bluuebunny/crossref_metadata_2025_split huggingface dataset:
D-dopachrome tautomerase activates COX2/PGE2 pathway of astrocytes to mediate inflammation following spinal cord injury
Authors: Ji Huiyuan , Zhang Yuxin , Chen Chen , Li Hui , He Bingqiang , Yang Ting , Sun Chunshuai , Hao Huifei , Zhang Xingyuan , Wang Yingjie , Zhou Yue , Zhu Zhenjie , Hu Yuming , Li Aihong , Guo Aisong , Wang Yongjun 
Published: June 2021

Abstract
Background
Astrocytes are the predominant glial cell type in the central nervous system (CNS) that can secrete various cytokines and chemokines mediating neuropathology in response to danger signals. D-dopachrome tautomerase (D-DT), a newly described cytokine and a close homolog of macrophage migration inhibitory factor (MIF) protein, has been revealed to share an overlapping function with MIF in some ways. However, its cellular distribution pattern and mediated astrocyte neuropathological function in the CNS remain unclear.

Methods
A contusion model of the rat spinal cord was established. The protein levels of D-DT and PGE2 synthesis-related proteinase were assayed by Western blot and immunohistochemistry. Primary astrocytes were stimulated by different concentrations of D-DT in the presence or absence of various inhibitors to examine relevant signal pathways. The post-injury locomotor functions were assessed using the Basso, Beattie, and Bresnahan (BBB) locomotor scale.

Results
D-DT was inducibly expressed within astrocytes and neurons, rather than in microglia following spinal cord contusion. D-DT was able to activate the COX2/PGE2 signal pathway of astrocytes through CD74 receptor, and the intracellular activation of mitogen-activated protein kinases (MAPKs) was involved in the regulation of D-DT action. The selective inhibitor of D-DT was efficient in attenuating D-DT-induced astrocyte production of PGE2 following spinal cord injury, which contributed to the improvement of locomotor functions.

Conclusion
Collectively, these data reveal a novel inflammatory activator of astrocytes following spinal cord injury, which might be beneficial for the development of anti-inflammation drug in neuropathological CNS.
Enhanced expression of miR-889 forecasts an unfavorable prognosis and facilitates cell progression in hepatocellular carcinoma
Authors: Wang He , Wang Huiwen , Cui Wenyu , Zhang Qiao , Li Jing , Zhang Qi 
Published: June 2021

Abstract
Background
As a new type of molecular marker, microRNAs (miRNAs) can be used for early diagnosis and prognosis prediction of malignant tumors, and has broad clinical application prospects. This paper mainly studies the important role of miR-889 in the occurrence and development of hepatocellular carcinoma and the prognostic significance of miR-889 in hepatocellular carcinoma.

Methods
Quantitative real-time PCR analysis detected the expression levels of miR-889 in hepatocellular carcinoma tissues and cell lines. Kaplan-Meier curve and Cox regression analysis were used to explore the prognostic significance of miR-889 in hepatocellular carcinoma. The CCK-8 and Transwell assays assay were used to assess cell proliferation, migration, and invasion abilities ability.

Results
The expression of miR-889 in hepatocellular carcinoma tissues was significantly higher than that in adjacent tissues. Overexpression of miR-889 was significantly associated with TNM stage, hepatitis B virus infection, and cirrhosis. Patients with high miR-889 expression had shorter overall survival than those with low miR-889 expression. And functional studies in two hepatocellular carcinoma cell lines have shown that overexpression of miR-889 significantly promoted cell proliferation, migration, and invasion in vitro.

Conclusions
Overall, miR-889 was upregulated in hepatocellular carcinoma tissues and cell lines, and overexpression of miR-889 promoted cell proliferation, migration, and invasion in hepatocellular carcinoma cells. Based on our findings, high expression of miR-889 may promote the progression of hepatocellular carcinoma, and high expression of miR-889 is also forecasted for an unfavorable prognosis in hepatocellular carcinoma.
Dual inhibition of complement component 5 and leukotriene B4 by topical rVA576 in atopic keratoconjunctivis: TRACKER phase 1 clinical trial results
Authors: Sánchez-Tabernero Sara , Fajardo-Sanchez Julia , Weston-Davies Wynne , Parekh Mohit , Kriman Jaime , Kaye Stephen , Ahmad Sajjad 
Published: June 2021

Abstract
Purpose
To evaluate the safety and preliminary efficacy of topical rVA576, a dual inhibitor of complement component 5 (C5) and leukotriene B4 (LTB4), in patients with recalcitrant atopic keratoconjunctivitis (AKC) in the open label phase 1 TRACKER clinical trial.

Methods
Three patients diagnosed with moderate or severe AKC who had been on maximal topical treatment (antihistamines and ciclosporin) for at least three months prior to entry, and showed persistent symptoms and signs of inflammation, were recruited into the trial. Patients received rVA576 eye drops twice a day for 8 weeks. Patients were seen at baseline and weeks 1, 2, 4, 6 and 8. Safety data was recorded and a composite sum score of symptoms and signs was obtained. This score comprised symptoms such as itching, mucous discharge and photophobia, and conjunctival and corneal signs such as hyperemia, tarsal papillae, punctate keratitis and corneal neovascularization, all rated individually from 0 to 3 for a maximum score of 33.

Results
Two of the three patients completed the initial open label phase of the trial. The third patient was unable to attend appointments and terminated the study early at day 14. Topical rVA576 was well tolerated with no serious adverse events reported. There was an average improvement in overall clinical score of 53%, composed of an improvement in symptoms of 65% [63.64–66.67%] and signs of 40% [40–40.12%] by day 56.

Conclusions
In this open label phase 1 TRACKER trial, rVA576 eye drops were well tolerated and showed a response across signs and symptoms of active inflammation. This study is exploratory but supports topical rVA576 safety and shows promising efficacy for recalcitrant AKC. A phase 2 randomised control trial is currently underway.
Feasibility of achieving different protein targets using a hypocaloric high-protein enteral formula in critically ill patients
Authors: Singer Pierre , Bendavid Itai , BenArie Ilana , Stadlander Liran , Kagan Ilya 
Published: June 2021

Abstract
Background and aims
Combining energy and protein targets during the acute phase of critical illness is challenging. Energy should be provided progressively to reach targets while avoiding overfeeding and ensuring sufficient protein provision. This prospective observational study evaluated the feasibility of achieving protein targets guided by 24-h urinary nitrogen excretion while avoiding overfeeding when administering a high protein-to-energy ratio enteral nutrition (EN) formula.

Methods
Critically ill adult mechanically ventilated patients with an APACHE II score > 15, SOFA > 4 and without gastrointestinal dysfunction received EN with hypocaloric content for 7 days. Protein need was determined by 24-h urinary nitrogen excretion, up to 1.2 g/kg (Group A, N = 10) or up to 1.5 g/kg (Group B, N = 22). Variables assessed included nitrogen intake, excretion, balance; resting energy expenditure (REE); phase angle (PhA); gastrointestinal tolerance of EN.

Results
Demographic characteristics of groups were similar. Protein target was achieved using urinary nitrogen excretion measurements. Nitrogen balance worsened in Group A but improved in Group B. Daily protein and calorie intake and balance were significantly increased in Group B compared to Group A. REE was correlated to PhA measurements. Gastric tolerance of EN was good.

Conclusions
Achieving the protein target using urinary nitrogen loss up to 1.5 g/kg/day was feasible in this hypercatabolic population. Reaching a higher protein and calorie target did not induce higher nitrogen excretion and was associated with improved nitrogen balance and a better energy intake without overfeeding. PhA appears to be related to REE and may reflect metabolism level, suggestive of a new phenotype for nutritional status.
Trial registration 0795-18-RMC.
Perioperative liberal versus restrictive fluid strategies and postoperative outcomes: a systematic review and metanalysis on randomised-controlled trials in major abdominal elective surgery
Authors: Messina Antonio , Robba Chiara , Calabrò Lorenzo , Zambelli Daniel , Iannuzzi Francesca , Molinari Edoardo , Scarano Silvia , Battaglini Denise , Baggiani Marta , De Mattei Giacomo , Saderi Laura , Sotgiu Giovanni , Pelosi Paolo , Cecconi Maurizio 
Published: June 2021

Abstract
Background
Postoperative complications impact on early and long-term patients’ outcome. Appropriate perioperative fluid management is pivotal in this context; however, the most effective perioperative fluid management is still unclear. The enhanced recovery after surgery pathways recommend a perioperative zero-balance, whereas recent findings suggest a more liberal approach could be beneficial. We conducted this trial to address the impact of restrictive vs. liberal fluid approaches on overall postoperative complications and mortality.

Methods
Systematic review and meta-analysis, including randomised controlled trials (RCTs). We performed a systematic literature search using MEDLINE (via Ovid), EMBASE (via Ovid) and the Cochrane Controlled Clinical trials register databases, published from 1 January 2000 to 31 December 2019. We included RCTs enrolling adult patients undergoing elective abdominal surgery and comparing the use of restrictive/liberal approaches enrolling at least 15 patients in each subgroup. Studies involving cardiac, non-elective surgery, paediatric or obstetric surgeries were excluded.

Results
After full-text examination, the metanalysis finally included 18 studies and 5567 patients randomised to restrictive (2786 patients; 50.0%) or liberal approaches (2780 patients; 50.0%). We found no difference in the occurrence of severe postoperative complications between restrictive and liberal subgroups [risk difference (95% CI) = 0.009 (− 0.02; 0.04); p value = 0.62; I2 (95% CI) = 38.6% (0–66.9%)]. This result was confirmed also in the subgroup of five studies having a low overall risk of bias. The liberal approach was associated with lower overall renal major events, as compared to the restrictive [risk difference (95% CI) = 0.06 (0.02–0.09); p value  = 0.001]. We found no difference in either early (p value  = 0.33) or late (p value  = 0.22) postoperative mortality between restrictive and liberal subgroups

Conclusions
In major abdominal elective surgery perioperative, the choice between liberal or restrictive approach did not affect overall major postoperative complications or mortality. In a subgroup analysis, a liberal as compared to a restrictive perioperative fluid policy was associated with lower overall complication renal major events, as compared to the restrictive.

Trial Registration
CRD42020218059; Registration: February 2020, https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=218059.
Therapeutic potential of targeting Tfr/Tfh cell balance by low-dose-IL-2 in active SLE: a post hoc analysis from a double-blind RCT study
Authors: Miao Miao , Xiao Xian , Tian Jiayi , Zhufeng Yunzhi , Feng Ruiling , Zhang Ruijun , Chen Jiali , Zhang Xiaoying , Huang Bo , Jin Yuebo , Sun Xiaolin , He Jing , Li Zhanguo 
Published: June 2021

Abstract
Objective
To investigate the regulation of T follicular regulatory (Tfr) and T follicular (Tfh) cell subtypes by low-dose IL-2 in systemic lupus erythematosus (SLE) in a randomized, double-blind, placebo-controlled clinical trial.

Methods
A post hoc analysis was performed in a randomized cohort of SLE patients (n=60) receiving low-dose IL-2 therapy (n=30) or placebo (n=30), along with the standard of care treatment. The primary endpoint was the attainment of SLE responder index-4 (SRI-4) at week 12 in the trial. Twenty-three healthy controls were enrolled for T cell subset detection at the same time as the trial. The t-stochastic neighbor embedding (tSNE) analysis of CD4 T subsets based on immune cells flow cytometry markers was performed to distinguish Tfh, Tfh1, Tfh2, Tfh17, and Tfr cell subsets.

Results
Compared with HC, the frequency of Tfr (CXCR5+PD-1low Treg and CXCR5+PD-1high Treg) cells was significantly reduced, while the pro-inflammatory Tfh cells were increased in patients with SLE. The imbalanced Tfh cell was associated with several pathogenic factors (anti-dsDNA antibodies (r=0.309, P=0.027) and serum IL-17 (r=0.328, P=0.021)) and SLE Disease Activity Index (SLEDAI) score (r=0.273, P=0.052). Decreased CXCR5+PD-1low Treg/Tfh and CXCR5+PD-1low Treg/Tfh17 were both associated with increased immunoglobulin M (IgM) (r=−0.448, P=0.002 and r=−0.336, P=0.024, respectively). Efficacy of low-dose IL-2 therapy was associated with a restored Tfr/Tfh cell balance.

Conclusion
These data support the hypothesis that promotion of Tfr is associated with decreased disease activities and that low-dose IL-2 therapy can recover Tfr/Tfh immune balance.

Trial registration number
ClinicalTrials.gov Registries (NCT02465580).
Chlamydia pecorum detection in aborted and stillborn lambs from Western Australia
Authors: Clune Tom , Besier Shane , Hair Sam , Hancock Serina , Lockwood Amy , Thompson Andrew , Jelocnik Martina , Jacobson Caroline 
Published: June 2021

AbstractLamb survival is an important welfare and productivity issue for sheep industries worldwide. Lower lamb survival has been reported for primiparous ewes, but the causes of this are not well studied. The aim of this study was to determine causes of perinatal deaths for lambs born to primiparous ewes in Western Australia, and identify if infectious diseases are implicated. Lamb mortality from birth to marking were determined for 11 primiparous ewe flocks on 10 farms in Western Australia. Lamb mortality from birth to marking averaged 14% for single-born and 26% for multiple-born lambs. Lamb necropsies (n = 298) identified starvation–mismosthering–exposure (34%), dystocia (24%) and stillbirth (15%) as the most common causes of perinatal lamb death. There was no evidence of exotic abortigenic pathogens in aborted and stillborn lambs (n = 35). Chlamydia pecorum was detected by qPCR in 15/35 aborted and stillborn lambs on 5/6 farms. Preliminary molecular characterisation of C. pecorum detected in samples from aborted and stillborn lambs (n = 8) using both Multilocus Sequence Typing and ompA genotyping indicated all strains were genetically identical to previously described pathogenic livestock strains, denoted ST23, and dissimilar to gastrointestinal strains. High frequency of detection of a pathogenic C. pecorum strains ST23 associated with ovine abortion and stillbirth on multiple farms located across a wide geographic area has not been previously reported. Chlamydia pecorum may contribute to reproductive wastage for primiparous sheep in Western Australia. Further investigation to understand C. pecorum epidemiology and impact on sheep reproduction is warranted.
Seven-year follow-up of posterior chamber phakic intraocular lens with central port design
Authors: Fernández-Vega-Cueto Luis , Alfonso-Bartolozzi Belén , Lisa Carlos , Madrid-Costa David , Alfonso José F. 
Published: June 2021

Abstract
Background
To assess the clinical outcomes of the Visian Implantable Collamer Lens (ICL) with a central port throughout 7 years of follow-up.

Methods
Eighty-four eyes of 52 patients were evaluated over a follow-up period of 7 years after V4c ICL implantation. Uncorrected (UDVA) and corrected (CDVA) distance visual acuities, refraction, intraocular pressure (IOP), endothelial cell density (ECD) and vault were analysed.

Results
The mean postoperative UDVA (logMAR) was 0.04 ± 0.11, 0.13 ± 0.19 and 0.17 ± 0.23 at 1-, 5- and 7-years, respectively (P < 0.0001). The mean CDVA (logMAR) remains unchanged throughout a 7-year follow-up period (0.02 ± 0.08 and 0.02 ± 0.08, at 5- and 7-years, respectively, P = 0.2). At all follow-up visits, more than 95% of the eyes achieved a CDVA of 20/25 or better and more than 85% a CDVA of 20/20. At the end of the follow-up (7 years), no eye lost more lines of CDVA, 56 eyes (66.7%) and 28 eyes (33.3%) gained lines of CDVA. At 7-years, the spherical equivalent was − 0.62 ± 0.62 D. No significant increase in IOP (> 20 mmHg or an increase higher than 5 mmHg) occurred in any case throughout the 7-year of follow-up. The loss in ECD from the preoperative baseline at the last follow-up visit was 2.6%. No intraoperative or postoperative complications or adverse events occurred during the follow-up period.

Conclusions
The outcomes of this study show the long-term viability of the V4c ICL implantation as a surgical option for the correction of myopia.
In the Wake of Visual Failure
Authors: Sung Wendy 
Published: June 2021

AbstractThis article examines the role of the visual in instances of recorded anti-Black racial violence and pushes against dominant discourses of the technological rescue narrative—that technology and more visibility will lead to different outcomes of accountability, protection, and safety. Instead, this article argues that the tightly bound association of anti-Black racial violence's recognizability to the visual has created a dynamic that simultaneously moves us closer to and further away from its ontological truths. Examining Twitter as a multisensorial platform and its users’ imaginative engagements with the #IfIDieInPoliceCustody hashtag memorializing Sandra Bland's death, the author identifies that users craft an anticipatory nonspectatorship, a mode of imaginative witnessing arising from the contexts of technological and visual failure and the situated imaginations of Black epistemologies. These users register a deep suspicion of the evidentiary and refuse the spectacular of racial violence's visual form, instead highlighting its ubiquitous and quotidian nature by asserting themselves into their own scenes of visual failure and becoming witnesses to their own imagined deaths. Finally, in identifying the visual failures surrounding Sandra Bland's jail cell, the author illuminates how the ontology of the glitch can demonstrate the mechanics of white supremacy's operations.
Social Reading? On the Rise of a “Bookish” Reading Culture Online
Authors: Birke Dorothee 
Published: June 2021

AbstractWhile the internet is often seen as having destroyed book culture, this article is interested in those areas in our contemporary media environment where book and internet culture actually converge. Focusing on the example of BookTube, the author examines how book culture is “done” on the internet and analyzes the values attached to the media practices involved. In particular, in millennial book culture, social aspects of reading are often emphasized. This trend is usually associated with the new affordances of social media and either assessed positively (e.g., by proponents of the internet as a democratizing force) or negatively (e.g., by detractors of the internet as fostering superficiality). The author argues that such a simplistic binary view can be transcended if one takes a historical perspective, reflecting on how sociality and self-fashioning have been integral aspects of book culture for centuries. At the same time, she shows the extent to which BookTube provides new opportunities to socialize around reading.
In Search of Pure Sound: Sanqu Songs, Genre Aesthetics, and Translation Tactics
Authors: Sieber Patricia , De Grandis Mario , Wang Ke , Yao Hui , Gao Jingying , McNally Ian , Yichun Xu , Nunes Jenn Marie 
Published: June 2021

Abstract
This article consists of an introduction by Patricia Sieber and six short essays on translation approaches together with actual translations of sanqu songs by Mario De Grandis, Ke Wang, Hui Yao, Jingying Gao and Ian McNally, Xu Yichun, and Jenn Marie Nunes. The introduction provides a short history of the translation of sanqu songs into English, followed by a reflection on which distinctive features of the genre beg for attention in the translation process. In particular, it argues that the different sonic features of sanqu merit close consideration, the loss of the notational contours of the original tunes notwithstanding. Rather than bemoaning the absence of the underlying music, it suggests that, in keeping with Walter Benjamin's vision of the “task of the translator,” translation into another language can be an opportunity to reinvent that musicality in different ways. The six short essays that follow consider sanqu songs from the corpus of diasporic writers from the Yuan dynasty, with a view toward enriching the repertoire of translation strategies for sanqu in terms of musicality and other salient features of the genre. The six essays discuss, respectively, pronouns, rhyme, punctuation, language registers, allusion, and citational practice. In contextualizing such strategies theoretically and illustrating them with examples, the short essays seek to contribute more broadly to the theory and practice of the literary translation of Chinese poetic forms.
Super-resolution microscopy reveals the arrangement of inner membrane protein complexes in mammalian mitochondria
Authors: Palmer Catherine S. , Lou Jieqiong , Kouskousis Betty , Pandzic Elvis , Anderson Alexander J. , Kang Yilin , Hinde Elizabeth , Stojanovski Diana 
Published: June 2021

ABSTRACT
The mitochondrial inner membrane is a protein-rich environment containing large multimeric complexes, including complexes of the mitochondrial electron transport chain, mitochondrial translocases and quality control machineries. Although the inner membrane is highly proteinaceous, with 40-60% of all mitochondrial proteins localised to this compartment, little is known about the spatial distribution and organisation of complexes in this environment. We set out to survey the arrangement of inner membrane complexes using stochastic optical reconstruction microscopy (STORM). We reveal that subunits of the TIM23 complex, TIM23 and TIM44 (also known as TIMM23 and TIMM44, respectively), and the complex IV subunit COXIV, form organised clusters and show properties distinct from the outer membrane protein TOM20 (also known as TOMM20). Density based cluster analysis indicated a bimodal distribution of TIM44 that is distinct from TIM23, suggesting distinct TIM23 subcomplexes. COXIV is arranged in larger clusters that are disrupted upon disruption of complex IV assembly. Thus, STORM super-resolution microscopy is a powerful tool for examining the nanoscale distribution of mitochondrial inner membrane complexes, providing a ‘visual’ approach for obtaining pivotal information on how mitochondrial complexes exist in a cellular context.
Substratum stiffness tunes membrane voltage in mammary epithelial cells
Authors: Silver Brian B. , Zhang Sherry X. , Rabie Emann M. , Nelson Celeste M. 
Published: June 2021

ABSTRACT
Membrane voltage (Vm) plays a critical role in the regulation of several cellular behaviors, including proliferation, apoptosis and phenotypic plasticity. Many of these behaviors are affected by the stiffness of the underlying extracellular matrix, but the connections between Vm and the mechanical properties of the microenvironment are unclear. Here, we investigated the relationship between matrix stiffness and Vm by culturing mammary epithelial cells on synthetic substrata, the stiffnesses of which mimicked those of the normal mammary gland and breast tumors. Although proliferation is associated with depolarization, we surprisingly observed that cells are hyperpolarized when cultured on stiff substrata, a microenvironmental condition that enhances proliferation. Accordingly, we found that Vm becomes depolarized as stiffness decreases, in a manner dependent on intracellular Ca2+. Furthermore, inhibiting Ca2+-gated Cl− currents attenuates the effects of substratum stiffness on Vm. Specifically, we uncovered a role for cystic fibrosis transmembrane conductance regulator (CFTR) in the regulation of Vm by substratum stiffness. Taken together, these results suggest a novel role for CFTR and membrane voltage in the response of mammary epithelial cells to their mechanical microenvironment.