bluuebunny/crossref_metadata_2025 huggingface dataset:
Cordyceps militaris Exerts Anticancer Effect on Non–Small Cell Lung Cancer by Inhibiting Hedgehog Signaling via Suppression of TCTN3
Authors: Jo Eunbi , Jang Hyun-Jin , Shen Lei , Yang Kyeong Eun , Jang Min Su , Huh Yang Hoon , Yoo Hwa-Seung , Park Junsoo , Jang Ik Soon , Park Soo Jung
Published: May 2020

This study aimed to investigate the effect of Cordyceps militaris extract on the proliferation and apoptosis of non–small cell lung cancer (NSCLC) cells and determine the underlying mechanisms. We performed a CCK-8 assay to detect cell proliferation, detection of morphological changes through transmission electron microscopy (TEM), annexin V–FITC/PI double staining to analyze apoptosis, and immunoblotting to measure the protein expression of apoptosis and hedgehog signaling–related proteins, with C militaris treated NSCLC cells. In this study, we first found that C militaris reduced the viability and induced morphological disruption in NSCLC cells. The gene expression profiles indicated a reprogramming pattern of genes and transcription factors associated with the action of TCTN3 on NSCLC cells. We also confirmed that the C militaris–induced inhibition of TCTN3 expression affected the hedgehog signaling pathway. Immunoblotting indicated that C militaris–mediated TCTN3 downregulation induced apoptosis in NSCLC cells, involved in the serial activation of caspases. Moreover, we demonstrated that the C militaris negatively modulated GLI1 transcriptional activity by suppressing SMO/PTCH1 signaling, which affects the intrinsic apoptotic pathway. When hedgehog binds to the PTCH1, SMO dissociates from PTCH1 inhibition at cilia. As a result, the active GLI1 translocates to the nucleus. C militaris clearly suppressed GLI1 nuclear translocation, leading to Bcl-2 and Bcl-xL down-regulation. These results suggested that C militaris induced NSCLC cell apoptosis, possibly through the downregulation of SMO/PTCH1 signaling and GLI1 activation via inhibition of TCTN3. Taken together, our findings provide new insights into the treatment of NSCLC using C militaris.
Can Racial Diversity Swing Competitive Congressional Elections?
Authors: Bader Michael
Published: May 2020

Control of Congress after the 2020 election will depend on how well each party and candidate appeal to voters in both multiracial and less racially diverse districts.
Simultaneous Transcatheter Aortic Valve Implantation and Infrarenal Aortic Aneurysm Repair for Severe Aortic Stenosis and Abdominal Aortic Aneurysm: Report of 2 Cases and Literature Review
Authors: Koutsias Stylianos , Karaolanis Georgios I. , Papafaklis Michail I. , Peroulis Michail , Tzimas Petros , Lakkas Lampros , Mitsis Michail , Naka Katerina K. , Michalis Lampros K.
Published: May 2020

The prevalence of concomitant abdominal aortic aneurysm (AAA) and severe aortic stenosis (AS) has been increasing in the elderly population. Both conditions have adverse outcomes, if not adequately managed. No clear recommendations are available in the literature until today, in regards of the management sequence making thus the decision-making challenging. We report 2 cases of AAA and significant AS treated with endovascular aortic repair (EVAR) and transcatheter aortic valve implantation (TAVI) during the same procedure and a review of the literature on this topic. Based on our experience, the combined procedure with TAVI followed by EVAR seems to be feasible, safe, and effective while detailed preoperative planning and a carefully tailored management strategy by a multidisciplinary team are essential.
Model of an alternative navigation system for high-precision weapons
Authors: Savchenko Vitalii , Tolubko Volodymyr , Berkman Liubov , Syrotenko Anatolii , Shchypanskyi Pavlo , Matsko Oleksander , Tiurin Vitalii , Open’ko Pavlo
Published: May 2020

The article explores the problem of alternative navigation support for high-precision weapons that use guidance based on signals from global navigation systems. It proposes the use of an autonomous navigation system replacing satellite navigation in the case where major Global Positioning System-like systems are unavailable. It suggests the idea and the model of a moving navigation field that can move along the weapon trajectory. The model of accuracy for the pseudolite navigation system uses the least squares method as its basis. The study looks into the accuracy parameters of the moving navigation field. The results of the study show the advantages of a moving field when compared with a stationary navigation field in case of autonomous use. This research also shows the possibility of using an autonomous system for Special Forces, search and rescue operations, and robotic and unmanned aerial, ground, and sea-based vehicles.
Incidental Gynecomastia on Thoracic Computed Tomography in Clinical Practice: Characteristics, Radiologic Features, and Correlation With Possible Causes in South Korean Men
Authors: Kim Min Seon , Kim Jun Ho , Lee Kyung Hee , Suh Young Ju
Published: May 2020

Gynecomastia is a common incidental finding on thoracic computed tomography (CT). This study aimed to retrospectively determine the prevalence, imaging characteristics, and possible causes of incidental gynecomastia on thoracic CT. Records of male patients who underwent thoracic CT in 2015 were reviewed. The size and morphologic types (nodular, dendritic, and diffuse) were recorded for patients with breast glandular tissue larger than 1 cm, and the cutoff value of gynecomastia was defined as 2 cm. Additionally, the possible causes of gynecomastia obtained by reviewing patients’ charts were recorded. CT-depicted gynecomastia was identified in 12.7% (650 of 5,501) of patients. The median size of the breast glandular tissue was 2.5 cm (interquartile range 2.2–3.1), and 36.8% of patients (239 of 650) had unilateral gynecomastia. The age distribution provided a bimodal pattern with two peaks in the age groups from 20 to 29 years old and greater than 70 years old. Chronic liver disease (CLD; p < .001), all stages of chronic kidney disease (CKD; p < .001), and medications ( p = .002) were significantly associated with gynecomastia. Gynecomastia did not correlate with body mass index ( p = .962). The size of breast glandular tissue was identified to be correlated with the morphologic type of breast tissue and the severity of CLD or CKD. The prevalence of incidental gynecomastia seen on thoracic CT was 12.7%. CT-depicted gynecomastia is not associated with obesity but with CLD, CKD, and medications. When gynecomastia is detected on CT, further evaluations and management might be required for patients with a treatable cause.
Flame-retardant treatment of wool and wool-rich blends: A study of bath composition
Authors: Kaynak Elif , Üreyen Mustafa Erdem , Koparal Ali Savaş , Mutlu Adem
Published: May 2020

Wool and wool-polyamide blended yarns (88.6% wool–11.4% polyamide 6,6 and 78.5% wool–21.5% polyamide 6,6) were knitted and the produced fabrics were treated by exhaustion method with zirconium complexes. Six different baths containing potassium hexafluorozirconate and zirconium acetate were studied. The flammability hazard was evaluated considering parameters such as the spread of flame, the heat release and the smoke release rate. Regardless of the blend composition, the untreated fabrics could not pass the vertical flammability test. 100% wool fabric could pass the vertical flammability test when treated with only 1% potassium hexafluorozirconate and 10% zirconium acetate solution. Higher compositions of metal complexes were required for the blended fabrics to pass the vertical flammability test. In the cone calorimeter test, 100% wool treated with 5% potassium hexafluorozirconate and 10% zirconium acetate solution gave the lowest peak heat release and smoke release rate values as 146.4 kW/m2 and 1.2 s−1, respectively.
Improved salt rejection, hydrophilicity and mechanical properties of novel thermoplastic polymer/chitosan nanofibre membranes
Authors: Al-Mubaddel Fahad S , AlRomaih Hamad S , Karim Mohammad Rezaul , Luqman Monis , Al-Rashed Maher M , Al-Mutairi Abdullah S
Published: May 2020

The present study reports on the preparation of novel nanofibre membranes from the thermoplastic polymer polyvinylidene fluoride coated with chitosan to enhance membrane properties such as hydrophilicity, mechanical properties, water flux and salt rejection. Initially, a supporting layer was produced from polyvinylidene fluoride using phase inversion methods, followed by being coated with chitosan using either electrospinning or immersion methods. Two types of fabricated membranes with different coating methods were characterized and tested for physical and chemical performance using field-emission scanning electron microscopy, tensile tests, permeation tests (water flux and salt rejection) and contact angle measurements. It was found that the support membrane (polyvinylidene fluoride) produced by the phase inversion method that was coated with chitosan using electrospinning showed better performance, with a salt rejection up to 70% for MgSO4, a decreased the contact angle (52°) and improved the elongation at the breaking point (~82%).
In acute ischemic stroke patients with smoking incidence, are more women than men more likely to be included or excluded from thrombolysis therapy?
Authors: Rotimi Oluyemi R , Ajani Iretioluwa F , Penwell Alexandria , Lari Shyyon , Walker Brittany , Nathaniel Thomas I
Published: May 2020

Background:

Clinical factors associated with exclusion from recombinant tissue plasminogen activator in both men and women are not completely understood. The aim of this study is to determine whether there is a gender difference in clinical risk factors that excluded ischemic stroke patients with a history of smoking from recombinant tissue plasminogen activator.

Methods:

Retrospective data from a stroke registry were analyzed, and multivariable linear regression models were used to determine gender differences. Logistic regression models determined exclusion clinical risk factors for thrombolysis in male and female acute ischemic stroke patients with a history of smoking, while sequentially adjusting for sociodemographic, clinical, and stroke-related variables. The Kaplan–Meier survival analysis was used to determine the exclusion probabilities of men and women with a history of smoking within the stroke population.

Results:

Of the 1,446 acute ischemic stroke patients eligible for recombinant tissue plasminogen activator, 379 patients with a history of smoking were examined, of which 181 received recombinant tissue plasminogen activator while 198 were excluded from receiving recombinant tissue plasminogen activator. Of the 198 patients, 75 females and 123 males were excluded from receiving recombinant tissue plasminogen activator. After multivariable adjustment for age, National Institutes of Health scores, and stroke-related factors, females who present with weakness/paresis on initial examination (OR = 0.117, 95% CI, 0.025–0.548) and men who present with a history of previous transient ischemic attack (OR = 0.169, 95% CI, 0.044–0.655), antiplatelet medication use (OR = 0.456, 95% CI, 0.230–0.906), and weakness/paresis on initial examination (OR = 0.171, 95% CI, 0.056–0.521) were less likely to be excluded from recombinant tissue plasminogen activator (thrombolysis therapy).

Conclusions:

In an ischemic stroke population with a history of smoking, female smokers are more likely to be excluded from thrombolysis therapy in comparison to men, even after adjustment for confounding variables.
A censored sequential posterior odd test method in testability demonstration test planning
Authors: Zhang Yong , Wang Chao , Lin Xin , Liu Guanjun , Yang Peng , Qiu Jing
Published: May 2020

Testability demonstration tests can effectively verify product capabilities of fault detection and isolation; however, they suffer from insufficient samples, long cycles and high costs due to destructiveness of fault injection tests, which leads to an increasing demand for small sample tests. The sequential posterior odd test can effectively reduce sample sizes, but test results can be random and the sample size may be large. In this article, a censored sequential posterior odd test method is proposed, which can control the incremental risk caused by forced censoring within a contracted range by risk splitting. The development process of the testability demonstration test based on the censored sequential posterior odd test is designed. The number of censored tests and the calculation method of the censored threshold are presented. The case application shows that with the same prior distribution and constraint parameters, the average sample size of the proposed method is smaller than that of the sequential posterior odd test and of the classical method considering risks for both producers and consumers. The presented method can further reduce the risk of misjudgment and the number of test samples, contributing to the reduction of the test cycle and costs.
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.
Openness, Closure, and Transformation in Proverb Translation
Authors: Millar Suzanna R.
Published: May 2020

Proverbs are characteristically open to multiple interpretations. This is problematic for the translator: (how) should she convey this “openness” in translation? This article confronts the problem by zooming out to see translation as part of a larger “proverb process.” This process involves interpreting, applying, transmitting, and translating the proverb. Focusing on Prov 10–29, I trace a single saying (Prov 18.4) through these stages. I show how, at each stage, “openness” is important. But so too are the dynamics of “closure” and “transformation,” for they give the proverb applicability and power. As such, the translator who closes down and transforms meanings (while arguably lacking faithfulness to the linguistic nuances of the Hebrew) may be showing great faithfulness to the nature, genre, and function of the proverb.
The Pinoy Version: A Revelation
Authors: del Corro Anicia
Published: May 2020

Pinoy is a heterogeneous language that incorporates elements of English into an oral version of Tagalog, the national language of the Philippines. In 2018 the Philippine Bible Society published a written version of the New Testament in Pinoy. This study seeks to explain the success of the translation. The thesis is that any formulation that deviates from the current and natural way of saying something as articulated in its oral form makes the sentence more difficult to understand. (As in any language, it takes a native speaker to discern if a construction is natural.) The Pinoy New Testament translation was undertaken with the goal of reflecting the spoken form so that it would be easy to read and understand.
Cross-Validation: A Method Every Psychologist Should Know
Authors: de Rooij Mark , Weeda Wouter
Published: May 2020

Cross-validation is a statistical procedure that every psychologist should know. Most are possibly familiar with the procedure in a global way but have not used it for the analysis of their own data. We introduce cross-validation for the purpose of model selection in a general sense, as well as an R package we have developed for this kind of analysis, and we present examples illustrating the use of this package for types of research problems that are often encountered in the social sciences. Cross-validation can be an easy-to-use alternative to null-hypothesis testing, and it has the benefit that it does not make as many assumptions.
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

Metabolic 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

The 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.
Identification of two DNA methylation subtypes of Waldenström's macroglobulinemia with plasma and memory B cell features
Authors: Roos-Weil Damien , Giacopelli Brian , Armand Marine , Della Valle Véronique , Ghamlouch Hussein , Decaudin Camille , Metzner Marlen , Lu Junyan , Le Garff-Tavernier Magali , Leblond Veronique , Vyas Paresh , Zenz Thorsten , Nguyen-Khac Florence , Bernard Olivier A , Oakes Christopher C.
Published: May 2020

Epigenetic changes during B cell differentiation generates distinct DNA methylation signatures specific for B cell subsets, including memory B cells (MBCs) and plasma cells (PCs). Waldenström's macroglobulinemia (WM) is a complex B cell malignancy uniquely comprised of a mixture of lymphocytic and plasmacytic phenotypes. Here we integrated genome-wide DNA methylation, transcriptome, mutation and other phenotypic features of tumor cells from 35 MYD88-mutated WM patients in relation to normal plasma and B cell subsets. We discovered that WM patients naturally segregate into two groups according to DNA methylation patterns, related to normal MBC and PC profiles, and reminiscent of other memory and plasma cell-derived malignancies. Concurrent analysis of DNA methylation changes in normal and WM development were used to capture tumor-specific events, highlighting a selective reprogramming of enhancer regions in MBC-like WM and repressed and heterochromatic regions in PC-like WM. MBC-like WM hypomethylation was enriched in motifs belonging to PU.1, TCF3 and OCT2 transcription factors and involved elevated MYD88/TLR pathway activity. PC-like WM displayed marked global hypomethylation and selective overexpression of histone genes. Finally, WM subtypes exhibited differential genetic, phenotypic and clinical features. MBC-like WM harbored significantly more clonal CXCR4 mutations (P=0.015), deletion 13q (P=0.006), splenomegaly (P=0.02) and thrombocytopenia (P=0.004), while PC-like WM harbored more deletion 6q (P=0.012), gain 6p (P=0.033), had increased frequencies of IGHV3 genes (P=0.002), CD38 surface expression (P=4.1e-5), and plasmacytic differentiation features (P=0.008). Together our findings illustrate a novel approach to subclassify WM patients using patterns of DNA methylation and reveal divergent molecular signatures among WM patients.
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

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

Well 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

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.
Correction to: Effects of transversus abdominis plane block versus quadratus lumborum block on postoperative analgesia: a meta-analysis of randomized controlled trials
Authors: Wang Yanqing , Wang Xiaojia , Zhang Kexian
Published: May 2020

An amendment to this paper has been published and can be accessed via the original article.
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

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.
A rare case of brain abscess caused by Actinomyces meyeri
Authors: Sah Ranjit , Nepal Gaurav , Sah Sanjit , Singla Sonam , Upadhyay Priti , Rabaan Ali A. , Dhama Kuldeep , Rodriguez-Morales Alfonso J. , Ghimire Rabindra
Published: May 2020

Background

Brain abscesses are the rare and most severe form of actinomycosis, which usually manifests as abscesses of the occipital or parietal lobe due to direct expansion from an adjacent area, the oral cavity. In the medical literature, there are only a few reported cases of brain abscess caused by Actinomyces meyeri. In this report, we present a 35-year-old male patient who experienced an insidious headache and left-sided weakness and was diagnosed with an Actinomyces meyeri brain abscess.

Case presentation

A 35-year-old Nepalese man came to our institute with the primary complaint of insidious onset of headache and left-sided weakness. His physical examination was remarkable for the left-sided weakness with power 2/5 on both upper and lower limbs, hypertonia, hyperreflexia and positive Babinski sign, with intact sensory function. Cardiac examination revealed systolic murmur with regular S1 and S2, and lung examination was normal. The patient had poor dental hygiene. Biochemistry and haematology panel were normal. Urinalysis, chest X-ray and electrocardiogram revealed no abnormality. A transthoracic echocardiogram revealed mitral regurgitation. However, there was no evidence of valvular vegetation. A magnetic resonance imaging (MRI) of the brain was performed, which showed a bi-lobed rim enhancing lesion with a conglomeration of two adjoining round lesions in the right parietal parasagittal region. Perilesional oedema resulting in mass effect over the right lateral ventricle and mid-right uncal herniation with midline shift was noted. Craniotomy was performed, and the lesion was excised. Gram staining of the extracted sample revealed gram variable filamentous rods. Creamy white, moist, confluent colonies were observed after performing anaerobic culture in chocolate agar. On the gram staining, they showed gram-positive filamentous rods. Actinomyces meyeri was identified based on matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) technology. Based on the susceptibilities, he was successfully treated with ampicillin-sulbactam.

Conclusions

In conclusion, Actinomyces should be considered in the differential diagnosis of brain abscess in patients with poor dental hygiene, and early diagnosis and appropriate treatment can lead to better results.
Identification of a novel SDHB c.563 T > C mutation responsible for Paraganglioma syndrome and genetic analysis of the SDHB gene in China: a case report
Authors: Chen Heye , Yao Wei , He Qing , Yu Xuefang , Bian Bo
Published: May 2020

Background

Pheochromocytoma/paraganglioma (PPGL) is a rare neuroendocrine tumor. Succinate dehydrogenase (SDH) deficiency has been confirmed to be associated with PPGL in various studies. SDHB mutations play an important role in PPGL. However, genetic screening of PPGL patients has not been widely carried out in clinics in China, and only a few related studies have been reported.

Case presentation

We report a case of a 23-year-old woman with paraganglioma (PGL) caused by a novel missense SDHB mutation, c.563 T > C (p.Leu188Pro), who presented with paroxysmal hypertension. Computed tomography (CT) and magnetic resonance imaging (MRI) revealed a PGL in the right retroperitoneum and no metastasis. The patient was treated with surgical excision and did not have postsurgerical paroxysmal hypertension. In addition, we searched the literature related to variations in SDHB genes in Chinese patients with PPGL using multiple online databases, including PubMed, China Hospital Knowledge Database and Wanfang Data. Ultimately, 14 studies (published between 2006 and 2019) comprising 34 cases of SDHB-related PGL or pheochromocytoma (PCC) were found. In total, 35 patients were enrolled in this study, and 25 mutations were identified. The common genetic alterations of SDHB in China were c.136C > T (11.4%), c.18C > A (11.4%) and c.725G > A (8.5%). Some carriers of SDHB mutations (28.1%) developed metastatic PPGL, and a high frequency of head and neck PGLs (HNPGLs) (59.4%) was reported.

Conclusions

We describe a classic case with a novel SDHB c.563 T > C mutation. Based on our literature review, common SDHB gene mutations in Chinese PPGL patients are c.136C > T, c.18C > A and c.725G > A.
Discrimination between clinical significant and insignificant prostate cancer with apparent diffusion coefficient – a systematic review and meta analysis
Authors: Meyer Hans-Jonas , Wienke Andreas , Surov Alexey
Published: May 2020

Background

Prostate MRI has become a corner stone in diagnosis of prostate cancer (PC). Diffusion weighted imaging and the apparent diffusion coefficient (ADC) can be used to reflect tumor microstructure. The present analysis sought to compare ADC values of clinically insignificant with clinical significant PC based upon a large patient sample.

Methods

MEDLINE library and SCOPUS databases were screened for the associations between ADC and Gleason score (GS) in PC up to May 2019. The primary endpoint of the systematic review was the ADC value of PC groups according to Gleason score. In total 26 studies were suitable for the analysis and included into the present study. The included studies comprised a total of 1633 lesions.

Results

Clinically significant PCs (GS ≥ 7) were diagnosed in 1078 cases (66.0%) and insignificant PCs (GS 5 and 6) in 555 cases (34.0%). The pooled mean ADC value derived from monoexponenantially fitted ADCmean of the clinically significant PC was 0.86 × 10− 3 mm2/s [95% CI 0.83–0.90] and the pooled mean value of insignificant PC was 1.1 × 10− 3 mm2/s [95% CI 1.03–1.18]. Clinical significant PC showed lower ADC values compared to non-significant PC. The pooled ADC values of clinically insignificant PCs were no lower than 0.75 × 10− 3 mm2/s.

Conclusions

We evaluated the published literature comparing clinical insignificant with clinically prostate cancer in regard of the Apparent diffusion coefficient values derived from magnetic resonance imaging. We identified that the clinically insignificant prostate cancer have lower ADC values than clinically significant, which may aid in tumor noninvasive tumor characterization in clinical routine.