bluuebunny/crossref_metadata_2025_split huggingface dataset:
Nomogram for predicting cancer-specific survival in undifferentiated pleomorphic sarcoma: A Surveillance, Epidemiology, and End Results -based study
Authors: Xu Fengshuo , Zhao Fanfan , Feng Xiaojie , Li Chengzhuo , Han Didi , Zheng Shuai , Liu Yue , Lyu Jun 
Published: August 2021

Introduction The purpose of this study was to construct and validate a nomogram for predicting cancer-specific survival (CSS) in undifferentiated pleomorphic sarcoma (UPS) patients at 3, 5, and 8 years after the diagnosis. Methods Data for UPS patients were extracted from the SEER (Surveillance, Epidemiology, and End Results) database. The patients were randomly divided into a training cohort (70%) and a validation cohort (30%). The backward stepwise Cox regression model was used to select independent prognostic factors. All of the factors were integrated into the nomogram to predict the CSS rates in UPS patients at 3, 5, and 8 years after the diagnosis. The nomogram’ s performance was then validated using multiple indicators, including the area under the time-dependent receiver operating characteristic curve (AUC), consistency index (C-index), calibration curve, decision-curve analysis (DCA), integrated discrimination improvement (IDI), and net reclassification improvement (NRI). Results This study included 2,009 UPS patients. Ten prognostic factors were identified after analysis of the Cox regression model in the training cohort, which were year of diagnosis, age, race, primary site, histological grade, T, N, M stage, surgery status, and insurance status. The nomogram was then constructed and validated internally and externally. The relatively high C-indexes and AUC values indicated that the nomogram has good discrimination ability. The calibration curves revealed that the nomogram was well calibrated. NRI and IDI values were both improved, indicating that our nomogram was superior to the AJCC (American Joint Committee on Cancer) system. DCA curves demonstrated that the nomogram was clinically useful. Conclusions The first nomogram for predicting the prognosis of UPS patients has been constructed and validated. Its usability and performance showed that the nomogram can be applied to clinical practice. However, further external validation is still needed.
Impacts of three glyphosate formulations on gonadal development of Xenopus laevis
Authors: Babalola Oluwaseun O , Truter J Christoff , van Wyk Johannes H 
Published: August 2021

The emergence of widespread morphological malformations in the reproductive system of wildlife is generating increasing concerns. This concern is because the observed malformities may be linked to pollution by pesticides and other chemicals. The amphibian declines, for example, have been linked to pesticide pollution among other factors. Using an extended Xenopus Metamorphosis Assay protocol, until the tadpoles metamorphosized, the exposure impacts of three glyphosate formulations, namely, Roundup, Kilo Max and Enviro Glyphosate, were assessed on the reproductive system of Xenopus laevis, vis-a-vis the body mass, sex ratios and morphological malformations as endpoints. The exposure concentrations ranged between 0.2–0.6 mg/L, 0.9–28 mg/L and 90–280 mg/L for Roundup, Enviro Glyphosate, and Kilo Max, respectively. Both Kilo Max and Enviro Glyphosate formulations significantly reduced the body mass of the metamorphs compared to the control. In sex ratios, only Kilo Max altered the percentage sex ratio of the treated frogs at a ratio of 68:32 (F:M) compared to 50:50 ratio in the control. In reproductive malformations, the three formulations showed abnormality index range of 22.3–49%, 17.5–37.5% and 20–30% for the Kilo Max, Enviro Glyphosate and Roundup formulations, respectively, compared to 7.5% in the control. Observed reproductive malformations include mixed sex, translucence, aplasia, segmented hypertrophy and segmented aplasia and translucence. This result indicates that some of the glyphosate formulations have the capacity to cause widespread reproductive malformations in a way that could reduce the reproductive fitness of the amphibian. Care must therefore be taken to reduce the application rate of these formulations, particularly in aquatic environments.
rAAV9‐mediated supplementation of miR-29b improve angiotensin-II induced renal fibrosis in mice
Authors: Zhang Ju-hong , Li Jing , Ye Yang , Yu Wang-qi 
Published: August 2021

Abstract
Background
Renin–angiotensin–aldosterone system activation is the critical factor in renal remodeling and dysfunction. Our previous study suggested that miR-29b may attenuate AngII-induced renal intestinal fibrosis in vitro. In the present study, we aimed to determine whether recombinant rAAV9-mediated miR-29b delivery protects against AngII-induced renal fibrosis and dysfunction.

Method
Mice were treated with AngII via osmotic mini-pumps, or phosphate-buffered saline. rAAV9 vectors were produced using the rBac-based system in SF9 cells. rAAV9-miR-29b or rAAV9-control-miR was injected into the kidneys of mice subjected to the model of AngII infusion. The role of miR-29b in renal fibrosis was assessed using quantitative polymerase chain reaction, western blot, and histology.

Results
In AngII-induced fibrotic kidney tissue, miR-29b expression was downregulated. rAAV9-miR-29b delivery significantly reversed renal injury as indicated by decreased serum creatinine and injury related gene expression in AngII-infused mice. Regarding organ remodeling, tubulointerstitial fibrosis and deposition of extracellular matrix components such as collagen type I and type III were significantly decreased in renal tissue from mice delivered rAAV9-miR-29b.

Conclusion
Our results demonstrate great potential for use of rAAV9 as an applicable vector for delivery of miR-29b as an antifibrogenic factor for treatment of tubulointerstitial fibrosis-induced renal injury.
Effects of long-term nonylphenol exposure on myocardial fibrosis and cardiac function in rats
Authors: Liu Chao , Ni Chengyu , Liu Weichu , Yang Xiaolian , Zhang Renyi , Zhang Jianling , Luo Man , Xu Jie , Yu Jie 
Published: August 2021

Abstract
Background
Myocardial fibrosis is a critical pathological basis for the poor prognosis of cardiovascular diseases. Studies have found that myocardial fibrosis is closely associated with exposure to environmental estrogens such as nonylphenol (NP), as a representative of environmental estrogens. The aim of this study was to examine the effects of NP chronic exposure on myocardial fibrosis as well as cardiac structure and function. Forty Sprague–Dawley rats were randomly divided into four groups (n = 10): control group (C), low NP dose (0.4 mg/kg, L), medium NP dose (4 mg/kg, M), and high NP dose (40 mg/kg, H) groups. The NP dose groups were gavaged with NP for 180 days.

Results
The NP level in the heart of the NP groups was significantly higher than those in the control group (F = 43.658, P < 0.001). Serum aspartate aminotransferase (AST), creatine kinase (CK), creatine kinase isozyme (CK-MB), lactate dehydrogenase (LDH) and α-hydroxybutyrate dehydrogenase (α-HBDH) significantly increased in the NP groups compared with the control group (P < 0.05). Histopathological examination of the heart biopsy illustrates that in the medium and high NP groups, the fibrous connective tissue had a disordered and loose gridding shape, muscle fibers had fractured, and muscle fibers were loose with a widened gap. Extensive inflammatory cell infiltration and fibroblast proliferation in the myocardial interstitium were also found. With increasing NP dose, the degree of muscle fiber loosing and disorder became more significant in the NP-treatment groups, and the collagen volume fraction (CVF) was higher than that in the control group (P < 0.01). Compared with the control group, the expression of collagen I and collagen III increased significantly in the medium and high NP groups (P < 0.05). The values of the systolic thickness of the left ventricular anterior wall (LVAWs), the diastolic thickness of the left ventricular posterior wall (LVPWd), the systolic thickness of the left ventricular posterior wall (LVPWs), and the left ventricular anterior wall (LVAWd) in the NP groups are were slightly lower than those in of the control group. The values of left ventricular end systolic dimensions (LVIDs) in the NP groups increased compared with the control group.

Conclusions
Long-term NP exposure could lead to fibrosis in the rat myocardium, which is characterized by increased expressions of myocardial collagen I and collagen III, as well as elevated cardiac enzymes. In addition, the cardiac structure was affected and changes were observed in the thinner ventricular wall and as an enlarged ventricular cavity.
Cost of septic and aseptic revision total knee arthroplasty: a systematic review
Authors: Okafor Charles , Hodgkinson Brent , Nghiem Son , Vertullo Christopher , Byrnes Joshua 
Published: August 2021

AbstractBackgroundThe increasing incidence of primary total knee arthroplasty (TKA) has led to an increase in both the incidence and the cost burden of revision TKA procedures. This study aimed to review the literature on the cost of revision TKA for septic and aseptic causes and to identify the major cost components contributing to the cost burden.MethodsWe searched MEDLINE (OvidSp), Embase, Web of Science, Cochrane Library, EconLit, and Google Scholar to identify relevant studies. Selection, data extraction and assessment of the risk of bias and cost transparency within the studies were conducted by two independent reviewers, after which the cost data were analysed narratively for 1- or 2-stage septic revision without re-revision; 2-stage septic revision with re-revision; and aseptic revision with and without re-revision, respectively. The major cost components identified in the respective studies were also reported.ResultsThe direct medical cost from the healthcare provider perspective for high-income countries for 2-stage septic revision with re-revision ranged from US$66,629 to US$81,938, which can be about 2.5 times the cost of 1- or 2-stage septic revision without re-revision, (range: US$24,027 – US$38,109), which can be about double the cost of aseptic revision without re-revision (range: US$13,910 – US$29,213). The major cost components were the perioperative cost (33%), prosthesis cost (28%), and hospital ward stay cost (22%).ConclusionsSeptic TKA revision with re-revision for periprosthetic joint infection (PJI) increases the cost burden of revision TKA by 4 times when compared to aseptic single-stage revision and by 2.5 times when compared to septic TKA revision that does not undergo re-revision. Cost reductions can be achieved by reducing the number of primary TKA that develop PJI, avoidance of re-revisions for PJI, and reduction in the length of stay after revision.Trial registrationPROSPERO;CRD42020171988.
Effects of mechanical strain on periodontal ligament fibroblasts in presence of Aggregatibacter actinomycetemcomitans lysate
Authors: Schröder Agnes , Stumpf Julia , Paddenberg Eva , Neubert Patrick , Schatz Valentin , Köstler Josef , Jantsch Jonathan , Deschner James , Proff Peter , Kirschneck Christian 
Published: August 2021

Abstract
Purpose
Many adult orthodontic patients suffer from periodontitis, which is caused by oral pathogens such as the gram-negative Aggregatibacter actinomycetemcomitans (Agac). Like orthodontic tooth movement, periodontitis is associated with inflammation and alveolar bone remodelling thereby affecting orthodontic treatment. Interactions of both processes, however, are not sufficiently explored, particularly with regard to oxidative stress.

Methods
After preincubation with Agac lysate for 24 h periodontal ligament fibroblasts (PDLF) were either stretched or compressed for further 48 h simulating orthodontic forces in vitro. We analysed the expression of genes and proteins involved in the formation of reactive oxygen species (NOX-4, ROS) and nitric oxide (NOS-2), inflammation (TNF, IL-6, PTGS-2) and bone remodelling (OPG, RANKL).

Results
Agac lysate elevated the expression of NOX-4, NOS-2, inflammatory IL-6 and PTGS-2 and the bone-remodelling RANKL/OPG ratio during compressive, but not tensile mechanical strain. Agac lysate stimulated pressure-induced inflammatory signalling, whereas surprisingly ROS formation was reduced. Pressure-induced downregulation of OPG expression was inhibited by Agac lysate.

Conclusions
Agac lysate impact on the expression of genes and proteins involved in inflammation and bone remodelling as well as ROS formation, when PDLF were subjected to mechanical forces occurring during orthodontic tooth movement.
The perspectives of Swedish registered nurses about managing difficult calls to emergency medical dispatch centres: a qualitative descriptive study
Authors: Holmström Inger K. , Kaminsky Elenor , Lindberg Ylva , Spangler Douglas , Winblad Ulrika 
Published: August 2021

Abstract
Background
Telephone triage at emergency medical dispatch centres is often challenging for registered nurses due to lack of visual cues, lack of knowledge about the patient, and time pressure – and making the right decision can be a matter of life and death. Some calls may be more difficult to handle, and more knowledge is needed about these calls to develop education and coping strategies. Therefore, the aim of this study was to describe the perspectives of registered nurses’ views about managing difficult calls to emergency medical dispatch centres.

Methods
A descriptive design with a qualitative inductive approach was used. Three dispatch centers in mid-Sweden were investigated, covering about 950,000 inhabitants and handling around 114,000 calls per year. Individual interviews were carried out with a purposeful sample of 24 registered nurses. Systematic text condensation was conducted.

Results
Seven themes were generated: calls with communication barriers, calls from agitated or rude callers, calls about psychiatric illness, calls from third parties, calls about rare or unclear situations, calls with unknown addresses and calls regarding immediate life-threatening conditions. There was a strong consensus among the registered nurses about which calls were experienced as difficult, with the exception of calls about immediate life-threatening conditions. Some registered nurses thought calls about immediate life-threatening conditions were easy to handle as they simply adhered to protocol, while others described these calls as difficult and were emotionally affected.

Conclusion
The registered nurses’ descriptions of difficult calls focused on the callers, while their own role, the organisational framework, and leadership were not mentioned. Many types of calls included difficulties, which could be related to the caller, their symptoms, or different circumstances. The registered nurses pointed to language barriers and rude, agitated callers as increasing problems. An investigation of actual emergency calls is warranted to examine the extent and nature of such calls.
Treatment outcomes of passive scattering proton beam therapy for stage I non-small cell lung cancer
Authors: Bayasgalan Unurjargal , Moon Sung Ho , Jeong Jong Hwi , Kim Tae Hyun , Cho Kwan Ho , Suh Yang-Gun 
Published: August 2021

Abstract
Introduction
To investigate the treatment outcomes of passive scattering proton beam therapy using stereotactic ablative radiotherapy (SABR) or hypofractionated radiation therapy (RT) for inoperable patients or those who refused surgery for stage I non-small cell lung cancer (NSCLC).

Methods
From January 2016 to December 2019, we retrospectively analyzed 42 patients with stage I NSCLC treated with proton beam therapy. The initially intended dose regimen was 60 cobalt Gray equivalents (CGE) in 4 fractions; however, sequentially modified dose regimens were used when the dose-volume constraints could not be met. The median total dose was 50 CGE (range 50–70 CGE), while the corresponding median biologically effective dose using $$\alpha{/}\beta$$

α
/
β

= 10 (BED10) was 112.5 CGE (range 96–150 CGE).

Results
The median follow-up time was 40 months (interquartile range 32–48 months). Among the 42 treated patients, 33 had pathologically proven cancers of which most were adenocarcinoma (n = 21, 64%). The 3-year overall survival rate was 71.8%. The estimated rates of local control and progression free survival at 3 years were 91.5% and 66.9%, respectively. Thirteen patients experienced disease progression consisting of three local, six regional, and nine distant failures. No grade 4 or 5 toxicities were observed.

Conclusion
Passive scattering proton beam therapy for stage I NSCLC using SABR or hypofractionated RT was safe and showed high LC rates.
SIRT1 regulates the phosphorylation and degradation of P27 by deacetylating CDK2 to promote T-cell acute lymphoblastic leukemia progression
Authors: Wang Fangce , Li Zheng , Zhou Jie , Wang Guangming , Zhang Wenjun , Xu Jun , Liang Aibin 
Published: August 2021

Abstract
Background
Despite marked advances in the clinical therapies, clinical outcome of most T-cell acute lymphoblastic leukemia (T-ALL) patients remains poor, due to the high risk of relapse, even after complete remission. Previous studies suggest that the NAD-dependent deacetylase sirtuin 1 (SIRT1) has a dual role in hematologic malignancies, acting as a tumor suppressor or tumor promoter depending on the tumor type. However, little is known about the expression and functions of SIRT1 in T-ALL leukemogenesis.

Methods
Public RNA-seq data, a Notch1 driven T-ALL mouse model and γ-secretase inhibitor were used to identify SIRT1 expression in T-ALL. We knocked down SIRT1 expression with ShRNAs and assessed the impacts of SIRT1 deficiency on cell proliferation, colony formation, the cell cycle and apoptosis. Transgenic SIRT1 knockout mice were used to determine the function of SIRT1 in vivo. RT-PCR, western blot, co-immunoprecipitation and ubiquitination analyses were used to detect SIRT1, p27 and CDK2 expression and their interactions.

Results
SIRT1 protein expression was positively correlated with the activation of Notch1. Downregulation of SIRT1 expression suppressed the proliferation and colony formation of T-ALL cell lines, which was reversed by SIRT1 overexpression. SIRT1 silencing prolonged the lifespan of T-ALL model mice. We demonstrated that p27 was involved in the downstream mechanism of cell cycle arrest induced by silencing SIRT1. SIRT1 increased the phosphorylation of p27 on Thr187 by deacetylating CDK2 and enhanced the interaction between p27 and SKP2 leading to the degradation of p27.

Conclusion
Our findings suggest that SIRT1 is a promising target in T-ALL and offer a mechanistic link between the upregulation of SIRT1 and downregulation of p27.
An evaluation of the process of informed consent: views from research participants and staff
Authors: O’ Sullivan Lydia , Feeney Laura , Crowley Rachel K. , Sukumar Prasanth , McAuliffe Eilish , Doran Peter 
Published: August 2021

Abstract
Background
The process of informed consent for enrolment to a clinical research study can be complex for both participants and research staff. Challenges include respecting the potential participant’s autonomy and information needs while simultaneously providing adequate information to enable an informed decision. Qualitative research with small sample sizes has added to our understanding of these challenges. However, there is value in garnering the perspectives of research participants and staff across larger samples to explore the impact of contextual factors (time spent, the timing of the discussion and the setting), on the informed consent process.

Methods
Research staff and research participants from Ireland and the UK were invited to complete an anonymous survey by post or online (research participants) and online (research staff). The surveys aimed to quantify the perceptions of research participants and staff regarding some contextual factors about the process of informed consent. The survey, which contained 14 and 16 multiple choice questions for research participants and staff respectively, was analysed using descriptive statistics. Both surveys included one optional, open-ended question, which were analysed thematically.

Results
Research participants (169) and research staff (115) completed the survey. Research participants were predominantly positive about the informed consent process but highlighted the importance of having sufficient time and the value of providing follow-up once the study concludes, e.g. providing results to participants. Most staff (74.4%) staff reported that they felt very confident or confident facilitating informed consent discussions, but 63% felt information leaflets were too long and/or complicated, 56% were concerned about whether participants had understood complex information and 40% felt that time constraints were a barrier. A dominant theme from the open-ended responses to the staff survey was the importance of adequate time and resources.

Conclusions
Research participants in this study were overwhelmingly positive about their experience of the informed consent process. However, research staff expressed concern about how much participants have understood and studies of patient comprehension of research study information would seem to confirm these fears. This study highlights the importance of allocating adequate time to informed consent discussions, and research staff could consider using Teach Back techniques.

Trial Registration
Not applicable
Humeral metastasis as the only recurrence of a 5-year resected gastrointestinal stromal tumor: a case report
Authors: Braunstein C. , Sirveaux F. , Kalbacher E. , Aubry S. , Delroeux D. , Hubert P. , Marie B. , Meynard G. , Mihai I. , Chaigneau L. 
Published: August 2021

Abstract
Introduction
Gastrointestinal stromal tumors represent the most frequently encountered primary mesenchymal tumors. Whereas the liver and the peritoneum are known to be the preferential metastasis sites, no therapeutic standard has yet been established for the management of bone metastases because of their very low incidence. We report a unique example of a single humerus metastasis of a jejunal gastrointestinal stromal tumor.

Case presentation
We report the case of a 72-year-old European woman whose jejunal gastrointestinal stromal tumor was resected in 2013 and treated during the following 3 years with imatinib (400 mg daily). In 2018, she developed a single humeral bone lesion that was identified as a gastrointestinal stromal tumor metastasis. After 7 months of imatinib intake, reconstructive surgery was performed. Pathologists confirmed the satisfactory histological regression and assessed the complete tumor resection. The patient is still on imatinib maintenance therapy, with no recurrence reported so far. She fully recovered the upper limb function after following an appropriate rehabilitation program.

Discussion
Current literature and published case reports indicate that bones are one of the rarest locations of gastrointestinal stromal tumor metastasis (about 1%), with occurrence mainly in the spine. Patients initially diagnosed with gastrointestinal stromal tumor of the small intestine and stomach are more likely to suffer from bone metastasis, compared with other gastrointestinal stromal tumor locations. The median overall survival rate is higher for patients with isolated bone metastasis compared with those having liver metastasis. Metastasis occurs on average 4 years after the primary, but it may take up to 20 years, emphasizing the need for long-term clinical and radiological monitoring. Although specific guidelines for such cases have not yet been established, we suggest that a multimodal concerted approach involving surgery or radiotherapy associated with tyrosine kinase inhibitor intake should be considered.

Conclusion
Bones are one of the rarest locations of gastrointestinal stromal tumor metastasis. A multidisciplinary collaboration was set up to allow conservative surgery of our patient after several months of imatinib treatment. A year and a half later, the patient is still in complete remission. This specific case supports the concept of an intermediate stage between local and oligometastatic disease that should be managed with a curative aim, as much as possible.