bluuebunny/crossref_metadata_2025_split huggingface dataset:
The cancer‐associated fibroblasts related gene CALD1 is a prognostic biomarker and correlated with immune infiltration in bladder cancer
Authors: Du YiHeng , Jiang Xiang , Wang Bo , Cao Jin , Wang Yi , Yu Jiang , Wang XiZhi , Liu HaiTao 
Published: May 2021

Abstract
Background
Stromal components of the tumor microenvironment contribute to bladder cancer progression, and Cancer-Associated Fibroblasts (CAFs) were reported to play an important role. Accumulating pieces of evidence indicate that CAFs participate in the crosstalk with tumor cells and have a complex interaction network with immune components. Further studies on the role of CAFs in the bladder cancer microenvironment and searching for possible specific markers are important for a deeper understanding of CAFs in bladder cancer progression and immunomodulation.

Methods
In the present study, we examined the abundance of CAFs in the TCGA and GEO datasets using the MCP-COUNTER algorithm. Additionally, the expression of genes related to CAFs was analyzed through the Weighted Gene Co-expression Network Analysis (WGCNA). The CIBERSORT and ESTIMATE algorithms were used to discuss the correlation of the key CAFs-related gene and the tumor microenvironment components. Immunohistochemistry analysis in clinical samples was used to validate the results of bioinformatics analysis.

Results
The results showed that CAFs were closely associated with the progression and prognosis of bladder cancer. WGCNA also revealed that CALD1 was a key CAFs-related gene in bladder cancer. Moreover, further in-depth analysis showed that CALD1 significantly affected the progression and prognosis of bladder cancer. The CIBERSORT and ESTIMATE algorithms demonstrated significant correlations between CALD1 and the tumor microenvironment components, including CAFs, macrophages, T cells, and multiple immune checkpoint related genes. Finally, immunohistochemistry results validated the strong association of CALD1 with CAFs and macrophages.

Conclusions
In the present study, we confirmed the cancer-promoting roles of CAFs in bladder cancer. Being a key gene associated with CAFs, CALD1 may promote bladder cancer progression by remodeling the tumor microenvironment. The bioinformatics methods, including the CIBERSORT, MCP-COUNTER and ESTIMATE algorithms, may provide important value for studying the tumor microenvironment.
GM-CSF mediates immune evasion via upregulation of PD-L1 expression in extranodal natural killer/T cell lymphoma
Authors: Rong Qi-xiang , Wang Fang , Guo Zhi-xing , Hu Yi , An Sai-nan , Luo Min , Zhang Hong , Wu Shao-cong , Huang Hui-qiang , Fu Li-wu 
Published: May 2021

Abstract
Background
Granulocyte-macrophage colony stimulating factor (GM-CSF) is a cytokine that is used as an immunopotentiator for anti-tumor therapies in recent years. We found that some of the extranodal natural killer/T cell lymphoma (ENKTL) patients with the treatment of hGM-CSF rapidly experienced disease progression, but the underlying mechanisms remain to be elucidated. Here, we aimed to explore the mechanisms of disease progression triggered by GM-CSF in ENKTL.

Methods
The mouse models bearing EL4 cell tumors were established to investigate the effects of GM-CSF on tumor growth and T cell infiltration and function. Human ENKTL cell lines including NK-YS, SNK-6, and SNT-8 were used to explore the expression of programmed death-ligand 1 (PD-L1) induced by GM-CSF. To further study the mechanisms of disease progression of ENKTL in detail, the mutations and gene expression profile were examined by next-generation sequence (NGS) in the ENKTL patient’s tumor tissue samples.

Results
The mouse-bearing EL4 cell tumor exhibited a faster tumor growth rate and poorer survival in the treatment with GM-CSF alone than in treatment with IgG or the combination of GM-CSF and PD-1 antibody. The PD-L1 expression at mRNA and protein levels was significantly increased in ENKTL cells treated with GM-CSF. STAT5A high-frequency mutation including p.R131G, p.D475N, p.F706fs, p.V707E, and p.S710F was found in 12 ENKTL cases with baseline tissue samples. Importantly, STAT5A-V706fs mutation tumor cells exhibited increased activation of STAT5A pathway and PD-L1 overexpression in the presence of GM-CSF.

Conclusions
These findings demonstrate that GM-CSF potentially triggers the loss of tumor immune surveillance in ENKTL patients and promotes disease progression, which is associated with STAT5 mutations and JAK2 hyperphosphorylation and then upregulates the expression of PD-L1. These may provide new concepts for GM-CSF application and new strategies for the treatment of ENKTL.
Small airway dysfunction and poor asthma control: a dangerous liaison
Authors: Cottini Marcello , Licini Anita , Lombardi Carlo , Bagnasco Diego , Comberiati Pasquale , Berti Alvise 
Published: May 2021

AbstractAsthma is a common chronic condition, affecting approximately 339 million people worldwide. The main goal of the current asthma treatment guidelines is to achieve clinical control, encompassing both the patient symptoms and limitations and the future risk of adverse asthma outcomes. Despite randomized controlled trials showing that asthma control is an achievable target, a substantial proportion of asthmatics remain poorly controlled in real life. The involvement of peripheral small airways has recently gained greater recognition in asthma, and many studies suggest that the persistent inflammation at these sites leads to small airway dysfunction (SAD), strongly contributing to a worse asthma control. Overall, the impulse oscillometry (IOS), introduced in the recent years, seems to be able to sensitively assess small airways, while conventional spirometry does not. Therefore, IOS may be of great help in characterizing SAD and guiding therapy choice. The aim of this article is to review the literature on SAD and its influence on asthma control, emphasizing the most recent evidence.
Protein nanoparticles in drug delivery: animal protein, plant proteins and protein cages, albumin nanoparticles
Authors: Kianfar Ehsan 
Published: May 2021

AbstractIn this article, we will describe the properties of albumin and its biological functions, types of sources that can be used to produce albumin nanoparticles, methods of producing albumin nanoparticles, its therapeutic applications and the importance of albumin nanoparticles in the production of pharmaceutical formulations. In view of the increasing use of Abraxane and its approval for use in the treatment of several types of cancer and during the final stages of clinical trials for other cancers, to evaluate it and compare its effectiveness with conventional non formulations of chemotherapy Paclitaxel is paid. In this article, we will examine the role and importance of animal proteins in Nano medicine and the various benefits of these biomolecules for the preparation of drug delivery carriers and the characteristics of plant protein Nano carriers and protein Nano cages and their potentials in diagnosis and treatment. Finally, the advantages and disadvantages of protein nanoparticles are mentioned, as well as the methods of production of albumin nanoparticles, its therapeutic applications and the importance of albumin nanoparticles in the production of pharmaceutical formulations.
Evaluation of sleep disorder in orthopedic trauma patients: a retrospective analysis of 1129 cases
Authors: Yang Hai , Liu Yi-jia , Ye Jia-lu , Zhao Li-hong , Li Ling-li , Hou Xiao-ling 
Published: May 2021

Abstract
Background
In the trauma center wards, it is not unusual for patients to have sleep disorders, especially patients with an acute injury. Meanwhile, there is substantial evidence that sleep disorder is a predictor of depression and is an important feature of posttraumatic stress disorder.

Methods
All orthopedic trauma patients confined in a trauma ward in West China Hospital of Sichuan University between April 2018 and July 2019 were included in this retrospective study. Patients with mental impairment or craniocerebral injuries were excluded from the study. Basic demographic data and the Injury Severity Score (ISS) classification based on medical records were collected. The Pittsburgh sleep quality index (PSQI) was used to evaluate sleep quality, the visual analog scale (VAS) was used to evaluate physical pain, and the Barthel Index (BI) was used to evaluate activities of daily living (ADL). Univariate linear regression analysis and multivariate linear regression analysis were used to identify independently related factors.

Results
The average PSQI score was 6.3 (± 4.0). A total of 581 (51.4%) patients had a PSQI score > 5, indicating the presence of sleep disorders. The PSQI score was > 10 in 174 (15.4%) patients. Univariate statistical analysis showed that age, sex, education, ADL, and ISS classification were associated with increased PSQI scores. Marital status and pain were not associated with increased PSQI scores. When we used multivariate analysis to control for confounding variables, sex, ADL, and ISS classification remained independently associated with PSQI (P = 0.002, < 0.000, and 0.002, respectively).

Conclusions
In our study, sleep disorders were common (51.4% with PSQI > 5) and serious (15.4% with PSQI > 10) in patients with traumatic orthopedic injury. The following factors were closely associated with sleep disorders: sex, ADL, and ISS classification. Moreover, age and educational attainment have an independent impact on sleep quality. Unexpectedly, the VAS score for pain was not independently associated with the seriousness of sleep quality, which may be related to preemptive and multimodal analgesia. Further studies are required to clarify this ambiguity.
Genes associated with inflammation and bone remodeling are highly expressed in the bone of patients with the early-stage cam-type femoroacetabular impingement
Authors: Gao Guanying , Wu Ruiqi , Liu Rongge , Wang Jianquan , Ao Yingfang , Xu Yan 
Published: May 2021

Abstract
Background
Recent studies have shown high expression levels of certain inflammatory, anabolic, and catabolic genes in the articular cartilage from the impingement zone of the hips with femoroacetabular impingement (FAI), representing an increased metabolic state. Nevertheless, little is known about the molecular properties of bone tissue from the impingement zone of hips with FAI.

Methods
Bone tissue samples from patients with early-stage cam-type FAI were collected during hip arthroscopy for treatment of cam-type FAI. Control bone tissue samples were collected from six patients who underwent total hip replacement because of a femoral neck fracture. Quantitative real-time polymerase chain reaction (PCR) was performed to determine the gene expression associated with inflammation and bone remodeling. The differences in the gene expression in bone tissues from the patients with early-stage cam-type FAI were also evaluated based on clinical parameters.

Results
In all, 12 patients with early-stage cam-type FAI and six patients in the control group were included in this study. Compared to the control samples, the bone tissue samples from patients with FAI showed higher expression levels of interleukin-6 (IL-6), alkaline phosphatase (ALP), receptor activator of nuclear factor-kB ligand (RANKL), and osteoprotegerin (OPG) (P < 0.05). IL-1 expression was detected only in the control group. On the other hand, there was no significant difference in IL-8 expression between the patients with FAI and the control group. The patients with FAI having a body mass index (BMI) of >24 kg/m2 showed higher ALP expression (P < 0.05). Further, the expression of IL-6 and ALP was higher in the patients with FAI in whom the lateral center-edge angle was >30° (P < 0.05).

Conclusions
Our results indicated the metabolic condition of bone tissues in patients with early-stage cam-type FAI differed from that of normal bone in the femoral head-neck junction. The expression levels of the genes associated with inflammation and bone remodeling were higher in the bone tissue of patients with early-stage cam-type FAI than in the patients with normal bone tissue.
Anatomical basis of the support of fibula to tibial plateau and its clinical significance
Authors: Jiang Wen-Bin , Sun Shi-Zhu , Li Chan , Adds Philip , Tang Wei , Chen Wei , Yu Sheng-Bo , Sui Hong-Jin 
Published: May 2021

AbstractBackgroundThe fibula is only indirectly involved in the composition of the human knee joint and has therefore been neglected in the research on knee osteoarthritis. Nonuniform settlement of the proximal tibia plateau is clinically defined as when the height of the medial tibial plateau is lower than that of the lateral side in medial compartment knee osteoarthritis (KOA). The non-uniform settlement of the proximal tibia plateau may be caused by fibular support on the lateral side. Orthopedic surgeons practice partial fibulectomy based on the clinical manifestation of nonuniform settlement, and this technique has been shown to reduce pain and improve function in patients with medial compartment KOA. However, this hypothesis of the mechanism of nonuniform settlement lacks an anatomical basis.MethodsThe P45 polyester plastination technique was used to prepare sections of the proximal tibiofibular joint to investigate the distribution of the bone trabeculae in the region of the lateral tibial plateau.ResultsThere was uneven distribution of trabeculae in the lateral condyle of the tibia and the head and neck of the fibula. The fibula and the posterolateral cortex of the shaft of the tibia united to form an arch beam via the tibiofibular joint. Many thick, dense trabeculae were present in a longitudinal direction above the tibiofibular arch.ConclusionsThe fibula supports the lateral tibial plateau, and the trabeculae were concentrated above the tibiofibular arch.
Coronary sinus atrial septal defects in adults over the past 20 years at new Tokyo hospital: case series
Authors: Sugimori Haruhiko , Nakao Tatsuya , Ikegaya Yuki , Iwahashi Daisuke , Tsuda Shoichi , Kume Nao , Onishi Hirokazu , Nakamura Sunao 
Published: May 2021

Abstract
Background
An isolated coronary sinus (CS) atrial septal defect (ASD) is defined as a CS unroofed in the terminal portion without a persistent left superior vena cava or other anomalies. This defect is rare and part of the wide spectrum of unroofed CS syndrome (URCS). Recently, several reports have described this finding. The database of New Tokyo Hospital was searched to determine the incidence of this defect. Additionally, to raise awareness of this condition, the findings from five patients with CS ASD who underwent surgical repair at New Tokyo Hospital are discussed.

Case presentation
The patients were three women and two men with an age range of 63–77 years. All patients underwent transthoracic echocardiography and computed tomography, and one underwent magnetic resonance imaging. In two patients, the defect was found unexpectedly intraoperatively; left-to-right shunting was apparent in the other three patients preoperatively. The pulmonary-to-systemic blood flow ratio ranged from 1.42 to 3.1 following cardiac catheterization, and oxygen saturation step-up was seen on the right side of the heart. Valvular regurgitation was seen in 4/5 patients with different combinations and degrees of mitral, tricuspid, and aortic valve involvement. Right atrial and ventricular dilation were seen in 4/5 patients; three patients had left atrial dilation. Three patients experienced atrial fibrillation, and one of these also experienced paroxysmal ventricular contractions. All patients underwent surgical repair, and some underwent multiple procedures. One patient who had previously undergone kidney transplantation died approximately 1 year postoperatively; the remaining four patients are currently experiencing good activities of daily living without symptoms.

Conclusions
CS ASD (Kirklin and Barratt–Boyes type IV URCS) comprised 1.3% of adult congenital heart surgeries and 0.07% of adult open-heart surgeries at New Tokyo Hospital from 1999 to 2019. At New Tokyo Hospital, cardiac surgery is performed mainly for patients with acquired cardiac disease, and CS ASD is rare. Early diagnosis is important, as well as early surgical repair in symptomatic patients, especially those with blood access shunts, which may overload the heart. The case of a poor prognosis in this series is noteworthy, as similar cases have not been reported previously.
Large papillary fibroelastoma of right atrium, an unusual case of respiratory distress in a young man
Authors: Ho Yan Le , Ng Pui Fong , Krishinan Sotheenathan , Abdul Kareem Basheer Ahamed 
Published: May 2021

Abstract
Background
Papillary fibroelastomas are rare but benign cardiac tumour that are often found on cardiac valvular surfaces. Their clinical manifestations ranging from clinically asymptomatic to substantial complications that are usually secondary to systemic embolism. Multiple theories have been proposed to explain the pathophysiology of its formation.

Case presentation
We reported a rare case of large papillary fibroelastoma in the right atrium of a young gentleman which was complicated with pulmonary embolism. Transthoracic echocardiography identified a large pedunculated mass measuring 3.4cmX3.4cmX2cm in right atrium with stalk attached to interatrial septum. The intracardiac mass was resected surgically, which revealed papillary fibroelastoma in histology examination.

Conclusion
Differential diagnosis of intracardiac masses requires clinical information, laboratory tests and imaging modalities including echocardiography. Incidentally discovered papillary fibroelastomas are treated on the basis of their sizes, site, mobility and potential embolic complications. Due to the embolic risk inherent to intraacardiac masses, surgical resection represents an effective curative protocol in treating both symptomatic and asymptomatic right sided and left sided papillary fibroelastomas, with excellent long term postoperative prognosis.
Survival of pediatric patients after cardiopulmonary resuscitation for in-hospital cardiac arrest: a systematic review and meta-analysis
Authors: Bimerew Melaku , Wondmieneh Adam , Gedefaw Getnet , Gebremeskel Teshome , Demis Asmamaw , Getie Addisu 
Published: May 2021

AbstractBackgroundIn-hospital cardiac arrest is a major public health issue. It is a serious condition; most probably end up with death within a few minutes even with corrective measures. However, cardiopulmonary resuscitation is expected to increase the probability of survival and prevent neurological disabilities in patients with cardiac arrest. Having a pooled prevalence of survival to hospital discharge after cardiopulmonary resuscitation is vital to develop strategies targeted to increase probability of survival among patients with cardiac arrest. Therefore, this systematic review and meta-analysis was aimed to assess the pooled prevalence of survival to hospital discharge among pediatric patients who underwent cardiopulmonary resuscitation for in-hospital cardiac arrest.MethodsPubMed, Google Scholar, and Cochrane review databases were searched. To have current (five-year) evidence, only studies published in 2016 to 2020 were included. The weighted inverse variance random-effects model at 95%CI was used to estimate the pooled prevalence of survival. Heterogeneity assessment, test of publication bias, and subgroup analyses were also employed accordingly.ResultsTwenty-five articles with a total sample size of 28,479 children were included in the final analysis. The pooled prevalence of survival to hospital discharge was found to be 46% (95% CI = 43.0–50.0%; I2 = 96.7%;p < 0.001). Based on subgroup analysis by “continent” and “income level”, lowest prevalence of pooled survival was observed in Asia (six studies; pooled survival =36.0% with 95% CI = 19.01–52.15%; I2 = 97.4%;p < 0.001) and in low and middle income countries (six studies, pooled survival = 34.0% with 95% CI = 17.0–51.0%, I2 = 97.67%,p < 0.001) respectively.ConclusionAlthough there was an extremely high heterogeneity among reported results (I2 = 96.7%), in this meta-analysis more than half of pediatric patients (54%) who underwent cardiopulmonary resuscitation for in-hospital cardiac arrest did not survived to hospital discharge. Therefore, developing further strategies and encouraging researches might be crucial.
Fidelity is not easy! Challenges and guidelines for assessing fidelity in complex interventions
Authors: Ginsburg Liane R. , Hoben Matthias , Easterbrook Adam , Anderson Ruth A. , Estabrooks Carole A. , Norton Peter G. 
Published: May 2021

Abstract
Background
Fidelity in complex behavioural interventions is underexplored and few comprehensive or detailed fidelity studies report on specific procedures for monitoring fidelity. Using Bellg’s popular Treatment Fidelity model, this paper aims to increase understanding of how to practically and comprehensively assess fidelity in complex, group-level, interventions.

Approach and lessons learned
Drawing on our experience using a mixed methods approach to assess fidelity in the INFORM study (Improving Nursing home care through Feedback On perfoRMance data—INFORM), we report on challenges and adaptations experienced with our fidelity assessment approach and lessons learned. Six fidelity assessment challenges were identified: (1) the need to develop succinct tools to measure fidelity given tools tend to be intervention specific, (2) determining which components of fidelity (delivery, receipt, enactment) to emphasize, (3) unit of analysis considerations in group-level interventions, (4) missing data problems, (5) how to respond to and treat fidelity ‘failures’ and ‘deviations’ and lack of an overall fidelity assessment scheme, and (6) ensuring fidelity assessment doesn’t threaten internal validity.

Recommendations and conclusions
Six guidelines, primarily applicable to group-level studies of complex interventions, are described to help address conceptual, methodological, and practical challenges with fidelity assessment in pragmatic trials. The current study offers guidance to researchers regarding key practical, methodological, and conceptual challenges associated with assessing fidelity in pragmatic trials. Greater attention to fidelity assessment and publication of fidelity results through detailed studies such as this one is critical for improving the quality of fidelity studies and, ultimately, the utility of published trials.

Trial registration
ClinicalTrials.gov NCT02695836. Registered on February 24, 2016
High pressure systems as sustainable extraction and pre-treatment technologies for a holistic corn stover biorefinery
Authors: Noppawan Pakin , Lanctôt Adrienne Gallant , Magro Maria , Navarro Pablo Gil , Supanchaiyamat Nontipa , Attard Thomas M. , Hunt Andrew J. 
Published: May 2021

AbstractThis mini-review assesses supercritical carbon dioxide (scCO2) extraction and high-pressure carbon dioxide pre-treatment technologies for valorisation of corn stover agricultural residues with particular focus on showing how these can aid in the creation of a holistic biorefineries. Corn stover is currently the largest source of agriculture residues in the USA, as such there is significant potential for exploitation to yield valuable chemicals. ScCO2 extraction could lead to the recovery of a variety of different chemicals which include flavonoids, sterols, steroid ketones, hydrocarbons, saturated fatty acids, unsaturated fatty acids, fatty alcohols, phenolics and triterpenoids. Importantly, recent studies have not only demonstrated that supercritical extraction can be utilized for the recovery of plant lipids for use in consumer products, including nutraceuticals and personal care, but the processing of treated biomass can lead to enhanced yields and recovery of other products from biorefinery processes. Despite the great potential and opportunities for using scCO2 and high-pressure systems in a biorefinery context their real-world application faces significant challenges to overcome before it is widely applied. Such challenges have also been discussed in the context of this mini-review.