bluuebunny/crossref_metadata_2025_split huggingface dataset:
Treatment with eFT-508 increases chemosensitivity in breast cancer cells by modulating the tumor microenvironment
Authors: Yang Zhao-ying , Jiang Cheng-wei , Zhang Wen-long , Sun Guang 
Published: June 2022

Abstract
Background
Patients with triple-negative breast cancer (TNBC) are better responders to neoadjuvant chemotherapy; however, they are poor in the durability of response with decreased overall and progression-free survival.

Methods
Given that significant improvements have been reported with PD-L1-PD-1 blockade in different cancers, we evaluated the in vitro and in vivo effectiveness of Tomivosertib (eFT-508), an anthracycline, adriamycin, and MNK1/2 inhibitor, which has been previously shown to inhibit translation of PD-L1 in mice model of liver cancer, alone or in combination using BC cell lines and an orthotopic xenograft mice model using the TNBC cell line MDA-MB-231.

Results
Within the context of The Cancer Genome Atlas (TCGA) dataset, expression of CD274 mRNA, which encodes programmed death-ligand 1 (PD-L1), was found to be significantly overexpressed in TNBC patients compared to patients with HER2 + or luminal breast cancer (BC). Even within TNBC sub-types, CD274 expression was significantly higher in the immune modulatory subtype (TNBC-IM).
BC cells exhibited high IC50 = 0.85 ± 0.07 nM with Adriamycin and significantly lower IC50 = 0.23 ± 0.04 nM with eFT-508 (P < 0.01). Combination treatment showed in vitro synergism on chemosensitivity. Combination therapy also exhibited a synergistic effect on inhibition of tumor growth and lung colonization in vivo. Mass cytometry-based evaluation of the tumor microenvironment revealed significant attenuation of both PD-L1 and PD-L2 following mono- or combination therapy with eFT-508.

Conclusions
Treatment with eFT-508 restored effector and cytotoxic function of tumor-infiltrating CD8 + T cells in mice. The remarkable efficacy observed both in vitro and in vivo, and clinical synergism with adriamycin, highlights the potential of eFT-508 as an alternative, yet more efficacious, therapeutic option for patients with TNBC.
Quality improvement in juvenile idiopathic arthritis: a mixed-methods implementation pilot of the CAPTURE-JIA dataset
Authors: McErlane Flora , Anderson Chris , Lawson-Tovey Saskia , Lee Barbara , Lee Chris , Lunt Laura , McDonagh Janet E. , Smith Andrew D. , Smith Nicola , Cleary Gavin 
Published: June 2022

Abstract
Background
A significant proportion of children and young people with juvenile idiopathic arthritis (JIA) do not achieve inactive disease during the first two years following diagnosis. Refinements to clinical care pathways have the potential to improve clinical outcomes but a lack of consistent and contemporaneous clinical data presently precludes standard setting and implementation of meaningful quality improvement programmes.
This study was the first to pilot clinical data collection and analysis using the CAPTURE-JIA dataset, and to explore patient and clinician-reported feasibility and acceptability data.

Methods
A multiphase mixed-methods approach enabled prospective collection of quantitative data to examine the feasibility and efficacy of dataset collection and of qualitative data informing the context and processes of implementation. An initial paper pilot informed the design of a bespoke electronic data collection system (the Agileware system), with a subsequent electronic pilot informing the final CAPTURE-JIA data collection tool.

Results
Paper collection of patient data was feasible but time-consuming in the clinical setting. Phase 1 paper pilot data (121 patients) identified three themes: problematic data items (14/62 data items received >40% missing data), formatting of data collection forms and a clinician-highlighted need for digital data collection, informing Phase 2 electronic data collection tool development. Patients and families were universally supportive of the collection and analysis of anonymised patient data to inform clinical care. No apparent preference for paper / electronic data collection was reported by families.
Phase 3 electronic pilot data (38 patients) appeared complete and the system reported to be easy to use. Analysis of the study dataset and a dummy longitudinal dataset confirmed that all eleven JIA national audit questions can be answered using the electronic system.

Conclusions
Multicentre CAPTURE-JIA data collection is feasible and acceptable, with a bespoke data collection system highlighted as the most satisfactory solution. The study is informing ongoing work towards a streamlined and flexible national paediatric data collection system to drive quality improvement in clinical care.
Monogenic disorders as mimics of juvenile idiopathic arthritis
Authors: Furness Laura , Riley Phil , Wright Neville , Banka Siddharth , Eyre Stephen , Jackson Adam , Briggs Tracy A. 
Published: June 2022

Abstract
Background
Juvenile idiopathic arthritis is the most common chronic rheumatic disease of childhood. The term JIA encompasses a heterogenous group of diseases. The variability in phenotype of patients affected by the disease means it is not uncommon for mimics of JIA to be misdiagnosed.

Case presentation
We present four cases who were treated in single tertiary rheumatology centre for JIA who were subsequently diagnosed with a rare monogenic disease. All four patients shared the unifying features of presenting in early childhood and subsequently suffered with refractory disease, not amenable to usual standards of treatment. Multicentric Carpotarsal Osteolysis Syndrome and Camptodactyly-arthropathy-coxa vara-pericarditis syndrome are non-inflammatory conditions and patients typically present with arthropathy, normal inflammatory markers and atypical radiological features. Blau syndrome is an autosomal dominant condition and patients will typically have symmetrical joint involvement with a strong family history of arthritis, signifying the genetic aetiology.

Conclusions
We share our learning from these cases to add to the growing portfolio of JIA mimics and to highlight when to consider an alternative diagnosis. In cases of refractory disease and diagnostic uncertainty further imaging and genetic testing can play a crucial role in establishing the aetiology. In all of these cases the correct diagnosis was made due to careful, longitudinal clinical phenotyping and a close working relationship between rheumatology, radiology and clinical genetics; highlighting the importance of the multidisciplinary team in managing complex patients.
Construction of the SHP-GLOX lignin regulation system and its application in rice straw
Authors: Wang Qingdong , Zhang Jiayuan , Li Yan , Wang Ran 
Published: June 2022

Abstract
Background
There is great productivity of rice(Oryza sativa L. spp. japonica) straw in China, which is a potential source of biomass for biofuel and forage. However, the high levels of lignins in rice straw limited its usage and induced the formation of agricultural waste. In order to modify the lignins contents to improve biofuel production and forage digestibility, we selected Soybean hull peroxidase (SHP) and Glyoxal oxidase (GLOX) as candidate genes to improve quality of rice straw. SHP, a class III plant peroxidase, is derived from multiple sources. It has several advantages, such as high resistance to heat, high stability under acidic and alkaline conditions, and a broad substrate range. SHP is speculated to be useful for lignin degradation. Glyoxal oxidase (GLOX) is an extracellular oxidase that can oxidize glyoxal and methylglyoxal in the extracellular medium to generate H2O2.

Results
In the present study, the SHP and GLOX genes in pCAMBIA3301-glycine-rich protein (GRP)-SHP-GLOX, designated the K167 vector, were optimized and introduced into rice embryos using Agrobacterium-mediated transformation. Positive transgenic rice embryos were examined using molecular, physiological, biochemical and fermentation tests. The outcomes suggested that SHP degraded lignin effectively.

Conclusions
This research has created a rice breeding material with normal growth and yield but stalks that are more amenable to degradation in the later stage for use in breeding rice varieties whose stalks are easily used for energy. Our results will improve the industrial and commercial applications of rice straw.
Long-term follow-up of voice changes after cervical mediastinoscopy
Authors: Achbar Ikram , Li Wilson W. L. , Timman Simone T. , van der Heide Stefan M. , Schuurbiers Olga C. J. , van der Heijden Erik H. F. M. , Verhagen Ad F. T. M. 
Published: June 2022

Abstract
Background
Vocal cord palsy after cervical mediastinoscopy is usually reported at less than 1%. However, its incidence might be underestimated and no follow-up studies are available. Our study aimed to evaluate the incidence of voice changes after cervical mediastinoscopy and report on long-term outcomes, including quality of life, after at least one-year follow-up.

Methods
A retrospective cohort study was performed, considering all patients who underwent cervical mediastinoscopy in our center between January 2011 and April 2016. Patients with pre-existing voice changes, voice changes only after pulmonary resection and patients who underwent neoadjuvant chemo(radio)therapy were excluded. Voice changes with full recovery within 14 days were attributed to intubation-related causes. Follow-up questionnaires, including the standardized Voice Handicap Index, were sent to patients with documented voice changes.

Results
Of 270 patients who were included for final analysis, 17 (6.3%) experienced voice changes after cervical mediastinoscopy, which persisted > 2 years in 4 patients (1.5%), causing mild to moderate disabilities in daily living. Twelve patients (out of 17, 71%) were referred for otolaryngology consultation, and paresis of the left vocal cord suggesting recurrent laryngeal nerve injury was confirmed in 10 (3.7% of our total study group). Additionally, 83% of the patients who were referred for otolaryngology consultation received voice treatment. Recovery rate after vocal exercises therapy and injection laryngoplasty was respectively 71% and 33%.

Conclusions
Voice changes after cervical mediastinoscopy is an underreported complication, with an incidence of at least 6.3% in our retrospective study, with persisting complaints in at least 1.5% of patients, leading to mild to moderate disabilities in daily living. These findings highlight the need for appropriate patient education for this underestimated complication, as well as the exploration of possible preventive measures.
Unraveling protein dynamics to understand the brain – the next molecular frontier
Authors: Brewer Kyle D. , Shi Sophia M. , Wyss-Coray Tony 
Published: June 2022

AbstractThe technological revolution to measure global gene expression at the single-cell level is currently transforming our knowledge of the brain and neurological diseases, leading from a basic understanding of genetic regulators and risk factors to one of more complex gene interactions and biological pathways. Looking ahead, our next challenge will be the reliable measurement and understanding of proteins. We describe in this review how to apply new, powerful methods of protein labeling, tracking, and detection. Recent developments of these methods now enable researchers to uncover protein mechanisms in vivo that may previously have only been hypothesized. These methods are also useful for discovering new biology because how proteins regulate systemic interactions is not well understood in most cases, such as how they travel through the bloodstream to distal targets or cross the blood–brain barrier. Genetic sequencing of DNA and RNA have enabled many great discoveries in the past 20 years, and now, the protein methods described here are creating a more complete picture of how cells to whole organisms function. It is likely that these developments will generate another transformation in biomedical research and our understanding of the brain and will ultimately allow for patient-specific medicine on a protein level.
LILRB2-mediated TREM2 signaling inhibition suppresses microglia functions
Authors: Zhao Peng , Xu Yuanzhong , Jiang Lu-Lin , Fan Xuejun , Ku Zhiqiang , Li Leike , Liu Xiaoye , Deng Mi , Arase Hisashi , Zhu Jay-Jiguang , Huang Timothy Y. , Zhao Yingjun , Zhang Chengcheng , Xu Huaxi , Tong Qingchun , Zhang Ningyan , An Zhiqiang 
Published: June 2022

AbstractBackgroundMicroglia plays crucial roles in Alzheimer’s disease (AD) development. Triggering receptor expressed on myeloid cells 2 (TREM2) in association with DAP12 mediates signaling affecting microglia function. Here we study the negative regulation of TREM2 functions by leukocyte immunoglobulin-like receptor subfamily B member 2 (LILRB2), an inhibitory receptor bearing ITIM motifs.MethodsTo specifically interrogate LILRB2-ligand (oAβ and PS) interactions and microglia functions, we generated potent antagonistic LILRB2 antibodies with sub-nanomolar level activities. The biological effects of LILRB2 antagonist antibody (Ab29) were studied in human induced pluripotent stem cell (iPSC)–derived microglia (hMGLs) for migration, oAβ phagocytosis, and upregulation of inflammatory cytokines. Effects of the LILRB2 antagonist antibody on microglial responses to amyloid plaques were further studied in vivo using stereotaxic grafted microglia in 5XFAD mice.ResultsWe confirmed the expression of both LILRB2 and TREM2 in human brain microglia using immunofluorescence. Upon co-ligation of the LILRB2 and TREM2 by shared ligands oAβ or PS, TREM2 signaling was significantly inhibited. We identified a monoclonal antibody (Ab29) that blocks LILRB2/ligand interactions and prevents TREM2 signaling inhibition mediated by LILRB2. Further, Ab29 enhanced microglia phagocytosis, TREM2 signaling, migration, and cytokine responses to the oAβ-lipoprotein complex in hMGL and microglia cell line HMC3. In vivo studies showed significantly enhanced clustering of microglia around plaques with a prominent increase in microglial amyloid plaque phagocytosis when 5XFAD mice were treated with Ab29.ConclusionsThis study revealed for the first time the molecular mechanisms of LILRB2-mediated inhibition of TREM2 signaling in microglia and demonstrated a novel approach of enhancing TREM2-mediated microglia functions by blocking LILRB2-ligand interactions. Translationally, a LILRB2 antagonist antibody completely rescued the inhibition of TREM2 signaling by LILRB2, suggesting a novel therapeutic strategy for improving microglial functions.
Hypoalbuminemia predicts inferior outcome in patients with AIDS-related lymphoma
Authors: Zhang Jinxin , Xie Zhiman , Cai Shaohang , Qin Shanfang , Ruan Guangjing , Lu Aili , Wu Yihua , Chen Juanjuan , Peng Jie 
Published: June 2022

Abstract
Background
The prognostic value of serum albumin in acquired immunodeficiency syndrome (AIDS)-related lymphoma (ARL) remains covered.

Methods
We retrospectively analyzed de novo ARL patients from 2013 to 2019 across three centers. Factors correlated with progression-free survival (PFS) and overall survival (OS) were evaluated in Kaplan–Meier, univariate and multivariate Cox proportional hazard models.

Results
A total of 86 ARL patients were enrolled with a median follow-up of 34 months. In the cohort, the OS and 2-year PFS rates were 37.5% and 35.4%, respectively. In multivariate models, older age (PFS, hazard ratios [HR] = 1.035, p = 0.037; OS, HR = 1.034, p = 0.041) and hypoalbuminemia (OS, HR = 0.910, p = 0.038) predicted inferior survival. ARL patients with hypoalbuminemia showed worse OS and 2-year PFS (p = 0.028 and p = 0.01, respectively), which was associated with poor Eastern Cooperative Oncology Group performance status (ECOG PS) and higher International Prognosis Index (IPI) score.

Conclusion
In conclusion, serum albumin at diagnosis is an independent prognostic factor for overall survival in AIDS-related lymphoma.
COVID-19 and abducens nerve palsy in a 9-year-old girl—case report
Authors: Capponi Martina , Cinicola Bianca Laura , Brindisi Giulia , Guido Cristiana Alessia , Torcé Maria Cristina , Zicari Anna Maria , Spalice Alberto 
Published: June 2022

Abstract
Background
Coronavirus disease 2019 (COVID-19) is a disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Although many reports have detailed a range of neurological symptoms in SARS-CoV-2-infected patients, studies of neuro-ophthalmological manifestations are still scarce.

Case presentation
We report a 9-year-old girl with abducens nerve palsy after COVID-19 with no evidence of other neurological disease on neuroimaging. At 2-month follow-up clinical conditions were improved.

Conclusions
The palsy may have occurred due to a possible post-infectious immune-mediated mechanism underlying the neuropathy, as opposed to direct viral infiltration. Despite being rare, this complication must be taken into account.
Using text and charts to provide social norm feedback to general practices with high overall and high broad-spectrum antibiotic prescribing: a series of national randomised controlled trials
Authors: Gold Natalie , Sallis Anna , Saei Ayoub , Arambepola Rohan , Watson Robin , Bowen Sarah , Franklin Matija , Chadborn Tim 
Published: June 2022

Abstract
Background
Sending a social norms feedback letter to general practitioners who are high prescribers of antibiotics has been shown to reduce antibiotic prescribing. The 2017-9 Quality Premium for primary care in England sets a target for broad-spectrum prescribing, which should be at or below 10% of total antibiotic prescribing. We tested a social norm feedback letter that targeted broad-spectrum prescribing and the addition of a chart to a text-only letter that targeted overall prescribing.

Methods
We conducted three 2-armed randomised controlled trials, on different groups of practices: Trial A compared a broad-spectrum message and chart to the standard-practice overall prescribing letter (practices whose percentage of broad-spectrum prescribing was above 10% and who had relatively high overall prescribing). Trial C compared a broad-spectrum message and a chart to a no-letter control (practices whose percentage of broad-spectrum prescribing was above 10% and who had relatively moderate overall prescribing). Trial B compared an overall-prescribing message with a chart to the standard practice overall letter (practices whose percentage of broad-spectrum prescribing was below 10% but who had relatively high overall prescribing). Letters were posted to general practitioners, timed to be received on 1 November 2018. The primary outcomes were practices’ percentage of broad-spectrum prescribing (trials A and C) and overall antibiotic prescribing (trial B) each month from November 2018 to April 2019 (all weighted by the number and characteristics of patients registered in the practice).

Results
We randomly assigned 1909 practices; 58 closed or merged during the trial, leaving 1851 practices: 385 in trial A, 674 in trial C, and 792 in trial B. AR(1) models showed that there were no statistically significant differences in our primary outcome measures: trial A β = − .199, p = .13; trial C β = .006, p = .95; trial B β = − .0021, p = .81. In all three trials, there were statistically significant time trends, showing that overall antibiotic prescribing and total broad-spectrum prescribing were decreasing.

Conclusion
Our broad-spectrum feedback letters had no effect on broad-spectrum prescribing; adding a bar chart to a text-only letter had no effect on overall antibiotic prescribing. Broad-spectrum and overall prescribing were both decreasing over time.

Trial registration
ClinicalTrials.gov NCT03862794. March 5, 2019.
Effect of new biological patch in repairing intrauterine adhesion and improving clinical pregnancy outcome in infertile women: study protocol for a randomized controlled trial
Authors: Pang Wen-Juan , Zhang Qing , Ding Hai-Xia , Sun Ning-Xia , Li Wen 
Published: June 2022

Abstract
Background
Endometrial fibrosis caused by intrauterine adhesion (IUA) can lead to hypomenorrhea, amenorrhea, and even infertility and abortion. The postoperative recurrence rate of severe IUA remains high, giving rise to low pregnancy rates. An extracellular matrix (ECM) scaffold, a new biological material that can promote cell proliferation and differentiation at lesions, has been widely used in general surgery and neurosurgery. The present study applied ECM scaffolds in obstetrics and gynecology for the first time to improve endometrial fibrosis, repair severe IUA, and improve pregnancy outcomes for infertile patients.

Methods
This paper presents a prospective randomized single-blind controlled superiority study of infertile women aged ≤40 years with IUA. According to the scoring criteria for IUA established by the American Fertility Society, patients with moderate or severe IUA were randomized into two groups at a ratio of 1:1; patients in the experimental group were treated with an ECM scaffold (small intestinal submucosa [SIS]) + intrauterine balloon, while patients in the control group were treated with an intrauterine balloon only. A hysteroscopic examination of adhesion repair was performed again after 2 months of postoperative hormone replacement therapy. Endometrial tissue was sampled during the two operations, and immunohistochemistry was used to observe endometrial and microvascular proliferation. After thawing and resuscitation, a postoperative frozen embryo transfer was performed on the participants in both groups, and their endometrial thickness, intrauterine volume, endometrial vascularization flow index, endometrial flow index, and uterine artery blood flow resistance were evaluated by 3D ultrasonography. The rates of embryo implantation, clinical pregnancy, and early spontaneous abortion were observed.

Discussion
The ECM scaffold (SIS) + intrauterine balloon method was able to repair endometrial fibrosis and improve IUA. This new technique represents a novel treatment method for improving the pregnancy outcome of infertile patients with moderate/severe IUA.

Trial registration
Chinese Clinical Trial Register ChiCTR2100052027. Registered on October 14, 2021.
Can the prophylactic administration of tranexamic acid reduce the blood loss after robotic-assisted radical prostatectomy? Robotic Assisted Radical Prostatectomy with tranEXamic acid (RARPEX): study protocol for a randomized controlled trial
Authors: Balik M. , Kosina J. , Husek P. , Pacovsky J. , Brodak M. , Cecka F. 
Published: June 2022

Abstract
Background
The prophylactic administration of tranexamic acid reduces blood loss during procedures at high risk of perioperative bleeding. Several studies in cardiac surgery and orthopedics confirmed this finding. The aim of this prospective, double-blind, randomized study is to evaluate the effect of tranexamic acid on peri-and postoperative blood loss and on the incidence and severity of complications.

Methods/design
Based on the results of our pilot study, we decided to conduct this prospective, double-blind, randomized trial to confirm the preliminary data. The primary endpoint is to analyze the effect of tranexamic acid on perioperative and postoperative blood loss (decrease in hemoglobin levels) in robotic-assisted radical prostatectomy. The additional endpoint is to analyze the effect of tranexamic acid on postoperative complications and confirm the safety of tranexamic acid in robotic-assisted radical prostatectomy.

Discussion
No study to date has tested the prophylactic administration of tranexamic acid at the beginning of robotic-assisted radical prostatectomy. This study is designed to answer the question of whether the administration of tranexamic acid might lower the blood loss after the procedure or increase the rate and severity of complications.

Trial registration
ClinicalTrials.gov NCT04319614. Registered on 25 March 2020