bluuebunny/crossref_metadata_2025_split huggingface dataset:
Potential crosstalk between SPP1 + TAMs and CD8 + exhausted T cells promotes an immunosuppressive environment in gastric metastatic cancer
Authors: Du Yan , Lin Yilin , Gan Lin , Wang Shuo , Chen Shuang , Li Chen , Hou Sen , Hu Bozhi , Wang Bo , Ye Yingjiang , Shen Zhanlong 
Published: February 2024

Abstract
Background
Immunotherapy brings new hope to patients with advanced gastric cancer. However, liver metastases can reduce the efficacy of immunotherapy in patients. Tumor-associated macrophages (TAMs) may be the cause of this reduction in efficacy. SPP1 + TAMs are considered to have immunosuppressive properties. We aimed to investigate the involvement of SPP1 + TAMs in the metastasis of gastric cancer.

Methods
The single-cell transcriptome was combined with batched BULK datasets for analysis. Animal models were used to verify the analysis results.

Results
We reveal the interaction of SPP1 + TAMs with CD8 + exhausted T cells in metastatic cancer. Among these interactions, GDF15-TGFBR2 may play a key immunosuppressive role. We constructed an LR score to quantify interactions based on ligands and receptors. The LR score is highly correlated with various immune features and clinical molecular subtypes. The LR score may also guide the prediction of the efficacy of immunotherapy and prognosis.

Conclusions
The crosstalk between SPP1 + TAMs and CD8 + exhausted T cells plays a key immunosuppressive role in the gastric metastatic cancer microenvironment.

Graphical Abstract
Prevention of neointimal hyperplasia after coronary artery bypass graft via local delivery of sirolimus and rosuvastatin: network pharmacology and in vivo validation
Authors: Ryu Ji-yeon , Jang Eui Hwa , Lee JiYong , Kim Jung-Hwan , Youn Young-Nam 
Published: February 2024

Abstract
Background
Coronary artery bypass graft (CABG) is generally used to treat complex coronary artery disease. Treatment success is affected by neointimal hyperplasia (NIH) of graft and anastomotic sites. Although sirolimus and rosuvastatin individually inhibit NIH progression, the efficacy of combination treatment remains unknown.

Methods
We identified cross-targets associated with CABG, sirolimus, and rosuvastatin by using databases including DisGeNET and GeneCards. GO and KEGG pathway enrichment analyses were conducted using R studio, and target proteins were mapped in PPI networks using Metascape and Cytoscape. For in vivo validation, we established a balloon-injured rabbit model by inducing NIH and applied a localized perivascular drug delivery device containing sirolimus and rosuvastatin. The outcomes were evaluated at 1, 2, and 4 weeks post-surgery.

Results
We identified 115 shared targets between sirolimus and CABG among databases, 23 between rosuvastatin and CABG, and 96 among all three. TNF, AKT1, and MMP9 were identified as shared targets. Network pharmacology predicted the stages of NIH progression and the corresponding signaling pathways linked to sirolimus (acute stage, IL6/STAT3 signaling) and rosuvastatin (chronic stage, Akt/MMP9 signaling). In vivo experiments demonstrated that the combination of sirolimus and rosuvastatin significantly suppressed NIH progression. This combination treatment also markedly decreased the expression of inflammation and Akt signaling pathway-related proteins, which was consistent with the predictions from network pharmacology analysis.

Conclusions
Sirolimus and rosuvastatin inhibited pro-inflammatory cytokine production during the acute stage and regulated Akt/mTOR/NF-κB/STAT3 signaling in the chronic stage of NIH progression. These potential synergistic mechanisms may optimize treatment strategies to improve long-term patency after CABG.

Graphical Abstract
A single-domain antibody for the detection of pathological Tau protein in the early stages of oligomerization
Authors: De Leiris Nicolas , Perret Pascale , Lombardi Charlotte , Gözel Bülent , Chierici Sabine , Millet Philippe , Debiossat Marlène , Bacot Sandrine , Tournier Benjamin B. , Chames Patrick , Lenormand Jean-Luc , Ghezzi Catherine , Fagret Daniel , Moulin Marcelle 
Published: February 2024

Abstract
Background
Soluble oligomeric forms of Tau protein have emerged as crucial players in the propagation of Tau pathology in Alzheimer’s disease (AD). Our objective is to introduce a single-domain antibody (sdAb) named 2C5 as a novel radiotracer for the efficient detection and longitudinal monitoring of oligomeric Tau species in the human brain.

Methods
The development and production of 2C5 involved llama immunization with the largest human Tau isoform oligomers of different maturation states. Subsequently, 2C5 underwent comprehensive in vitro characterization for affinity and specificity via Enzyme-Linked Immunosorbent Assay and immunohistochemistry on human brain slices. Technetium-99m was employed to radiolabel 2C5, followed by its administration to healthy mice for biodistribution analysis.

Results
2C5 exhibited robust binding affinity towards Tau oligomers (Kd = 6.280 nM ± 0.557) and to Tau fibers (Kd = 5.024 nM ± 0.453), with relatively weaker binding observed for native Tau protein (Kd = 1791 nM ± 8.714) and amyloid peptide (Kd > 10,000 nM). Remarkably, this SdAb facilitated immuno-histological labeling of pathological forms of Tau in neurons and neuritic plaques, yielding a high-contrast outcome in AD patients, closely mirroring the performance of reference antibodies AT8 and T22. Furthermore, 2C5 SdAb was successfully radiolabeled with 99mTc, preserving stability for up to 6 h post-radiolabeling (radiochemical purity > 93%). However, following intravenous injection into healthy mice, the predominant uptake occurred in kidneys, amounting to 115.32 ± 3.67, 97.70 ± 43.14 and 168.20 ± 34.52% of injected dose per gram (% ID/g) at 5, 10 and 45 min respectively. Conversely, brain uptake remained minimal at all measured time points, registering at 0.17 ± 0.03, 0.12 ± 0.07 and 0.02 ± 0.01% ID/g at 5, 10 and 45 min post-injection respectively.

Conclusion
2C5 demonstrates excellent affinity and specificity for pathological Tau oligomers, particularly in their early stages of oligomerization. However, the current limitation of insufficient blood–brain barrier penetration necessitates further modifications before considering its application in nuclear medicine imaging for humans.
Development, implementation, and evaluation of the effectiveness of an intervention program to improve the sexual competence of young adult women about to get married: a protocol study
Authors: Mousavi Zahra Sadat , Janighorban Mojgan , Noroozi Mahnaz 
Published: February 2024

AbstractBackgroundHaving competence in initiating sexual interactions is one of the challenges of sexual health in any society. Given that the social, cultural, and religious background of some societies can prevent the acquisition of sexual competence in young women, this study will be done to design, implement, and determine the effectiveness of an intervention program to improve the sexual competence of young women on the eve of marriage.MethodsThe current research is a mixed-method study in a qualitative-quantitative sequence. In the first phase, a qualitative study will be conducted to explore the needs of sexual competence in young adult women about to get married and ways to improve it. Then, after the literature review and combining it with the results of the qualitative study, a draft of the intervention program will be developed. After reviewing the content of the program and validating it in the panel of experts, the final program will be developed. In the second phase, the effect of the program to promote the sexual competence of adult women about to get married will be determined in a quantitative study with a two-group quasi-experimental method.DiscussionProviding a comprehensive and practical intervention program to promote sexual competence based on cultural, social, and religious background can help to improve the quality of sexual interactions of young women about to get married, reduce harm caused by lack of sexual competence, and ensure women’s sexual health.
Intraoperative capsule protection can reduce the potential risk of adjacent segment degeneration acceleration biomechanically: an in silico study
Authors: Huang Fei , Huang Gang , Jia Junpengli , Lu Shihao , Li Jingchi 
Published: February 2024

Abstract
Background
The capsule of the zygapophyseal joint plays an important role in motion segmental stability maintenance. Iatrogenic capsule injury is a common phenomenon in posterior approach lumbar interbody fusion operations, but whether this procedure will cause a higher risk of adjacent segment degeneration acceleration biomechanically has yet to be identified.

Methods
Posterior lumbar interbody fusion (PLIF) with different grades of iatrogenic capsule injury was simulated in our calibrated and validated numerical model. By adjusting the cross-sectional area of the capsule, different grades of capsule injury were simulated. The stress distribution on the cranial motion segment was computed under different loading conditions to judge the potential risk of adjacent segment degeneration acceleration.

Results
Compared to the PLIF model with an intact capsule, a stepwise increase in the stress value on the cranial motion segment can be observed with a step decrease in capsule cross-sectional areas. Moreover, compared to the difference between models with intact and slightly injured capsules, the difference in stress values was more evident between models with slight and severe iatrogenic capsule injury.

Conclusion
Intraoperative capsule protection can reduce the potential risk of adjacent segment degeneration acceleration biomechanically, and iatrogenic capsule damage on the cranial motion segment should be reduced to optimize patients’ long-term prognosis.
m1A-Ensem: accurate identification of 1-methyladenosine sites through ensemble models
Authors: Suleman Muhammad Taseer , Alturise Fahad , Alkhalifah Tamim , Khan Yaser Daanial 
Published: February 2024

Abstract
Background
1-methyladenosine (m1A) is a variant of methyladenosine that holds a methyl substituent in the 1st position having a prominent role in RNA stability and human metabolites.

Objective
Traditional approaches, such as mass spectrometry and site-directed mutagenesis, proved to be time-consuming and complicated.

Methodology
The present research focused on the identification of m1A sites within RNA sequences using novel feature development mechanisms. The obtained features were used to train the ensemble models, including blending, boosting, and bagging. Independent testing and k-fold cross validation were then performed on the trained ensemble models.

Results
The proposed model outperformed the preexisting predictors and revealed optimized scores based on major accuracy metrics.

Conclusion
For research purpose, a user-friendly webserver of the proposed model can be accessed through https://taseersuleman-m1a-ensem1.streamlit.app/.
Comparative analysis of the Potter Tower and a new Track Sprayer for the application of residual sprays in the laboratory
Authors: Bonds Jane , Parsons George , Walker Kyle J. , Murphy Annabel , Lees Rosemary Susan , Nimmo Derric , Clayton John , Malone David 
Published: February 2024

Abstract
Background
Efforts to evaluate the residual efficacy of new indoor residual spraying (IRS) formulations have identified limitations with the industry standard laboratory sprayer, the Potter Spray Tower (PT). Calibrating the PT can be time-consuming, and the dosing of surfaces may not be as accurate or uniform as previously assumed.

Methods
To address these limitations, the Micron Horizontal Track Sprayer with Spray Cabinet (TS) was developed to provide higher efficiency, ease of operation and deposition uniformity equal to or better than the PT. A series of studies were performed using a fluorescent tracer and three IRS formulations (Actellic® 300CS, K-Othrine WG250 and Suspend PolyZone) sprayed onto surfaces using either the PT or the TS.

Results
Deposition volumes could be accurately calibrated for both spray systems. However, the uniformity of spray deposits was higher for the TS compared to the PT. Less than 12% of the volume sprayed using the PT reaches the target surface, with the remaining 88% unaccounted for, presumably vented out of the fume hood or coating the internal surfaces of the tower. In contrast, the TS deposits most of the spray on the floor of the spray chamber, with the rest contained therein. The total sprayed surface area in one run of the TS is 1.2 m2, and the operational zone for spray target placement is 0.7 m2, meaning that 58% of the applied volume deposits onto the targets. The TS can treat multiple surfaces (18 standard 15 × 15 cm tiles) in a single application, whereas the PT treats one surface at a time and a maximum area of around 0.0225 m2. An assessment of the time taken to perform spraying, including the setup, calibration and cleaning, showed that the cost of application using the TS was around 25–35 × less per tile sprayed. Standard operating procedures (SOPs) for calibration and use of both the Potter Tower and Track Sprayer have been developed.

Conclusions
Overall, the TS represents a significant improvement over the PT in terms of the efficiency and accuracy of IRS formulation applications onto test substrates and offers a useful additional tool for researchers and manufacturers wanting to screen new active ingredients or evaluate the efficacy of IRS or other sprayable formulations for insect control.

Graphical Abstract
Epigenome-wide association study of dietary fatty acid intake
Authors: Lange de Luna Julia , Nounu Aayah , Neumeyer Sonja , Sinke Lucy , Wilson Rory , Hellbach Fabian , Matías-García Pamela R. , Delerue Thomas , Winkelmann Juliane , Peters Annette , Thorand Barbara , Beekman Marian , Heijmans Bastiaan T. , Slagboom Eline , Gieger Christian , Linseisen Jakob , Waldenberger Melanie 
Published: February 2024

Abstract
Background
Dietary intake of n-3 polyunsaturated fatty acids (PUFA) may have a protective effect on the development of cardiovascular diseases, diabetes, depression and cancer, while a high intake of n-6 PUFA was often reported to be associated with inflammation-related traits. The effect of PUFAs on health outcomes might be mediated by DNA methylation (DNAm). The aim of our study is to identify the impact of PUFA intake on DNAm in the Cooperative Health Research in the Region of Augsburg (KORA) FF4 cohort and the Leiden Longevity Study (LLS).

Results
DNA methylation levels were measured in whole blood from the population-based KORA FF4 study (N = 1354) and LLS (N = 448), using the Illumina MethylationEPIC BeadChip and Illumina HumanMethylation450 array, respectively. We assessed associations between DNAm and intake of eight and four PUFAs in KORA and LLS, respectively. Where possible, results were meta-analyzed.
Below the Bonferroni correction threshold (p < 7.17 × 10–8), we identified two differentially methylated positions (DMPs) associated with PUFA intake in the KORA study. The DMP cg19937480, annotated to gene PRDX1, was positively associated with docosahexaenoic acid (DHA) in model 1 (beta: 2.00 × 10–5, 95%CI: 1.28 × 10–5-2.73 × 10–5, P value: 6.98 × 10–8), while cg05041783, annotated to gene MARK2, was positively associated with docosapentaenoic acid (DPA) in our fully adjusted model (beta: 9.80 × 10–5, 95%CI: 6.25 × 10–5-1.33 × 10–4, P value: 6.75 × 10–8). In the meta-analysis, we identified the CpG site (cg15951061), annotated to gene CDCA7L below Bonferroni correction (1.23 × 10–7) associated with eicosapentaenoic acid (EPA) intake in model 1 (beta: 2.00 × 10–5, 95% CI: 1.27 × 10–5–2.73 × 10–5, P value = 5.99 × 10–8) and we confirmed the association of cg19937480 with DHA in both models 1 and 2 (beta: 2.07 × 10–5, 95% CI: 1.31 × 10–5–2.83 × 10–5, P value = 1.00 × 10–7 and beta: 2.19 × 10–5, 95% CI: 1.41 × 10–5–2.97 × 10–5, P value = 5.91 × 10–8 respectively).

Conclusions
Our study identified three CpG sites associated with PUFA intake. The mechanisms of these sites remain largely unexplored, highlighting the novelty of our findings. Further research is essential to understand the links between CpG site methylation and PUFA outcomes.
New score to predict COVID-19 progression in vaccine and early treatment era: the COVID-19 Sardinian Progression Score (CSPS)
Authors: De Vito Andrea , Saderi Laura , Colpani Agnese , Puci Mariangela V. , Zauli Beatrice , Fiore Vito , Fois Marco , Meloni Maria Chiara , Bitti Alessandra , Moi Giulia , Maida Ivana , Babudieri Sergio , Sotgiu Giovanni , Madeddu Giordano 
Published: February 2024

Abstract
Background
Several scores aimed at predicting COVID-19 progression have been proposed. As the variables vaccination and early SARS-CoV-2 treatment were systematically excluded from the prognostic scores, the present study's objective was to develop a new model adapted to the current epidemiological scenario.

Methods
We included all patients evaluated by the Infectious Disease Unit in Sassari, with SARS-CoV-2 infection and without signs of respiratory failure at the first evaluation (P/F > 300). Disease progression was defined by the prescription of supplemental oxygen. In addition, variables related to demographics, vaccines, comorbidities, symptoms, CT scans, blood tests, and therapies were collected. Multivariate logistic regression modelling was performed to determine factors associated with progression; any variable with significant univariate test or clinical relevance was selected as a candidate for multivariate analysis. Hosmer–Lemeshow (HL) goodness of fit statistic was calculated. Odds ratio values were used to derive an integer score for developing an easy-to-use progression risk score. The discrimination performance of the risk index was determined using the AUC, and the best cut-off point, according to the Youden index, sensitivity, specificity, predictive value, and likelihood ratio, was chosen.

Results
1145 patients [median (IQR) age 74 (62–83) years; 53.5% males] were enrolled; 336 (29.3%) had disease progression. Patients with a clinical progression were older and showed more comorbidities; furthermore, they were less vaccinated and exposed to preventive therapy. In the multivariate logistic regression analysis, age ≥ 60 years, COPD, dementia, haematological tumours, heart failure, exposure to no or one vaccine dose, fever, dyspnoea, GGO, consolidation, ferritin, De Ritis ≥ 1.2, LDH, and no exposure to early anti-SARS-CoV-2 treatment were associated with disease progression. The final risk score ranged from 0 to 45. The ROC curve analysis showed an AUC of 0.92 (95% CI 0.90–0.93) with a 93.7% specificity and 72.9% sensitivity. Low risk was defined when the cut-off value was less than 23. Three risk levels were identified: low (0–23 points), medium (24–35), and high (≥ 36).

Conclusions
The proportion of patients with progression increases with high scores: the assessment of the risk could be helpful for clinicians to plan appropriate therapeutic strategies.
Smallpox and the Choctaw Civil War
Authors: Sparacio Matthew J. 
Published: February 2024

Abstract
The presence of chilakwa (smallpox) in Choctaw villages between 1747 and 1748 complicated factionalism and civil war. Utilizing Sharla Fett’s approach to health culture—defined as “the social relations of healing”—this article outlines how eighteenth-century Choctaws arrived at acceptable contingency plans when faced with illness and argues that community responses to smallpox helped ease factional tensions. Iksa (moiety) obligations for funeral rites—embodying the notion of iyyi kowa (generosity)—bridged political differences, accounting for a period of collaboration between groups best understood as the “smallpox peace.” Smallpox, therefore, surprisingly did not immediately contribute to political instability, although its indirect consequences proved significant during later stages of the civil war. Choctaw health culture informed individual and communal responses to chilakwa, which in turn shaped Choctaw factionalism.
Indigenous People and Smallpox in Argentina’s Desert Campaign, 1879–1881
Authors: Christensen Robert 
Published: February 2024

Abstract
Argentina’s 1879–85 Desert Campaign formed the basis for dispossessing the Indigenous community of its southern frontier. This article argues that the Desert Campaign should be understood as much as an epidemiological event as a military one, focusing on the most intense phase of a smallpox epidemic that ravaged communities of Indigenous survivors. More lives were lost to smallpox than to combat, particularly as the disease permeated prisoner camps. A general lack of concern for the health of Indigenous prisoners punctuated their experience of dispossession at the hands of the Argentine army and “distribution” into forced labor systems throughout the country.
Gaze tracking of large-billed crows (Corvus macrorhynchos) in a motion capture system
Authors: Itahara Akihiro , Kano Fumihiro 
Published: February 2024

ABSTRACT
Previous studies often inferred the focus of a bird's attention from its head movements because it provides important clues about their perception and cognition. However, it remains challenging to do so accurately, as the details of how they orient their visual field toward the visual targets remain largely unclear. We thus examined visual field configurations and the visual field use of large-billed crows (Corvus macrorhynchos Wagler 1827). We used an established ophthalmoscopic reflex technique to identify the visual field configuration, including the binocular width and optical axes, as well as the degree of eye movement. A newly established motion capture system was then used to track the head movements of freely moving crows to examine how they oriented their reconstructed visual fields toward attention-getting objects. When visual targets were moving, the crows frequently used their binocular visual fields, particularly around the projection of the beak-tip. When the visual targets stopped moving, crows frequently used non-binocular visual fields, particularly around the regions where their optical axes were found. On such occasions, the crows slightly preferred the right eye. Overall, the visual field use of crows is clearly predictable. Thus, while the untracked eye movements could introduce some level of uncertainty (typically within 15 deg), we demonstrated the feasibility of inferring a crow's attentional focus by 3D tracking of their heads. Our system represents a promising initial step towards establishing gaze tracking methods for studying corvid behavior and cognition.