bluuebunny/crossref_metadata_2025_split huggingface dataset:
Socioeconomic disparity in the natural history of cutaneous melanoma: evidence from two large prospective cohorts
Authors: Yang Songchun , Xiao Yi , Jing Danrong , Liu Hong , Su Juan , Shen Minxue , Chen Xiang 
Published: July 2024

Background
Previous studies on the associations between socioeconomic status (SES) and cutaneous malignant melanoma (CMM) failed to distinguish the effects of different SES factors under an individual-data-based prospective study design.

Methods
Based on UK Biobank (UKB) and China Kadoorie Biobank (CKB), we estimated the effects of four SES factors on transitions from baseline to CMM in situ, subsequently to invasive CMM and further CMM mortality by applying multistate models. We further explored to which extent the associations between SES and CMM incidence could be explained by potential mediators including sun exposure, lifestyle and ageing in UKB.

Results
In multistate analyses, good household income was independently associated with an increased risk of CMM in situ (HR=1.38, 95% CI: 1.21 to 1.58) and invasive CMM (HR=1.34, 95% CI: 1.22 to 1.48) in UKB. These findings were partly validated in CKB. Especially in UKB, we observed an increased risk of CMM in situ and invasive CMM among participants with good type of house; only good education was independently associated with lower risk of evolving to invasive CMM among patients with CMM in situ (HR=0.69, 95% CI: 0.52 to 0.92); only good household income was independently associated with lower risk of CMM mortality among patients with CMM (HR=0.65, 95% CI: 0.45 to 0.95). In mediation analysis, the proportions attributable to the mediating effect were <6% for all selected variables, including self-reported sun exposure-related factors.

Conclusion
SES factors have different effects on the incidence and progression of CMM. The association between SES and incident CMM is neither causal nor well explained by selected mediators.
Development and internal validation of a clinical risk score to predict incident renal and pulmonary tumours in people with tuberous sclerosis complex
Authors: Loubert Frédéric , House Andrew A , Larochelle Catherine , Major Philippe , Keezer Mark R 
Published: July 2024

Objective
This study aims to develop and internally validate a clinical risk score to predict incident renal angiomyolipoma (AML) and pulmonary lymphangioleiomyomatosis (LAM) in people with tuberous sclerosis complex (TSC).

Study design
Data from 2420 participants in the TSC Alliance Natural History Database were leveraged for these analyses. Logistic regression was used to predict AML and LAM development using 10 early-onset clinical manifestations of TSC as potential predictors, in addition to sex and genetic mutation. For our models, we divided AML into three separate outcomes: presence or absence of AML, unilateral or bilateral and whether any are ≥3 cm in diameter. The resulting regression models were turned into clinical risk scores which were then internally validated using bootstrap resampling, measuring discrimination and calibration.

Results
The lowest clinical risk scores predicted a risk of AML and LAM of 1% and 0%, while the highest scores predicted a risk of 99% and 73%, respectively. Calibration was excellent for all three AML outcomes and good for LAM. Discrimination ranged from good to strong. C-statistics of 0.84, 0.83, 0.83 and 0.92 were seen for AML, bilateral AML, AML with a lesion≥3 cm and LAM, respectively.

Conclusion
Our work is an important step towards identifying individuals who could benefit from preventative strategies as well as more versus less frequent screening imaging. We expect that our work will allow for more personalised medicine in people with TSC. External validation of the risk scores will be important to confirm the robustness of our findings.
Animal and farm factors affecting the fatty acid profile and amyloid a concentration of milk on Quebec dairy farms
Authors: Mowete S.Y. , Santschi D. , Kwiatkowski K. , Azevedo P.A. , De Neve N. , Fievez V. , Plaizier J.C. 
Published: July 2024

Relationships between farm and animal factors and the fatty acid (FA) profile and milk amyloid A (MAA) content of milk were determined in 336 Holstein dairy cows on 24 Quebec farms using multiple regression. Cows with a somatic cell count (SCC) >200 000, and farms feeding palm oil were excluded. Independent factors of the regression models included days in milk (DIM), parity, yield, fat and protein contents of milk, SCC, and the dietary contents of neutral detergent fiber (NDF) and crude fat (CFAT). Nonsignificant variables with P > 0.25 were stepwise removed. Models with high fits were those of total short-chain FA, medium-chain FA, odd- and branched-chain FA (OBCFA), and saturated long-chain FA with R2 of 0.33, 0.36, 0.34, and 0.41, respectively. The fat and protein contents and yield of milk did not affect the milk FA profile. Higher NDF increased the milk fat proportions of short-chain FA and OBCFA and decreased those of monounsaturated (MUFA) and polyunsaturated FA (PUFA). Higher CFAT reduced this proportion of short-chain FA but increased those of MUFA and PUFA. Increasing DIM reduced this proportion of short-chain FA and increased that of medium-chain FA. Higher SCC increased MAA.
The Holocene to modern Fraser River Delta, Canada: geological history, processes, deposits, natural hazards, and coastal management
Authors: La Croix Andrew D. , Dashtgard Shahin E. , Hill Philip R. , Ayranci Korhan , Clague John J. 
Published: July 2024

The Fraser River Delta (FRD) is a large sedimentary system and home to Metro Vancouver, situated within the unceded territories of several First Nations. This review provides an overview of the geological evolution of the FRD, connecting hydrodynamic processes with sedimentary deposits across its diverse environments, from the river to the delta slope. The study emphasizes the implications of sedimentation and delta evolution for natural hazards and coastal/delta management, pinpointing knowledge gaps. Comprising four main zones—river, delta plain, tidal flats, and delta slope—the FRD is subject to several natural hazards, including subsidence, flooding, earthquakes, liquefaction, and tsunamis. The delta plain, bordering the Fraser River's distributary channels, hosts tidal marshes and flats, including both active and abandoned areas. Active tidal flats like Roberts Bank and Sturgeon Bank receive sediment directly from the Fraser River, while abandoned tidal flats, like those at Boundary Bay and Mud Bay, no longer receive sediment. The tidal flats transition into the delta slope, characterized by sand in the south and mud in the north of the Main Channel. The FRD's susceptibility to hazards necessitates protective measures, with approximately 250 km of dykes shielding the delta plain from river floods and storm surges. Subsidence amplifies the impact of rising sea levels. Earthquakes in the region can induce tsunamis, submarine slope failures, and liquefaction of delta sediments, emphasizing the importance of incorporating sedimentation patterns and delta evolution into management strategies for sustainable urban development, habitat restoration, and coastal defence initiatives.
Streamlined Intraoperative Brain Tumor Classification and Molecular Subtyping in Stereotactic Biopsies Using Stimulated Raman Histology and Deep Learning
Authors: Reinecke David , Ruess Daniel , Meissner Anna-Katharina , Fürtjes Gina , von Spreckelsen Niklas , Ion-Margineanu Adrian , Khalid Florian , Blau Tobias , Stehle Thomas , Al-Shugri Abdulkader , Büttner Reinhard , Goldbrunner Roland , Ruge Maximilian I. , Neuschmelting Volker 
Published: July 2024

Abstract

Purpose:
Recent artificial intelligence algorithms aided intraoperative decision-making via stimulated Raman histology (SRH) during craniotomy. This study assesses deep learning algorithms for rapid intraoperative diagnosis from SRH images in small stereotactic-guided brain biopsies. It defines a minimum tissue sample size threshold to ensure diagnostic accuracy.

Experimental Design:
A prospective single-center study examined 121 SRH images from 84 patients with unclear intracranial lesions undergoing stereotactic brain biopsy. Unprocessed, label-free samples were imaged using a portable fiber laser Raman scattering microscope. Three deep learning models were tested to (i) identify tumorous/nontumorous tissue as qualitative biopsy control; (ii) subclassify into high-grade glioma (central nervous system World Health Organization grade 4), diffuse low-grade glioma (central nervous system World Health Organization grades 2–3), metastases, lymphoma, or gliosis; and (iii) molecularly subtype IDH and 1p/19q statuses of adult-type diffuse gliomas. Model predictions were evaluated against frozen section analysis and final neuropathologic diagnoses.

Results:
The first model identified tumorous/nontumorous tissue with 91.7% accuracy. Sample size on slides impacted accuracy in brain tumor subclassification (81.6%, κ = 0.72 frozen section; 73.9%, κ = 0.61 second model), with SRH images being smaller than hematoxylin and eosin images (4.1 ± 2.5 mm2 vs. 16.7 ± 8.2 mm2, P &lt; 0.001). SRH images with more than 140 high-quality patches and a mean squeezed sample of 5.26 mm2 yielded 89.5% accuracy in subclassification and 93.9% in molecular subtyping of adult-type diffuse gliomas.

Conclusions:
Artificial intelligence–based SRH image analysis is non-inferior to frozen section analysis in detecting and subclassifying brain tumors during small stereotactic-guided biopsies once a critical squeezed sample size is reached. Beyond frozen section analysis, it enables valid molecular glioma subtyping, allowing faster treatment decisions in the future; however, refinement is needed for long-term application.
Tumor Mutational Load: A Novel Predictor for Clinical Benefit of Pembrolizumab
Authors: Hsu Fang-Chi , Yen Yun 
Published: July 2024

Summary
A recent study evaluated the efficacy of pembrolizumab across various cancers, classified according to tumor mutational load (TML) defined by whole-genome sequencing. Tumors exhibiting intermediate to high TML showed improved clinical benefit from pembrolizumab. This proof-of-concept study highlights clinical value of TML in patient selection, advancing precision immunotherapy and treatment strategies.
See related article by Geurts et al., p. 3735
Inhomogeneous magnetization transfer (ihMT) imaging reveals variable recovery profiles of active MS lesions according to size and localization
Authors: Soustelle Lucas , Mchinda Samira , Hertanu Andreea , Gherib Soraya , Pini Lauriane , Guye Maxime , Ranjeva Jean-Philippe , Varma Gopal , Alsop David C. , Pelletier Jean , Girard Olivier M. , Duhamel Guillaume 
Published: July 2024

Abstract
This work aims at exploiting the unique myelin specificity of the inhomogeneous magnetization transfer (ihMT) technique to characterize the recovery dynamics of active multiple sclerosis (MS) lesions. IhMT and three other myelin-sensitive techniques, conventional MT, T1-weighted, and diffusion tensor imaging, were applied in a 12-month longitudinal study performed on relapsing-remitting MS patients. An exponential recovery model was used to fit the variations over time of the metrics derived from each MR technique within new active lesions. A principal component analysis was performed on the model parameters obtained for all MR myelin-sensitive techniques across all active lesions of all patients to identify specific recovery profiles. The results show that the recovery profiles of myelin-sensitive MR metrics in active MS lesions vary according to the localization and size of lesions. The distance of lesions from the ventricles is positively associated with the recovery rates of ihMTR and T1w-MPRAGE: the further the lesion is from the ventricles, the higher the recovery rate of these metrics. Lesion size is positively associated with initial loss and negatively associated with final recovery of ihMTR and other MR metrics: small lesions have lower initial loss and greater final recovery of MR metrics than large lesions. Thanks to the specificity of the ihMT technique for myelin, these features can be interpreted in terms of remyelination. This study thus provides longitudinal in vivo support for the pathological observations of higher remyelination in small lesions compared with large ones and faster remyelination in lesions away from the ventricles. These results support the use of ihMT and other measures for quantifying remyelination rates in clinical studies of remyelination therapies.
White matter and cortical gray matter microstructural abnormalities in new daily persistent headache: a NODDI study
Authors: Li Zhilei , Mei Yanliang , Wang Wei , Wang Lei , Wu Shouyi , Zhang Kaibo , Qiu Dong , Xiong Zhonghua , Li Xiaoshuang , Yuan Ziyu , Zhang Peng , Zhang Mantian , Tong Qiuling , Zhang Zhenchang , Wang Yonggang 
Published: July 2024

Abstract
Background
New daily persistent headache (NDPH) is a rare primary headache with unclear pathogenesis. Neuroimaging studies of NDPH are limited, and controversy still exists. Diffusion tensor imaging (DTI) is commonly used to study the white matter. However, lacking specificity, the potential pathological mechanisms of white matter microstructural changes remain poorly understood. In addition, the intricacy of gray matter structures impedes the application of the DTI model. Here, we applied an advanced diffusion model of neurite orientation dispersion and density imaging (NODDI) to study the white matter and cortical gray matter microstructure in patients with NDPH.

Methods
This study assessed brain microstructure, including 27 patients with NDPH, and matched 28 healthy controls (HCs) by NODDI. The differences between the two groups were assessed by tract-based spatial statistics (TBSS) and surface-based analysis (SBA), focusing on the NODDI metrics (neurite density index (NDI), orientation dispersion index (ODI), and isotropic volume fraction (ISOVF)). Furthermore, we performed Pearson’s correlation analysis between the NODDI indicators and clinical characteristics.

Results
Compared to HCs, patients with NDPH had a reduction of density and complexity in several fiber tracts. For robust results, the fiber tracts were defined as comprising more than 100 voxels, including bilateral inferior fronto-occipital fasciculus (IFOF), left superior longitudinal fasciculus (SLF) and inferior longitudinal fasciculus (ILF), as well as right corticospinal tract (CST). Moreover, the reduction of neurite density was uncovered in the left superior and middle frontal cortex, left precentral cortex, and right lateral orbitofrontal cortex and insula. There was no correlation between the NODDI metrics of these brain regions and clinical variables or scales of relevance after the Bonferroni correction.

Conclusions
Our research indicated that neurite loss was detected in both white matter and cortical gray matter of patients with NDPH.
Epigenetic control of skeletal muscle atrophy
Authors: Liang Wenpeng , Xu Feng , Li Li , Peng Chunlei , Sun Hualin , Qiu Jiaying , Sun Junjie 
Published: July 2024

AbstractSkeletal muscular atrophy is a complex disease involving a large number of gene expression regulatory networks and various biological processes. Despite extensive research on this topic, its underlying mechanisms remain elusive, and effective therapeutic approaches are yet to be established. Recent studies have shown that epigenetics play an important role in regulating skeletal muscle atrophy, influencing the expression of numerous genes associated with this condition through the addition or removal of certain chemical modifications at the molecular level. This review article comprehensively summarizes the different types of modifications to DNA, histones, RNA, and their known regulators. We also discuss how epigenetic modifications change during the process of skeletal muscle atrophy, the molecular mechanisms by which epigenetic regulatory proteins control skeletal muscle atrophy, and assess their translational potential. The role of epigenetics on muscle stem cells is also highlighted. In addition, we propose that alternative splicing interacts with epigenetic mechanisms to regulate skeletal muscle mass, offering a novel perspective that enhances our understanding of epigenetic inheritance’s role and the regulatory network governing skeletal muscle atrophy. Collectively, advancements in the understanding of epigenetic mechanisms provide invaluable insights into the study of skeletal muscle atrophy. Moreover, this knowledge paves the way for identifying new avenues for the development of more effective therapeutic strategies and pharmaceutical interventions.
Exploring cost performance tradeoffs and uncertainties for electric- and autonomous electric trucks using computational experiments
Authors: Engholm Albin , Allström Andreas , Akbarian Mehdi 
Published: July 2024

AbstractThe recent development of battery electric trucks (BETs) suggests that they could play a vital role in transitioning to zero-emission road freight. To facilitate this transition, it is important to understand under which conditions BETs can be a viable alternative to internal combustion engine trucks (ICETs). Concurrently, the advancement of autonomous driving technology adds uncertainty and complexity to analyzing how the cost competitiveness of future zero-emissions trucks, such as autonomous electric trucks (AETs) may develop. This study examines the cost performance of BETs and AETs compared to ICETs, and how it varies over different market and technology conditions, charging strategies, and transport applications. Focus is on heavy-duty tractor-trailer trucks operating full truckload shuttle-flows in Sweden. Due to the inherent uncertainty and interactions among the analyzed factors, the analysis is performed as computational experiments using a simulation model of BET, AET, and ICET shuttle flow operations and associated costs. In total, 19,200 experiments are performed by sampling the model across 1200 scenarios representing various transport applications and technical and economic conditions for sixteen charging strategies with different combinations of depot, destination, and en route charging. The results indicate that both BETs and AETs are cost competitive compared to ICETs in a large share of scenarios. High asset utilization is important for offsetting additional investment costs in vehicles and chargers, highlighting the importance of deploying these vehicles in applications that enable high productivity. The cost performance for BETs is primarily influenced by energy related costs, charging strategy, and charging infrastructure utilization. The AET cost performance is in addition heavily affected by remote operations cost, and costs for the automated driving system. When feasible, relying only on depot charging is in many scenarios the most cost-effective charging strategy, with the primary exceptions being highly energy-demanding scenarios with long distances and heavy goods in which the required battery is too heavy to operate the truck within vehicle weight regulations if not complemented by destination, or en route charging. However, many experiments do not lead to a reduced payload capacity for BETs and AETs compared to ICETs, and a large majority of the considered scenarios are feasible to operate with a BET or AET within current gross vehicle weight regulations.
Gut microbiota regulation of T lymphocyte subsets during systemic lupus erythematosus
Authors: Lian Fen-Ping , Zhang Fen , Zhao Chun-Miao , Wang Xu-Xia , Bu Yu-Jie , Cen Xing , Zhao Gui-Fang , Zhang Sheng-Xiao , Chen Jun-Wei 
Published: July 2024

Abstract
Background
Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by disturbance of pro-inflammatory and anti-inflammatory lymphocytes. Growing evidence shown that gut microbiota participated in the occurrence and development of SLE by affecting the differentiation and function of intestinal immune cells. The purpose of this study was to investigate the changes of gut microbiota in SLE and judge its associations with peripheral T lymphocytes.

Methods
A total of 19 SLE patients and 16 HCs were enrolled in this study. Flow cytometry was used to detect the number of peripheral T lymphocyte subsets, and 16 s rRNA was used to detect the relative abundance of gut microbiota. Analyzed the correlation between gut microbiota with SLEDAI, ESR, ds-DNA and complement. SPSS26.0 software was used to analyze the experimental data. Mann–Whitney U test was applied to compare T lymphocyte subsets. Spearman analysis was used for calculating correlation.

Results
Compared with HCs, the proportions of Tregs (P = 0.001), Tfh cells (P = 0.018) and Naïve CD4 + T cells (P = 0.004) significantly decreased in SLE patients, and proportions of Th17 cells (P = 0.020) and γδT cells (P = 0.018) increased in SLE. The diversity of SLE patients were significantly decreased. Addition, there were 11 species of flora were discovered to be distinctly different in SLE group (P < 0.05). In the correlation analysis of SLE, Tregs were positively correlated with Ruminococcus2 (P = 0.042), Th17 cells were positively correlated with Megamonas (P = 0.009), γδT cells were positively correlated with Megamonas (P = 0.003) and Streptococcus (P = 0.004), Tfh cells were positively correlated with Bacteroides (P = 0.040), and Th1 cells were negatively correlated with Bifidobacterium (P = 0.005). As for clinical indicators, the level of Tregs was negatively correlated with ESR (P = 0.031), but not with C3 and C4, and the remaining cells were not significantly correlated with ESR, C3 and C4.

Conclusion
Gut microbiota and T lymphocyte subsets of SLE changed and related to each other, which may break the immune balance and affect the occurrence and development of SLE. Therefore, it is necessary to pay attention to the changes of gut microbiota and provide new ideas for the treatment of SLE.
LCP1 correlates with immune infiltration: a prognostic marker for triple-negative breast cancer
Authors: Pan Shuaikang , Wan Mengting , Jin Hongwei , Ning Ran , Zhang Jinguo , Han Xinghua 
Published: July 2024

Abstract
Objective
Triple-Negative Breast Cancer (TNBC) is known for its aggressiveness and treatment challenges due to the absence of ER, PR, and HER2 receptors. Our work emphasizes the prognostic value of LCP1 (Lymphocyte cytosolic protein 1), which plays a crucial role in cell processes and immune cell activity, to predict outcomes and guide treatments in TNBC.

Methods
We explored LCP1 as a potential biomarker in TNBC and investigated the mRNA and protein expression levels of LCP1. We investigated different databases, including GTEX, TCGA, GEO, cBioPortal and Kaplan-Meier Plotter. Immunohistochemistry on TNBC and benign tumor samples was performed to examine LCP1's relationship with patient clinical characteristics and macrophage markers. We also assessed survival rates, immune cell infiltration, and drug sensitivity related to LCP1 using various bioinformatics tools.

Results
The results indicated that LCP1 expression was higher in TNBC tissues compared to adjacent normal tissues. However, high expression of LCP1 was significantly associated with favorable survival outcomes in patients with TNBC. Enrichment analysis revealed that genes co-expressed with LCP1 were significantly enriched in various immune processes. LCP1 showed a positive correlation with the infiltration of resting dendritic cells, M1 macrophages, and memory CD4 T cells, and a negative correlation with M2 macrophages. Further analysis suggested a link between high levels of LCP1 and increased survival outcomes in cancer patients receiving immunotherapy.

Conclusion
LCP1 may serve as a potential diagnostic and prognostic biomarker for TNBC, which was closely associated with immune cell infiltration, particularly M1 and M2 macrophages. Our findings may provide valuable insights into immunotherapeutic strategies for TNBC patients.