incident stroke cases were documented. Advanced liver fibrosis assessed by the Fibrosis‐4 index was associated with an increased risk of ischemic stroke (HR, 1.94 [95% CI, 1.70–2.22]), intracerebral hemorrhage (HR, 2.14 [95% CI, 1.63–2.81]), subarachnoid hemorrhage (HR, 1.90 [95% CI, 1.27–2.84), stroke‐related death (HR, 2.20 [95% CI, 1.73–2.80]), and all‐cause death (HR, 2.59 [95% CI, 2.46–2.73]). Using the aspartate aminotransferase to platelet ratio index as an alternative score, liver fibrosis was correlated with magnified risk of intracerebral hemorrhage (HR, 3.76 [95% CI, 2.38–5.93]) and subarachnoid hemorrhage (HR, 3.05 [95% CI, 1.51–6.13]) compared with ischemic stroke (HR, 1.58 [95% CI, 1.17–2.14]). Restricted cubic spline analysis showed nonlinear associations of the Fibrosis‐4 index and aspartate aminotransferase to platelet ratio index with stroke incidence and all‐cause death.

Conclusions
Liver fibrosis is associated with increased risk of incident stroke and death among people without previous stroke or cardiovascular events, with particularly greater risk of intracerebral hemorrhage and subarachnoid hemorrhage. Noninvasive indices of liver fibrosis may serve as an easily accessible marker to detect individuals facing elevated risk of stroke and death in the primary prevention settings.
Alternative Complement Pathway in Carotid Atherosclerosis: Low Plasma Properdin Levels Associate With Long‐Term Cardiovascular Mortality
Authors: Louwe Mieke C. , Gialeli Chrysostomi , Michelsen Annika E. , Holm Sverre , Edsfeldt Andreas , Skagen Karolina , Lekva Tove , Olsen Maria Belland , Bjerkeli Vigdis , Schjørlien Therese , Stø Kristine , Kong Xiang Yi , Dahl Tuva B. , Nilsson Per H. , Libby Peter , Aukrust Pål , Mollnes Tom Eirik , Ueland Thor , Skjelland Mona , Gonçalves Isabel , Halvorsen Bente 
Published: January 2025

Background
Complement activation may promote atherosclerosis. Yet, data on the to which extent complement, and more specifically the alternative complement pathway, is activated in patients with carotid atherosclerosis and related to adverse outcome in these patients, are scarce.

Methods and Results

We measured, by ELISA, plasma levels of factor D, properdin, C3bBbP (C3 convertase), and factor H in patients with advanced carotid atherosclerosis in a
Discovery
(n=324) and in a
Validation
(n=206) cohort in relation to adverse outcome (mean follow‐up 7.8 and 6.6 years, respectively). Our major findings were as follows. Compared with healthy controls, patients with carotid atherosclerosis had increased plasma levels of factor D, properdin, and C3bBbP (
P
<0.001), but not factor H, an inhibitor of the alternative complement pathway, compared with controls. Although patients with carotid atherosclerosis had elevated levels of properdin compared with controls, within these patients, low plasma levels of properdin (ie, <median levels of properdin in the patient group) were significantly associated with cardiovascular mortality. This was seen in both the
Discovery
(HR 2.31,
P
=0.019) and the
Validation
cohort (hazard ratio [HR], 2.81,
P
=0.014). In contrast to the low circulating levels, high intraplaque properdin levels (assessed by ELISA) correlated with markers of plaque vulnerability and symptomatology.

Conclusions
We show a strong and independent association of low plasma properdin levels with cardiovascular mortality in 2 cohorts. Conversely, the plaque properdin levels linked to features of plaque vulnerability, potentially reflecting increased deposition at the site of inflammation or local production of properdin in the atherosclerotic lesion indicating local enhanced alternative complement pathway activation.
Specifying Precision in Visual-orthographic Prediction Error Representations for a Better Understanding of Efficient Reading
Authors: Fu Wanlu , Gagl Benjamin 
Published: January 2025

Abstract
Efficient visual word recognition presumably relies on orthographic prediction error (oPE) representations. On the basis of a transparent neurocognitive computational model rooted in the principles of the predictive coding framework, we postulated that readers optimize their percept by removing redundant visual signals, allowing them to focus on the informative aspects of the sensory input (i.e., the oPE). Here, we explore alternative oPE implementations, testing whether increased precision by assuming all-or-nothing signaling and more realistic word lexicons results in adequate representations underlying efficient word recognition. We used behavioral and electrophysiological data (i.e., EEG) for model evaluation. More precise oPE representations (i.e., implementing a binary signaling and a frequency-sorted lexicon with the 500 most common five-letter words) explained variance in behavioral responses and electrophysiological data 300 msec after stimulus onset best. The original less-precise oPE representation still best explains early brain activation. This pattern suggests a dynamic adaption of represented visual-orthographic information, where initial graded prediction errors convert into binary representations, allowing accurate retrieval of word meaning. These results offer a neuro-cognitive plausible account of efficient word recognition, emphasizing visual-orthographic information in the form of prediction error representations central to the transition from perceptual processing to the access of word meaning.
The Art of Becoming Infinite
Authors: Stanchina Gabriella 
Published: January 2025

Mou Zongsan is arguably the most important Chinese philosopher of the twentieth century. This work delves into the philosopher's exploration of self and subjectivity, setting Mou Zongsan’s theories against Western paradigms. Mou contrasts Western ‘horizontal’ model, based on the separation of subject and object, and aimed at cognitive enhancement, with the ‘vertical’ view dominant in the Confucian and Daoist tradition. The vertical model has, at its core, a practical-performative interpretation of the subject, based on the moral self-cultivation. This spiritual cultivation enables the finite human being to ‘become infinite,’ embodying the original unlimited moral mind that constitutes the Self and the universe.
In addressing fundamental questions of self-consciousness and self-identity, the book contextualizes Mou's philosophy within contemporary discussions in neuroscience and cognitive science. By placing Mou's ideas in dialogue with Western thought—examining thinkers like Husserl, Kant, Hegel, and Lévinas—as well as with Daoist and Confucian vision of mind, this work opens a pathway to understanding selfhood beyond purely epistemological boundaries.
This book will be of interest to readers and scholars interested in the contemporary debate about mind and the Self, as well as those intrigued by the new horizons opened by a cross-cultural Western-Chinese approach to subjectivity.
Pixels and Predictions: Potential of GPT-4V in Meteorological Imagery Analysis and Forecast Communication
Authors: Lawson John R. , Trujillo-Falcón Joseph E. , Schultz David M. , Flora Montgomery L. , Goebbert Kevin H. , Lyman Seth N. , Potvin Corey K. , Stepanek Adam J. 
Published: January 2025

Abstract
Generative artificial intelligence (AI), such as OpenAI’s GPT-4V large-language model, has rapidly entered mainstream discourse. Novel capabilities in image processing and natural-language communication may augment existing forecasting methods. Large language models further display the potential to better communicate weather hazards in a style honed for diverse communities and different languages. This study evaluates GPT-4V’s ability to interpret meteorological charts and communicate weather hazards appropriately to the user, despite challenges of hallucinations, where generative AI delivers coherent, confident, but incorrect responses. We assess GPT-4V’s competence in two tasks: 1) generating a severe-weather outlook from weather-chart analysis and conducting self-evaluation, revealing an outlook that corresponds well with a Storm Prediction Center human-issued forecast, and 2) producing hazard summaries in Spanish and English from weather charts. Responses in Spanish, however, resemble direct (not idiomatic) translations from English to Spanish, yielding poorly translated summaries that lose critical idiomatic precision required for optimal communication. Our findings advocate for cautious integration of tools like GPT-4V in meteorology, underscoring the necessity of human oversight and development of trustworthy, explainable AI.

Significance Statement
The integration of generative AI such as GPT-4V into meteorology brings opportunity for improving forecast communication of weather hazards across languages and communities. This study evaluates GPT-4V’s capacity to create plausible severe-weather outlooks and communicate hazards in both Spanish and English, from inputs of weather charts and texts. The weather outlook generally aligns with a human-generated forecast product but displays vagueness and incorrect reasoning. Further, translations lack idiomatic precision and display poor grasp of cultural nuance. Despite this, GPT-4V shows the potential for advancement in meteorological application. We advocate for cautious AI integration, emphasizing the need for human oversight and reliable, trustworthy output.
Unforced Millennial-Scale Oscillations in a Coupled Climate–Carbon System
Authors: Zhu Fangze , Rose Brian E. J. 
Published: January 2025

Abstract
We identify and investigate spontaneous unforced millennial-scale oscillations in an idealized global coupled climate–carbon model under nearly ice-free conditions. The oscillations first appear due to gradual loss of deep polar ocean stratification in a global warming scenario, which triggers the onset of a subpolar deep circulation, with important implications for ocean carbon storage. The analysis focuses on the residual mean meridional overturning circulation (MOC) due to the significant eddy-driven component. The subpolar deep MOC further invigorates the subtropical deep MOC, increasing global air–sea CO2 fluxes and atmospheric CO2 through upwelling of deep dissolved inorganic carbon (DIC). The increasing atmospheric CO2 leads to global surface warming that further warms and stratifies the subsurface polar ocean, shutting down the subpolar deep MOC and completing a delayed negative feedback which reverses the oscillation phase. Mechanism-denial experiments reveal that the CO2 radiative feedback and time-varying MOC and polar stratification are all essential components of the oscillator mechanism, while winter sea ice and time-varying biological nutrients are not. The millennial time scale is determined by the delayed response of atmospheric CO2 to variations in polar stratification and subpolar deep MOC. This study sheds light on the coupled climate–carbon dynamics behind the internal millennial-scale variability of an ice-free warm climate. We discuss the relevance to understanding observed millennial-scale climate variability during the last glacial period.
Possible Mechanisms behind Dominant Modes of Seasonal Cycle of Rainfall over India
Authors: Bhattacharyya Sujatra , Chakraborty Arindam 
Published: January 2025

Abstract
The South Asian summer monsoon that occurs over 4 months from near summer solstice (June) to near autumnal equinox (September) evolves within the season due to interactions with other climate components. Since most climate patterns are seasonally phase-locked, their interaction and feedback with monsoon should also be season-dependent. Here, using rain gauge–based precipitation over India for 74 years, we show that the onset phase of the monsoon (June) is uncorrelated with the rest of the season (July–September). The propagation of the Madden–Julian oscillation (MJO) over the Indian Ocean triggers northward propagation of precipitable water that plays a key role during the onset phase. The MJO appears over the western equatorial Indian Ocean during both the early and late central Indian onset years. Normal and slow MJO phase propagation during early and late onset years, respectively, gives rise to interannual variations in June rainfall. After onset, till the end of the monsoon season, the interannual variability of the dominant seasonal mode of precipitation is regulated by the phase of El Niño–Southern Oscillation (ENSO) through anomalous moisture convergence. We show that, in June, ENSO does not play a key role because of the opposing impact on wind and moisture. However, from July to September, ENSO perturbs wind and moisture in a way that gives rise to positive feedback between monsoon, ENSO, and large-scale circulation. Such feedback of monsoon with ENSO results in a coherent impact of ENSO on monsoon precipitation in July–September. Our results suggest that the dominant mechanisms for interannual variations in Indian monsoon rainfall in June and the rest of the season are different.

Significance Statement
The variations in rainfall within the monsoon season in India are extremely important for agriculture and water resource management. For such purposes, prediction of the variations in rainfall within the season is more important than the prediction of the seasonal mean. However, very little study has been done to understand the generalized physical processes that govern the monthly variations in rainfall every year without assuming a particular intraseasonal feature. Here, we try to find the existence of the physical modes that are responsible for monthly variations in rainfall every year. We show that the dominant mechanisms behind the interannual variabilities of June and post-June rainfall are different. While June rainfall is governed by equatorial waves, post-June rainfall is a function of feedback between monsoon and ENSO. If the climate models capture these physical modes accurately, the prediction of the seasonal cycle of rainfall will improve substantially.
Secondary Subtalar Arthrodesis: Surgical Outcome and Predictors of Functional Outcome and Quality of Life After Bone Block Distraction vs In Situ Technique
Authors: Eelsing Robin , Al-Sheikh Sally , Halm Jens A. , Schepers Tim 
Published: January 2025

Background: The outcome of a secondary subtalar arthrodesis after prior calcaneal fracture has been widely described. However, the surgical treatment has evolved significantly over the past decade, paralleling the shifts observed in primary repair strategies. Therefore, we describe the outcome following a secondary arthrodesis after an intra-articular calcaneal fracture, comparing the in situ (ISA) and bone block distraction arthrodesis (BBDA) techniques. Methods: In total, 339 patients who underwent a subtalar arthrodesis between January 1998 and November 2022 were screened for eligibility. Inclusion criteria were age ≥16 years, having undergone a subtalar arthrodesis following a calcaneal fracture, and a minimal follow-up of 1 year. Exclusion criteria were subtalar arthrodesis before January 2010 and a subtalar arthrodesis within 6 weeks of injury. A total of 259 patients did not meet the inclusion criteria, resulting in the inclusion of 80 patients with 82 fractured calcanei. Results: No significant differences between ISA and BBDA in surgical outcome were seen. Subtalar fusion was achieved in 78 of the patients (95.1%). Additionally, a deep surgical site infection occurred in 6 patients (7.8%). The American Orthopaedic Foot & Ankle Society ankle-hindfoot scale (AOFAS) and Foot Function Index (FFI) scores and the EuroQol–5 dimensions (EQ5D) index were similar between the 2 groups. However, a significantly higher EQ5D-VAS was reported by the subjects who received a BBDA (median [interquartile range], 70.0 [52.0-82.0] vs 81.0 [70.0-90.3], P = .021). Multiple regression revealed that a higher Böhler angle before the initial fracture reconstruction significantly improved the AOFAS score, whereas the FFI significantly improved by an initial conservative treatment and implant removal after arthrodesis. Finally, increasing age significantly improved the EQ5D index. Conclusion: Our study presents comparable surgical outcomes between ISA and BBDA for secondary subtalar arthrodesis following calcaneal fractures. Functional outcomes, as measured by the AOFAS and FFI scores, were also similar between the 2 techniques, although patients undergoing BBDA reported higher EQ5D visual analog scale scores. Level of Evidence: Level III, retrospective cohort study.
Physical, chemical and biological properties of MTA Angelus and novel AGM MTA: an in vitro analysis
Authors: Nashibi Sara , Amdjadi Parisa , Ahmadi SeyedehSana , Hekmatian Sara , Torshabi Maryam 
Published: January 2025

Abstract

Introduction
Mineral trioxide aggregate (MTA) is a calcium silicate-based cement that has changed conventional dental therapeutic approaches. This study aimed to evaluate physical, chemical and biological properties of novel AGM MTA, in comparison with MTA Angelus.

Methods
The samples were prepared according to the manufacturer’s instructions. The initial and final setting times were measured via a Gillmore needle following the ISO 6876:2012 standard. The radiopacity of the materials was evaluated against an aluminium step wedge on the basis of the ISO 6876 and 13,116 standards. The pH changes were measured at intervals of 3, 6, 24, 72, 96 and 144 h postimmersion in Hank’s solution and calcium ion release was analysed after 168 h of immersion via inductively coupled plasma optical emission spectroscopy (ICP‒OES). Moreover, the cytotoxicity was assessed through the MTT assay on human dental pulp stem cells (hDPSCs) after 24 and 72 h of exposure to the set/fresh status of various dilutions of MTA extracts, following the ISO 10993-12 standard.

Results
No significant difference was found between the initial setting times of the two materials (Angelus: 11.0 ± 1.0 min, AGM: 10.3 ± 1.5 min); however, MTA Angelus demonstrated a significantly shorter final setting time. Both materials met the minimum radiopacity requirements according to the ISO 6876 standard, with MTA Angelus exhibiting greater radiopacity than AGM MTA. Both materials created an alkaline environment without presenting any differences in each time point and AGM MTA released significantly greater amounts of calcium ions. In the cytotoxicity assessment, while the diluted extracts of both materials did not elicit any cytotoxic effects, the nondiluted samples, after 72 h of exposure, as well as the 30-min set AGM MTA after 24 h of exposure, were shown to be cytotoxic.

Conclusions
In conclusion, MTA Angelus presented a faster setting time and lower cytotoxicity, while AGM MTA demonstrated greater calcium ion release. However, both materials presented clinically acceptable properties and AGM MTA could be a potential alternative to MTA Angelus. However, further clinical studies are required to confirm its application.