bluuebunny/crossref_metadata_2025_split huggingface dataset:
Multiplexed evaluation of immunity against SARS-CoV-2 variants using surface enhanced fluorescence from a nanostructured plasmonic chip
Authors: Hu Ruibin , Yang Yang , Liu Ying , Liao Tao , Liu Yiyi , Tang Jiahu , Wang Guanghui , Wang Guoxin , Liang Yongye , Yuan Jing , Zhang Bo 
Published: December 2022

AbstractGenerated by the immune system post-infection or through vaccination, the effectiveness of antibodies against emerging SARS-CoV-2 variants is crucial for protecting individuals from the COVID-19 pandemic. Herein, a platform for the multiplexed evaluation of SARS-CoV-2 neutralizing antibodies against various variants was designed on the basis of near-infrared (NIR) surface enhanced fluorescence by nano-plasmonic gold chip (pGOLD). Antibody level across variants (Wild-type, Alpha, Beta, Delta, Omicron) was confirmed by the sera from recovered-individuals who were unvaccinated and had infected with Wild-type, Delta, Omicron variants. However, the neutralizing activity against Omicron variant was markedly decreased for individuals infected by Wild-type (~ 5.6-fold) and Delta variant (~ 19.1-fold). To the opposite, neutralizing antibody from individuals recovered from Omicron variant infection showed weak binding strength against non-Omicron variants. Antibody evolution over time was studied with individuals 196–530 days post Wild-type infection. Decreasing IgG antibody titer accompanied by increasing IgG binding avidity with elongated post-infection period were observed for the sera from Wild-type recovered-individuals with different post-infection times, suggesting that after the primary infection, a great number of antibodies were generated and then gradually decreased, while the antibody matured over time. By comparing the IgG level of individuals vaccinated for 27–51 days with individual post-infection, we found that ca. 1 month after two doses of vaccination, the antibody level was comparable to that of 500 days post-infection, and vaccination could enhance IgG avidity more efficiently. This work demonstrated a platform for the multiplexed, high-throughput and rapid screening of acquired immunity against SARS-CoV-2 variants, providing a new approach for the analysis of vaccine effectiveness, immunity against emerging variants, and related serological study.
Graphical Abstract
Adherence to Canadian 24-Hour Movement Guidelines among infants and associations with development: a longitudinal study
Authors: Carson Valerie , Zhang Zhiguang , Predy Madison , Pritchard Lesley , Hesketh Kylie D. 
Published: December 2022

Abstract
Background
To examine: 1) longitudinal adherence to the Canadian 24-Hour Movement Guidelines in a sample of infants and 2) associations between adherence to the guidelines over time and development.

Methods
Participants were 250 parent-infant dyads from the Early Movers project in Edmonton, Alberta. At 2, 4, and 6 months of age, physical activity, sedentary behaviour, sleep, and development were measured with a parental questionnaire that included items from the Ages & Stages Questionnaire (ASQ-3). Parents also reported the dates six major gross motor milestones were acquired during the first 18 months of life according to World Health Organization criteria. In a sub-sample (n = 93), movement behaviours were also measured with a time-use diary at 2, 4, and 6 months and gross motor development was measured by a physiotherapist using the Alberta Infant Motor Scale (AIMS) at 6 months. Guideline adherence was defined as: 1) ≥ 30 min/day of tummy time, 2) no screen time, some reading time, no restrained bouts > 1 h (time-use diary only), and 3) 14–17 h (2 months) or 12–16 h (4 and 6 months) of sleep per 24-h period. Generalized estimating equations were conducted as well as linear mixed models and linear regression models that adjusted for demographic characteristics.

Results
Few infants met the guidelines at all time-points (questionnaire: 2%; time-use diary: 0%). Infants that met a recommendation at 2 months, compared to those that did not, were 1.8–8.2 times more likely to meet that recommendation at subsequent time-points. Meeting more recommendations across time-points, according to both measures, was associated with a higher mean ASQ-3 gross motor score. Each additional time-point of tummy time recommendation adherence (questionnaire-measured) was associated with a 5–11-day earlier acquisition of independent sitting, crawling, and independent standing milestones. In the sub-sample, each additional time-point of guideline adherence was associated with a 16% higher AIMS score at 6 months.

Conclusions
Guideline adherence was low across the first 6 months of infancy. Overall, meeting more recommendations over this period appeared important for gross motor development. Parents and caregivers should be targeted as early as possible with guideline dissemination and activation strategies to promote healthy infant development.
Biomarkers of cell damage, neutrophil and macrophage activation associated with in-hospital mortality in geriatric COVID-19 patients
Authors: Cardelli M. , Pierpaoli E. , Marchegiani F. , Marcheselli F. , Piacenza F. , Giacconi R. , Recchioni R. , Casoli T. , Stripoli P. , Provinciali M. , Matacchione G. , Giuliani A. , Ramini D. , Sabbatinelli J. , Bonafè M. , Di Rosa M. , Cherubini A. , Di Pentima C. , Spannella F. , Antonicelli R. , Bonfigli A. R. , Olivieri F. , Lattanzio F. 
Published: December 2022

Abstract
Background
The risk for symptomatic COVID-19 requiring hospitalization is higher in the older population. The course of the disease in hospitalised older patients may show significant variation, from mild to severe illness, ultimately leading to death in the most critical cases. The analysis of circulating biomolecules involved in mechanisms of inflammation, cell damage and innate immunity could lead to identify new biomarkers of COVID-19 severity, aimed to improve the clinical management of subjects at higher risk of severe outcomes.
In a cohort of COVID-19 geriatric patients (n= 156) who required hospitalization we analysed, on-admission, a series of circulating biomarkers related to neutrophil activation (neutrophil elastase, LL-37), macrophage activation (sCD163) and cell damage (nuclear cfDNA, mithocondrial cfDNA and nuclear cfDNA integrity). The above reported biomarkers were tested for their association with in-hospital mortality and with clinical, inflammatory and routine hematological parameters. Aim of the study was to unravel prognostic parameters for risk stratification of COVID-19 patients.

Results
Lower n-cfDNA integrity, higher neutrophil elastase and higher sCD163 levels were significantly associated with an increased risk of in-hospital decease. Median (IQR) values observed in discharged vs. deceased patients were: 0.50 (0.30-0.72) vs. 0.33 (0.22-0.62) for n-cfDNA integrity; 94.0 (47.7-154.0) ng/ml vs. 115.7 (84.2-212.7) ng/ml for neutrophil elastase; 614.0 (370.0-821.0) ng/ml vs. 787.0 (560.0-1304.0) ng/ml for sCD163. The analysis of survival curves in patients stratified for tertiles of each biomarker showed that patients with n-cfDNA integrity < 0.32 or sCD163 in the range 492-811 ng/ml had higher risk of in-hospital decease than, respectively, patients with higher n-cfDNA integrity or lower sCD163. These associations were further confirmed in multivariate models adjusted for age, sex and outcome-related clinical variables. In these models also high levels of neutrophil elastase (>150 ng/ml) appeared to be independent predictor of in-hospital death. An additional analysis of neutrophil elastase in patients stratified for n-cfDNA integrity levels was conducted to better describe the association of the studied parameters with the outcome.

Conclusions
On the whole, biomarkers of cell-free DNA integrity, neutrophil and macrophage activation might provide a valuable contribution to identify geriatric patients with high risk of COVID-19 in-hospital mortality.
MicroRNAs: a crossroad that connects obesity to immunity and aging
Authors: Rakib Ahmed , Kiran Sonia , Mandal Mousumi , Singh Udai P. 
Published: December 2022

AbstractObesity is characterized by an elevated amount of fat and energy storage in the adipose tissue (AT) and is believed to be the root cause of many metabolic diseases (MDs). Obesity is associated with low-grade chronic inflammation in AT. Like obesity, chronic inflammation and MDs are prevalent in the elderly. The resident immune microenvironment is not only responsible for maintaining AT homeostasis but also plays a crucial role in stemming obesity and related MDs. Mounting evidence suggests that obesity promotes activation in resident T cells and macrophages. Additionally, inflammatory subsets of T cells and macrophages accumulated into the AT in combination with other immune cells maintain low-grade chronic inflammation. microRNAs (miRs) are small non-coding RNAs and a crucial contributing factor in maintaining immune response and obesity in AT. AT resident T cells, macrophages and adipocytes secrete various miRs and communicate with other cells to create a potential effect in metabolic organ crosstalk. AT resident macrophages and T cells-associated miRs have a prominent role in regulating obesity by targeting several signaling pathways. Further, miRs also emerged as important regulators of cellular senescence and aging. To this end, a clear link between miRs and longevity has been demonstrated that implicates their role in regulating lifespan and the aging process. Hence, AT and circulating miRs can be used as diagnostic and therapeutic tools for obesity and related disorders. In this review, we discuss how miRs function as biomarkers and impact obesity, chronic inflammation, and aging.Graphical Abstract
Activating transcription factor 3 inhibits NF‑κB p65 signaling pathway and mediates apoptosis and cell cycle arrest in cervical cancer cells
Authors: Akbarpour Arsanjani Amirhossein , Abuei Haniyeh , Behzad-Behbahani Abbas , Bagheri Zahra , Arabsolghar Rita , Farhadi Ali 
Published: December 2022

Abstract
Background
As a novel tumor suppressor mediator, activating transcription factor 3 (ATF3) has recently aroused an interest in its possible therapeutic applications in various cancers. In this study, we evaluated the effect of ATF3 overexpression on the cellular level of nuclear factor kappa B (NF-κB) in human papillomavirus (HPV)-infected Ca Ski cells. Further, we examined whether ATF3 could mediate cell cycle arrest and alter the apoptosis level of Ca Ski cells.

Methods
The biological behavior of Ca Ski cells was evaluated prior and subsequent to the overexpression of ATF3 by MTT assay, fluorescence microscopy, cell cycle and annexin V/PI flow cytometric analysis. The effect of ectopic ATF3 expression on the cellular level of NF-κB in HPV-positive cells was evaluated by western blotting assay.

Results
The overexpression of ATF3 in Ca Ski cells led to significant apoptosis and cell cycle arrest in the G1 phase. Western blotting assay revealed a discernible reduction of NF-κB p65 level in cervical cancer cells.

Conclusion
ATF3 acts as a tumor suppressor factor in HPV16-infected Ca Ski cells and exerts anti-cancer effects on HPV16-related cervical cancer cells potentially by hindering cell growth and inducing cell cycle arrest through the down-regulation of NF-κB. Our results suggest that ATF3 induction or NF-κB suppression may be useful targets for HPV16-related cervical cancer prevention and treatment.
Comparison of the neuromuscular effects of two infusion rates of rocuronium in anesthetized pigs
Authors: Pedersen Kamilla , Kruhøffer Linda Loisa , Lykkesfeldt Jens , Kousholt Birgitte Saima 
Published: December 2022

AbstractBackground:Neuromuscular blocking agents are frequently administered to pigs used for research. In humans, administration of the drugs is not without risk and may result in accidental awareness under general anaesthesia and postoperative residual neuromuscular blockade that can lead to serious respiratory complications. Despite the extensive administration, the pharmacodynamics of neuromuscular blocking agents are not thoroughly studied in pigs. Therefore, this study investigates the neuromuscular response of two infusion rates of rocuronium, a commonly used non-depolarizing neuromuscular blocking agent. A group of 14 female Danish Landrace-Yorkshire-Duroc pigs used for supervised surgical training, weighing 40.3 ± 2.1 kg (mean ± SD), were included in the study. They received a loading dose of 0.85 mg/kg rocuronium intravenously followed by infusion of either 2.5 mg/kg/hour (L, low dose) or 5 mg/kg/hour (H, high dose) rocuronium for 30 min. Neuromuscular monitoring was performed with acceleromyography using train-of-four (TOF) stimulation. Onset time, time to reappearance of T1, T4, TOF ratio 90% and 100% were recorded.Results:All pigs in group H experienced loss of T1 throughout rocuronium infusion, whereas six out of seven pigs in group L had reappearance of T1 during rocuronium infusion, with additional reappearance of T4 in three of these pigs. The time to recovery of TOF ratio 90% was 14.0 ± 5.4 (L) and 21.7 ± 6.1 (H) minutes and recovery to TOF ratio 100% was 18.7 ± 6.5 (L) and 27.9 ± 9.2 min (H) (mean ± SD). Substantial inter-animal variation in neuromuscular recovery time was observed.ConclusionThe large inter-animal variation in pharmacodynamic profiles emphasizes that individual neuromuscular monitoring and titration to effect should be used routinely in research protocols that include rocuronium. In addition to other important measures, these actions are key in order to avoid overdosing and limit the risk of residual neuromuscular blockade.
IGF2BP2-induced circRUNX1 facilitates the growth and metastasis of esophageal squamous cell carcinoma through miR-449b-5p/FOXP3 axis
Authors: Wang Chang , Zhou Mingxia , Zhu Peiyu , Ju Chenxi , Sheng Jinxiu , Du Dan , Wan Junhu , Yin Huiqing , Xing Yurong , Li Hongle , He Jing , He Fucheng 
Published: December 2022

Abstract
Background
Esophageal squamous cell carcinoma (ESCC) is one of the most common digestive malignancies with relatively high morbidity and mortality. Emerging evidence suggests circular RNAs (circRNAs) play critical roles in tumor cell malignancy. However, the biological function and clinical significance of many circRNAs in ESCC remain elusive.

Methods
The expression level and clinical implication of circRUNX1 in ESCC tissues were evaluated using qRT-PCR. In vitro and in vivo functional studies were conducted to investigate the underlying biological effects of circRUNX1 on ESCC cell growth and metastasis. Moreover, bioinformatics analysis, RNA sequencing (RNA-seq), RNA immunoprecipitation (RIP) assays, dual-luciferase reporter assays, and rescue experiments were performed to explore the relationships between circRUNX1, miR-449b-5p, Forkhead box protein P3 (FOXP3), and insulin-like growth factor 2 mRNA-binding protein 2 (IGF2BP2).

Results
CircRUNX1 was found to be significantly up-regulated in ESCC tissues and associated with TNM stage and differentiation grade. Functionally, circRUNX1 promoted ESCC cell proliferation and metastasis in vitro and in vivo. CircRUNX1 enhanced FOXP3 expression by competitively sponging miR-449b-5p. Notably, both miR-449b-5p mimics and FOXP3 knockdown restored the effects of circRUNX1 overexpression on cell proliferation and metastasis. Furthermore, IGF2BP2 binding to circRUNX1 prevented its degradation.

Conclusions
IGF2BP2 mediated circRUNX1 functions as an oncogenic factor to facilitate ESCC progression through the miR-449b-5p/FOXP3 axis, implying that circRUNX1 has the potential to be a promising diagnostic marker and therapeutic target for ESCC patients.
Isolation and characterization of two newly established thymoma PDXs from two relapses of the same patient: a new tool to investigate thymic malignancies
Authors: Mendogni Paolo , Affatato Roberta , Cabri Enrico , Chiappa Michela , Ndembe Gloriana , Tosi Davide , Del Gobbo Alessandro , Fratelli Maddalena , Pardini Eleonora , Petrini Iacopo , Rosso Lorenzo , Broggini Massimo , Marabese Mirko 
Published: December 2022

Abstract
Background
Thymic malignancies are a heterogeneous group of rare cancers for which systemic chemotherapy is the standard treatment in the setting of advanced, recurrent or refractory diseases. Both environmental and genetic risk factors have not been fully clarified and few target-specific drugs have been developed for thymic epithelial tumors. A major challenge in studying thymic epithelial tumors is the lack of preclinical models for translational studies.

Main body
Starting from bioptic material of two consecutive recurrences of the same patient, we generated two patient-derived xenografts. The patient-derived xenografts models were characterized for histology by immunohistochemistry and mutations using next-generation sequencing. When compared to the original tumors resected from the patient, the two patient-derived xenografts had preserved morphology after the stain with hematoxylin and eosin, although there was a moderate degree of de-differentiation. From a molecular point of view, the two patient-derived xenografts maintained 74.3 and 61.8% of the mutations present in the human tumor of origin.

Short conclusion
The newly generated patient-derived xenografts recapitulate both the molecular characteristics and the evolution of the thymoma it derives from well, allowing to address open questions for this rare cancer.
The traditional chinese medicine monomer Ailanthone improves the therapeutic efficacy of anti-PD-L1 in melanoma cells by targeting c-Jun
Authors: Yu Pian , Wei Hui , Li Kaixuan , Zhu Shiguo , Li Jie , Chen Chao , Zhang Detian , Li Yayun , Zhu Lei , Yi Xiaoqing , Liu Nian , Liu Panpan , Zhao Shuang , Chen Xiang , Peng Cong 
Published: December 2022

Abstract
Background
C-Jun, a critical component of AP-1, exerts essential functions in various tumors, including melanoma, and is believed to be a druggable target for cancer therapy. Unfortunately, no effective c-Jun inhibitors are currently approved for clinical use. The advent of immune checkpoint inhibitor (ICI) has brought a paradigm shift in melanoma therapy, but more than half of patients fail to exhibit clinical responses. The exploration of new combination therapies has become the current pursuit of melanoma treatment strategy. This study aims to screen out Chinese herbal monomers that can target c-Jun, explore the combined effect of c–Jun inhibitor and ICI, and further clarify the related molecular mechanism.

Methods
We adopted a combinatorial screening strategy, including molecular docking, ligand-based online approaches and consensus quantitative structure-activity relationship (QSAR) model, to filter out c-Jun inhibitors from a traditional Chinese medicine (TCM) library. A mouse melanoma model was used to evaluate the therapeutic efficacy of monotherapy and combination therapy. Multicolor flow cytometry was employed to assess the tumor microenvironment (TME). Multiple in vitro assays were performed to verify down-streaming signaling pathway. CD4 + T-cell differentiation assay was applied to investigate Treg differentiation in vitro.

Results
Ailanthone (AIL) was screened out as a c-Jun inhibitor, and inhibited melanoma cell growth by directly targeting c-Jun and promoting its degradation. Surprisingly, AIL also facilitated the therapeutic efficacy of anti-programmed death ligand-1 (PD-L1) in melanoma cells by reducing the infiltration of Tregs in TME. Additionally, AIL treatment inhibited c-Jun-induced PD-L1 expression and secretion. As a consequence, Treg differentiation was attenuated after treatment with AIL through the c-Jun/PD-L1 axis.

Conclusion
Our findings identified AIL as a novel c-Jun inhibitor, and revealed its previously unrecognized anti-melanoma effects and the vital role in regulating TME by Treg suppression, which provides a novel combination therapeutic strategy of c-Jun inhibition by AIL with ICI.

Graphical Abstract
AIL down-regulates c-Jun by reducing its stability, and inhibits the function of Tregs via AIL-c-Jun-PD-L1 pathway, ultimately suppressing melanoma progression and enhancing the efficacy of anti-PD-L1.
Aedes aegypti Malpighian tubules are immunologically activated following systemic Toll activation
Authors: Sneed Sarah D. , Dwivedi Sutopa B. , DiGate Cameron , Denecke Shane , Povelones Michael 
Published: December 2022

Abstract
Background
Canine heartworm is a widespread and potentially fatal mosquito-borne disease caused by infections with the parasitic nematode, Dirofilaria immitis. We have previously shown that systemic activation of the Toll immune pathway via silencing of the negative regulator Cactus in Aedes aegypti blocks parasite development in the Malpighian tubules (MT), the mosquito renal organ. However, it was not established whether the MT were directly responding to Toll activation or were alternatively responding to upregulated proteins or other changes to the hemolymph driven by other tissues. Distinguishing these possibilities is crucial for developing more precise strategies to block D. immitis while potentially avoiding the fitness cost to the mosquito associated with Cactus silencing.

Methods
This study defines the transcriptional response of the MT and changes to the hemolymph proteome of Ae. aegypti after systemic Toll activation via intra-thoracic injection of double-stranded Cactus (dsCactus) RNA.

Results
Malpighian tubules significantly increased expression of the Toll pathway target genes that significantly overlapped expression changes occurring in whole mosquitoes. A significant overlap between the transcriptional response of the MT and proteins upregulated in the hemolymph was also observed.

Conclusions
Our data show that MT are capable of RNA interference-mediated gene silencing and directly respond to dsCactus treatment by upregulating targets of the canonical Toll pathway. Although not definitive, the strong correspondence between the MT transcriptional response and the hemolymph proteomic responses provides evidence that the MT may contribute to mosquito humoral immunity.

Graphical Abstract
Lifestyle characteristics in adolescent female football players: data from the Karolinska football Injury Cohort
Authors: Fältström Anne , Skillgate Eva , Weiss Nathan , Källberg Henrik , Lyberg Victor , Waldén Markus , Hägglund Martin , Asker Martin , Tranaeus Ulrika 
Published: December 2022

Abstract
Background
Normative values of lifestyle characteristics in adolescent female football players may be used by clinicians and coaches to take actions because the potential important for well-being, performance on the pitch, and risk of injury. The aim was to report descriptive characteristics of lifestyle factors in adolescent female football players and potential changes over 1 year.

Methods
We included 419 adolescent competitive female football players from 12 clubs and 27 teams (age 14 ± 1 years, range 12–17 years) and 286 were followed over 1 year. The players completed an extensive questionnaire regarding demographics, football-related factors, and lifestyle factors including tobacco consumption, alcohol use, medicine intake, eating and sleeping habits, well-being, stress, coping, and passion. Baseline data are presented for the total cohort and separately for 4 age groups (12, 13, 14, and 15–17 years).

Results
12% skipped breakfast, 8% skipped lunch and 11% used protein supplements several days per week. 16% slept less than 8 h/night, 8% had impaired sleep with daytime consequences, and 22% stated that they were tired in daily activities several days per week. 32% experienced stress some or most days/week and 24% were classified as having psychological distress. Medicine intake (23% vs. 34%), skipping breakfast or lunch several days per week (10% vs. 47% and 20 vs. 33%), tiredness (20% vs. 27%), stress (26% vs. 40%), and psychological distress (27% vs. 37%) increased significantly (P = 0.031 to < 0.001) at the 1-year follow-up.

Conclusion
Many adolescent female football players skip breakfast and lunch, have insufficient sleep, experience stress and are classified as having psychological distress. These factors increased over 1 year.