bluuebunny/crossref_metadata_2025_split huggingface dataset:
Determination of distinctive hypomethylated genes in African American colorectal neoplastic lesions
Authors: Ashktorab Hassan , Washington Kareem , Zarnogi Shatha , Shakoori Afnan , Varma Sudhir , Lee Edward , Shokrani Babak , Laiyemo Adeyinka , Brim Hassan 
Published: May 2020

Background: Few studies have analyzed progressive demethylation in the path to cancer. This is of utmost importance, especially in populations such as African Americans, who display aggressive tumors at diagnosis, and for whom markers of early neoplastic transformation are needed. Here, we determined hypomethylated targets in the path to colorectal cancer (CRC) using Reduced Representation Bisulfite Sequencing (RRBS). Methods: DNA was extracted from fresh frozen tissues of patients with different colon lesions (normal, tubular adenoma, tubulovillous adenoma, and five cancers). RRBS was performed on these DNA extracts to identify hypomethylated gene targets. Alignment, mapping, and methylation analyses were performed. Pathways affected by the hypomethylated gene targets were determined using Ingenuity Pathway Analysis (IPA). Results: Pairwise analyses of samples led to the identification of the following novel hypomethylated genes: ELMO3 (Engulfment and cell motility 3), SLC6A2 (Solute carrier family 6 member 2), SYNM (Synemin), and HMX2 (Homeobox 2). The ELMO3 promoter was significantly hypomethylated at five CpG sites, SYNM at two CpG sites, SLC6A2 at one CpG site, and the HMX2 gene at one CpG site. IPA placed these genes within important carcinogenic pathways. Conclusions: This work provides insight into the role of hypomethylation in colon carcinogenesis in African Americans. The identified targets affected many important pathways, as demonstrated through IPA. These targets might serve as biomarkers for early diagnosis and potential targets for therapy.
Successful muscle regeneration by a homologous microperforated scaffold seeded with autologous mesenchymal stromal cells in a porcine esophageal substitution model
Authors: Marzaro Maurizio , Algeri Mattia , Tomao Luigi , Tedesco Stefano , Caldaro Tamara , Balassone Valerio , Contini Anna Chiara , Guerra Luciano , Federici D’Abriola Giovanni , Francalanci Paola , Caristo Maria Emiliana , Lupoi Lorenzo , Boskoski Ivo , Bozza Angela , Astori Giuseppe , Pozzato Gianantonio , Pozzato Alessandro , Costamagna Guido , Dall’Oglio Luigi 
Published: May 2020

Background: Since the esophagus has no redundancy, congenital and acquired esophageal diseases often require esophageal substitution, with complicated surgery and intestinal or gastric transposition. Peri-and-post-operative complications are frequent, with major problems related to the food transit and reflux. During the last years tissue engineering products became an interesting therapeutic alternative for esophageal replacement, since they could mimic the organ structure and potentially help to restore the native functions and physiology. The use of acellular matrices pre-seeded with cells showed promising results for esophageal replacement approaches, but cell homing and adhesion to the scaffold remain an important issue and were investigated. Methods: A porcine esophageal substitute constituted of a decellularized scaffold seeded with autologous bone marrow-derived mesenchymal stromal cells (BM-MSCs) was developed. In order to improve cell seeding and distribution throughout the scaffolds, they were micro-perforated by Quantum Molecular Resonance (QMR) technology (Telea Electronic Engineering). Results: The treatment created a microporous network and cells were able to colonize both outer and inner layers of the scaffolds. Non seeded (NSS) and BM-MSCs seeded scaffolds (SS) were implanted on the thoracic esophagus of 4 and 8 pigs respectively, substituting only the muscle layer in a mucosal sparing technique. After 3 months from surgery, we observed an esophageal substenosis in 2/4 NSS pigs and in 6/8 SS pigs and a non-practicable stricture in 1/4 NSS pigs and 2/8 SS pigs. All the animals exhibited a normal weight increase, except one case in the SS group. Actin and desmin staining of the post-implant scaffolds evidenced the regeneration of a muscular layer from one anastomosis to another in the SS group but not in the NSS one. Conclusions: A muscle esophageal substitute starting from a porcine scaffold was developed and it was fully repopulated by BM-MSCs after seeding. The substitute was able to recapitulate in shape and function the original esophageal muscle layer.
The association between circulating levels of vitamin D and inflammatory markers in the first 2 years after colorectal cancer diagnosis
Authors: Wesselink Evertine , Balvers Michiel , Bours Martijn J. L. , de Wilt Johannes H. W. , Witkamp Renger F. , van Baar Harm , Geijsen Anne J. M. R. , van Halteren Henk , Keulen Eric T. P. , Kok Dieuwertje E. , Kouwenhoven Ewout A. , van den Ouweland Jody , van Zutphen Moniek , Weijenberg Matty P. , Kampman Ellen , van Duijnhoven Fränzel J. B. 
Published: May 2020

Background: Calcitriol, the active form of vitamin D, may inhibit colorectal cancer (CRC) progression, which has been mechanistically linked to an attenuation of a pro-inflammatory state. The present study investigated the associations between circulating 25 hydroxy vitamin D3 (25(OH)D3) levels and inflammatory markers (IL10, IL8, IL6, TNFα and hsCRP) in the 2 years following CRC diagnosis. Methods: Circulating 25(OH)D3 levels and inflammatory markers were assessed at diagnosis, after 6, 12 and 24 months from 798 patients with sporadic CRC participating in two prospective cohort studies. Associations between 25(OH)D3 levels and individual inflammatory markers as well as a summary inflammatory z-score were assessed at each time point by multiple linear regression analyses. To assess the association between 25(OH)D3 and inflammatory markers over the course of 2 years, linear mixed model regression analyses were conducted. Results: Higher 25(OH)D3 levels were associated with lower IL6 levels at diagnosis, at 6 months after diagnosis and over the course of 2 years (β −0.06, 95% CI −0.08 to −0.04). In addition, 25(OH)D3 levels were inversely associated with the summary inflammatory z-score at diagnosis and over the course of 2 years (β −0.17, 95% CI −0.25 to −0.08). In addition, a significant inverse association between 25(OH)D3 levels and IL10 was found over the course of 2 years. Intra-individual analyses showed an inverse association between 25(OH)D3 and IL10, IL6 and TNFα. No statistically significant associations between 25(OH)D3 and IL8 and hsCRP levels were observed. Conclusions: Serum 25(OH)D3 levels were inversely associated with the summary inflammatory z-score and in particular with IL6 in the years following CRC diagnosis. This is of potential clinical relevance as IL6 has an important role in chronic inflammation and is also suggested to stimulate cancer progression. Further observational studies should investigate whether a possible 25(OH)D3-associated reduction of inflammatory mediators influences treatment efficacy and CRC recurrence.
Corneal side effects induced by EGFR-inhibitor antibody–drug conjugate ABT-414 in patients with recurrent glioblastoma: a prospective clinical and confocal microscopy study
Authors: Parrozzani Raffaele , Lombardi Giuseppe , Midena Edoardo , Leonardi Francesca , Londei Davide , Padovan Marta , Caccese Mario , Marchione Giulia , Bini Silvia , Zagonel Vittorina , Frizziero Luisa 
Published: May 2020

Background: The aim of this study was to prospectively analyse, for the first time worldwide by in vivo clinical confocal microscopy (CCM), corneal side effects secondary to the use of epidermal growth factor receptor (EGFR) inhibitor depatuxizumab mafodotin (ABT-414) in a cohort of patients affected by EGFR-amplified recurrent glioblastoma. Methods: Each enrolled patient underwent full ophthalmologic examination including in vivo CCM of the cornea. Each patient was examined at baseline and every 2 weeks during treatment as long as patient conditions allowed it. Results: A total of 10 patients were consecutively enrolled. Median follow-up was 5 months. No Common Terminology Criteria for Adverse Events Version 4.0 grade 4 toxicity was documented. Two (20%) grade 3 toxicities were documented at week 8. CCM examination detected in all eyes multiple and diffuse hyperreflective white round spots in the corneal basal epithelial layers (100%), progressive subbasal nerve plexus layer fibres fragmentation followed by full disappearance (100%) and appearance of round cystic structures in the corneal epithelium (100%). All CCM documented side effects reached the peak of prevalence and severity after a median of 3 infusions. After treatment discontinuation, the reversibility of corneal side effects was documented at CCM after a median of 4 weeks. Conclusion: ABT-414 toxicity is not only directed to the corneal epithelium, but also to corneal nerves. Side effects are detectable in all treated patients and CCM documents early corneal epithelium and subbasal nerve plexus toxicity, with subsequent progressive restoration after treatment discontinuation. Ocular side effects due to ABT-414 can be manageable.
Casting in infantile idiopathic scoliosis as a temporising measure: A systematic review and meta-analysis
Authors: Alassaf Nabil , Tabard-Fougère Anne , Dayer Romain 
Published: May 2020

Objective: Treatment of infantile idiopathic scoliosis remains vague. Because implantation of temporary telescopic devices carries a high risk of complications, interest in the older technique of serial casting is growing as a temporising measure before invasive procedures. The goal of this review was to meta-analyse studies examining the effect and safety of casting in infantile idiopathic scoliosis. Methods: Two reviewers independently searched for relevant studies in PubMed and Embase databases through November 2018. The studies included were limited to infantile idiopathic scoliosis patients who underwent casting, had a mean Cobb angle of 20 or more and written in English. The methodological quality of the chosen studies was assessed. The primary outcome was the difference in Cobb angle means from before and after casting. The secondary outcome was adverse events of casting. Heterogeneity was explored and a funnel plot was drawn. Results: Of the 366 studies screened, 10 studies were included in the meta-analysis (243 subjects) and all were non-randomised. The casting was consistently associated with a reduction in the mean Cobb angle. The pooled mean difference was 24.85° (95% confidence interval: 19.25 to 30.46, p < 0.001). A number of reversible adverse events were reported, most commonly skin irritation and transient pulmonary symptoms. Heterogeneity between studies was high. In the meta-regression analysis, the starting Cobb angle did not influence Cobb angle change, but there was an inverse correlation between the mean difference in Cobb angle and mean age. Conclusion: Casting seems to be effective and safe in decreasing Cobb angle even in high curve magnitudes. In older patients, casting showed less Cobb angle correction.
Identifying Vulnerable Plaque in Rheumatoid Arthritis Using Novel Microbubble Contrast-Enhanced Carotid Ultrasonography and Serum Biomarkers
Authors: Wang Linda F. , Li Yaming , Landsittel Douglas P. , Reis Steven E. , Levesque Marc C. , Jones Donald M. , Gartland Rachel , Avolio Jennifer , Shoushtari Ali , Qi Zengbiao , Dezfulian Cameron , Moreland Larry W. , Liang Kimberly P. 
Published: May 2020

Objective: Rheumatoid arthritis (RA) is associated with increased risk of cardiovascular disease. Adventitial vasa vasorum density (aVVD), the vessel density of the vasa vasorum, is a surrogate measure for atherosclerotic plaque vulnerability. The purpose of this study was to compare the adventitial vasa vasorum density (aVVD) in RA and non-RA control participants using novel carotid artery contrast-enhanced ultrasound (CEUS). In addition, we investigate associations of aVVD with traditional cardiovascular (CV) risk factors, vascular and inflammatory biomarkers, and RA disease activity. Methods: The study was a cross-sectional analysis of patients with RA and control participants without RA or other autoimmune disease. CV disease risk, biomarkers, and CEUS images were collected on all patients. Results: aVVD was quantified in 86 patients with RA and 95 non-RA control participants. Nitrite, CD40L, E-selectin, matrix metalloproteinase 9, intercellular adhesion molecule 1, vascular cell adhesion molecule 1, myeloperoxidase (MPO), high-sensitivity C-reactive protein (hsCRP), and erythrocyte sedimentation rate were measured. Median aVVD was higher in patients with RA (0.59 [0.47–0.69] vs 0.64 [0.54–0.62]; P = .02). In patients with RA, MPO was lower (253.5 [153.2–480] vs 470.8 [274.2–830.1] ng/mL; P = .0002) and ESR was higher (15.5 [11–25] vs 13 [9–20] mm/h; P = .02). aVVD was correlated with MPO ( r = −0.33, P = .001) and hsCRP ( r = 0.25, P = .02) in control participants only, associations that remained significant after adjusting for number of CV risk factors and age. No significant correlations were found between aVVD and RA disease activity measures. Conclusions: Using a novel application of CEUS, we found that aVVD, an early measure of plaque vulnerability, was significantly higher in RA than control subjects, even after adjusting for CV risk factors. Differences in correlation of aVVD with vascular biomarkers and CV risk factors suggest RA-related differences in atherosclerotic progression.
Aldehyde dehydrogenase 3a2 protects AML cells from oxidative death and the synthetic lethality of ferroptosis inducers
Authors: Yusuf Rushdia Zareen , Saez Borja , Sharda Azeem , van Gastel Nick , Yu Vionnie W. C. , Baryawno Ninib , Scadden Elizabeth W. , Acharya Sanket , Chattophadhyay Shrikanta , Huang Cherrie , Viswanathan Vasanthi , S'aulis Dana , Cobert Julien , Sykes David B. , Keibler Mark A. , Das Sudeshna , Hutchinson John N. , Churchill Michael , Mukherjee Siddhartha , Lee Dongjun , Mercier Francois , Doench John , Bullinger Lars , Logan David J. , Schreiber Stuart , Stephanopoulos Gregory , Rizzo William B. , Scadden David T. 
Published: May 2020

AbstractMetabolic alterations in cancer represent convergent effects of oncogenic mutations. We hypothesized that a metabolism-restricted genetic screen, comparing normal primary mouse hematopoietic cells and their malignant counterparts in an ex vivo system mimicking the bone marrow microenvironment, would define distinctive vulnerabilities in acute myeloid leukemia (AML). Leukemic cells, but not their normal myeloid counterparts, depended on the aldehyde dehydrogenase 3a2 (Aldh3a2) enzyme that oxidizes long-chain aliphatic aldehydes to prevent cellular oxidative damage. Aldehydes are by-products of increased oxidative phosphorylation and nucleotide synthesis in cancer and are generated from lipid peroxides underlying the non–caspase-dependent form of cell death, ferroptosis. Leukemic cell dependence on Aldh3a2 was seen across multiple mouse and human myeloid leukemias. Aldh3a2 inhibition was synthetically lethal with glutathione peroxidase-4 (GPX4) inhibition; GPX4 inhibition is a known trigger of ferroptosis that by itself minimally affects AML cells. Inhibiting Aldh3a2 provides a therapeutic opportunity and a unique synthetic lethality to exploit the distinctive metabolic state of malignant cells.
Multispecies RNA tomography reveals regulators of hematopoietic stem cell birth in the embryonic aorta
Authors: Yvernogeau Laurent , Klaus Anna , Maas Joris , Morin-Poulard Ismaël , Weijts Bart , Schulte-Merker Stefan , Berezikov Eugene , Junker Jan Philipp , Robin Catherine 
Published: May 2020

AbstractThe defined location of a stem cell within a niche regulates its fate, behavior, and molecular identity via a complex extrinsic regulation that is far from being fully elucidated. To explore the molecular characteristics and key components of the aortic microenvironment, where the first hematopoietic stem cells are generated during development, we performed genome-wide RNA tomography sequencing on zebrafish, chicken, mouse, and human embryos. The resulting anterior-posterior and dorsal-ventral transcriptional maps provided a powerful resource for exploring genes and regulatory pathways active in the aortic microenvironment. By performing interspecies comparative RNA sequencing analyses and functional assays, we explored the complexity of the aortic microenvironment landscape and the fine-tuning of various factors interacting to control hematopoietic stem cell generation, both in time and space in vivo, including the ligand-receptor couple ADM-RAMP2 and SVEP1. Understanding the regulatory function of the local environment will pave the way for improved stem cell production in vitro and clinical cell therapy.
Pinocembrin mitigates depressive-like behaviors induced by chronic unpredictable mild stress through ameliorating neuroinflammation and apoptosis
Authors: Wang Wei , Zheng Lili , Xu Lijun , Tu Jianglong , Gu Xunhu 
Published: May 2020

Abstract
Background
The majority of patients with chronic fatigue have a risk of comorbidity with depression. Pinocembrin (PB) is a kind of flavonoid molecule isolated from honey and propolis and has antimicrobial, anti-inflammatory, antioxidant, and anticancer function. The purpose of the current study was to determine the possible function of PB on treatment of depression.

Methods
A chronic unpredictable mild stress (CUMS) mouse model was established to mimic the depressive-like behaviors in vivo. The depressive-like behaviors of CUMS mice were measured by sucrose preference test (SPT), open field test (OFT), forced swim test (FST) and tail suspension test (TST). The concentration of reactive oxygen species (ROS), malondialdehyde (MDA) and the activity or superoxide dismutase (SOD) were detected by commercial kit. The inflammatory factor including interleukin (IL)-1β, tumor necrosis factor (TNF)-α, IL-10 and transforming growth factor (TGF)-β were examined.

Results
We found that PB alleviated the decreasing of sucrose preference and body weight. CUMS mice significantly increased the immobility time but decreased latency to abandon in FST, increased the immobility time in TST, and reduced crossing score and rearing score in OFT, whereas these changes were reversed by PB treatment. More importantly, PB decreased the concentration of ROS and MDA, but increased the SOD activity, suggesting that it could protected against oxidative stress in CUMS mice. Interestingly, PB inhibited cell apoptosis and regulated inflammatory factors expression in hippocampus of CUMS mice. Moreover, PB activated Nrf2/HO-1 signal pathway but inhibited the phosphorylation of NF-kB.

Conclusions
In conclusion, PB mitigated CUMS-induced depressive-like behaviors through ameliorating neuroinflammation and apoptosis.

Trial registration
Not Applicable.
Multidisciplinary approach to assess the toxicities of arsenic and barium in drinking water
Authors: Kato Masashi , Ohgami Nobutaka , Ohnuma Shoko , Hashimoto Kazunori , Tazaki Akira , Xu Huadong , Kondo-Ida Lisa , Yuan Tian , Tsuchiyama Tomoyuki , He Tingchao , Kurniasari Fitri , Gu Yishuo , Chen Wei , Deng Yuqi , Komuro Kanako , Tong Keming , Yajima Ichiro 
Published: May 2020

AbstractWell water could be a stable source of drinking water. Recently, the use of well water as drinking water has been encouraged in developing countries. However, many kinds of disorders caused by toxic elements in well drinking water have been reported. It is our urgent task to resolve the global issue of element-originating diseases. In this review article, our multidisciplinary approaches focusing on oncogenic toxicities and disturbances of sensory organs (skin and ear) induced by arsenic and barium are introduced. First, our environmental monitoring in developing countries in Asia showed elevated concentrations of arsenic and barium in well drinking water. Then our experimental studies in mice and our epidemiological studies in humans showed arsenic-mediated increased risks of hyperpigmented skin and hearing loss with partial elucidation of their mechanisms. Our experimental studies using cultured cells with focus on the expression and activity levels of intracellular signal transduction molecules such as c-SRC, c-RET, and oncogenic RET showed risks for malignant transformation and/or progression arose from arsenic and barium. Finally, our original hydrotalcite-like compound was proposed as a novel remediation system to effectively remove arsenic and barium from well drinking water. Hopefully, comprehensive studies consisting of (1) environmental monitoring, (2) health risk assessments, and (3) remediation will be expanded in the field of environmental health to prevent various disorders caused by environmental factors including toxic elements in drinking water.
Characterization of a potential probiotic bacterium Lactococcus raffinolactis WiKim0068 isolated from fermented vegetable using genomic and in vitro analyses
Authors: Jung Min Young , Lee Changsu , Seo Myung-Ji , Roh Seong Woon , Lee Se Hee 
Published: May 2020

Abstract
Background
Lactococcus members belonging to lactic acid bacteria are widely used as starter bacteria in the production of fermented dairy products. From kimchi, a Korean food made of fermented vegetables, Lactococcus raffinolactis WiKim0068 was isolated and its genome was analyzed.

Results
The complete genome of the strain WiKim0068 consists of one chromosome and two plasmids that comprises 2,292,235 bp, with a G + C content of 39.7 mol%. Analysis of orthoANI values among Lactococcus genome sequences showed that the strain WiKim0068 has > 67% sequence similarity to other species and subspecies. In addition, it displayed no antibiotic resistance and can metabolize nicotinate and nicotinamide (vitamin B3).

Conclusion
These results augments our understanding of the genus Lactococcus and suggest that this new strain has potential industrial applications.
A review of the use of propensity score diagnostics in papers published in high-ranking medical journals
Authors: Granger Emily , Watkins Tim , Sergeant Jamie C. , Lunt Mark 
Published: May 2020

Abstract
Background
Propensity scores are widely used to deal with confounding bias in medical research. An incorrectly specified propensity score model may lead to residual confounding bias; therefore it is essential to use diagnostics to assess propensity scores in a propensity score analysis. The current use of propensity score diagnostics in the medical literature is unknown. The objectives of this study are to (1) assess the use of propensity score diagnostics in medical studies published in high-ranking journals, and (2) assess whether the use of propensity score diagnostics differs between studies (a) in different research areas and (b) using different propensity score methods.

Methods
A PubMed search identified studies published in high-impact journals between Jan 1st 2014 and Dec 31st 2016 using propensity scores to answer an applied medical question. From each study we extracted information regarding how propensity scores were assessed and which propensity score method was used. Research area was defined using the journal categories from the Journal Citations Report.

Results
A total of 894 papers were included in the review. Of these, 187 (20.9%) failed to report whether the propensity score had been assessed. Commonly reported diagnostics were p-values from hypothesis tests (36.6%) and the standardised mean difference (34.6%). Statistical tests provided marginally stronger evidence for a difference in diagnostic use between studies in different research areas (p = 0.033) than studies using different propensity score methods (p = 0.061).

Conclusions
The use of diagnostics in the propensity score medical literature is far from optimal, with different diagnostics preferred in different areas of medicine. The propensity score literature may improve with focused efforts to change practice in areas where suboptimal practice is most common.