bluuebunny/crossref_metadata_2025_split huggingface dataset:
Zoledronic Acid Versus Denosumab for Prevention of Spinal Cord Compression in Advanced Cancers With Spine Metastasis: A Meta-Analysis of Randomized Controlled Trials
Authors: Al Farii Humaid , Frazer Abbey , Farahdel Leila , Alfayez Saud , Weber Michael 
Published: October 2019

Study Design: Meta-analysis of randomized controlled trials (RCTs). Objectives: The aim was to analyze the efficacy of zoledronic acid (ZA) versus denosumab in the prevention of spinal cord compression in patients with spine metastases from advanced cancers, by evaluating all available RCTs on this subject. Methods: A systematic search of electronic databases (PubMed and MEDLINE) was performed to identify all published RCTs comparing ZA with denosumab in prevention of spinal cord compressions in spine metastases. Risk of bias of the studies was assessed. The primary outcomes evaluated were spinal cord compression. Results: Three RCTs (5274 patients) were included. Denosumab was not significantly superior to ZA in reducing the likelihood of spinal cord compression, when all tumor types were combined (odds ratio [OR] 0.92, 95% confidence interval [CI; 0.66, 1.28], P = .66). Denosumab was not significantly favored over ZA in endodermal origin (breast and prostate; OR 0.72, 95% CI [0.43, 1.19], P = .20) and mesodermal origin tumors (solid tumors and multiple myeloma; OR 1.10, 95% CI [0.72, 1.69], P = .66). Conclusion: Denosumab does not significantly reduce the likelihood of spinal cord compressions in comparison to ZA in patients with spine metastases. When spinal cord compressions were grouped by tumor origin (endodermal or mesodermal), there remained no significant difference between denosumab and ZA. Further long-term studies are needed to determine the effectiveness of these treatment regimens.
The Presence of Wnt Signaling Mutations in Patients With Diabetic Retinopathy
Authors: Moinuddin Omar , Rao Prethy , Wood Edward H. , Stem Maxwell S. , Drenser Kimberly A. , Wolfe Jeremy D. 
Published: October 2019

Purpose: The relationship between poor hemoglobin A1c (HbA1c) control and risk of proliferative diabetic retinopathy (PDR) is well known. Nevertheless, some patients have discordant disease (controlled HbA1c and severe PDR or vice versa). One potential explanation for this discrepancy is the presence of underlying genetic mutations in the Wingless-related integration site (Wnt) signaling pathway. However, minimal clinical data exist on the presence of Wnt signaling mutations in patients with diabetes mellitus (DM) and the correlation with diabetic retinopathy. Methods: Retrospective, nonconsecutive case review of patients with type 1 or 2 DM who underwent genetic testing for at least 1 recognized Wnt signaling pathway mutation from 2011 to 2016. The clinical course and retinal images were reviewed for patients with identifiable mutations. Results: Thirty-six patients, ages 13 to 79 years, consented for genetic analysis. Three patients (8.3%) exhibited at least 1 recognized genetic mutation in the Wnt signaling pathway. Case 1 was a 65-year-old female with type 1 diabetes for > 20 years, HbA1c <7.0%, and no findings of diabetic retinopathy (Tetraspanin 12). Case 2 was a 13-year-old male with type 1 diabetes for 8 years, moderate HbA1c control (7.6-8.3%), and absence of diabetic retinopathy (Norrin). Case 3 was a 48-year-old male with severe PDR requiring multiple laser and antivascular endothelial growth factor (anti-VEGF) treatments despite well-controlled HbA1c (6.0%) (Frizzled-4). Conclusion: Wnt signaling pathway mutations exist in patients with DM. Further studies investigating the prevalence and clinical significance of these mutations in a larger diabetic population are warranted. Identification of these patients with genetic testing may enable earlier medical intervention.
Presumed Choroidal Metastasis From Oncocytic Carcinoma of the Parotid Gland: A Case Report
Authors: Cruz-Iñigo Yousef J. , De Souza Stephen A.M. 
Published: October 2019

Purpose: This article reports a case of presumed choroidal metastasis from an oncocytic carcinoma of the parotid gland. Methods: A 70-year-old man with history of an oncocytic carcinoma of the parotid gland presented owing to a 1-month history of progressive blurred central vision shortly after metastatic surveillance workup revealed liver, lung, and spine metastases. Fundus examination of the right eye showed a yellow choroidal mass surrounding the optic nerve and extending inferonasally, which is associated with subretinal fluid involving the foveal center. A-scan and B-scan ultrasonography were remarkable for a dome-shaped choroidal mass with medium-to-high internal reflectivity. Fluorescein angiography revealed pinpoint foci of hyperfluorescence over the choroidal lesion with late leakage. Magnetic resonance imaging of the brain showed evidence of metastatic disease to the cerebellum. While the patient underwent systemic chemotherapy, external beam radiotherapy was used to treat the eye. Results: Four months later, visual acuity improved, the tumor reduced in size, and the subretinal fluid resolved. Systemic workup disclosed no new metastases. Conclusion: Oncocytic carcinoma of the parotid gland is a rare and aggressive malignant neoplasm with frequent recurrences and distant metastases. The current case suggests that oncocytic carcinoma can metastasize to the choroid and, consequently, ocular metastasis surveillance is advised in these patients.
Diagnostic yield and safety of transbronchial cryobiopsy in sarcoidosis
Authors: Jacob Maria , Bastos Hélder Novais , Mota Patrícia Caetano , Melo Natália , Cunha Rui , Pereira José Miguel , Guimarães Susana , Souto Moura Conceição , Morais António 
Published: October 2019

IntroductionTransbronchial lung cryobiopsy (TBLC) is an endoscopic technique proven to be useful in diagnostic approach to interstitial lung disease (ILD), but its role in sarcoidosis is not fully established. The aim of the present study was to assess the diagnostic yield of TBLC in sarcoidosis and its safety profile.MethodsRetrospective analysis of patients, evaluated in a tertiary hospital ILD outpatient clinic, who underwent TBLC in the diagnostic work-up. TBLC was performed in accordance with the 2018 expert statement from the Cryobiopsy Working Group.Results32 patients were included (mean±sdage 47.7±12.6 years, 59.4% male) and divided into three groups: highly likely sarcoidosis (n=21), possible sarcoidosis (n=6) and unlikely sarcoidosis (n=5). A mean of 2.8±0.8 TBLCs were performed. The definitive diagnosis was established by TBLC in 20 out of 27 patients with suspected sarcoidosis. Two patients were diagnosed with sarcoidosis by other methods performed afterwards. TBLC leaded to other diagnosis as well, such as fungal infection (n=1), hypersensitivity pneumonitis (n=1) and silicosis (n=3), making the diagnostic yield for suspected sarcoidosis of TBLC of 92.6%. TBLC was also able to show compatible histological features in five patients whom sarcoidosis was not previously considered. The complications reported overall were pneumothorax in five (15.6%) patients and moderate bleeding in one (3.1%) case.ConclusionIn this cohort, TBLC was a safe, reliable and useful procedure in sarcoidosis diagnosis. These results suggest that TBLC can be used successfully in those cases where a definitive diagnosis could not be reached with the usual and less-invasive diagnostic tools.
Radiosensitizing Effect of Gadolinium Oxide Nanocrystals in NSCLC Cells Under Carbon Ion Irradiation
Authors: Li Feifei , Li Zihou , Jin Xiaodong , Liu Yan , Li Ping , Shen Zheyu , Wu Aiguo , Zheng Xiaogang , Chen Weiqiang , Li Qiang 
Published: October 2019

Abstract
Gadolinium-based nanomaterials can not only serve as contrast agents but also contribute to sensitization in the radiotherapy of cancers. Among radiotherapies, carbon ion irradiation is considered one of the superior approaches with unique physical and biological advantages. However, only a few metallic nanoparticles have been used to improve carbon ion irradiation. In this study, gadolinium oxide nanocrystals (GONs) were synthesized using a polyol method to decipher the radiosensitizing mechanisms in non-small cell lung cancer (NSCLC) cell lines irradiated by carbon ions. The sensitizer enhancement ratio at the 10% survival level was correlated with the concentration of Gd in NSCLC cells. GONs elicited an increase in hydroxyl radical production in a concentration-dependent manner, and the yield of reactive oxygen species increased obviously in irradiated cells, which led to DNA damage and cell cycle arrest. Apoptosis and cytostatic autophagy were also significantly induced by GONs under carbon ion irradiation. The GONs may serve as an effective theranostic material in carbon ion radiotherapy for NSCLC.

Graphical Abstract
PlantSimLab - a modeling and simulation web tool for plant biologists
Authors: Ha S. , Dimitrova E. , Hoops S. , Altarawy D. , Ansariola M. , Deb D. , Glazebrook J. , Hillmer R. , Shahin H. , Katagiri F. , McDowell J. , Megraw M. , Setubal J. , Tyler B. M. , Laubenbacher R. 
Published: October 2019

AbstractBackgroundAt the molecular level, nonlinear networks of heterogeneous molecules control many biological processes, so that systems biology provides a valuable approach in this field, building on the integration of experimental biology with mathematical modeling. One of the biggest challenges to making this integration a reality is that many life scientists do not possess the mathematical expertise needed to build and manipulate mathematical models well enough to use them as tools for hypothesis generation. Available modeling software packages often assume some modeling expertise. There is a need for software tools that are easy to use and intuitive for experimentalists.ResultsThis paper introduces PlantSimLab, a web-based application developed to allow plant biologists to construct dynamic mathematical models of molecular networks, interrogate them in a manner similar to what is done in the laboratory, and use them as a tool for biological hypothesis generation. It is designed to be used by experimentalists, without direct assistance from mathematical modelers.ConclusionsMathematical modeling techniques are a useful tool for analyzing complex biological systems, and there is a need for accessible, efficient analysis tools within the biological community. PlantSimLab enables users to build, validate, and use intuitive qualitative dynamic computer models, with a graphical user interface that does not require mathematical modeling expertise. It makes analysis of complex models accessible to a larger community, as it is platform-independent and does not require extensive mathematical expertise.
A framework for TRIM21-mediated protein depletion in early mouse embryos: recapitulation of Tead4 null phenotype over three days
Authors: Israel Steffen , Casser Ellen , Drexler Hannes C.A. , Fuellen Georg , Boiani Michele 
Published: October 2019

AbstractBackgroundWhile DNA and RNA methods are routine to disrupt the expression of specific genes, complete understanding of developmental processes requires also protein methods, because: oocytes and early embryos accumulate proteins and these are not directly affected by DNA and RNA methods. When proteins in the oocyte encounter a specific antibody and theTRIpartiteMotiv-containing21(TRIM21) ubiquitin-protein ligase, they can be committed to degradation in the proteasome, producing a transient functional knock-out that reveals the role of the protein. However, there are doubts about whether this targeted proteolysis could be successfully used to study mammalian development, because duration of the transient effect is unknown, and also because amounts of reagents delivered must be adequate in relation to the amount of target protein, which is unknown, too.ResultsWe show that the mouse egg contains up to 1E-02 picomoles/protein, as estimated by mass spectrometry using the intensity-based absolute quantification (iBAQ) algorithm. However, the egg can only accommodate ≈1E-04 picomoles of antibody or TRIM21 without incurring toxic effects. Within this framework, we demonstrate that TRIM21-mediated protein depletion efficiently disrupts the embryonic process of trophectoderm formation, which critically depends on theTEA domain family member 4(Tead4) gene. TEAD4 depletion starting at the 1-cell stage lasts for 3 days prior to a return of gene and protein expression to baseline. This time period is long enough to result in a phenotype entirely consistent with that of the published null mutation and RNA interference studies: significant underexpression of trophectodermal genesCdx2andGata3and strongly impaired ability of embryos to cavitate and implant in the uterus. Omics data are available via ProteomeXchange (PXD012613) and GEO (GSE124844).ConclusionsTRIM21-mediated protein depletion can be an effective means to disrupt gene function in mouse development, provided the target gene is chosen carefully and the method is tuned accurately. The knowledge gathered in this study provides the basic know-how (prerequisites, requirements, limitations) to expedite the protein depletion of other genes besidesTead4.
Immune cell infiltration characteristics and related core genes in lupus nephritis: results from bioinformatic analysis
Authors: Cao Yiling , Tang Weihao , Tang Wanxin 
Published: October 2019

Abstract

Background
Lupus nephritis (LN) is a common complication of systemic lupus erythematosus that presents a high risk of end-stage renal disease. In the present study, we used CIBERSORT and gene set enrichment analysis (GSEA) of gene expression profiles to identify immune cell infiltration characteristics and related core genes in LN.

Results
Datasets from the Gene Expression Omnibus, GSE32591 and GSE113342, were downloaded for further analysis. The GSE32591 dataset, which included 32 LN glomerular biopsy tissues and 14 glomerular tissues from living donors, was analyzed by CIBERSORT. Different immune cell types in LN were analyzed by the Limma software. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis based on GSEA were performed by clusterProfiler software. Lists of core genes were derived from Spearman correlation between the most significant GO term and differentially expressed immune cell gene from CIBERSORT. GSE113342 was employed to validate the association between selected core genes and clinical manifestation. Five types of immune cells revealed important associations with LN, and monocytes emerged as having the most prominent differences. GO and KEGG analyses indicated that immune response pathways are significantly enriched in LN. The Spearman correlation indicated that 15 genes, including FCER1G, CLEC7A, MARCO, CLEC7A, PSMB9, and PSMB8, were closely related to clinical features.

Conclusions
This study is the first to identify immune cell infiltration with microarray data of glomeruli in LN by using CIBERSORT analysis and provides novel evidence and clues for further research of the molecular mechanisms of LN.
Altered activity in the nucleus raphe magnus underlies cortical hyperexcitability and facilitates trigeminal nociception in a rat model of medication overuse headache
Authors: Potewiratnanond Prangtip , le Grand Supang Maneesri , Srikiatkhachorn Anan , Supronsinchai Weera 
Published: October 2019

AbstractBackgroundThe pathogenesis of medication overuse headache (MOH) involves hyperexcitability of cortical and trigeminal neurons. Derangement of the brainstem modulating system, especially raphe nuclei may contribute to this hyperexcitability. The present study aimed to investigate the involvement of the nucleus raphe magnus (NRM) in the development of cortical and trigeminal hyperexcitability in a rat model of MOH.ResultsChronic treatment with acetaminophen increased the frequency of cortical spreading depression (CSD) and the number of c-Fos-immunoreactive (Fos-IR) neurons in the trigeminal nucleus caudalis (TNC). In the control group, muscimol microinjected into the NRM increased significantly the frequency of CSD-evoked direct current shift and Fos-IR neurons in the TNC. This facilitating effect was not found in rats with chronic acetaminophen exposure. In a model of migraine induced by intravenous systemic infusion of nitroglycerin (NTG), rats with chronic exposure to acetaminophen exhibited significantly more frequent neuronal firing in the TNC and greater Fos-IR than those without the acetaminophen treatment. Muscimol microinjection increased neuronal firing in the TNC in control rats, but not in acetaminophen-treated rats. The number of Fos-IR cells in TNC was not changed significantly.ConclusionChronic exposure to acetaminophen alters the function of the NRM contributing to cortical hyperexcitability and facilitating trigeminal nociception.
Longitudinal study of electrical, functional and structural remodelling in an equine model of atrial fibrillation
Authors: Hesselkilde Eva Zander , Carstensen Helena , Flethøj Mette , Fenner Merle , Kruse Ditte Dybvald , Sattler Stefan M. , Tfelt-Hansen Jacob , Pehrson Steen , Braunstein Thomas Hartig , Carlson Jonas , Platonov Pyotr G. , Jespersen Thomas , Buhl Rikke 
Published: October 2019

Abstract

Background
Large animal models are important in atrial fibrillation (AF) research, as they can be used to study the pathophysiology of AF and new therapeutic approaches. Unlike other animal models, horses spontaneously develop AF and could therefore serve as a bona fide model in AF research. We therefore aimed to study the electrical, functional and structural remodelling caused by chronic AF in a horse model.

Method
Nine female horses were included in the study, with six horses tachypaced into self-sustained AF and three that served as a time-matched sham-operated control group. Acceleration in atrial fibrillatory rate (AFR), changes in electrocardiographic and echocardiographic variables and response to medical treatment (flecainide 2 mg/kg) were recorded over a period of 2 months. At the end of the study, changes in ion channel expression and fibrosis were measured and compared between the two groups.

Results
AFR increased from 299 ± 33 fibrillations per minute (fpm) to 376 ± 12 fpm (p < 0.05) and atrial function (active left atrial fractional area change) decreased significantly during the study (p < 0.05). No changes were observed in heart rate or ventricular function. The AF group had more atrial fibrosis compared to the control group (p < 0.05). No differences in ion channel expression were observed.

Conclusion
Horses with induced AF show signs of atrial remodelling that are similar to humans and other animal models.
VWF/ADAMTS13 ratio as a potential biomarker for early detection of hepatocellular carcinoma
Authors: Takaya Hiroaki , Namisaki Tadashi , Kitade Mitsuteru , Kaji Kosuke , Nakanishi Keisuke , Tsuji Yuki , Shimozato Naotaka , Moriya Kei , Seki Kenichiro , Sawada Yasuhiko , Saikawa Soichiro , Sato Shinya , Kawaratani Hideto , Akahane Takemi , Noguchi Ryuichi , Matsumoto Masanori , Yoshiji Hitoshi 
Published: October 2019

AbstractBackgroundTo investigate the von Willebrand factor to ADAMTS13 ratio as a potential biomarker for early detection of hepatocellular carcinoma (HCC) in cirrhosis.MethodsSerum levels of alpha-fetoprotein, des-γ-carboxy prothrombin,Lens culinarisagglutinin-reactive fraction of alpha-fetoprotein (alpha-fetoprotein-L3%), vascular endothelial growth factor, and vascular endothelial growth factor receptor-2, as well as the plasma levels of von Willebrand factor antigen (von Willebrand factor: Ag) and ADAMTS13 activity (ADAMTS13:AC), were evaluated in 41 cirrhotic patients with HCC undergoing radiofrequency ablation and in 20 cirrhotic patients without HCC. The diagnostic accuracy of each biomarker was evaluated using the receiver operating characteristic curve analysis.ResultsThe von Willebrand factor: Ag and von Willebrand factor: Ag/ADAMTS13:AC ratios were significantly higher in cirrhotic patients with HCC than in those without HCC (p < 0.05 andp < 0.01, respectively), whereas ADAMTS13:AC was significantly lower in those with HCC than those without HCC (p < 0.05). However, no relationship was observed between the von Willebrand factor: Ag/ADAMTS13:AC ratio and serum tumor markers such as alpha-fetoprotein, des-γ-carboxy prothrombin, and alpha-fetoprotein-L3%. Multivariate regression analysis identified von Willebrand factor: Ag/ADAMTS13:AC ratio and alpha-fetoprotein-L3% as significant factors of HCC development. Receiver operating characteristic analysis showed that the von Willebrand factor: Ag/ADAMTS13:AC ratio and alpha-fetoprotein-L3% had a better performance than alpha-fetoprotein, des-γ-carboxy prothrombin, alpha-fetoprotein-L3%, vascular endothelial growth factor, and vascular endothelial growth factor receptor-2, von Willebrand factor: Ag, and ADAMTS13:AC. The von Willebrand factor: Ag/ADAMTS13:AC ratio was exclusively correlated with tumor volume and stage as well as serum vascular endothelial growth factor levels.ConclusionsThe von Willebrand factor: Ag/ADAMTS13:AC ratio can potentially serve as a novel biomarker for early diagnosis of HCC in cirrhotic patients.
The clinical presentation of Legionella arthritis reveals the mode of infection and the bacterial species: case report and literature review
Authors: Ibranosyan Marine , Beraud Laetitia , Lemaire Hélène , Ranc Anne-Gaëlle , Ginevra Christophe , Jarraud Sophie , Descours Ghislaine 
Published: October 2019

Abstract

Background
While Legionella is a common cause of pneumonia, extrapulmonary infections like arthritis are scarce. Here, we describe a case of monoarthritis due to Legionella bozemanii, with no history of pneumonia. We provide a literature review of the 9 previously published Legionella arthritis and highlight a dichotomous epidemiology suggesting different physiopathological pathways leading to joint infection.

Case presentation
A 56-year old woman under immunosuppressive treatment by oral and intra-articular corticosteroids, methotrexate, and tocilizumab for an anti-synthetase syndrome was hospitalized for worsening pain and swelling of the left wrist for 3 days. Clinical examination showed left wrist synovitis and no fever. The arthritis occurred a few days after an accidental fall on wet asphalt responsible for a cutaneous wound followed by a corticosteroid intra-articular injection. Due to both the negativity of conventional culture of articular fluid and suspicion of infection, 16S rRNA and specific PCRs were performed leading to the identification of L. bozemanii. Legionella-specific culture of the articular fluid was performed retrospectively and isolated L. bozemanii. The empiric antibiotic therapy was switched for oral levofloxacin and rifampin and the patient recovered after a 12-week treatment.

Conclusion
We report a case of L. bozemanii monoarthritis in an immunosuppressed woman, following a fall on wet asphalt and intra-articular corticosteroid injection. The review of the literature found that the clinical presentation reveals the mode of infection and the bacterial species. Monoarthritis more likely occurred after inoculation in patients under immunosuppressive therapy and were associated with non-Legionella pneumophila serogroup 1 (Lp1) strains that predominate in the environment. Polyarthritis were more likely secondary legionellosis localizations after blood spread of Lp1, the most frequently found in pneumonia. In both settings, 16S rRNA and Legionella-specific PCR were key factors for the diagnosis.