bluuebunny/crossref_metadata_2025_split huggingface dataset:
An integrated “Engage & Evasion” approach for mononuclear phagocyte system escape and efficient extracellular vesicle therapy
Authors: Liu Hongman , Li Mengting , Xiang Bing , Yang Ziying , Cao Shiyu , Gong Wen , Li Jingjing , Zhou Wenjing , Ding Liang , Tang Qingsong , Wang Shengnan , Tang Jin , Fan Zixuan , He Ke , Jiang Xuan , Shen Zhenya , Chen Weiqian , Hui Jie 
Published: December 2024

AbstractIschemic diseases are major contributors to global morbidity and mortality, posing a substantial threat to human health. Extracellular vesicles (EVs) play an essential role in enhancing neovascularization in ischemic tissues, thereby facilitating tissue repair and regeneration. However, the utilization of EVs is hindered by their rapid uptake and clearance by the mononuclear phagocyte system (MPS), which markedly impedes their therapeutic efficacy and organ-specific accumulation. Notably, CD47, upon binding to signal regulatory protein alpha, initiates a “don’t eat me” signal, enabling immune evasion from the MPS. Our research has demonstrated that phagocytes predominantly engulf CD47low dendritic DC2.4 cell-derived EVs (DV), while engineered CD47high EVs (MV47) experience minimal ingestion. Leveraging these findings, we have developed a dual-faceted “Engage & Evasion” strategy. Initially, DVs were employed to saturate the MPS, serving as the “engage” component. Subsequently, MV47, fortified with CD47, was introduced for “evasion” purposes. This approach effectively minimized entrapment by the liver and spleen, boosted serum concentration, and enhanced final accumulation in non-MPS organs. In summary, our “Engage & Evasion” therapeutic strategy offers a promising avenue to enhance EV therapeutic potential against ischemic challenges through improved systemic distribution.
Metabolism-related proteins as biomarkers for predicting prognosis in polycystic ovary syndrome
Authors: Ding Nan , Wang Ruifang , Wang Peili , Wang Fang 
Published: December 2024

Abstract
Objective
The study aimed to explore the role of metabolism-related proteins and their correlation with clinical data in predicting the prognosis of polycystic ovary syndrome (PCOS).

Methods
This research involves a secondary analysis of proteomic data derived from endometrial samples collected from our study group, which includes 33 PCOS patients and 7 control subjects. A comprehensive identification and analysis of 4425 proteins were conducted to screened differentially expressed proteins (DEPs). Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were subsequently performed on the DEPs. To identify independent prognostic metabolism-related proteins, univariate Cox regression and LASSO regression were applied. The expression levels of these proteins were then used to develop a prognostic model, with their predictive accuracy evaluated through receiver operating characteristic (ROC) curves, decision curve analysis (DCA), and calibration curves. Furthermore, we also investigate the correlation between clinical data and prognostic proteins.

Results
The study identified 285 DEPs between the PCOS and control groups. GO enrichment analysis revealed significant involvement in metabolic processes, while KEGG pathway analysis highlighted pathways such as glycolysis/gluconeogenesis and glucagon signaling. Ten key metabolism-related proteins (ACSL5, ANPEP, CYB5R3, ENOPH1, GLS, GLUD1, LDHB, PLCD1, PYCR2, and PYCR3) were identified as significant predictors of PCOS prognosis. Patients were separated into high and low-risk groups according to the risk score. The ROC curves for predicting outcomes at 6, 28, and 37 weeks demonstrated excellent predictive performance, with AUC values of 0.98, 1.0, and 1.0, respectively. The nomogram constructed from these proteins provided a reliable tool for predicting pregnancy outcomes. DCA indicated a net benefit of the model across various risk thresholds, and the calibration curve confirmed the model’s accuracy. Additionally, we also found BMI exhibited a significant negative correlation with the expression of GLS (r =-0.44, p = 0.01) and CHO showed a significant positive correlation with the expression of LDHB (r = 0.35, p = 0.04).

Conclusion
The identified metabolism-related proteins provide valuable insights into the prognosis of PCOS. The protein based prognostic model offers a robust and reliable tool for risk stratification and personalized management of PCOS patients.
Trophic niche adaptation of mountain frogs around the Sichuan Basin: individual specialization and response to climate variations
Authors: Cui Kaiyue , Yang Shengnan , Hu Junhua 
Published: December 2024

Abstract
Background
Climatic and geographic variations have profound effects on the resource utilization of individuals and populations. Evaluating resource use in different environments is crucial for understanding species ecological adaptation strategies and promoting biodiversity conservation. Stable isotopes are widely used to assess trophic niches, providing quantitative indicators of ecological interactions between organisms and resource use in ecosystems. This study assesses the trophic niche traits of spiny-bellied frogs (Quasipaa boulengeri) in the marginal mountains of the Sichuan Basin in southwestern China using stable isotopes. Trophic niche variation under different time periods and environmental conditions is explored.

Results
The spiny-bellied frogs experienced a significant reduction in trophic niche width during the past breeding season. The populations in the northwestern Sichuan Basin had a greater trophic niche width than the southeastern populations, and their δ15N values showed a positive correlation with temperature seasonality and a negative correlation with annual precipitation. Despite differences between the northwestern and southeastern populations, there was a consistent trend of increased individual specialization with latitude in both the northwestern and southeastern regions.

Conclusions
Ontogenetic niche shifts and differences in trophic niche traits between the northwestern and southeastern populations indicate diverse adaptation strategies in mountain frogs. The findings underscore the impact of geographical and climate variations on the resource utilization of amphibians. In addition, patterns of individual specialization highlight the significance of considering intra- and interpopulational changes when studying ecological adaptation.
Accuracy deficits during robotic time-constrained reaching are related to altered prefrontal cortex activity in children with cerebral palsy
Authors: Khan Owais A. , Singh Tarkeshwar , Barany Deborah A. , Modlesky Christopher M. 
Published: December 2024

Abstract
Background
The prefrontal cortex (PFC) is an important node for action planning in the frontoparietal reaching network but its role in reaching in children with cerebral palsy (CP) is unexplored. This case–control study combines a robotic task with functional near-infrared spectroscopy (fNIRS) to concurrently assess reaching accuracy and PFC activity during time-constrained, goal-directed reaching in children with CP. We hypothesized that reaching accuracy in children with CP would be lower than in typically developing children and would be related to PFC activity.

Methods
Fourteen children with spastic CP (5-11 y; Manual Ability Classification System level I-II) and 14 age-, sex- and arm dominance-matched typically developing controls performed seated uniplanar reaches with a robotic arm (KINARM End-Point Lab) to hit visual targets projected onto a screen. Four blocks of 10 reaching trials each were performed for each arm. Time constraint (high, low) was varied across blocks by changing the time participants had to hit the target.

Results
Children with CP displayed lower reaching accuracy compared to controls, with greater deficits observed in the non-preferred arm (d = 1.916, p < 0.001) than the preferred arm (d = 1.033, p = 0.011). Inter-limb differences in accuracy were observed only in children with CP (d = 0.839, p < 0.001). PFC activity differed across groups during preferred arm reaching, with PFC deactivation observed in children with CP under high time constraints compared to PFC activation in controls (d = 1.086, p = 0.006). Children with CP also exhibited lower PFC activity under high time constraint compared to low time constraint in the preferred arm (d = 0.702, p = 0.001). PFC activity was positively related to reaching accuracy across time constraints in both arms in children with CP, but not in controls.

Conclusions
Contrasting patterns of PFC activity observed in children with CP compared to age- and sex-matched controls during a robotic reaching task lends support for the concurrent use of fNIRS and robotics to assess goal-directed reaching in CP.
Trial Registration: Data collected as part of a larger randomized controlled trial; https://clinicaltrials.gov/ct2/show/NCT03484078
Quality assurance of hyperspectral imaging systems for neural network supported plant phenotyping
Authors: Detring Justus , Barreto Abel , Mahlein Anne-Katrin , Paulus Stefan 
Published: December 2024

Abstract
Background
This research proposes an easy to apply quality assurance pipeline for hyperspectral imaging (HSI) systems used for plant phenotyping. Furthermore, a concept for the analysis of quality assured hyperspectral images to investigate plant disease progress is proposed. The quality assurance was applied to a handheld line scanning HSI-system consisting of evaluating spatial and spectral quality parameters as well as the integrated illumination. To test the spatial accuracy at different working distances, the sine-wave-based spatial frequency response (s-SFR) was analysed. The spectral accuracy was assessed by calculating the correlation of calibration-material measurements between the HSI-system and a non-imaging spectrometer. Additionally, different illumination systems were evaluated by analysing the spectral response of sugar beet canopies. As a use case, time series HSI measurements of sugar beet plants infested with Cercospora leaf spot (CLS) were performed to estimate the disease severity using convolutional neural network (CNN) supported data analysis.

Results
The measurements of the calibration material were highly correlated with those of the non-imaging spectrometer (r>0.99). The resolution limit was narrowly missed at each of the tested working distances. Slight sharpness differences within individual images could be detected. The use of the integrated LED illumination for HSI can cause a distortion of the spectral response at 677nm and 752nm. The performance for CLS diseased pixel detection of the established CNN was sufficient to estimate a reliable disease severity progression from quality assured hyperspectral measurements with external illumination.

Conclusion
The quality assurance pipeline was successfully applied to evaluate a handheld HSI-system. The s-SFR analysis is a valuable method for assessing the spatial accuracy of HSI-systems. Comparing measurements between HSI-systems and a non-imaging spectrometer can provide reliable results on the spectral accuracy of the tested system. This research emphasizes the importance of evenly distributed diffuse illumination for HSI. Although the tested system showed shortcomings in image resolution, sharpness, and illumination, the high spectral accuracy of the tested HSI-system, supported by external illumination, enabled the establishment of a neural network-based concept to determine the severity and progression of CLS. The data driven quality assurance pipeline can be easily applied to any other HSI-system to ensure high quality HSI.
Integrated analysis of metabolome, lipidome, and gut microbiome reveals the immunomodulation of Astragali radix in healthy human subjects
Authors: Gui Wan-Yu , Yin Jun-Gang , Liao Jian-Cheng , Luo Hui-Zhi , You Qing , Gong Jia-Hui , Xiang Jie , Zou Jian-Dong , Li Chang-Yin 
Published: December 2024

Abstract
Background
As a typical medicinal food homology species, Chinese herbal medicine Astragali radix (AR) has been widely used to regulate the human immune system worldwide. However, the human immunomodulation of AR and its corresponding mechanisms remain unclear.

Methods
First, following a fortnight successive AR administration, the changes in immune cytokines and immune cells from 20 healthy human subjects were used as immune indicators to characterize the immunomodulatory effects of AR. Subsequently, ultra-high-performance liquid chromatography coupled with quadrupole-time-of-flight mass spectrometry (UHPLC-Q-TOF/MS) based lipidomics and metabolomics analysis was performed on human serum, urine, and feces samples to investigate the changes in metabolic profiles. Then, 16S rRNA gene sequencing of feces samples was adopted for the changes of human gut microbiota. Finally, correlation analysis was conducted on the gut microbiome, metabolome/lipidome data, and immune indicators.

Results
AR displayed good safety in clinical use and posed a minor impact on gut microbiota major genera, global metabolic profiles, and immune cells. Meanwhile, AR could significantly up-regulate anti-inflammatory cytokines, down-regulate serum creatinine and pro-inflammatory cytokines, promote the anabolism of arginine, glycerolipid, sphingolipid, and purine, and the catabolism of phenylalanine and glycerophospholipid. Moreover, these AR-induced changes were closely correlated with significantly decreased Granulicatella, slightly higher Bifidobacterium, Ruminococcus, and Subdoligranulum, and slightly lower Blautia.

Conclusion
The study clearly demonstrated that AR could modulate the human immune, by modifying the metabolism of amino acids, lipids, and purines in a microbiota-related way.
Trial registration ChiCTR, ChiCTR2100054765. Registered 26 December 2021-Prospectively registered, https://www.chictr.org.cn/historyversionpub.html?regno=ChiCTR2100054765
Neuronal ceroid lipofuscinoses type 7 (CLN7): a case series reporting cross sectional and retrospective clinical data to evaluate validity of standardized tools to assess disease progression, quality of life, and adaptive skills
Authors: Kayani Saima , BordesEdgar Veronica , Lowden Andrea , Nettesheim Emily R. , Dahshi Hamza , Messahel Souad , Minassian Berge A. , Greenberg Benjamin M. 
Published: December 2024

Abstract
Background
This study evaluated the clinical characteristics of neuronal ceroid lipofuscinosis type 7 or CLN7 disease spectrum to characterize the clinical, electrophysiologic and neuroimaging phenotypes.

Methods
We performed a single-center cross sectional data collection along with retrospective medical chart review in patients with a genetic diagnosis of CLN7. This study received ethical approval by the University of Texas Southwestern Medical Center Institutional Review Board. A total of 8 patients were included between the ages of 4 to 6 years. All patients had a genetic diagnosis of CLN7 with homozygous or compound heterozygous mutations in the MFSD8 gene. The information collected includes patient demographics, developmental history, neurological events including seizures and neurodevelopmental regression along with further evaluation of brain magnetic resonance imaging and electrophysiological findings. The clinical phenotype is described through cross sectional and retrospective data collection and standardized tools assessing quality of life and functional skills.

Results
Our findings in this cohort of CLN7 patients indicated that development is initially normal with onset of clinical symptoms as early as two years of age. Language problems were noted prior to or at the onset of seizures in all cases. Gait problems were noted prior to seizure onset in 3 of 8 patients, and at or within 6 months after the onset of seizures in 5 of 8 patients. All patients followed a progressive course of language, motor, and neurocognitive deterioration. Congruent with the medical history, our patients had significantly low scores on adaptive abilities. Natural history data such as this can be used to support future clinical trial designs.

Conclusions
This study provides a comprehensive description of CLN7 disease, highlighting clinical data alongside standardized neuropsychological assessments, neuroimaging, and electrophysiologic data. It emphasizes the value of importance of standardized tools for understanding disease phenotype and their potential use as endpoints in future clinical trials. The findings established can provide a baseline for developing future prospective natural history studies and potential therapeutic clinical trials.
FOLR2+ macrophage depletion from intestinal metaplasia to early gastric cancer: single-cell sequencing insight into gastric cancer progression
Authors: He Yuxin , Wang Jiayu , Deng Zilin , Feng Huang , Du Mingzhan , Zhang Deqing , Zhang Guangbo , Shi Tongguo , Chen Weichang 
Published: December 2024

Abstract
Background
The immune landscape associated with different subtypes of intestinal metaplasia (IM) and early gastric cancer (EGC) remains unclear. This study aimed to investigate the immune landscape of complete intestinal metaplasia (CIM), incomplete intestinal metaplasia (IIM), and EGC, as well as the underlying mechanisms of EGC progression.

Methods
Gastric biopsy samples were collected from five patients with CIM, six patients with IIM, and four patients with EGC, followed by single-cell RNA sequencing. Multiplex immunohistochemical staining was employed to validate the samples from the aforementioned patients. To elucidate the potential mechanisms involved, in vitro coculture experiments were conducted using FOLR2+/FOLR2− macrophages and CD8+ T cells. Flow cytometry was utilized to investigate the biological functions of FOLR2+ macrophages in the progression of EGC.

Results
Five subpopulations of macrophages were identified in CIM, IIM and EGC samples. FOLR2+ macrophages possess antitumor immune potential, and the proportion of FOLR2+ macrophage gradually decreased from the CIM stage to the IIM and EGC stages. FOLR2+ macrophages were significantly positively correlated with CD8+ T cells and activated the cytotoxicity of CD8+ T cells via antigen cross-presentation. Additionally, during the progression of EGC, epithelial cells progressively upregulated APP expression, thus inducing necroptosis of FOLR2+ macrophages via the APP‒TNFRSF21 axis.

Conclusions
Our work provides an understanding of the potential mechanisms underlying the malignant transformation of IM mediated by FOLR2+ macrophages.

Graphical Abstract
Efficacy and safety of tofacitinib in an open-label, long-term extension study in patients with psoriatic arthritis who received adalimumab or tofacitinib in a Phase 3 randomized controlled study: a post hoc analysis
Authors: Gladman Dafna D. , Nash Peter , Mease Philip J. , FitzGerald Oliver , Duench Stephanie , Cadatal Mary Jane , Masri Karim R. 
Published: December 2024

Abstract
Background
Data on treatment switching directly from tumor necrosis factor inhibitors to tofacitinib in psoriatic arthritis (PsA) are limited. This post hoc analysis assessed efficacy and safety outcomes in patients with PsA who directly switched to tofacitinib in a long-term extension (LTE) study after receiving adalimumab (ADA) in a Phase 3 study, compared with those who continued to receive tofacitinib.

Methods
Patients with active PsA received tofacitinib 5 mg twice daily (BID) or ADA 40 mg once every 2 weeks in a 12-month, randomized, double-blind study (OPAL Broaden) and then continued or switched to tofacitinib 5 mg BID and maintained this dose in an open-label LTE study (OPAL Balance). Efficacy was assessed 3 months before the last visit and at the last visit in the Phase 3 study, and at month 3 (or month 6 for select outcomes) in the LTE study and included rates of ≥ 20/50/70% improvement in American College of Rheumatology response criteria, Psoriasis Area and Severity Index ≥ 75% improvement, Health Assessment Questionnaire-Disability Index (HAQ-DI) response (decrease from baseline ≥ 0.35 for patients with baseline HAQ-DI ≥ 0.35), Psoriatic Arthritis Disease Activity Score ≤ 3.2, and minimal disease activity; and change from baseline in Functional Assessment of Chronic Illness Therapy-Fatigue score. Safety was assessed at months 3 and 12 in both studies via incidence rates (patients with first events/100 patient-years).

Results
Overall, 180 patients were included (ADA→tofacitinib 5 mg BID: n = 91; continuing tofacitinib 5 mg BID: n = 89). At Phase 3 baseline, patients in the ADA→tofacitinib 5 mg BID group tended to be younger and have less active disease compared with those continuing tofacitinib. Efficacy was similar between groups in the Phase 3 study, and was maintained to month 3 or 6 in the LTE study. Treatment-emergent adverse events (AEs), serious AEs, and serious infections were generally similar in the Phase 3 and LTE studies, and between groups within each study.

Conclusion
Tofacitinib efficacy and safety were similar in patients with PsA who directly switched from ADA to tofacitinib and those who continued tofacitinib, suggesting that patients can be directly switched from ADA to tofacitinib without any washout period.

Trial registration
NCT01877668; NCT01976364
Evaluation of some fungicides for inhibiting proteolytic fungi isolated from leather binding of a historical manuscript dated back to the Mamluk period
Authors: Abdel-Hamied Mostafa , Abdelhafez Ahmed A. M. , Ahmed Rania F. , Abd-Alrahman Sherif H. , Abdel-Maksoud Gomaa 
Published: December 2024

Abstract
Fungi have an essential role in deterioration of historical leather bindings, leading to major problems in the preservative state of these artifacts. This study aims to evaluate the efficiency of some fungicides and nanoparticles materials against fungal activity of historical leather bindings. Historical leather binding from an illuminated paper manuscript dating back to the Mamluk period (1250–1516 AD) at the Al-Azhar library, Cairo, Egypt was examined for fungal infection, and isolation. Results of the present study showed, 21 fungal isolates were isolated and identified using morphological and molecular techniques as Alternaria alternate (5%), Aspergillus fumigatus (43%), Aspergillus niger (43%), Aspergillus terrus (5%), and Penicillium chrysogenum (5%). All fungal isolates exhibited proteolytic activity. Aspergillus niger (2–7) and Aspergillus fumigatus (3–4) achieved the highest proteolytic activity amongst obtained fungal strains. Seven fungicides, difenoconazole, propiconazole, azoxystrobin, pyraclostrobin, boscalid, dimethomorph, and thiophanate-methyl as individual active ingredient and two mixtures [difenoconazole combined with propiconazole (1:1)] and [boscalid combined with pyraclostrobin (2:1)] were evaluated at different concentrations against A. fumigatus and A. niger. Additionally, the effect of titanium and silicon dioxides nanoparticles, against the highest proteolytic fungi A. fumigatus and A. niger was evaluated. The fungal growth inhibition was assessed by the disc diffusion method (DDM). The results revealed that individual or mixed boscalid and pyraclostrobin fungicides at 300 ppm achieved the highest inhibition activity against A. fumigatus, but the linear diagram showed that individual boscalid and pyraclostrobin fungicides at 200 ppm was the ideal concentration for application with the leather samples in the future study. The mixture of boscalid + pyraclostrobin (2:1) exhibited the best preservation effect against A. niger achieving 65.9%, and 82.4% microbial inhibition at 150, and 300 ppm, respectively, followed by individual boscalid fungicide.