bluuebunny/crossref_metadata_2025_split huggingface dataset:
ER stress inhibition enhances formation of triacylglcerols and protects endothelial cells from lipotoxicity
Authors: Kovacevic Igor , Schmidt Paula Henriette , Kowalski Annkatrin , Helms Bernd J. , Lest Chris H. A. van de , Kluttig Alexander , Posern Guido 
Published: June 2024

AbstractElevated concentrations of palmitate in serum of obese individuals can impair endothelial function, contributing to development of cardiovascular disease. Although several molecular mechanisms of palmitate-induced endothelial dysfunction have been proposed, there is no consensus on what signaling event is the initial trigger of detrimental palmitate effects. Here we report that inhibitors of ER stress or ceramid synthesis can rescue palmitate-induced autophagy impairment in macro- and microvascular endothelial cells. Furthermore, palmitate-induced cholesterol synthesis was reverted using these inhibitors. Similar to cell culture data, autophagy markers were increased in serum of obese individuals. Subsequent lipidomic analysis revealed that palmitate changed the composition of membrane phospholipids in endothelial cells and that these effects were not reverted upon application of above-mentioned inhibitors. However, ER stress inhibition in palmitate-treated cells enhanced the synthesis of trilglycerides and restored ceramide levels to control condition. Our results suggest that palmitate induces ER-stress presumably by shift in membrane architecture, leading to impaired synthesis of triglycerides and enhanced production of ceramides and cholesterol, which altogether enhances lipotoxicity of palmitate in endothelial cells.
Migraine self-management at work: a qualitative study
Authors: Knauf Clara , Heinrichs Katherina , Süllwold Rolf , Icks Andrea , Loerbroks Adrian 
Published: June 2024

Abstract
Background
Migraine is common and can be highly disabling. Adequate migraine self-management (SM) can mitigate the potentially adverse health effects of migraine. However, adequate SM can be challenging to implement in everyday life, for instance, at the workplace. We aimed to explore how migraine SM is carried out at work and which occupational factors may determine effective implementation according to employees with migraine. We also explored the potential impact of the COVID-19 pandemic and the associated re-arrangement of working conditions on migraine SM at work.

Methods
We conducted semi-structured qualitative interviews (08/2020–01/2021). Participants were eligible if they have worked for at least six months with a minimum of twenty hours per week and with a migraine diagnosis. The interviews were transcribed and content-analyzed using MAXQDA.

Results
Migraine SM was perceived to be influenced by social interactions at work (e.g., in terms of understanding vs. stigmatization), the level of job decision latitude (JDL, i.e., the extent to which one is able to influence work processes, e.g., when working from home), and workplace design (e.g., in terms of opportunities to withdraw from work). During the COVID-19 pandemic, especially increased JDL appeared to favorably influence migraine SM.

Conclusions
Migraine SM at work is fostered or complicated by various psychosocial working conditions. By considering these facilitators and barriers, more migraine-friendly workplaces can be created.
The IMPACT Survey: the economic impact of osteogenesis imperfecta in adults
Authors: Hart Tracy , Westerheim Ingunn , van Welzenis Taco , Semler Oliver , Raggio Cathleen , Rauch Frank , Dadzie Ruby , Prince Samantha , Wekre Lena Lande 
Published: June 2024

Abstract
Background
The IMPACT survey aimed to elucidate the humanistic, clinical and economic burden of osteogenesis imperfecta (OI) on individuals with OI, their families, caregivers and wider society. Research methodology, demographics and initial insights from the survey have been previously reported. The cost of illness (healthcare resource use, productivity loss, out-of-pocket spending) and drivers of the economic impact of OI are reported here.

Methods
IMPACT was an international mixed-methods online survey in eight languages (fielded July–September 2021) targeting adults (aged ≥ 18 years) or adolescents (aged ≥ 12–17 years) with OI, caregivers with or without OI and other close relatives. Survey domains included demographics, socioeconomic factors, clinical characteristics, treatment patterns, quality of life and health economics. The health economic domain for adults, which included questions on healthcare resource use, productivity loss and out-of-pocket spending, was summarised. Regression and pairwise analyses were conducted to identify independent drivers and associations with respondent characteristics.

Results
Overall, 1,440 adults with OI responded to the survey. Respondents were mostly female (70%) and from Europe (63%) with a median age of 43 years. Within a 12-month period, adults with OI reported visiting a wide range of healthcare professionals. Two-thirds (66%) of adults visited a hospital, and one-third (33%) visited the emergency department. The mean total number of diagnostic tests undergone by adults within these 12 months was 8.0. Adults had undergone a mean total of 11.8 surgeries up to the time point of the survey. The proportions of adults using queried consumables or services over 12 months ranged from 18–82%, depending on the type of consumable or service. Most adults (58%) were in paid employment, of which nearly one-third (29%) reported missing a workday. Of the queried expenses, the mean total out-of-pocket spending in 4 weeks was €191. Respondent characteristics such as female sex, more severe self-reported OI and the experience of fractures were often associated with increased economic burden.

Conclusion
IMPACT provides novel insights into the substantial cost of illness associated with OI on individuals, healthcare systems and society at large. Future analyses will provide insights into country-specific economic impact, humanistic impact and the healthcare journey of individuals with OI.
AI-based prediction of protein–ligand binding affinity and discovery of potential natural product inhibitors against ERK2
Authors: Yang Ruoqi , Zhang Lili , Bu Fanyou , Sun Fuqiang , Cheng Bin 
Published: June 2024

AbstractDetermination of protein–ligand binding affinity (PLA) is a key technological tool in hit discovery and lead optimization, which is critical to the drug development process. PLA can be determined directly by experimental methods, but it is time-consuming and costly. In recent years, deep learning has been widely applied to PLA prediction, the key of which lies in the comprehensive and accurate representation of proteins and ligands. In this study, we proposed a multi-modal deep learning model based on the early fusion strategy, called DeepLIP, to improve PLA prediction by integrating multi-level information, and further used it for virtual screening of extracellular signal-regulated protein kinase 2 (ERK2), an ideal target for cancer treatment. Experimental results from model evaluation showed that DeepLIP achieved superior performance compared to state-of-the-art methods on the widely used benchmark dataset. In addition, by combining previously developed machine learning models and molecular dynamics simulation, we screened three novel hits from a drug-like natural product library. These compounds not only had favorable physicochemical properties, but also bound stably to the target protein. We believe they have the potential to serve as starting molecules for the development of ERK2 inhibitors.
Enhancing anaerobic digestion of lignocellulosic biomass by mechanical cotreatment
Authors: Bharadwaj Anahita , Holwerda Evert K. , Regan John M. , Lynd Lee R. , Richard Tom L. 
Published: June 2024

Abstract
Background
The aim of this study was to increase the accessibility and accelerate the breakdown of lignocellulosic biomass to methane in an anaerobic fermentation system by mechanical cotreatment: milling during fermentation, as an alternative to conventional pretreatment prior to biological deconstruction. Effluent from a mesophilic anaerobic digester running with unpretreated senescent switchgrass as the predominant carbon source was collected and subjected to ball milling for 0.5, 2, 5 and 10 min. Following this, a batch fermentation test was conducted with this material in triplicate for an additional 18 days with unmilled effluent as the ‘status quo’ control.

Results
The results indicate 0.5 – 10 min of cotreatment increased sugar solubilization by 5– 13% when compared to the unmilled control, with greater solubilization correlated with increased milling duration. Biogas concentrations ranged from 44% to 55.5% methane with the balance carbon dioxide. The total biogas production was statistically higher than the unmilled control for all treatments with 2 or more minutes of milling (α = 0.1). Cotreatment also decreased mean particle size. Energy consumption measurements of a lab-scale mill indicate that longer durations of milling offer diminishing benefits with respect to additional methane production.

Conclusions
Cotreatment in anaerobic digestion systems, as demonstrated in this study, provides an alternative approach to conventional pretreatments to increase biogas production from lignocellulosic grassy material.
Harder, better, faster, stronger: understanding and improving the tractability of large energy system models
Authors: Bröchin Manuel , Pickering Bryn , Tröndle Tim , Pfenninger Stefan 
Published: June 2024

Abstract
Background
Energy system models based on linear programming have been growing in size with the increasing need to model renewables with high spatial and temporal detail. Larger models lead to high computational requirements. Furthermore, seemingly small changes in a model can lead to drastic differences in runtime. Here, we investigate measures to address this issue.

Results
We review the mathematical structure of a typical energy system model, and discuss issues of sparsity, degeneracy and large numerical range. We introduce and test a method to automatically scale models to improve numerical range. We test this method as well as tweaks to model formulation and solver preferences, finding that adjustments can have a substantial impact on runtime. In particular, the barrier method without crossover can be very fast, but affects the structure of the resulting optimal solution.

Conclusions
We conclude with a range of recommendations for energy system modellers: first, on large and difficult models, manually select the barrier method or barrier+crossover method. Second, use appropriate units that minimize the model’s numerical range or apply an automatic scaling procedure like the one we introduce here to derive them automatically. Third, be wary of model formulations with cost-free technologies and dummy costs, as those can dramatically worsen the numerical properties of the model. Finally, as a last resort, know the basic solver tolerance settings for your chosen solver and adjust them if necessary.
In vivo diagnosis of TDP-43 proteinopathies: in search of biomarkers of clinical use
Authors: López-Carbonero Juan I. , García-Toledo Irene , Fernández-Hernández Laura , Bascuñana Pablo , Gil-Moreno María J. , Matías-Guiu Jordi A. , Corrochano Silvia 
Published: June 2024

AbstractTDP-43 proteinopathies are a heterogeneous group of neurodegenerative disorders that share the presence of aberrant, misfolded and mislocalized deposits of the protein TDP-43, as in the case of amyotrophic lateral sclerosis and some, but not all, pathological variants of frontotemporal dementia. In recent years, many other diseases have been reported to have primary or secondary TDP-43 proteinopathy, such as Alzheimer’s disease, Huntington’s disease or the recently described limbic-predominant age-related TDP-43 encephalopathy, highlighting the need for new and accurate methods for the early detection of TDP-43 proteinopathy to help on the stratification of patients with overlapping clinical diagnosis. Currently, TDP-43 proteinopathy remains a post-mortem pathologic diagnosis. Although the main aim is to determine the pathologic TDP-43 proteinopathy in the central nervous system (CNS), the ubiquitous expression of TDP-43 in biofluids and cells outside the CNS facilitates the use of other accessible target tissues that might reflect the potential TDP-43 alterations in the brain. In this review, we describe the main developments in the early detection of TDP-43 proteinopathies, and their potential implications on diagnosis and future treatments.
Mendelian randomization evidence based on European ancestry for the causal effects of leukocyte telomere length on prostate cancer
Authors: Wu Xinrui , Hu Cong , Wu Tianyang , Du Xinxing , Peng Zehong , Xue Wei , Chen Yonghui , Dong Liang 
Published: June 2024

Abstract
Background
Several lines of evidence suggest that leukocyte telomere length (LTL) can affect the development of prostate cancer (PC).

Methods
Here, we employed single nucleoside polymorphisms (SNPs) as instrumental variables (IVs) for LTL (n = 472,174) and conducted Mendelian randomization analysis to estimate their causal impact on PCs (79,148 patients/61,106 controls and 6311 patients/88,902 controls).

Results
Every 1-s.d extension of LTL increased the risk of PCs by 34%. Additionally, the analysis of candidate mediators between LTL and PCs via two-step Mendelian randomization revealed that among the 23 candidates, Alzheimer’s disease, liver iron content, sex hormone binding global levels, naive CD4–CD8-T cell% T cell, and circulating leptin levels played substantial mediating roles. There is no robust evidence to support the reverse causal relationship between LTL and the selected mediators of PCs. Adjusting for the former four mediators, rather than adjusting for circulating leptin levels, decreased the impact of LTL on PCs.

Conclusion
This study provides potential intervention measures for preventing LTL-induced PCs.
Does clinical T1N0 GGN really require checking for distant metastasis during initial staging for lung cancer?
Authors: Imai Kazuhiro , Kurihara Nobuyasu , Konno Motoko , Mori Naoko , Takashima Shinogu , Kuriyama Shoji , Demura Ryo , Suzuki Haruka , Harata Yuzu , Fujibayashi Tatsuki , Shibano Sumire , Wakita Akiyuki , Nagaki Yushi , Sato Yusuke , Nomura Kyoko , Minamiya Yoshihiro 
Published: June 2024

Abstract
Background
Accurate clinical staging is crucial for selection of optimal oncological treatment strategies in non-small cell lung cancer (NSCLC). Although brain MRI, bone scintigraphy and whole-body PET/CT play important roles in detecting distant metastases, there is a lack of evidence regarding the indication for metastatic staging in early NSCLCs, especially ground-grass nodules (GGNs). Our aim was to determine whether checking for distant metastasis is required in cases of clinical T1N0 GGN.

Methods
This was a retrospective study of initial staging using imaging tests in patients who had undergone complete surgical R0 resection for clinical T1N0 Stage IA NSCLC.

Results
A total of 273 patients with cT1N0 GGNs (n = 183) or cT1N0 solid tumors (STs, n = 90) were deemed eligible. No cases of distant metastasis were detected on initial routine imaging evaluations. Among all cT1N0M0 cases, there were 191 incidental findings on various modalities (128 in the GGN). Most frequently detected on brain MRI was cerebral leukoaraiosis, which was found in 98/273 (35.9%) patients, while cerebral infarction was detected in 12/273 (4.4%) patients. Treatable neoplasms, including brain meningioma and thyroid, gastric, renal and colon cancers were also detected on PET/CT (and/or MRI). Among those, 19 patients were diagnosed with a treatable disease, including other-site cancers curable with surgery.

Conclusions
Extensive staging (MRI, scintigraphy, PET/CT etc.) for distant metastasis is not required for patients diagnosed with clinical T1N0 GGNs, though various imaging modalities revealed the presence of adventitious diseases with the potential to increase surgical risks, lead to separate management, and worsen patient outcomes, especially in elderly patients. If clinically feasible, it could be considered to complement staging with whole-body procedures including PET/CT.
Role of cellular senescence in inflammation and regeneration
Authors: Saito Yuki , Yamamoto Sena , Chikenji Takako S. 
Published: June 2024

AbstractCellular senescence is the state in which cells undergo irreversible cell cycle arrest and acquire diverse phenotypes. It has been linked to chronic inflammation and fibrosis in various organs as well as to individual aging. Therefore, eliminating senescent cells has emerged as a potential target for extending healthy lifespans. Cellular senescence plays a beneficial role in many biological processes, including embryonic development, wound healing, and tissue regeneration, which is mediated by the activation of stem cells. Therefore, a comprehensive understanding of cellular senescence, including both its beneficial and detrimental effects, is critical for developing safe and effective treatment strategies to target senescent cells. This review provides an overview of the biological and pathological roles of cellular senescence, with a particular focus on its beneficial or detrimental functions among its various roles.
Seventy years of study on ethnic paleography in China
Authors: Shi Jinbo , Huang Runhua 
Published: June 2024

AbstractThis paper systematically presents the development process of studying ancient Chinese ethnic scripts over the past seven decades since the founding of the People’s Republic of China in 1949, including the establishment of related research institutions and academic disciplines. Firstly, it records the establishment of the Chinese Association for Ethnic Paleography, the emergence of ancient scripts of ethnic groups in China as an academic discipline, and the conduction of a comprehensive and in-depth study of ancient Chinese ethnic literature in history. Secondly, this paper outlines the establishment of the National Leading Group for Compilation and Publication Planning of Ancient Ethnic Books, the census of ancient books written in ethnic scripts, the specialized preservation and conservation of ancient ethnic books in Xizang and Xinjiang, the promotion of compiling and publishing ancient ethnic books, and how the promotion further drives the protection of and research on ancient books written in ethnic scripts. Thirdly, the paper lists many innovative outcomes in studying ancient ethnic books. Fourthly, the paper proposes to conduct further censuses and in-depth research in this area, establish a grading system for ancient ethnic books, and utilize the resource of ancient ethnic books written in ethnic scripts in a modern context to further promote the excellent cultural heritages of the Chinese nation and enhancing ethnic unity and national unity.
In-depth Correlation Power Analysis Attacks on a Hardware Implementation of CRYSTALS-Dilithium
Authors: Wang Huaxin , Gao Yiwen , Liu Yuejun , Zhang Qian , Zhou Yongbin 
Published: June 2024

AbstractDuring the standardisation process of post-quantum cryptography, NIST encourages research on side-channel analysis for candidate schemes. As the recommended lattice signature scheme, CRYSTALS-Dilithium, when implemented on hardware, has seen limited research on side-channel analysis, and current attacks are incomplete or requires a substantial quantity of traces. Therefore, we conducted a more complete analysis to investigate the leakage of an FPGA implementation of CRYSTALS-Dilithium using the Correlation Power Analysis (CPA) method, where with a minimum of 70,000 traces partial private key coefficients can be recovered. Furthermore, we optimise the attack by extracting Point-of-Interests using known information due to parallelism (named CPA-PoI) and by iteratively utilising parallel leakages (named CPA-ITR). Our experimental results show that CPA-PoI reduces the number of traces by up to 16.67%, CPA-ITR by up to 25%, and both increase the number of recovered key coefficients by up to 55.17% and 93.10% using the same number of traces. They outperfom the CPA method. As a result, it suggests that the FPGA implementation of CRYSTALS-Dilithium is more vulnerable than thought before to side-channel analysis.
Dobutamine stress cardiac magnetic resonance-feature tracking in assessment of myocardial ischemia and viability
Authors: Ibrahim Ghada S. , AbdelDayem Emad H. , Abbas Sherif N. , Mozy Wesam E. El , Ibrahim Ahmed S. 
Published: June 2024

Abstract
Background
Cardiovascular magnetic resonance-feature tracking (CMR-FT) is a novel quantitative objective noninvasive technique in the assessment of myocardial deformation. The purpose of that study was to assess the capability of the CMR-FT in the detection of myocardial ischemia and viability. We investigated 30 patients (n = 480 myocardial segments), with known or suspected coronary artery disease (CAD). Dobutamine stress cardiovascular magnetic resonance (DS-CMR) and late gadolinium enhancement (LGE) were used to identify the viable non-ischemic, ischemic, and non-viable myocardial segments. Cine images at rest were used to calculate the segmental radial (Err), circumferential (Ecc), and longitudinal (Ell) strain parameters by manual contouring of endocardial and epicardial borders using Segment Software.

Results
Of the 480 myocardial segments and based on the DS-CMR and LGE results, 338 segments were defined as viable non-ischemic (remote), 101 segments were viable ischemic, and 41 segments were non-viable. Rest segmental Ecc, Err, and Ell values were significantly impaired in the non-viable (mean ± SD = − 3.94 ± 4.99%, 11.81 ± 12.55%, and − 7.50 ± 6.96%, respectively) compared to both viable groups, p < 0.001. Ecc and Err significantly differentiated between the non-ischemic and ischemic groups (mean ± SD = − 19.14 ± 7.20% vs − 13.18 ± 8.57% and 44.03 ± 19.56% vs 32.79 ± 17.91% respectively), p < 0.001. However, Ell showed no statistical significance between them (mean ± SD = − 16.44 ± 8.78% vs − 16.12 ± 10.00%, p = 0.945).

Conclusions
CMR-FT can differentiate between viable and non-viable as well as ischemic and non-ischemic myocardial segments. So, such a noninvasive technique has a promising additional objective diagnostic role in conjunction with CMR in ischemia and viability assessment or even may replace stress and LGE studies in the future.