bluuebunny/crossref_metadata_2025_split huggingface dataset:
Immunohistochemical Analysis of Tn Neoantigen Expression in Colorectal Adenocarcinoma and Precursor Lesions
Authors: Dombek Gabrielle E. , Ore Ana Sofia , Cheng Jane , Matsumoto Yasuyuki , Glickman Jonathan N. , Fleishman Aaron , Heimburg-Molinaro Jamie , Poylin Vitaliy Y. , Fabrizio Anne , Cataldo Thomas , Messaris Evangelos , Cummings Richard D. 
Published: May 2022

Abstract
Background
The Tn neoantigen (CD175) is an O-glycan expressed in various types of human adenocarcinomas, including colorectal cancer (CRC), though prior studies have relied heavily upon poorly characterized in-house generated antibodies and lectins. In this study, we explored Tn expression in CRC using ReBaGs6, a well-characterized recombinant murine antibody with high specificity for clustered Tn antigen.
Methods
Using well-defined monoclonal antibodies, expression patterns of Tn and sialylated Tn (STn) antigens were characterized by immunostaining in CRC, in matched peritumoral [transitional margin (TM)] mucosa, and in normal colonic mucosa distant from the tumor, as well as in adenomas. Vicia villosa agglutinin lectin was used to detect terminal GalNAc expression. Histo-scoring (H scoring) of staining was carried out, and pairwise comparisons of staining levels between tissue types were performed using paired samples Wilcoxon rank sum tests, with statistical significance set at 0.05.
Results
While minimal intracellular Tn staining was seen in normal mucosa, significantly higher expression was observed in both TM mucosa (p < 0.001) and adenocarcinoma (p < 0.001). This pattern was reflected to a lesser degree by STn expression in these tissue types. Interestingly, TM mucosa demonstrates a Tn expression level even higher than that of the adenocarcinoma itself (p = 0.019). Colorectal adenomas demonstrated greater Tn and STn expression relative to normal mucosa (p < 0.001 and p = 0.012, respectively).
Conclusions
In summary, CRC is characterized by alterations in Tn/STn antigen expression in neoplastic epithelium as well as peritumoral benign mucosa. Tn/STn antigens are seldom expressed in normal mucosa. This suggests that TM mucosa, in addition to CRC itself, represents a source of glycoproteins rich in Tn that may offer future biomarker targets.
Efficacy and safety of the investigational complement C5 inhibitor zilucoplan in patients hospitalized with Covid-19: an open-label randomized controlled trial
Authors: De Leeuw Elisabeth , Damme Karel F.A. Van , Declercq Jozefien , Bosteels Cedric , Maes Bastiaan , Tavernier Simon J. , Detalle Laurent , Smart Trevor , Glatt Sophie , Debeuf Nincy , Deckers Julie , Lameire Sahine , Vandecasteele Stefaan J , De Neve Nikolaas , Demedts Ingel K. , Govaerts Elke , Knoop Christiane , Vanhove Karolien , Moutschen Michel , Terryn Wim , Depuydt Pieter , Braeckel Eva Van , Haerynck Filomeen , Hendrickx Tine C.J. , Parrein Vanessa , Lalla Marianna , Brittain Claire , Lambrecht Bart N. 
Published: May 2022

Abstract
Background: The efficacy and safety of complement inhibition in Covid-19 patients is unclear.Methods: A multicenter randomized controlled, open-label trial. Hospitalized Covid-19 patients with signs of hyperinflammation and hypoxemia (PaO2/FiO2 below 350 mHg) were randomized (2:1 ratio) to receive standard of care with or without the C5 inhibitor zilucoplan daily for 14 days, under antibiotic prophylaxis. The primary outcome was improvement in oxygenation at day 6 and 15.Results: 81 patients were randomly assigned to zilucoplan (n=55) or the control group (n=26). 78 patients were included in the safety and primary analysis. Most were men (87%) and the median age was 63 years. The mean improvement in PaO2/FiO2 from baseline to day 6 was 56·4 mmHg in the zilucoplan group and 20·6 mmHg in the control group (mean difference +35.8; 95% confidence interval (CI) -9.4 to 80.9; p=0.12), an effect also observed at day 15. Day 28 mortality was 9% in the zilucoplan and 21% in the control group (odds ratio 0·4; 95% CI 0·1 to 1·5) At long-term follow up, the distance walked in a 6 min test was 539·7 m in zilucoplan and 490·6 m in the control group (p=0·18). Zilucoplan lowered serum C5b-9 (p<0·001) and interleukin-8 (p=0·03) concentration compared with control. No relevant safety differences between the zilucoplan and control group were identified.Conclusion: Administration of zilucoplan to Covid-19 patients in this proof-of-concept randomized trial was well tolerated under antibiotic prophylaxis. While not reaching statistical significance, indicators of respiratory function and clinical outcome suggest that C5 inhibition might be beneficial, although this requires further research in larger randomized studies.(Funded by UCB and Ghent University Special Research Fund for COVID-19 Research; ClinicalTrials.gov, NCT04382755 – May 11, 2020; EudraCT, 2020-002130-33 – May 6, 2020)
Multi-omics analysis revealed the association of human gut microbiota composition and metabolic functions with the daily diet of the additive Ficus hirta Vahl
Authors: Lin Ying , Xiao Ruiming , Luo Guangjuan , Liao Wanci , Chen Shuting , Han Shuangyan , Liang Shuli 
Published: May 2022

Abstract
Ficus hirta Vahl (FHV), a traditional herbal ingredient of the tonic diet, receives increasing popularity in southern China. However, it is largely unknown that how a FHV diet (FHVD) affects the human gut microbiome. A total of 43 healthy individuals were randomized into the FHVD (n=25) and Control (n=18) groups to receive diet intervention for 8 weeks. 16S rRNA sequencing, metagenomic sequencing and metabolic profile of participants were measured to assess the association between FHV diet and gut microbiome. A preservation effect of Faecalibacterium and enrichment of Dialister, Veillonella, Clostridium, and Lachnospiraceae were found during the FHVD. Accordingly, the pathway of amino acid synthesis, citrate cycle, coenzyme synthesis, and partial B vitamin synthesis were found to be more abundant in the FHVD. In addition, serine, glutamine, gamma-aminobutyric acid, tryptamine, and short-chain fatty acids (SCFAs) were higher after the FHVD. The conjoint analysis of FHV components and in-vitro fermentation confirmed that the improved SCFAs concentration was collectively contributed by the increasing abundance of key enzyme genes and available substrates. In conclusion, the muti-omics analysis showed that the FHVD optimized the structure of the gut microbial community and its metabolic profile, leading to a healthy tendency, with a small cluster of bacteria driving the variation rather than a single taxon.
ATPase Thorase Deficiency Causes α-synucleinopathy and Parkinson’s Disease-Like Behavior by Impairing PINK1/Parkin-Mediated Mitophagy
Authors: Zhang Jianmin , Gao Fei , Yang Jia , Cai Menghua , Yang Qi , Zhang Han , Li Chao , Wang Huaishan , Fu Yi , Wang Dongdong , Xu Yi , Chen Hui , Hu Yu , He Wei 
Published: May 2022

Abstract
Mitophagy is essential for the maintenance of mitochondrial quality control (MQC) and neuronal survival. Defects in mitophagy have been implicated in the onset and progression of Parkinson’s disease (PD). However, the underlying mechanisms of mitophagy in the pathogenesis of PD remains unclear. Here, the AAA+ ATPase Thorase was identified being essential for mitophagy. Mice lacking Thorase exhibited PD-like behavior and α-synucleinopathy in the brains. Genetic deletion of Thorase exacerbated phenotypes of α-synucleinopathy in a familial PD-like A53T mouse model, whereas overexpression of Thorase prevented α-syn accumulation in vivo. Thorase regulates the balance of mitochondrial fusion/fission.Thorase deficiency resulted in more fragmented mitochondria and the blockage of dysfunctional mitochondrion degradation through PINK1/Parkin-mediated mitophagy. Thorase directly interacted with α-syn and regulated ubiquitinated α-syn degradation through mitophagy. The discoveries in this study place Thorase as a novel druggable target for pharmaceutical intervention of PD.
The maximum standardized uptake value in patients with recurrent or persistent prostate cancer after radical prostatectomy and PSMA-PET-guided salvage radiotherapy–a multicenter retrospective analysis
Authors: Spohn Simon , Farolfi Andrea , Schandeler Sarah , Vogel Marco M.E. , Ruf Juri , Mix Michael , Kirste Simon , Ceci Francesco , Fanti Stefano , Lanzafame Helena , Serani Francesca , Gratzke Christian , Sigle August , Combs Stephanie E. , Bernhardt Denise , Gschwend Juergen E. , Buchner Josef A. , Trapp Christian , Belka Claus , Bartenstein Peter , Eiber Matthias , Nekolla Stephan G. , Schiller Kilian , Grosu Anca L. , Schmidt-Hegemann Nina-Sophie , Zamboglou Constantinos , Peeken Jan C. 
Published: May 2022

Abstract
Purpose:
This study aims to evaluate the association of the maximum standardized uptake value (SUVmax) in positron-emission tomography targeting prostate-specific-membrane-antigen (PSMA-PET) prior to savage radiotherapy (sRT) on biochemical recurrence free survival (BRFS) in a large multicenter cohort.
Methods:
Patients who underwent 68Ga-PSMA11-PET prior to sRT were enrolled in four high-volume centers in this retrospective multicenter study. Only patients with PET-positive local recurrence (LR) and/or nodal recurrence (NR) within the pelvis were included. Patients were treated with intensity-modulated-sRT to the prostatic fossa and elective lymphatics in case of nodal disease. Dose escalation was delivered to PET-positive LR and NR. Androgen deprivation therapy was administered at the discretion of the treating physician. LR and NR were manually delineated using and SUVmax was extracted for LR and NR. Cox-regression was performed to analyze the impact of clinical parameters and the SUVmax-derived values on BRFS.
Results:
235 patients with a median follow up (FU) of 24 months were included in the final cohort. 2-years and 4-years BRFS for all patients were 68% and 56%. The presence of LR was associated with favorable BRFS (p = 0.016). Presence of NR was associated with unfavorable BRFS (p = 0.007). While there was a trend for SUVmax values ≥ median (p = 0.071), SUVmax values ≥ 75%quartile in LR were significantly associated with unfavorable BRFS (p = 0.022, HR: 2.1, 95%CI 1.1–4.6). SUVmax value in NR was not significantly associated with BRFS. SUVmax in LR stayed significant in multivariate analysis (p = 0.030). Sensitivity analysis with patients for who had a FU of > 12 months (n = 197) and only LR confirmed these results.
Conclusion
The non-invasive biomarker SUVmax can prognosticate outcome in patients undergoing sRT and recurrence confined to the prostatic fossa in PSMA-PET. Its addition might contribute to improve risk-stratification of patients with recurrent PCa and to guide personalized treatment decisions in terms of treatment intensity adaption.
2-hydroxyethyl methacrylate-derived reactive oxygen species stimulate ATP release via TRPA1 in human dental pulp cells
Authors: Orimoto Ai , Kitamura Chiaki , Ono Kentaro 
Published: May 2022

Abstract
Extracellular ATP (adenosine triphosphate) and transient receptor potential ankyrin 1 (TRPA1) channels are involved in calcium signaling in odontoblasts and dental pain. The resin monomer 2-hydroxyethyl methacrylate (HEMA), used in dental restorative procedures, is related to apoptotic cell death via oxidative stress. Although the TRPA1 channel is highly sensitive to reactive oxygen species (ROS), the effect of HEMA-induced ROS on ATP release to the extracellular space and the TRPA1 channel has not been clarified in human dental pulp. In this study, we investigated the extracellular ATP signaling and TRPA1 activation by HEMA-derived ROS in immortalized human dental pulp cells (hDPSC-K4DT). Among the ROS-sensitive TRP channels, TRPA1 expression was highest in undifferentiated hDPSC-K4DT cells, and its expression levels were further enhanced by osteogenic differentiation. In differentiated hDPSC-K4DT cells, 30 mM HEMA increased intracellular ROS production and ATP release, although 3 mM HEMA had no effect. Pretreatment with the free radical scavenger PBN (N-tert-butyl-α-phenylnitrone) or TRPA1 antagonist HC-030031 suppressed HEMA-induced responses. These results suggest that ROS production induced by a higher dose of HEMA activates the TRPA1 channel in human dental pulp cells, leading to ATP release. These findings may contribute to the understanding of the molecular and cellular pathogenesis of tertiary dentin formation and pain in response to dental biomaterials.
Isotopic profile and functioning of hyperseasonal savannas threatened by Australian acacia invasion
Authors: Meira-Neto João Augusto Alves , Villa Pedro Manuel , Silva Nathália , Silva Maria Carolina Nunes Alves , Tolentino Glaucia Soares , Buttschardt Tillmann , Ulm Florian , Máguas Cristina 
Published: May 2022

Abstract
The hyperseasonal savanna experiences regular flooding, drought stresses and is a neotropical vegetation type threatened by global change including Acacia spp. invasion. To deepen the understanding of hyperseasonal savannas after Acacia invasion in a climate change scenario, we aimed to answer whether: i) the plants are separated into different metabolic groups of plants; ii) Acacia invasion can change the functioning for different metabolic groups of plants; iii) invasive Acacia uptake water differently from native species; iv) there are different threats of Acacia invasion on different metabolic groups of plants. We detected both C3 and C4 metabolic groups of plants. Two C3 species are possibly CAM facultative. The functioning of C3 plants as a functional group was not affected by the Acacia invasion, but this result does not exclude an expected species turnover between C3 herbs and C3 trees. The C4 plants of invaded Mussununga lost their response of increasing water use efficiency to the increasing Leaf N%. Plants depend on the same water source as the soil water from recent rains. There are differences in d18O among species possibly because some grow mostly during the rainy season with the 18O-enriched water meanwhile the invader Acacia mangium grows throughout the year whenever it rains. C3 plants largely dominate these ecosystems. There is a possible threat to C4 plants. Hyperseasonal savannas should be considered critically endangered by global change, especially after Acacia invasions. Initiatives for conservation of hyperseasonal savannas should be considered for effective conservation of these ecosystems.
SS-31 Modification Inhibits Pro-inflammatory Effect of Macrophages Induced by Superparamagnetic Iron Oxide Nanoparticles
Authors: Lu Qizheng , Liu Haibo , Zheng Hao , Zhang Youming , Ou Jinbo , You Jieyun , Zhang Qi , Pi Jingjiang , Yao Xiaobo , Xu Jing , Wang Xingxu , Wang Yunkai , Pei Ning , Shen Yunli 
Published: May 2022

Abstract
Superparamagnetic iron oxide nanoparticles (SPION) could induce macrophage polarization into the pro-inflammatory M1-like subtype. The adverse effect is very likely to restrict the diagnostic or therapeutic applications of SPION in the cardiovascular field. To inhibit the pro-inflammatory effect, a mitochondrial targeted antioxidant peptide SS-31 modifying SPION (SPION@SS-31) was constructed. The macrophages (RAW 264.7) were incubated with SPION or SPION@SS-31 at the concentration of 50 µg Fe3O4/mL for 24 hours. Compared to the SPION group, the SPION@SS-31 group demonstrated significantly reduced macrophage damage, evidenced by maintained cell viability, a decrease of early cells apoptosis and reactive oxygen species (ROS) production. Moreover, the pro-inflammatory factor TNF-α and M1-like cell surface markers CD86 and CD80 were significantly down-regulated in the SPION@SS-31 group. Notably, higher levels of anti-inflammatory factors IL-10 and TGF-β and M2-like cell surface marker CD163 were detected in the SPION@SS-31 group by enzyme-linked immunosorbent assay (ELISA) and flow cytometric analysis. Besides, severe disruption of mitochondrial microstructure was observed by transmission electron microscope (TEM) in the SPION group, but less in the SPION@SS-31 group. Co-loading mitochondria-targeted antioxidant peptide SS-31 could significantly mitigate the pro-inflammatory effect of macrophages induced by SPION, indicating that the modification strategy has the potential to promote macrophages M2-like polarization in vitro study.
Cofactors in food allergy: a retrospective study on a cohort of Sardinian patients sensitized to Omega-5 gliadin and Pru p 3
Authors: Costanzo Giulia , Matolo Annalisa , Saderi Laura , Messina Maria Rita , Firinu Davide , Barca Maria Pina , Serra Paolo , Corso Nicoletta , Sotgiu Giovanni , Giacco Stefano Del 
Published: May 2022

Abstract
Purpose: Aim of this study is to clarify the impact of cofactors on allergic reactions in patients sensitized to LTP and ω-5-gliadin.Materials and methods: We retrospectively examined the charts of our outpatients from January 2015 to July 2019 and identified 157 patients seen for urticaria/angioedema or anaphylaxis after a meal, in presence or absence of cofactors and sensitized to LTPs (Pru p 3 and/or Tri a 14) and/or ω-5-gliadin (Tri a 19). Results: we compared LTPs-positive patients and those sensitized to Tri a 19 in order to assess the difference in cofactors involved and in frequency of clinical presentation. Our data show that exercise is the most frequent cofactor in FDEIAn and the involvement of exercise, alcohol and multiple cofactors was more frequently found in males than in females. We found that exercise, pollen counts peaks and multiple cofactors were more often related to anaphylaxis than mild reactions. Finally, we performed a comparison between LTPs+ patients and Tri a 19+ patients that showed, in this latter group, a lower frequency of allergic comorbidities, a higher median age at the onset of symptoms and frequency of alcohol exposure.Conclusions:Our data show that the search for possible cofactors involved in food allergy is essential not only for diagnostic purposes, but also for risk assessment strategies.
Profiles of GPs with High and Low Physician Empathy: Personal, Professional, and Antibiotic Prescribing Characteristics
Authors: Kristensen Troels , Ejersted Charlotte , Ahnfeldt-Mollerup Peder , Søndergaard Jens , Charles Justin 
Published: May 2022

Abstract
Background
General Practitioner’s (GPs) professional empathy has been hypothesized to have substantial impact on their delivered healthcare and use of medicine. This study compares profiles of personal, professional, and antibiotic prescribing characteristics of GPs with high and low empathy.
Methods
We apply an extreme group design and a unique combined set of survey and drug register data. The survey was sent to a stratified sample of 1,196 GPs comprising 30% of the Danish GP population and 464 GPs responded(38,8%). GPs in the top and bottom decile of empathy levels were identified. The applied Jefferson Scale of Empathy for Health Professionals includes 20 items that fall into three factors: perspective taking, compassionate care, walking in patient’s shoes. Total scores, factor scores, and individual item scores were calculated to disentangle the differences between the profiles. All intra- and inter-profile descriptive statistics and differences were bootstrapped to estimate the variability and related confidence intervals (CIs).
Results
61% of GPs in the top decile of the empathy score were female. GPs in this group reported the following person-centered factors as more important for their job satisfaction than the bottom decile: The Patient-physician relationship, interaction with colleagues, and intellectual stimulation. High-empathy scoring GPs prescribed significantly less penicillin than the low-empathy GPs. This was true for most penicillin subcategories. There were no significant differences in age, practice setting (urban vs. rural), practice type (partnership vs. single-handed), overall job satisfaction, or GP’s value of prestige and economic profit for their job satisfaction. The intra profile variation index and CIs show less prescribing uncertainty among GPs with high empathy.
Conclusions
This study reveals that high empathy GPs may have different personal, professional, and antibiotic prescribing characteristics than low empathy GPs and have less variable empathy levels as a group. Furthermore, person-centered high empathy GPs on average seem to prescribe less penicillins than low empathy GPs.
 Correlation and Influence of Seasonal variation of Diet with Gut Microbiota diversity and Metabolism Profile of chipmunk
Authors: Teng Wei , Maqsood Iram , Huan Wang , Rong Ke , Ma Jianzhang 
Published: May 2022

Abstract
Background: Tamias Sibiricus is the only member of genus Tamias, which is a very important and vigorous seed distributors, and also a vital food for their predators. No information is known about the strict diet, Gut microbiota structure and metabolism profile of chipmunk and how it divers seasonally. Analysis of above mentioned factors, and flexibility toward seasonal shift is crucial to define its growth rates, health, survivorship, and population stability.Results: In this study, we explored the diet, gut microbiota composition, and chipmunk metabolism. Additionally, the influence of different seasons was also investigated by using next-generation sequencing. Results revealed that seasons had a strong effect on a diet : as streptophyte accounted for 37% in spring, which was lowest in summer (34.3%) and autumn (31.4%). Further, Ascomycota was observed 43.8% in spring which reduced to 36.6% in summer and lowest (31.3%) in autumn. Whereas, Nematoda showd maximum abundance from spring (15.8%) to summer (20.6%) and autumn (24.1%). These results are signifying the insectivorous nature of the chipmunk in summer and autumn. While herbivorous and fungivorous nature in spring. The DNA analysis revealed that chipmunk mainly feeds on fungi, including Aspergillus and Penicillium genus. Like diet composition, microbiome also exhibited highly significant dissimilarity (p<0.001, R=0.235) between spring/autumn and spring/summer seasons. Proteobacteria (35.45%), Firmicutes (26.7%) and Bacteroidetes (23.59%) were shown to be the better discriminators as they contributed most to cause differences between seasons. Moreover, PICRUSt was exposed that the assimilation of nutritions were also variated seasonally. The abundance of carbohydrate, lipid, nucleotide, xenobiotics, energy, terpenoids and polyketides metabolism were highest in spring than other seasons. Conclusions: Our study illustrates that seasonal reconstruction in chipmunk diet have a significant role in shaping temporal variations in gut microbial community structure and metabolism profile.