bluuebunny/crossref_metadata_2025 huggingface dataset:
Identifying small RNAs derived from maternal- and somatic-type rRNAs in zebrafish development
Authors: Locati Mauro D. , Pagano Johanna F.B. , Abdullah Farah , Ensink Wim A. , van Olst Marina , van Leeuwen Selina , Nehrdich Ulrike , Spaink Herman P. , Rauwerda Han , Jonker Martijs J. , Dekker Rob J. , Breit Timo M.
Published: February 2018

rRNAs are non-coding RNAs present in all prokaryotes and eukaryotes. In eukaryotes there are four rRNAs: 18S, 5.8S, 28S, originating from a common precursor (45S), and 5S. We have recently discovered the existence of two distinct developmental types of rRNA: a maternal-type, present in eggs and a somatic-type, expressed in adult tissues. Lately, next-generation sequencing has allowed the discovery of new small-RNAs deriving from longer non-coding RNAs, including small-RNAs from rRNAs (srRNAs). Here, we systemically investigated srRNAs of maternal- or somatic-type 18S, 5.8S, 28S, with small-RNAseq from many zebrafish developmental stages. We identified new srRNAs for each rRNA. For 5.8S, we found srRNA consisting of the 5′ or 3′ halves, with only the latter having different sequence for the maternal- and somatic-types. For 18S, we discovered 21 nt srRNA from the 5′ end of the 18S rRNA with a striking resemblance to microRNAs; as it is likely processed from a stem-loop precursor and present in human and mouse Argonaute-complexed small-RNA. For 28S, an abundant 80 nt srRNA from the 3′ end of the 28S rRNA was found. The expression levels during embryogenesis of these srRNA indicate they are not generated from rRNA degradation and might have a role in the zebrafish development.
Signs and stability in higher-derivative gravity
Authors: Narain Gaurav
Published: February 2018

Perturbatively renormalizable higher-derivative gravity in four space–time dimensions with arbitrary signs of couplings has been considered. Systematic analysis of the action with arbitrary signs of couplings in Lorentzian flat space–time for no-tachyons, fixes the signs. Feynman [Formula: see text] prescription for these signs further grants necessary convergence in path-integral, suppressing the field modes with large action. This also leads to a sensible wick rotation where quantum computation can be performed. Running couplings for these sign of parameters make the massive tensor ghost innocuous leading to a stable and ghost-free renormalizable theory in four space–time dimensions. The theory has a transition point arising from renormalization group (RG) equations, where the coefficient of [Formula: see text] diverges without affecting the perturbative quantum field theory (QFT). Redefining this coefficient gives a better handle over the theory around the transition point. The flow equations push the flow of parameters across the transition point. The flow beyond the transition point is analyzed using the one-loop RG equations which shows that the regime beyond the transition point has unphysical properties: there are tachyons, the path-integral loses positive definiteness, Newton’s constant [Formula: see text] becomes negative and large, and perturbative parameters become large. These shortcomings indicate a lack of completeness beyond the transition point and need of a nonperturbative treatment of the theory beyond the transition point.
Entanglement entropy of AdS5 × S5 with massless flavors at nonzero temperature
Authors: Hu Sen , Wu Guozhen
Published: February 2018

We consider backreacted [Formula: see text] coupled with [Formula: see text] massless flavors introduced by D7-branes at nonzero temperature. The backreacted geometry is in the Veneziano limit. The temperature of this system is related to the event horizon at [Formula: see text]. Dividing one of the spatial directions into a line segment with length [Formula: see text], we will calculate the holographic entanglement entropy (HEE) between the two subspaces. We study the behavior near the event horizon, and finally find that there exists confinement/deconfinement phase transition phenomenon near the horizon since the difference between the entanglement entropy of the connected minimal surface and the disconnected one changes sign.
Organisational Information and Knowledge Sharing: Uncovering Mediating Effects of Perceived Trustworthiness Using the PROCESS Approach
Authors: Max Evans M. , Frissen Ilja , Wensley Anthony K. P.
Published: February 2018

Many organisations are confronted with challenges in getting employees to effectively participate in information and knowledge sharing (IKS). Further, IKS is embedded in multifaceted social contexts, which are influenced by several different social and cognitive factors. This study is in support of the hypothesis that perceived trustworthiness is widely implicated as a mediating factor between those social–cognitive factors and IKS. Previous work, however, uncovered only a handful of such mediating effects. It is argued here that the paucity may have been due to limitations of the statistical methods. This study employs PROCESS, a more powerful current method for mediation analysis in an attempt to uncover previously hidden relationships. Analyses were performed on data collected from 275 knowledge workers (legal professionals and paralegals) engaged in shared legal project work, at one of Canada’s largest multijurisdictional law firms. Social–cognitive factors that were considered were shared language, shared vision, tie strength, age/gender/educational homophily and relationship length. IKS outcomes were willingness to share, willingness to use and perceived receipt of useful information/knowledge. Consistent with the hypothesis, the more powerful method revealed a large number of significant mediating effects of perceived trustworthiness. Out of possible 112 simple mediation models, 62 were significant, 44 of which had been previously undiscovered. The results highlight the importance of trust as well as the power of current methods for mediation analysis and serve as a strong argument for their use. The paper concludes with implications for research and practice.
Demystifying traditional Chinese medicines:Lycium barbarumas a model therapeutic
Authors: Manthey Abby Leigh , Chiu Kin , So Kwok-Fai
Published: February 2018

The practice of Traditional Chinese Medicine (TCM) focuses on holistic treatment of the body. This often includes preparation and application of medicinal herbs, either alone or in combination with other supplements. Lycium barbarum (LB), for example, is a commonly used herbal supplement in many Asian countries, being most well-known for improving kidney, liver, and eye health. It is also one of the most widely scientifically researched TCMs and a large body of literature is available describing its effects on various tissues and organ systems. In this perspective, we briefly expand upon how LB can be used as a model TCM in the systematic study of other herbal medicines, highlighting two of the primary barriers to their use in modern medicine worldwide.
Definability of Cai-Fürer-Immerman Problems in Choiceless Polynomial Time
Authors: Pakusa Wied , Schalthöfer Svenja , Selman Erkal
Published: February 2018

Choiceless Polynomial Time (CPT) is one of the most promising candidates in the search for a logic capturing P
time
. The question whether there is a logic that expresses exactly the polynomial-time computable properties of finite structures, which has been open for more than 30 years, is one of the most important and challenging problems in finite model theory.

The strength of Choiceless Polynomial Time is its ability to perform isomorphism-invariant
computations
over structures, using hereditarily finite sets as data structures. But, because of isomorphism-invariance, it is choiceless in the sense that it cannot select an arbitrary element of a set—an operation that is crucial for many classical algorithms. CPT can define many interesting P
time
queries, including (a certain version of) the Cai-Fürer-Immerman (CFI) query. The CFI-query is particularly interesting, because it separates fixed-point logic with counting from P
time
and has since remained the main benchmark for the expressibility of logics within P
time
.

The CFI-construction associates with each connected graph a set of CFI-graphs that can be partitioned into exactly two isomorphism classes called odd and even CFI-graphs. The problem is to decide, given a CFI-graph, whether it is odd or even. For the case where the CFI-graphs arise from ordered graphs, Dawar, Richerby, and Rossman proved that the CFI-query is CPT-definable. However, definability of the CFI-query over general graphs remains open.

Our first contribution generalises the result by Dawar, Richerby, and Rossman to the variant of the CFI-query derived from graphs with colour classes of logarithmic size, instead of colour class size one. Second, we consider the CFI-query over graph classes where the maximal degree is linear in the size of the graphs. For the latter, we establish CPT-definability using only sets of small, constant rank, which is known to be impossible for the general case.

In our CFI-recognising procedures we strongly make use of the ability of CPT to create sets, rather than tuples only, and we further prove that, if CPT worked over tuples instead, then no such procedure would be definable. We introduce a notion of “sequencelike objects” based on the structure of the graphs’ symmetry groups, and we show that no CPT-program that only uses sequencelike objects can decide the CFI-query over complete graphs, which have linear maximal degree. From a broader perspective, this generalises a result by Blass, Gurevich, and van den Bussche about the power of isomorphism-invariant machine models (for polynomial time) to a setting with counting.
Openness in Education and Digital Scholarship: An interview with Bonnie Stewart
Authors: Bozkurt Aras , Koseoglu Suzan
Published: February 2018

Bonnie Stewart, a researcher at University of Prince Edward Island, Canada, sat down with eLearn Magazine to discuss openness in education, scholarship, and Antigonish 2.0.
Platelets Enhance Multiple Myeloma Progression via IL-1β Upregulation
Authors: Takagi Satoshi , Tsukamoto Shokichi , Park Jihye , Johnson Kelly E. , Kawano Yawara , Moschetta Michele , Liu Chia-Jen , Mishima Yuji , Kokubun Katsutoshi , Manier Salomon , Salem Karma Z. , Huynh Daisy , Sacco Antonio , Forward Jodi , Roccaro Aldo M. , Battinelli Elisabeth M. , Ghobrial Irene M.
Published: February 2018

Purpose: Tumor cell–platelet interactions contribute to tumor progression and metastasis in solid tumors. However, the role of platelets in hematological malignancies is not clear. We investigated the association of platelet activation status with clinical stages in multiple myeloma (MM) patients and explored the role of platelets in MM progression.

Experimental Design: Platelets were obtained from healthy donors and MM patients. We examined platelet activation status in MM patients by flow cytometry and transmission electron microscopy. We also observed the enriched pathways that are involved with platelet activation in RNA sequencing of platelets. MM cell lines were used to assess the effect of platelets on MM cell proliferation in vitro and their engraftment in vivo. RNA sequencing of MM cell lines was performed to explore molecular mechanisms underlying MM cell–platelet interaction and a CRISPR/Cas9 knockout approach was used for validation.

Results: Platelets from MM patients were highly activated with disease progression. RNA sequencing of platelets revealed that genes involved in platelets were enriched in patients with smoldering MM (SMM) or MM. Platelets promoted MM cell proliferation in vitro and contributed to tumor engraftment in bone marrow in vivo. RNA sequencing revealed that IL-1β was upregulated in MM cell lines co-cultured with platelets, whereas IL-1β knockout in MM cell lines abrogated the effects of platelets on MM cell proliferation and engraftment in vivo.

Conclusions: Platelets from MM patients were highly activated with disease progression. IL-1β is critical to platelet-mediated MM progression and might be a potential target for MM treatment. Clin Cancer Res; 24(10); 2430–9. ©2018 AACR.
Pan-Cancer Molecular Classes Transcending Tumor Lineage Across 32 Cancer Types, Multiple Data Platforms, and over 10,000 Cases
Authors: Chen Fengju , Zhang Yiqun , Gibbons Don L. , Deneen Benjamin , Kwiatkowski David J. , Ittmann Michael , Creighton Chad J.
Published: February 2018

Purpose: The Cancer Genome Atlas data resources represent an opportunity to explore commonalities across cancer types involving multiple molecular levels, but tumor lineage and histology can represent a barrier in moving beyond differences related to cancer type.

Experimental Design: On the basis of gene expression data, we classified 10,224 cancers, representing 32 major types, into 10 molecular-based “classes.” Molecular patterns representing tissue or histologic dominant effects were first removed computationally, with the resulting classes representing emergent themes across tumor lineages.

Results: Key differences involving mRNAs, miRNAs, proteins, and DNA methylation underscored the pan-cancer classes. One class expressing neuroendocrine and cancer-testis antigen markers represented ∼4% of cancers surveyed. Basal-like breast cancers segregated into an exclusive class, distinct from all other cancers. Immune checkpoint pathway markers and molecular signatures of immune infiltrates were most strongly manifested within a class representing ∼13% of cancers. Pathway-level differences involving hypoxia, NRF2-ARE, Wnt, and Notch were manifested in two additional classes enriched for mesenchymal markers and miR200 silencing.

Conclusions: All pan-cancer molecular classes uncovered here, with the important exception of the basal-like breast cancer class, involve a wide range of cancer types and would facilitate understanding the molecular underpinnings of cancers beyond tissue-oriented domains. Numerous biological processes associated with cancer in the laboratory setting were found here to be coordinately manifested across large subsets of human cancers. The number of cancers manifesting features of neuroendocrine tumors may be much higher than previously thought, which disease is known to occur in many different tissues. Clin Cancer Res; 24(9); 2182–93. ©2018 AACR.
Targeting HSF1: A Prime Integrator of Proteotoxic Stress Response in Myeloma
Authors: Parekh Samir
Published: February 2018

The HSF1 transcription factor is an integrator of the cellular stress response, and its expression has demonstrated poor prognosis in multiple myeloma. The novel anti-HSF1 small-molecule inhibitors CCT251236 and KRIB11 demonstrate in vitro and in vivo antimyeloma activity, representing a novel approach for targeting the heat shock response in myeloma. Clin Cancer Res; 24(10); 2237–8. ©2018 AACR.

See related article by Fok et al., p. 2395
Transient Receptor Potential Ankyrin 1 and Substance P Mediate the Development of Gastric Mucosal Lesions in a Water Immersion Restraint Stress Rat Model
Authors: Xu Yan , Jia Ji , Xie Chuangbo , Wu Youping , Tu Weifeng
Published: February 2018

Background: Activation of substance P (SP) contributes to the development and maintenance of gastric lesions, but the mechanisms underlying the release of SP and SP-mediated damage to the gastric mucosa remain unknown. Transient receptor potential ankyrin 1 (TRPA1) is expressed in SP-positive neurons in the dorsal root ganglion (DRG) and stomach of rats. We hypothesized that water immersion restraint stress (WIRS) may activate and sensitize TRPA1 in DRG neurons, subsequently inducing the release of SP from DRG and stomach cells, causing the development of acute gastric mucosal lesions (AGML). Methods: Changes in TRPA1 and SP expression in T8–11 DRG sensory neurons and the stomach in an AGML rat model were determined by reverse transcription polymerase chain reaction, western blotting and immunohistochemistry. The SP levels of serum and gastric mucosa were measured by using an enzyme-linked immunosorbent assay (ELISA). Gastric lesions were evaluated by histopathological changes. The TRPA1 antagonist HC-030031 and TRPA1 agonists allyl isothiocyanate were used to verify effect of TRPA1 and SP on AGML. Results: SP and TRPA1 in the DRG and stomach were upregulated, and the serum and gastric mucosa levels of SP were increased after WIRS, which are closely associated with AGML. The release of SP was suppressed and AGML were alleviated following a selective TRPA1 antagonist HC-030031. TRPA1 agonists AITC increased release of SP and led to moderate gastric lesions. We confirmed that WIRS induced the release of SP in the DRG, stomach, serum and gastric mucosa, and in a TRPA1-dependent manner. Conclusions: Upregulated SP and TRPA1 in the DRG and stomach and increased serum and gastric mucosa SP levels may contribute to stress-induced AGML. TRPA1 is a potential drug target to reduce stress-induced AGML development in patients with acute critical illnesses. This study may contribute to the discovery of drugs for AGML treatment.
Correlation between B-Type Natriuretic Peptide and N-Terminal pro-B-Type Natriuretic Peptide in a Large Japanese Population at Risk of Stage A Heart Failure
Authors: Taki Mizuri , Hoshide Satoshi , Kono Ken , Kario Kazuomi
Published: February 2018

Background: The measurements of B-type natriuretic peptide (BNP) and N-terminal pro-B-type natriuretic peptide (NT-proBNP) are useful for ruling out heart failure and as prognostic markers in not only heart failure populations but also general populations. It is not clear whether these two biomarkers are elevated in parallel or associated with demographic characteristics in large populations at risk of stage A heart failure. Here we investigated the relationship between BNP and NT-proBNP and extended the evaluation of this association to known demographic disparities in stage A heart failure. Methods: Of 4,310 ambulatory patients, we analyzed the cases of the 3,643 (mean age 65 ± 11 years, 46% male, and 79% on antihypertensive medication) patients whose serum BNP and NT-proBNP levels were both measured and who had a history of and/or risk factors for cardiovascular disease from the Japan Morning Surge-Home Blood Pressure (J-HOP) Study dataset. Results: The median (25th–75th percentiles) BNP and NT-proBNP values were 18.7 (9.3–38.5) pg/mL and 50.3 (25.5–97.4) pg/mL. There was a significant association between log-transformed BNP and log-transformed NT-proBNP (r = 818, p < 0.001). A multiple linear regression analysis showed that log-transformed NT-proBNP was significantly associated with log-transformed BNP (beta coefficient = 0.774, p < 0.001). When stratified by demographic characteristics, these associations remained (all p < 0.001). Conclusion: In a large Japanese population at risk of stage A heart failure, there was a significant association between BNP and NT-proBNP after adjustment and stratification by demographics.
Sesquiterpene-Enriched Extract of Curcuma aeruginosa Roxb. Retards Axillary Hair Growth: A Randomised, Placebo-Controlled, Double-Blind Study
Authors: Srivilai Jukkarin , Nontakhot Kanjana  , Nutuan Thanawan , Waranuch Neti , Khorana Nantaka , Wisuthiprot Wudtichai , Scholfield C. Norman , Champachaisri Katechan , Ingkaninan Kornkanok
Published: February 2018

Background: Sesquiterpenes in Curcuma aeruginosa Roxb. inhibit steroid 5α-reductase and dihydrotestosterone production, and reverse androgenic alopecia. This study sought to show that a high sesquiterpene C. aeruginosa extract (CA-ext) retards axillary hair growth in women. Methods: Thirty women (age 20–52 years) were recruited into a 12-week, double-blind, placebo-controlled intervention for CA-ext treatment, where they were randomly allocated to a left or right armpit group. At weekly intervals, axillary hair length was measured videometrically, the hair was shaved, and lotion was applied (to the contralateral axilla) twice daily via roll-on applicators containing either CA-ext or placebo. The primary endpoint of the study was hair growth. Results: Participants showed 22% (range 8–56%, p < 0.0001) reduced axillary hair growth with CA-ext compared to placebo, albeit delayed by 6 weeks. Participants were satisfied with the treatment and no apparent adverse effects were reported. The quantities of lotion used for each axilla were identical between test and placebo throughout the trial for each participant. Participants reported having shorter and finer armpit hair with the test lotion but disliked its smell, even though it was perfumed. The “free of irritation” description gained the highest questionnaire ratings. Conclusion: CA-ext in lotion is an efficacious inhibitor of axillary hair growth, the preparation was well accepted and matched the effectiveness of finasteride. Thus, with some refinement, it should provide an alternative pharmacological treatment for unwanted androgenic hair.
A Combination of the Aerosolized PPAR-γ Agonist Pioglitazone and a Synthetic Surfactant Protein B Peptide Mimic Prevents Hyperoxia-Induced Neonatal Lung Injury in Rats
Authors: Sakurai Reiko , Lee Cindy , Shen Humphrey , Waring Alan J. , Walther Frans J. , Rehan Virender K.
Published: February 2018

Background: Despite improvements in perinatal care, bronchopulmonary dysplasia (BPD) in extremely premature infants has not decreased. Postnatal surfactant therapy provides symptomatic relief from respiratory distress syndrome, but does not translate into a reduction in BPD. Therefore, the search for effective interventions to prevent BPD continues. Objectives: Since PPAR-γ agonists have been demonstrated to promote neonatal lung maturation and injury repair, we hypothesized that a formulation of a PPAR-γ agonist, pioglitazone (PGZ) and a synthetic lung surfactant (a surfactant protein B peptide mimic, B-YL) combined would stimulate lung maturation and block hyperoxia-induced neonatal lung injury more effectively than either modality alone. Methods: One-day-old Sprague-Dawley rat pups were administered PGZ + B-YL via nebulization every 24 h for up to 72 h. The pups were exposed to either 21 or 95% O2, and then sacrificed. Their lungs were examined for markers of lung maturation (levels of PPAR-γ, SP-C and choline-phosphate cytidylyltransferase [CCT-α] and [3H]triolein uptake) and injury repair (bronchoalveolar lavage cell count and protein content, and levels of LEF-1, fibronectin, ALK5, and β-catenin) by Western blot analysis. Results: Markers of alveolar epithelial/mesenchymal maturation (PPAR-γ, SP-C, CCT-α, and triolein uptake) increased significantly in the PGZ + B-YL group, more than with either drug alone. Similarly, markers of hyperoxia-induced lung injury were blocked effectively with PGZ + B-YL treatment. Conclusions: Nebulized PPAR-γ agonist PGZ with a synthetic lung surfactant accelerates lung maturation and prevents neonatal hyperoxia-induced lung injury more than either modality alone, with the potential to provide more effective prevention of BPD.
Elevated Global DNA Methylation Is Not Exclusive to Amyotrophic Lateral Sclerosis and Is Also Observed in Spinocerebellar Ataxia Types 1 and 2
Authors: Hamzeiy Hamid , Savaş Doruk , Tunca Ceren , Şen Nesli Ece , Gündoğdu Eken Aslı , Şahbaz Irmak , Calini Daniela , Tiloca Cinzia , Ticozzi Nicola , Ratti Antonia , Silani Vincenzo , Başak A. Nazlı
Published: February 2018

Adult-onset neurological disorders are caused and influenced by a multitude of different factors, including epigenetic modifications. Here, using an ELISA kit selected upon careful testing, we investigated global 5-methylcytosine (5-mC) levels in sporadic and familial amyotrophic lateral sclerosis (sALS and fALS), spinocerebellar ataxia types 1 and 2 (SCA1 and SCA2), Huntington’s disease, Friedreich’s ataxia, and myotonic dystrophy type 1. We report a significant elevation in global 5-mC levels of about 2–7% on average for sALS (p < 0.01 [F(1, 243) = 9.159, p = 0.0027]) and various forms of fALS along with SCA1 (p < 0.01 [F(1, 83) = 11.285], p = 0.0012) and SCA2 (p < 0.001 [F(1, 122) = 29.996, p = 0.0001]) when compared to age- and sex-matched healthy controls. C9orf72 expansion carrier ALS patients exhibit the highest global 5-mC levels along with C9orf72 promoter hypermethylation. We failed to measure global 5-hydroxymethylcytosine (5-hmC) levels in blood, probably due to the very low levels of 5-hmC and the limitations of the commercially available ELISA kits. Our results point towards a role for epigenetics modification in ALS, SCA1, and SCA2, and help conclude a dispute on the global 5-mC levels in sALS blood.
Long-Lasting Response to Trabectedin in a Patient with Metastatic Uterine Leiomyosarcoma: A Case Report
Authors: Nteli Viktoria-Anna , Knauf Wolfgang , Janton-Klein Anja , El-Safadi Samer
Published: February 2018

Background: Uterine leiomyosarcoma (uLMS) is a rare tumor that accounts for 1% of all uterine malignancies. In spite of adequate surgical resection of uLMS, even in the early stage, patients remain at high risk for local and distant recurrence. Therefore, the treatment of advanced uLMS represents a considerable challenge. Methods: We report the case of a 47-year-old woman who presented with uLMS with abnormal vaginal bleeding. Results: The patient underwent a total hysterectomy and bilateral adnexectomy, which was followed by 1 year progression-free survival without adjuvant therapy. Thereafter, new lung metastases and local progression at the vaginal stump were observed. Chemotherapy with ifosfamide and doxorubicin was administered. However, after 4 cycles, a CT scan revealed disease progression in the lung metastases. Subsequently, the patient was treated with trabectedin at a dose of 1.5 mg/m2 for 6 cycles resulting in complete remission of the lung metastases as well as partial remission of the mass in the vaginal stump after 9 cycles of trabectedin. The patient is currently on maintenance therapy with trabectedin and has no recurrence. Conclusion: Trabectedin seems to be an efficient option for patients with uLMS as demonstrated by a long-lasting response in a pretreated patient with an acceptable safety profile with no signs of cumulative toxicity.
Intracranial Leptomeningeal Carcinomatosis: A Diagnostic Study with 18F-Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography
Authors: Nuvoli Susanna , Contu Silvia , Pung Bi Llie Joy , Solinas Patrizia , Madeddu Giuseppe , Spanu Angela
Published: February 2018

Leptomeningeal carcinomatosis (LC) diagnosis is based on cerebrospinal fluid (CSF) cytological analysis and contrast-enhanced magnetic resonance imaging (MRI); however, low sensitivity was evidenced in some cases delaying prompt and adequate treatments. Brain 18F-fluorodeoxyglucose positron emission tomography (18F-FDG PET) was also employed in doubtful cases. We retrospectively described 4 suspected LC cases with uncertain or undetectable MRI and initially negative CSF cytology. Whole-body (WB) and brain 18F-FDG PET/computed tomography (CT) were used, the latter showing intracranial tracer uptakes suspected for LC in 3/4 cases. In 2 of these 3 cases, WB scan also evidenced spinal cord lesion and pulmonary tumor, respectively, while both procedures were true negative in the fourth case. CSF cytology became positive after repeated exams in the 3 PET/CT-positive cases. In 1 of these 3 patients, it was also confirmed at MRI, while it stayed negative in the remaining PET/CT-negative case with uncertain MRI. 18F-FDG PET/CT could be a useful supportive diagnostic tool in doubtful intracranial and spinal LC.
High-Throughput Data of Circular RNA Profiles in Human Temporal Cortex Tissue Reveals Novel Insights into Temporal Lobe Epilepsy
Authors: Li Jiaxin , Lin Haijun , Sun Zhenrong , Kong Guanyi , Yan Xu , Wang Yujiao , Wang Xiaoxuan , Wen Yanhua , liu Xiang , Zheng Hongkun , Jia Mei , Shi Zhongfang , Xu Rong , Yang Shaohua , Yuan Fang
Published: February 2018

Background/Aims: Circular RNAs (circRNAs) are a class of long noncoding RNAs with a closed loop structure that regulate gene expression as microRNA sponges. CircRNAs are more enriched in brain tissue, but knowledge of the role of circRNAs in temporal lobe epilepsy (TLE) has remained limited. This study is the first to identify the global expression profiles and characteristics of circRNAs in human temporal cortex tissue from TLE patients. Methods: Temporal cortices were collected from 17 TLE patients and 17 non-TLE patients. Total RNA was isolated, and high-throughput sequencing was used to profile the transcriptome of dysregulated circRNAs. Quantitative PCR was performed for the validation of changed circRNAs. Results: In total, 78983 circRNAs, including 15.29% known and 84.71% novel circRNAs, were detected in this study. Intriguingly, 442 circRNAs were differentially expressed between the TLE and non-TLE groups (fold change≥2.0 and FDR≤0.05). Of these circRNAs, 188 were up-regulated, and 254 were down-regulated in the TLE patient group. Eight circRNAs were validated by real-time PCR. Remarkably, circ-EFCAB2 was intensely up-regulated, while circ-DROSHA expression was significantly lower in the TLE group than in the non-TLE group (P<0.05). Bioinformatic analysis revealed that circ-EFCAB2 binds to miR-485-5p to increase the expression level of the ion channel CLCN6, while circ-DROSHA interacts with miR-1252-5p to decrease the expression level of ATP1A2. Conclusions: The dysregulations of circRNAs may reflect the pathogenesis of TLE and circ-EFCAB2 and circ-DROSHA might be potential therapeutic targets and biomarkers in TLE patients.
ITRAQ-Based Proteomics Analysis of Triptolide On Human A549 Lung Adenocarcinoma Cells
Authors: Li Fangqiong , Zhao Dongxiao , Yang Suwen , Wang Juan , Liu Qin , Jin Xin , Wang Wei
Published: February 2018

Background/Aims: Triptolide (TP) is a diterpenoid triepoxide extracted from the traditional Chinese medical herb Tripterygium wilfordii that exerts prominent broad-spectrum anticancer activity to repress proliferation and induce cancer cell apoptosis through various molecular pathways. We previously observed that TP inhibits the progression of A549 cells and pancreatic cancer cells (PNCA-1) in vitro. However, the complex molecular mechanism underlying the anticancer activity of TP is not well understood. Methods: To explore the molecular mechanisms by which TP induces lung cancer cell apoptosis, we investigated changes in the protein profile of A549 cells treated with TP using a proteomics approach (iTRAQ [isobaric tags for relative and absolute quantitation] combined with NanoLC-MS/MS [nano liquid chromatography-mass spectrometry]). Changes in the profiles of the expressed proteins were analyzed using the bioinformatics tools OmicsBean and the Kyoto Encyclopedia of Genes and Genomes (KEGG) and were verified using western blotting. Apoptosis and cell cycle effects were analyzed using flow cytometry. Results: TP induced apoptosis in A549 cells and blocked A549 cells at the G2/M phase. Using iTRAQ technology, we observed 312 differentially expressed proteins associated in networks and implicated in different KEGG pathways. Gene Ontology (GO) analysis showed the overviews of dysregulated proteins in the biological process (BP), cell component (CC), and molecular function (MF) categories. Moreover, some candidate proteins involved in PARP1/AIF and nuclear Akt signaling pathways or metastasis processes were validated by western blotting. Conclusion: TP exerted anti-tumor activity on non-small cell lung cancer (NSCLC) A549 lung adenocarcinoma cells by dysregulating tumor-related protein expression. Herein, we provide a preliminary study of TP-related cytotoxicity on A549 cells using proteomics tools. These findings may improve the current understanding of the anti-tumor effects of TP on lung cancer cells and may reveal candidate proteins as potential targets for the treatment of lung cancer.
Ratio of Immune Response to Tumor Burden Predicts Survival Via Regulating Functions of Lymphocytes and Monocytes in Diffuse Large B-Cell Lymphoma
Authors: Ji Hongfei , Niu Xingjian , Yin Lei , Wang Yiran , Huang Lan , Xuan Qijia , Li Liru , Zhang Han , Li Jingtong , Yang Yue , An Weiwei , Zhang Qingyuan
Published: February 2018

Background/Aims: Diffuse large B-cell lymphoma (DLBCL) is an aggressive disease, and is the most common type of lymphoma in adults. Although significant progress in treatment has been made using chemotherapy combinations, there exist a large amount of relapse or refractory cases. Thus, effective clinical biomarkers for DLBCL are urgently needed. Our study aims to explore the predictive significance of using the immune response to tumor burden ratio [defined as the lymphocyte to monocyte ratio (LMR)/lactate dehydrogenase (LDH) levels] in 184 DLBCL patients and the potential mechanism underlying the use of the LMR to tumor burden ratio in predicting patient survival. Methods: The correlation between serum LDH levels and tumor levels assessed by PET-CT was determined using Spearman’s correlation analysis. Clinical data from 184 DLBCL patients was assessed using receiver operating characteristic curve analysis and survival analysis. The potential correlation between tumor burden and lymphocytes or monocytes was analyzed by immunohistochemical staining, flow cytometry, and ELISA analysis of patient samples. In addition, we performed in vitro studies to further determine the effects of tumor burden on the anti-tumor activity of T lymphocytes. Results: We observed that serum LDH was an excellent surrogate marker of tumor burden in DLBCL patients, and that the ratio of LMR to LDH was an independent prognostic biomarker capable of predicting survival in DLBCL patients. Further analysis showed that a high tumor burden was correlated with decreased Ki67 expression in T cells, either in the solid tumor tissue or in the circulating blood. In addition, based on an in vitro co-culture study, a higher tumor burden led to the suppression of the anti-tumor response of T cells. Furthermore, we found that a higher tumor burden was correlated with the differentiation of monocytes to tumor associated macrophages in the tumor micro-environment. Both results demonstrate the importance of considering both the immune system and tumor burden for prognostic analysis. Conclusion: Our study has identified a novel clinical biomarker, namely, the immune response to tumor burden ratio, that can be used to distinguish survival outcomes in DLBCL patients, and demonstrated the potential mechanism underlying the use of this biomarker, that incorporates both the immune system and tumor burden, for use in future clinical applications.
A Meta-Analysis of the Diagnostic Accuracy of Circular RNAs in Digestive System Malignancy
Authors: Chen Zhiqiang , Zhang Long , Han Guoyong , Zuo Xueliang , Zhang Yao , Zhu Qin , Wu Jindao , Wang Xuehao
Published: February 2018

Background/Aims: Circular RNAs (circRNAs), a novel class of noncoding RNAs, have been found to be dysregulated in various cancers. However, the clinical application value of these circRNAs in digestive system cancers remains to be clarified. We aimed to comprehensively explore the potential role of circRNAs as diagnostic indicators in digestive system malignancies. Methods: Relevant studies were systematically retrieved from PubMed, Web of Science and the Cochrane Library. The data that were required to complete 2 × 2 contingency tables were obtained from the included studies. Stratified analyses by cancer type, sample size and publication year were performed. Results: Thirteen studies with 2,276 individuals were included in the meta-analysis. The pooled sensitivity and specificity of circRNAs in the diagnosis of digestive system malignancy were 0.72 [95% confidence interval (CI): 0.65-0.77] and 0.77 (95% CI: 0.72-0.81), respectively. The overall positive likelihood ratio was 3.09 (95% CI: 2.64-3.62), and the overall negative likelihood ratio was 0.37 (95% CI: 0.31-0.44). The pooled diagnostic odds ratio was 8.38 (95% CI: 6.86-10.25), and the overall area under the curve was 0.81 (95% CI: 0.77-0.84), indicating good discriminative ability of circRNAs as biomarkers for digestive system malignancy. Conclusion: circRNAs distinguish patients with digestive system cancer from controls with relatively high diagnostic accuracy. circRNAs may be used as potential biomarkers for the diagnosis of digestive system malignancy.
MiR-124 Promotes the Growth of Retinal Ganglion Cells Derived from Müller Cells
Authors: He Ye , Li Hai-bo , Li Xin , Zhou Yi , Xia Xiao-bo , Song Wei-tao
Published: February 2018

Background/Aims: Retinal Müller cells could be induced to differentiate into retinal ganglion cells (RGCs), but RGCs derived from Müller cells have defects in axon growth, leading to a defect in signal conduction. In this study we aimed to explore the role of miR-124 in axon growth of RGCs derived from Müller cells. Methods: Müller cells were isolated from rat retina and induced to dedifferentiate into retinal stem cells. The stem cells were infected by PGC-FU-Atoh7-GFP lentivirus and then transfected with miR-124 or anti-miR-124, and the length of axon was compared. Furthermore, the cells were injected into the eyes of rat chronic ocular hypertension glaucoma model and axon growth in vivo was examined. The targeting of CoREST by miR-124 was detected by luciferase assay. Results: In retinal stem cells, the length of axon was 1,792±64.54 µm in miR-124 group, 509±21.35 µm in control group, and only 87.9±9.24 µm in anti-miR-124 group. In rat model, miR-124 promoted axon growth of RGCs differentiated from retinal stem cells. Furthermore, we found that miR-124 negatively regulated CoREST via directly targeting the binding site in CoREST 3′ UTR. Conclusions: We provide the first evidence that miR-124 regulates axon growth of RGCs derived from Müller cells, and miR-124 has translational potential for gene therapy of glaucoma.
Clusterin Reduces Cold Ischemia-Reperfusion Injury in Heart Transplantation Through Regulation of NF-kB Signaling and Bax/Bcl-xL Expression
Authors: Liu Guodong , Zhang Hongmei , Hao Fengyun , Hao Jing , Pan Lixiao , Zhao Qing , Wo Jinshan
Published: February 2018

Background/Aims: Ischemia-reperfusion (I/R) injury is an unavoidable event occurring during heart transplantation and is a key factor in graft failure and the long-term survival rate of recipients. Therefore, there is an urgent need for the development of new therapies to prevent I/R injury. Clusterin is a hetero-dimeric glycoprotein with an antiapoptotic function. In this study, we investigated whether clusterin was cardioprotective in heart transplantation against I/R injury using an in vivo rat model and an in vitro cell culture system, and examined the underlying mechanisms of I/R injury. Methods: Heart grafts from wild-type C57BL/6 mice were preserved in UW solution (control) or UW solution containing recombinant human apolipoprotein-J (hr clusterin) for 24 h. The preserved hearts were implanted into recipient mice of the same strain as the donors for 72 h, and the heart grafts were then taken for histopathological and gene expression analyses. An in vitro ischemia reperfusion model using H9C2 cells or H9C2/clusterin cDNA cells was constructed. The expression of clusterin, p65, Bax, Bcl-xL, IL-1β, and TNF-α protein and mRNA in heart tissue and H9C2 cells was detected by western blot, reverse transcription-polymerase chain reaction (RT-PCR), and quantitative RT-PCR assays; IL-1β and TNF-α protein was detected by enzyme-linked immunosorbent assays; NF-kB activity was detected by an electrophoretic mobility shift assay; cell apoptosis was detected by terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling and flow cytometric analyses. Results: Cold I/R caused severe morphologic myocardial injury to heart grafts from wild-type C57BL/6 mice, whereas grafts from hr clusterin preservation showed less damage, as demonstrated by decreased cell apoptosis/death, decreased neutrophil infiltration, and the preservation of the normal structure of the heart. Clusterin reduced the expression of p65, pre-inflammatory IL-1β, and TNF-α, and the pro-apoptotic gene Bax, while it enhanced the expression of the anti-apoptotic gene Bcl-xL in vitro and in vivo. Clusterin inhibited cell apoptosis/death and reduced pre-inflammatory. Conclusion: Clusterin is a promising target for preventing cold I/R injury in heart transplantation. This study also shows that the resultant protective effects of clusterin are mediated by NF-κB signaling and Bax/Bcl-xL expression.
Reduced Intravoxel Incoherent Motion Microvascular Perfusion Predicts Delayed Cerebral Ischemia and Vasospasm After Aneurysm Rupture
Authors: Heit Jeremy J. , Wintermark Max , Martin Blake W. , Zhu Guangming , Marks Michael P. , Zaharchuk Greg , Dodd Robert L. , Do Huy M. , Steinberg Gary K. , Lansberg Maarten G. , Albers Gregory W. , Federau Christian
Published: February 2018

Background and Purpose—

Proximal artery vasospasm and delayed cerebral ischemia (DCI) after cerebral aneurysm rupture result in reduced cerebral perfusion and microperfusion and significant morbidity and mortality. Intravoxel incoherent motion (IVIM) magnetic resonance imaging extracts microvascular perfusion information from a multi-b value diffusion-weighted sequence. We determined whether decreased IVIM perfusion may identify patients with proximal artery vasospasm and DCI.

Methods—

We performed a pilot retrospective cohort study of patients with ruptured cerebral aneurysms. Consecutive patients who underwent a brain magnetic resonance imaging with IVIM after ruptured aneurysm treatment were included. Patient demographic, treatment, imaging, and outcome data were determined by electronic medical record review. Primary outcome was DCI development with proximal artery vasospasm that required endovascular treatment. Secondary outcomes included mortality and clinical outcomes at 6 months.

Results—

Sixteen patients (11 females, 69%;
P
=0.9) were included. There were no differences in age, neurological status, or comorbidities between patients who subsequently underwent endovascular treatment of DCI (10 patients; DCI+ group) and those who did not (6 patients; DCI− group). Compared with DCI− patients, DCI+ patients had decreased IVIM perfusion fraction
f
(0.09±0.03 versus 0.13±0.01;
P
=0.03), reduced diffusion coefficient
D
(0.82±0.05 versus 0.92±0.07×10
−3
mm
2
/s;
P
=0.003), and reduced blood flow–related parameter
fD
* (1.18±0.40 versus 1.83±0.40×10
−3
mm
2
/s;
P
=0.009). IVIM pseudodiffusion coefficient
D
* did not differ between DCI− (0.011±0.002) and DCI+ (0.013±0.005 mm
2
/s;
P
=0.4) patients. No differences in mortality or clinical outcome were identified.

Conclusions—

Decreased IVIM perfusion fraction
f
and blood flow–related parameter
fD
* correlate with DCI and proximal artery vasospasm development after cerebral aneurysm rupture.
Thaumastic Acoustics
Authors: Passmore Oliver
Published: February 2018

This article considers Pindar’s use of the expression θαῦµα … ἀκοῦσαι, ‘a wonder to hear’, inPythian1 to describe the monster Typhoeus. I argue that the expression needs to be read against Hesiod’s use of a similar locution, θαύµατ’ ἀκοῦσαι, to describe Typhoeus in theTheogony. There, Hesiod adapts the common epic formula θαῦµα ἰδέσθαι, producing a unique phrase to indicate Typhoeus’ chaotic blending of sights and sounds, and at the same time his disruption of the rules of poetic communication. Typhoeus’ disharmonious poetics there stands in contrast to the orderly image of the choral Muses in the proem. I argue in turn that Pindar subtly reworks the Hesiodic formula to reflect Typhoeus’ defeat by Zeus, and thereby subsumes the monster’s ‘acoustics’ within the θαῦµα of the choral performance of the ode itself.
Inonotus castanopsidis sp. nov. (Hymenochaetaceae, Basidiomycota) from southwestern China
Authors: REN GUANG-JUAN , DAI YU-CHENG
Published: February 2018

A new species, Inonotus castanopsidis, is described from southwestern China on the basis of morphological characteristics and molecular evidence. It is characterized by having a perennial and resupinate to effused-reflected basidiomata with greyish yellow to lavender pore surface, a monomitic hyphal system with simple-septate generative hyphae, which are rarely branched, presence of both hyphoid and hymenial setae, and ellipsoid to subglobose, yellowish, thick-walled basidiospores. Detailed description with illustration is provided for the new species and its relationships with similar species are discussed.
Three new species of Impatiens (Balsaminaceae) from Myanmar
Authors: RUCHISANSAKUN SAROJ , SUKSATHAN PIYAKASET , VAN DER NIET TIMOTHEÜS , SMETS ERIK F. , LWIN SAW , JANSSENS STEVEN B.
Published: February 2018

Three new species of Impatiens (Balsaminaceae) from Myanmar are here described: I. decurva Ruchis. & S.B. Janssens, I. hartnolliae Hook. f. ex Ruchis. & Suksathan, and I. oblongata Ruchis. &Van der Niet. The 5-lobed short fusiform fruit of all three species suggests that they are members of subgen. Impatiens sect. Uniflorae Hook. f. & Thomson. For I. decurva and I. oblongata, subgenus membership was corroborated by phylogenetic analyses of a combined dataset of nuclear ITS and plastid atpB-rbcL intergenic spacer DNA sequences. This was not possible for I. hartnolliae, which is only known from a single herbarium specimen.
Nesting biology of Paragymnomerus signaticollis tauricus (Kostylev, 1940 (Hymenoptera: Vespidae: Eumeninae)
Authors: FATERYGA ALEXANDER V.
Published: February 2018

Nesting of a rare eumenine wasp, Paragymnomerus signaticollis tauricus, was observed in the Crimea. Females of this species inhabit untilled steppes and nest in clay loam soil. The nests are vertical burrows 55–120 mm deep and 7–9 mm wide, surmounted by more or less curved turrets that open sideways. The nests contain 1–4 cells and have either linear or branched structure. The cells are of the same width as the other parts of nest burrow and are 13–23 mm long. The species is univoltine; prepupae hibernate in the cocoon for one or two years. Females hunt for sawfly larvae of the genus Megalodontes; 3–5 larvae are stored per nest cell. Adult females feed on these same larvae. Males search for females at their hunting and nesting sites and feed on flowers of Teucrium spp. A cuckoo wasp tentatively identified as Chrysis valesiana is a cleptoparasite on P. signaticollis tauricus. Nesting activity of the female wasps is described. The differences between the nesting biology of P. signaticollis tauricus and P. spiricornis are discussed. The distribution of P. signaticollis tauricus in East Europe is confirmed.
Continental U.S. Hurricane Landfall Frequency and Associated Damage: Observations and Future Risks
Authors: Klotzbach Philip J. , Bowen Steven G. , Pielke Roger , Bell Michael
Published: February 2018

Continental United States (CONUS) hurricane-related inflation-adjusted damage has increased significantly since 1900. However, since 1900 neither observed CONUS landfalling hurricane frequency nor intensity shows significant trends, including the devastating 2017 season.

Two large-scale climate modes that have been noted in prior research to significantly impact CONUS landfalling hurricane activity are El Niño–Southern Oscillation on interannual time scales and the Atlantic multidecadal oscillation on multidecadal time scales. La Niña seasons tend to be characterized by more CONUS hurricane landfalls than El Niño seasons, and positive Atlantic multidecadal oscillation phases tend to have more CONUS hurricane landfalls than negative phases.

Growth in coastal population and regional wealth are the overwhelming drivers of observed increases in hurricane-related damage. As the population and wealth of the United States has increased in coastal locations, it has invariably led to the growth in exposure and vulnerability of coastal property along the U.S. Gulf and East Coasts. Unfortunately, the risks associated with more people and vulnerable exposure came to fruition in Texas and Florida during the 2017 season following the landfalls of Hurricanes Harvey and Irma. Total economic damage from those two storms exceeded $125 billion. Growth in coastal population and exposure is likely to continue in the future, and when hurricane landfalls do occur, this will likely lead to greater damage costs than previously seen. Such a statement is made recognizing that the vast scope of damage from hurricanes often highlights the effectiveness (or lack thereof) of building codes, flood maps, infrastructure, and insurance in at-risk communities.