bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cargo-eliminated osteosarcoma-derived small extracellular vesicles mediating competitive cellular uptake for inhibiting pulmonary metastasis of osteosarcoma
Authors: Lin Shanyi , Shu Longqiang , Guo Yuhang , Yuan Ji , Zhang Juntao , Wang Yang , Yang Yunlong , Yuan Ting 
Published: June 2024

AbstractOsteosarcoma (OS) derived small extracellular vesicles (OS-sEVs) have been shown to induce the formation of cancer-associated fibroblasts (CAFs), characterized by elevated pro-inflammatory factor expression and enhanced migratory and contractile abilities. These CAFs play a crucial role in priming lung metastasis by orchestrating the pre-metastatic niche (PMN) in the lung. Disrupting the communication between OS-sEVs and lung fibroblasts (LFs) emerges as a potent strategy to hinder OS pulmonary metastasis. Our previously established saponin-mediated cargo-elimination strategy effectively reduces the cancer-promoting ability of tumor-derived small extracellular vesicles (TsEVs) while preserving their inherent targeting capability. In this study, we observed that cargo-eliminated OS-sEVs (CE-sEVs) display minimal pro-tumoral and LFs activation potential, yet retain their ability to target LFs. The uptake of OS-sEVs by LFs can be concentration-dependently suppressed by CE-sEVs, preventing the conversion of LFs into CAFs and thus inhibiting PMN formation and pulmonary metastasis of OS. In summary, this study proposes a potential strategy to prevent LFs activation, PMN formation in the lung, and OS pulmonary metastasis through competitive inhibition of OS-sEVs’ function by CE-sEVs.
Associations between a normal-range free thyroxine concentration and ovarian reserve in infertile women undergoing treatment via assisted reproductive technology
Authors: Zhang Qiaoling , Zhang Dandan , Liu Haoyuan , Fu Jinyun , Tang Li , Rao Meng 
Published: June 2024

Abstract
Background
Some recent studies have shown that female subclinical hypothyroidism (SCH) is associated with diminished ovarian reserve (DOR). In this study, we aimed to investigate whether serum-free thyroxine (fT4) concentrations within the reference range are associated with ovarian reserve in women.

Methods
This cross-sectional study included 4933 infertile women with normal-range fT4 concentrations who received assisted reproductive technology treatment in our clinic. The data of women in different fT4 concentration tertiles (namely 12–15.33, 15.34–18.67, and 18.68–22 pmol/L) were compared with ovarian reserve markers, namely the anti-Müllerian hormone (AMH) concentration, the antral follicle count (AFC), and the number of aspirated oocytes. The primary outcomes were the AMH concentration and the risk of DOR, diagnosed as an AMH concentration < 1.1 ng/mL.

Results
The average ages of women in the low-normal, middle-normal, and high-normal fT4 tertiles were 33.20 (standard deviation [SD]: 5.11), 32.33 (SD: 5.13), and 31.61 (SD: 5.10) years, respectively (p < 0.0001). AMH concentrations (adjusted mean: 3.32 [95% confidence interval {CI}: 3.16 to 3.50] vs. 3.51 [3.40 to 3.62] vs. 3.64 [3.50 to 3.80] ng/mL, p = 0.022) were significantly different between the fT4 concentration tertiles. The risk of DOR was significantly increased in the low-normal (adjusted odds ratio: 1.61 [95% CI: 1.01 to 2.58]) and middle-normal (1.47 [95% CI: 1.00 to 2.16]) tertiles compared with the high-normal tertile. Subgroup analysis showed that AMH concentrations were significantly different among the fT4 concentration tertiles in women aged < 35 years (adjusted mean: 3.94 [95% CI: 3.70 to 4.20] vs. 4.25 [4.11 to 4.39] vs. 4.38 [4.18 to 4.58], p = 0.028), whereas this difference was not significant in women aged ≥ 35 years (p = 0.534). The general additive models using fT4 as a continuous variable indicated that a lower fT4 concentration within the normal range was significantly associated with a lower AMH concentration (p = 0.027), a lower AFC (p = 0.018), a lower number of aspirated oocytes (p = 0.001), and a higher risk of DOR (p = 0.007).

Conclusion
Low-normal fT4 concentrations are associated with lower ovarian reserve in infertile women.
Single-cell landscape of immunological responses in elderly patients with sepsis
Authors: He Wanxue , Yao Chen , Wang Kaifei , Duan Zhimei , Wang Shuo , Xie Lixin 
Published: June 2024

AbstractSepsis is a dysregulated host response to severe infections, and immune dysfunction plays a crucial role in its pathogenesis. Elderly patients, a special population influenced by immunosenescence, are more susceptible to sepsis and have a worse prognosis. However, the immunopathogenic mechanisms underlying sepsis in elderly patients remain unclear. Here, we performed single-cell RNA sequencing of peripheral blood samples from young and old subjects and patients with sepsis. By exploring the transcriptional profiles of immune cells, we analyzed immune cell compositions, phenotype shifts, expression heterogeneities, and intercellular communication. In elderly patients with sepsis, innate immune cells (e.g., monocytes and DCs) exhibit decreased antigen presentation, presenting an overactive inflammatory and senescent phenotype. However, the immunophenotype of T cells shifted to characterize effector, memory, and exhaustion. Moreover, we identified strong interferon-γ responses of T cells in both aging and sepsis groups and a deranged inflammaging status in elderly sepsis patients. Tregs in elderly patients with sepsis showed increased abundance and enhanced immunosuppressive effects. In addition, metabolism-associated pathways were upregulated in T cells in elderly patients with sepsis, and the lysine metabolism pathway was enriched in Tregs. Cell–cell interaction analysis showed that the expression profile of ligand-receptor pairs was probably associated with aggravated immune dysfunction in elderly patients with sepsis. A novel HLA-KIR interaction was observed between Tregs and CD8 + T cells. These findings illustrate the immunological hallmarks of sepsis in elderly patients, and highlight that immunosuppressive and metabolic regulatory pathways may undergo important alterations in elderly patients with sepsis.
Ecological study of the reach of congregate vs. grab-and-go summer meals in New York City
Authors: Harb Amanda A. , Koch Pamela A. , Roberts Katherine J. , McGuirt Jared T. , Cadenhead Jennifer W. , Wolf Randi L. 
Published: June 2024

AbstractParticipation in school meals is associated with many benefits. However, participation in school meals served in the summer through the Summer Food Service Program (SFSP) is low due to many barriers, including program requirements such as congregate feeding. During COVID-19, these requirements were waived, allowing grab-and-go meals. The purpose of this study is to compare the number of SFSP breakfast and lunch meals served during the summers of grab-and-go meals (2020 and 2021) to prior summers of congregate feeding (2014–2019) in New York City (NYC). This study is an ecological study of NYC public school geographic districts (n = 32). The primary outcome is the total number of SFSP meals served per student. Using the repeated-measures ANOVA, the results show a significant increase in the number of SFSP meals served per student during the first summer (2020) of grab-and-go meals compared to summers 2016–2019 (p ≤ 0.01) but no significant differences during the second summer (2021) of grab-and-go meals compared to summers 2014–2019. However, there was a significant increase in the number of breakfast meals served in August per student during both the first and second summer of grab-and-go meals compared to summers 2014–2019 (p < 0.05). Among NYC public schools, the waivers may increase the reach of breakfast meals served in August, when there are fewer summer school activities. While there is a need for more research, policymakers may consider making waivers that allow grab-and-go meals permanent flexibilities for the SFSP to increase access to summer meals.
Risk of major mental disorders in the offspring of parents with migraine
Authors: Li Dian-Jeng , Tsai Shih-Jen , Chen Tzeng-Ji , Liang Chih-Sung , Chen Mu-Hong 
Published: June 2024

Abstract
Background
Migraine has been associated with mental disorders, however whether parental migraine is associated with an increased risk of major mental disorders (MMDs) in offspring has not been investigated. We aimed to examine the risk of the development of MMDs in the offspring of parents with migraine compared with those of parents without migraine.

Methods
This study used data derived from the Taiwan National Health Insurance Research Database. Offspring of parents with migraine and a control group consisting of offspring of parents without migraine matched for demographic and parental mental disorders were included. Cox regression was used to estimate the risk of MMDs, including schizophrenia, depressive disorder, bipolar disorder, autistic spectrum disorder (ASD), and attention deficit/hyperactivity disorder (ADHD). Sub-analyses stratified by the fathers and mothers were further performed to separately clarify the risks of MMDs among the offspring.

Results
We included 22,747 offspring of parents with migraine and 227,470 offspring of parents without migraine as the controls. Parental migraine was significantly associated with an increased risk of ADHD (reported as hazard ratios with 95% confidence intervals: 1.37, 1.25–1.50), bipolar disorder (1.35, 1.06–1.71), and depressive disorder (1.33, 1.21–1.47) compared to the offspring of parents without migraine. Importantly, sub-analyses showed that only maternal migraine was significantly associated with these risks.

Conclusions
Due to the heavy burden of MMDs, healthcare workers should be aware of the risk of MMDs in the offspring of parents with migraine, particular in mothers.
Combining the fractional order derivative and machine learning for leaf water content estimation of spring wheat using hyper-spectral indices
Authors: Zununjan Zinhar , Turghan Mardan Aghabey , Sattar Mutallip , Kasim Nijat , Emin Bilal , Abliz Abdugheni 
Published: June 2024

AbstractLeaf water content (LWC) is a vital indicator of crop growth and development. While visible and near-infrared (VIS–NIR) spectroscopy makes it possible to estimate crop leaf moisture, spectral preprocessing and multiband spectral indices have important significance in the quantitative analysis of LWC. In this work, the fractional order derivative (FOD) was used for leaf spectral processing, and multiband spectral indices were constructed based on the band-optimization algorithm. Eventually, an integrated index, namely, the multiband spectral index (MBSI) and moisture index (MI), is proposed to estimate the LWC in spring wheat around Fu-Kang City, Xinjiang, China. The MBSIs for LWC were calculated from two types of spectral data: raw reflectance (RR) and the spectrum based on FOD. The LWC was estimated by combining machine learning (K-nearest neighbor, KNN; support vector machine, SVM; and artificial neural network, ANN). The results showed that the fractional derivative pretreatment of spectral data enhances the implied information of the spectrum (the maximum correlation coefficient appeared using a 0.8-order differential) and increases the number of sensitive bands, especially in the near-infrared bands (700–1100 nm). The correlations between LWC and the two-band index (RVI1156, 1628 nm), three-band indices (3BI-3(766, 478, 1042 nm), 3BI-4(1129, 1175, 471 nm), 3BI-5(814, 929, 525 nm), 3BI-6(1156, 1214, 802 nm), 3BI-7(929, 851, 446 nm)) based on FOD were higher than that of moisture indices and single-band spectrum, with r of − 0.71**, 0.74**, 0.73**, − 0.72**, 0.75** and − 0.76** for the correlation. The prediction accuracy of the two-band spectral indices (DVI(698, 1274 nm) DVI(698, 1274 nm) DVI(698, 1274 nm)) was higher than that of the moisture spectral index, with R2 of 0.81 and R2 of 0.79 for the calibration and validation, respectively. Due to a large amount of spectral indices, the correlation coefficient method was used to select the characteristic spectral index from full three-band indices. Among twenty seven models, the FWBI-3BI− 0.8 order model performed the best predictive ability (with an R2 of 0.86, RMSE of 2.11%, and RPD of 2.65). These findings confirm that combining spectral index optimization with machine learning is a highly effective method for inverting the leaf water content in spring wheat.
LncRNA MAGI2-AS3 promotes fracture healing through downregulation of miR-223-3p
Authors: Dong Zhiqiang , Hu Bingbing , Wang Shantao , Wang Mingwei , Sun Shengliang , Liu Xinsheng , Li Danzhi , Wu Dengjiang 
Published: June 2024

Abstract
Background
Long non-coding RNAs (LncRNAs) are recognized as a pivotal element in the processes of fracture healing and the osteogenic differentiation of stem cells. This study investigated the molecular mechanism and regulatory significance of lncRNA MAGI2-AS3 (MAGI2-AS3) in fracture healing.

Methods
Serum levels of MAGI2-AS3 in patients with normal and delayed fracture healing were verified by RT-qPCR assays. The predictive efficacy of MAGI2-AS3 for delayed fracture healing was analyzed by ROC curve. Osteogenic markers were quantified by RT-qPCR assays. MC3T3-E1 cell viability was detected using CCK-8 assay, and flow cytometry was utilized to measure cell apoptosis. The dual-luciferase reporter gene assay was used to determine the targeted binding between MAGI2-AS3 and miR-223-3p.

Results
Serum MAGI2-AS3 expression was decreased in patients with delayed fracture healing compared with patients with normal healing. Elevated MAGI2-AS3 resulted in an upregulation of the proliferative capacity of MC3T3-E1 cells and a decrease in mortality, along with increased levels of both osteogenic markers. However, after transfection silencing MAGI2-AS3, the trend was reversed. Additionally, miR-223-3p was the downstream target of MAGI2-AS3 and was controlled by MAGI2-AS3. miR-223-3p mimic reversed the promoting effects of MAGI2-AS3 overexpression on osteogenic marker levels and cell growth, and induced cell apoptosis.

Conclusion
The upregulation of MAGI2-AS3 may expedite the healing of fracture patients by targeting miR-223-3p, offering a novel biomarker for diagnosing patients with delayed healing.
Exploring new frontiers: a rare case of catheter ablation for persistent atrial fibrillation in a patient with cor triatriatum sinister guided by intracardiac echocardiography
Authors: Lai Hengli , Wu Bo , Tao Yu , Ding Haiqiang , Liu Yanfeng , Zhu Zhiyun , Huang Xiantao , Li Hongyan , Xu Zhicheng , Chen Zhenhuan , Zhou Haiwen 
Published: June 2024

Abstract
Background
Cor triatriatum sinister (CTS) is an uncommon congenital cardiac anomaly. Atrial fibrillation (AF) is commonly the initial symptom in patients with CTS, occurring in approximately 32% of the cases. The complexity of performing AF catheter ablation, particularly in cases with persistent AF, increases in patients with CTS due to its unique structural challenges.

Case presentation
We report the treatment course of a 60-year-old male patient diagnosed with CTS, who underwent catheter ablation of drug-refractory, persistent AF. The complex anatomical structure of the condition made catheter ablation of AF challenging. To navigate these challenges, we performed comprehensive assessments using transthoracic echocardiography and transesophageal echocardiography, along with cardiac computed tomography angiography, prior to treatment initiation. The intricate anatomy of CTS was further clarified during the procedure via intracardiac echocardiography (ICE). Additionally, the complexity of catheter manipulation was further reduced with the aid of the VIZIGO sheath and the vein of Marshall ethanol infusion to achieve effective mitral isthmus blockage, thereby circumventing the impact of the CTS membrane.

Conclusions
This case underscores the complexity and potential of advanced ablation techniques in managing cardiac arrhythmias associated with unusual cardiac anatomies. During the procedure, ICE facilitated detailed modeling of the left atrium, including the membranous structure and its openings, thus providing a clearer understanding of CTS. It is noteworthy that the membrane within the CTS may serve as a potential substrate for arrhythmias, which warrants further validation through larger sample studies.
Clinical value of measuring plasma D-dimer levels in patients with esophageal cancer
Authors: Chen Hao , Xu Bindong , Zhang Qiang , Chen Pengfei 
Published: June 2024

Abstract
Background
Esophageal cancer represents a significant public health concern; however, reliable diagnostic and prognostic markers have not been established. This study aimed to investigate the clinical value of plasma D-dimer levels in patients with esophageal cancer.

Methods
Overall, 120 patients with esophageal cancer who underwent radical surgical resection at our department between January 2019 and 2020 were included (esophageal cancer group). Plasma D-dimer levels were measured preoperatively and on postoperative days 1 and 14. Additionally, 60 healthy participants (control group) with measured plasma D-dimer levels were included. The preoperative D-dimer levels and positive D-dimer test rates were compared between the groups. The 3-year survival rate in patients with esophageal cancer was calculated using the Kaplan–Meier method.

Results
Preoperative D-dimer concentration in the esophageal cancer group was (0.65 ± 0.859 µg/mL) significantly higher than that in the control group (0.32 ± 0.369 µg/mL). The positivity rate in the esophageal cancer group (35.0%, 42/120) was significantly higher than that in the control group (15%, 9/60). D-dimer concentrations were significantly higher 1 day postoperatively than preoperatively. Conversely, D-dimer concentrations were significantly lower 14 days postoperatively than preoperatively. Patients in the esophageal cancer group with plasma D-dimer concentrations ≤ 0.5 µg/mL had significantly higher 3-year survival rates than those with higher concentrations. In the logistic multivariate analysis, tumor pathological stage and preoperative plasma D-dimer levels were independent prognostic factors of 3-year survival rates in patients with esophageal cancer.

Conclusion
Plasma D-dimer concentrations are clinically valuable in esophageal cancer diagnosis, postoperative recurrence monitoring, and prognosis prediction.
An international survey assessing the effects of the duration of attack-free period on health-related quality of life for patients with hereditary angioedema
Authors: Itzler Robbin , Lumry William R. , Sears John , Braverman Julia , Li Yinglei , Brennan Caroline J. , Koch Gary G. 
Published: June 2024

Abstract
Background
Hereditary angioedema (HAE) is characterized by unpredictable and often severe cutaneous and mucosal swelling that affects the extremities, face, larynx, gastrointestinal tract, or genitourinary area. Introduction of novel long-term prophylactic treatment options (lanadelumab, berotralstat, and C1-esterase inhibitor SC [human]) into the treatment armamentarium has substantially reduced HAE attacks, allowing patients to be attack free for longer with improvements to their quality of life. Using data drawn from a wide-ranging survey of patients with HAE, we examined the relationship between duration of time attack free and health-related quality of life (HRQoL), exploring the possibility that there is an association between observed improvement in HRQoL and attack-free duration.

Methods
A survey among patients with HAE on long-term prophylaxis (LTP) in six countries (the US, Australia, Canada, UK, Germany, and Japan) assessed the relationship between attack-free duration and mean Angioedema Quality of Life (AE-QoL) scores, quality of life benefits, and rescue medication used. Analysis of covariance (ANCOVA) was used to assess the roles of LTP and attack-free period (< 1 month, 1– < 6 months, ≥ 6 months) on total AE-QoL scores. Results include descriptive p-values for strength of association, without control for multiplicity. Descriptive statistics were used to show the relationship between time attack free and quality of life benefits.

Results
Longer durations of time for which participants reported being attack free at the time of the survey correlated with better AE-QoL scores and less use of rescue medication. The mean total AE-QoL scores were 51.8, 33.2, and 19.9 for those who reported having been attack free for < 1 month, 1– < 6 months, and ≥ 6 months, respectively, with higher scores reflecting more impairment. The ANCOVA results showed a strong association between attack-free duration and AE-QoL total score.

Conclusion
This study shows that longer attack-free duration has an influential role for better HRQoL in patients receiving LTP. Prolonging the attack-free period is an important goal of therapy and recent advances in LTP have increased attack-free duration. However, opportunities exist for new treatments to further increase attack-free duration and improve HRQoL for all patients with HAE.
Cytoplasmic TP53INP2 acts as an apoptosis partner in TRAIL treatment: the synergistic effect of TRAIL with venetoclax in TP53INP2-positive acute myeloid leukemia
Authors: Ren Jun , Huang Junpeng , Yang Zailin , Sun Minghui , Yang Jing , Lin Can , Jin Fangfang , Liu Yongcan , Tang Lisha , Hu Jiayuan , Wei Xingyu , Chen Xinyi , Yuan Zihao , Yang Zesong , Chen Yanmeng , Zhang Ling 
Published: June 2024

Abstract
Background
Acute myeloid leukemia (AML) is a hematopoietic malignancy with poor outcomes, especially in older AML patients. Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is considered a promising anticancer drug because it selectively induces the extrinsic apoptosis of tumor cells without affecting normal cells. However, clinical trials have shown that the responses of patients to TRAIL are significantly heterogeneous. It is necessary to explore predictable biomarkers for the preselection of AML patients with better responsiveness to TRAIL. Here, we investigated the critical role of tumor protein p53 inducible nuclear protein 2 (TP53INP2) in the AML cell response to TRAIL treatment.

Methods
First, the relationship between TP53INP2 and the sensitivity of AML cells to TRAIL was determined by bioinformatics analysis of Cancer Cell Line Encyclopedia datasets, Cell Counting Kit-8 assays, flow cytometry (FCM) and cell line-derived xenograft (CDX) mouse models. Second, the mechanisms by which TP53INP2 participates in the response to TRAIL were analyzed by Western blot, ubiquitination, coimmunoprecipitation and immunofluorescence assays. Finally, the effect of TRAIL alone or in combination with the BCL-2 inhibitor venetoclax (VEN) on cell survival was explored using colony formation and FCM assays, and the effect on leukemogenesis was further investigated in a patient-derived xenograft (PDX) mouse model.

Results
AML cells with high TP53INP2 expression were more sensitive to TRAIL in vitro and in vivo. Gain- and loss-of-function studies demonstrated that TP53INP2 significantly enhanced TRAIL-induced apoptosis, especially in AML cells with nucleophosmin 1 (NPM1) mutations. Mechanistically, cytoplasmic TP53INP2 maintained by mutant NPM1 functions as a scaffold bridging the ubiquitin ligase TRAF6 to caspase-8 (CASP 8), thereby promoting the ubiquitination and activation of the CASP 8 pathway. More importantly, simultaneously stimulating extrinsic and intrinsic apoptosis signaling pathways with TRAIL and VEN showed strong synergistic antileukemic activity in AML cells with high levels of TP53INP2.

Conclusion
Our findings revealed that TP53INP2 is a predictor of responsiveness to TRAIL treatment and supported a potentially individualized therapeutic strategy for TP53INP2-positive AML patients.