bluuebunny/crossref_metadata_2025 huggingface dataset:
Impeding Circulating Tumor Cell Reseeding Decelerates Metastatic Progression and Potentiates Chemotherapy
Authors: Qian Chen , Worrede-Mahdi Asurayya , Shen Fei , DiNatale Anthony , Kaur Ramanpreet , Zhang Qiang , Cristofanilli Massimo , Meucci Olimpia , Fatatis Alessandro
Published: August 2018

Circulating tumor cells (CTCs) are commonly detected in the systemic blood of patients with cancer with metastatic tumors. However, the mechanisms controlling the viability of cancer cells in blood and length of time spent in circulation, as well as their potential for generating additional tumors are still undefined. Here, it is demonstrated that CX3CR1, a chemokine receptor, drives reseeding of breast CTCs to multiple organs. Antagonizing this receptor dramatically impairs the progression of breast cancer cells in a relevant model of human metastatic disease, by affecting both tumor growth and numerical expansion. Notably, therapeutic targeting of CX3CR1 prolongs CTC permanence in the blood, both promoting their spontaneous demise by apoptosis and counteracting metastatic reseeding. These effects lead to containment of metastatic progression and extended survival. Finally, targeting CX3CR1 improves blood exposure of CTCs to doxorubicin and in combination with docetaxel shows synergistic effects in containing overall tumor burden.

Implications:

The current findings shed light on CTCs reseeding dynamics and support the development of CX3CR1 antagonism as a viable strategy to counteract metastatic progression.
Targeting the MTF2–MDM2 Axis Sensitizes Refractory Acute Myeloid Leukemia to Chemotherapy
Authors: Maganti Harinad B. , Jrade Hani , Cafariello Christopher , Manias Rothberg Janet L. , Porter Christopher J. , Yockell-Lelièvre Julien , Battaion Hannah L. , Khan Safwat T. , Howard Joel P. , Li Yuefeng , Grzybowski Adrian T. , Sabri Elham , Ruthenburg Alexander J. , Dilworth F. Jeffrey , Perkins Theodore J. , Sabloff Mitchell , Ito Caryn Y. , Stanford William L.
Published: August 2018

Deep sequencing has revealed that epigenetic modifiers are the most mutated genes in acute myeloid leukemia (AML). Thus, elucidating epigenetic dysregulation in AML is crucial to understand disease mechanisms. Here, we demonstrate that metal response element binding transcription factor 2/polycomblike 2 (MTF2/PCL2) plays a fundamental role in the polycomb repressive complex 2 (PRC2) and that its loss elicits an altered epigenetic state underlying refractory AML. Unbiased systems analyses identified the loss of MTF2–PRC2 repression of MDM2 as central to, and therefore a biomarker for, refractory AML. Thus, immature MTF2-deficient CD34+CD38− cells overexpress MDM2, thereby inhibiting p53 that leads to chemoresistance due to defects in cell-cycle regulation and apoptosis. Targeting this dysregulated signaling pathway by MTF2 overexpression or MDM2 inhibitors sensitized refractory patient leukemic cells to induction chemotherapeutics and prevented relapse in AML patient-derived xenograft mice. Therefore, we have uncovered a direct epigenetic mechanism by which MTF2 functions as a tumor suppressor required for AML chemotherapeutic sensitivity and identified a potential therapeutic strategy to treat refractory AML.

Significance: MTF2 deficiency predicts refractory AML at diagnosis. MTF2 represses MDM2 in hematopoietic cells and its loss in AML results in chemoresistance. Inhibiting p53 degradation by overexpressing MTF2 in vitro or by using MDM2 inhibitors in vivo sensitizes MTF2-deficient refractory AML cells to a standard induction-chemotherapy regimen. Cancer Discov; 8(11); 1376–89. ©2018 AACR.

See related commentary by Duy and Melnick, p. 1348.

This article is highlighted in the In This Issue feature, p. 1333
Reproducibility and Clinical Correlates of Supine Diaphragmatic Motion Measured by M-Mode Ultrasonography in Healthy Volunteers
Authors: Scarlata Simone , Mancini Damiana , Laudisio Alice , Benigni Augusto , Antonelli Incalzi Raffaele
Published: August 2018

Background: Assessing diaphragm mobility is important to detect malfunctions or impending exhaustion and to evaluate the effects of many chest and abdominal conditions on respiratory mechanics. Amongst several imaging methods, ultrasonography represents the only noninvasive, nonionizing imaging technique widely available for the direct assessment of diaphragm excursion. Objectives: the aim of this study is to prospectively assess the supine diaphragmatic motion amplitude, intra- and inter-observer agreement, and anthropometric correlates of diaphragm motion variability, measured through M-mode ultrasonography, in a sample of healthy volunteers. Methods: One-hundred healthy volunteers were considered eligible for the study. Instead of B-mode imaging, the M-mode technique was used to achieve a more accurate measurement of diaphragm motion. To assess intra-observer variability, 3 consecutive measurements (M-mode and B-mode) of the right dome motion were obtained at every session. To test for inter-rater reliability, the subjects were asked to provide 2 more diaphragm motion measurements every week, each performed by 2 experienced operators, and 42 subjects accepted. Results: Diaphragmatic motion was positively correlated with height and weight both at quiet (Spearman’s coefficient = 0.514, p < 0.001 and 0.314, p = 0.038) and deep breathing (Spearman’s coefficient = 0.342, p = 0.001 and 0.225, p = 0.024, respectively) and negatively correlated with age, but only during deep breathing (Spearman’s coefficient = –0.272, p = 0.006). Intra-observer agreement degree on all 3 measurements was excellent during both quiet and deep breathing, with a Cronbach’s alpha of 0.793 and 0.901, respectively, and an intra-class coefficient of 0.797 and 0.900, respectively. Similarly, the degree of inter-observer agreement achieved a Cronbach’s alpha of 0.638 and 0.776, and an inter-class coefficient of 0.632 and 0.778, respectively. Deep breathing was associated with sex only in linear multivariable models (B = –10.14; 95% confidence interval [CI] –17.86, –2.41; p = 0.011), while quiet breathing resulted to be affected by height only (B = 30.05; 95% CI 0.79–59.31; p = 0.044). Conclusions: Diaphragm excursion measurements using the M-mode technique were accurate and could be reproduced also when obtained in recumbent patients. After adjustments, the main predictors of diaphragmatic motion were sex and height, which should be considered to design a specifically tailored study and to develop normality reference equations.
Evaluation of First-Trimester Physiological Midgut Herniation Using Three-Dimensional Ultrasound
Authors: Bogers Hein , Baken Leonie , Cohen-Overbeek Titia E. , Koning Anton H.J. , Willemsen Sten P. , van der Spek Peter J. , Exalto Niek , Steegers Eric A.P.
Published: August 2018

Introduction: The aim of this study was to investigate the development of midgut herniation in vivo using three-dimensional (3D) ultrasonographic volume and distance measurements and to create reference data for physiological midgut herniation in ongoing pregnancies in a tertiary hospital population. Materials and Methods: The transvaginal 3D ultrasound volumes of 112 women, seen weekly during the first trimester of pregnancy, were obtained and subsequently analysed in a virtual reality environment. The width of the umbilical cord insertion, the maximum diameter of the umbilical cord, and the volume of midgut herniation were measured from 6 until 13 weeks gestational age (GA). Results: All parameters had a positive relation with GA, crown-rump length, and abdominal circumference. In approximately 1 of 10 volumes no midgut herniation could be observed at 9 and 10 weeks GA. In 5.0% of the fetuses the presence of midgut herniation could still be visualised at 12 weeks GA. Conclusion: Reference charts for several dimensions of physiological midgut herniation were created. In the future, our data might be used as a reference in the first trimester for comparison in case of a suspected pathological omphalocele.
Implementation of a Systematic Literature Search Strategy in a National Breast Cancer Guideline: The Relevance of Systemic Therapy in Lymph Node Recurrent Disease
Authors: Stüber Tanja N. , Stangl Stephanie , Jackisch Christian , Janni Wolfgang , Brucker Sara Y. , Hartkopf Andreas , Gerber Bernd , Budach Wilfried , Lux Michael P. , Wöckel Achim
Published: August 2018

Purpose:Our aim was to implement a structured literature search using PICO (patient/intervention/comparison/outcome) questions and a standardized consensus method for the German Guideline ‘Detection, diagnostics, therapy and follow-up of Breast Cancer' using, as an example, the significance of systemic therapy in lymph node recurrent disease (LNRD). Methods: We defined specified PICO questions according to the clinical significance of a recommendation for systemic therapies in locoregional LNRD. A methodologist performed a systematic literature search including randomized controlled trials, systematic reviews and observational studies (2007-2016). In a consensus conference, the level of evidence and consensus was determined and the clinical recommendation was adopted. Results: In total 143 publications were identified according to the search strategy including 14 duplicates, which were excluded. 4 publications were included based on experts' choice. The team excluded 119 publications, leaving 14 that were then screened by a full text search. Finally, 1 publication was found to be of methodologically and clinically reliable content. The conclusion of this publication in favor of systemic therapy for LNRD received strong consent from the consensus conference. Conclusions: The literature search strategy using PICO questions helped to achieve a fast and standardized selection of publications. The recommendation concerning systemic treatment of LNRD was first implemented in the update of the German Breast Cancer guideline.
Synchronous Primary Central Nervous System and Pulmonary Lymphoma in a 7-Year-Old Female with Unspecified T-Cell Immunodeficiency
Authors: Ghali Michael G.Z. , Samkari Ayman , Hou J. Steve , Balasubramanian Manjula , Besmer Sherri , Keisling Matthew , Narayan Prithvi
Published: August 2018

Primary central nervous system lymphoma (PCNSL) is rare in children with immunocompromise as an important risk factor. A 7-year-old girl with unspecified T-cell immunodeficiency presented with left-sided weakness and was found to have a right-sided frontal lobe mass on imaging. The mass was resected; histopathology and molecular studies evidenced diffuse large B-cell lymphoma. Prior chest imaging had revealed left upper lobe mass, and repeat chest imaging revealed multiple pulmonary nodules, initially concerning for metastasis. Video-assisted thoracoscopic surgical wedge resection of the lung mass was performed; the molecular profile was distinct from the PCNSL, suggesting synchronous de novo lymphomagenesis of brain and pulmonary primaries.
Interleukin 4 Leads to Sustained Phosphorylation of the STAT6 and ERK Pathways in the Retina and Disrupts Subcortical Visual Circuitry in Rodents
Authors: Goulart Vanessa Gama , Menezes Grasielle Duarte , Espírito-Santo Sheila , Faria-Melibeu Adriana da Cunha , Serfaty Claudio Alberto , Campello-Costa Paula
Published: August 2018

Objective: Interleukin 4 (IL-4) is an anti-inflammatory cytokine related to different aspects of central nervous system development such as survival, proliferation, and differentiation, among others. Our goals were to investigate the effect of intravitreous treatment with IL-4 on the activation of downstream signaling pathways in the retina and the distribution of retinal axons within the superior colliculus (SC). Material and Methods: Lister hooded rats were submitted to an intravitreous injection of either IL-4 (5 U/µL) or PBS (vehicle) at postnatal day 10 (PND10). At PND11 or PND14, retinas were processed for Western blot or immunohistochemistry. At PND13, a group of animals received an intraocular injection of an anterograde tracer in the left (untreated) eye in order to label the uncrossed retinotectal axons. Results: Our data revealed that intravitreous treatment with IL-4 at PND10 leads to a decrease in GFAP content and a sustained increase in the phosphorylation of STAT6 and ERK levels in the retina. IL-4 also increases retinal axonal arbors within the SC, compared to control groups. Conclusions: These data suggest that a single in vivo treatment with IL-4 during the early stages of development modulates signaling pathways in the retina, resulting in altered binocular subcortical visual connectivity.
A Novel Strategy to Identify Placebo Responders: Prediction Index of Clinical and Biological Markers in the EMBARC Trial
Authors: Trivedi Madhukar H. , South Charles , Jha Manish K. , Rush A. John , Cao Jing , Kurian Benji , Phillips Mary , Pizzagalli Diego A. , Trombello Joseph M. , Oquendo Maria A. , Cooper Crystal , Dillon Daniel G. , Webb Christian , Grannemann Bruce D. , Bruder Gerard , McGrath Patrick J. , Parsey Ramin , Weissman Myrna , Fava Maurizio
Published: August 2018

Background: One in three clinical trial patients with major depressive disorder report symptomatic improvement with placebo. Strategies to mitigate the effect of placebo responses have focused on modifying study design with variable success. Identifying and excluding or controlling for individuals with a high likelihood of responding to placebo may improve clinical trial efficiency and avoid unnecessary medication trials. Methods: Participants included those assigned to the placebo arm (n = 141) of the Establishing Moderators and Biosignatures for Antidepressant Response in Clinical Care (EMBARC) trial. The elastic net was used to evaluate 283 baseline clinical, behavioral, imaging, and electrophysiological variables to identify the most robust yet parsimonious features that predicted depression severity at the end of the double-blind 8-week trial. Variables retained in at least 50% of the 100 imputed data sets were used in a Bayesian multiple linear regression model to simultaneously predict the probabilities of response and remission. Results: Lower baseline depression severity, younger age, absence of melancholic features or history of physical abuse, less anxious arousal, less anhedonia, less neuroticism, and higher average theta current density in the rostral anterior cingulate predicted a higher likelihood of improvement with placebo. The Bayesian model predicted remission and response with an actionable degree of accuracy (both AUC > 0.73). An interactive calculator was developed predicting the likelihood of placebo response at the individual level. Conclusion: Easy-to-measure clinical, behavioral, and electrophysiological assessments can be used to identify placebo responders with a high degree of accuracy. Development of this calculator based on these findings can be used to identify potential placebo responders.
Fetal Goitrous Hypothyroidism and Polyhydramnios in a Patient with Compound Heterozygous DUOXA2 Mutations
Authors: Tanase-Nakao Kanako , Miyata Ichiro , Terauchi Ayako , Saito Maki , Wada Seiji , Hasegawa Tomonobu , Narumi Satoshi
Published: August 2018

Background: Fetal goiter is only rarely observed in pregnant women without autoimmune thyroid disorders, and there is no epidemiological data on its pathophysiology. Dual oxidase maturation factor 2 (DUOXA2), together with dual oxidase 2, serves pivotal roles in thyroid hormone biosynthesis. To date, all reported patients with DUOXA2 mutations were diagnosed postnatally through newborn screening for congenital hypothyroidism. Case Report: The mother of a male fetus presented at 33 + 4 gestational weeks (GW) with a fetal goiter and polyhydramnios. Cordocentesis revealed fetal hypothyroidism (TSH 253.4 mU/L, FT4 0.29 ng/dL). Intra-amniotic levothyroxine injections were performed at GW 34 + 3 and 35 + 3. The patient was born after spontaneous vaginal delivery at 35 + 6 GW without obstetrical complications. He was treated with levothyroxine until the age of 6 years when reevaluation of his thyroid functions showed normal results (TSH 1.32 mU/L, FT4 1.81 ng/dL). Eleven causative genes of CH, including DUOXA2, were analyzed with use of a next-generation sequencing technique. Results: A next-generation sequencing-based mutation screen led us to find that he was compound heterozygous for 2 previously reported nonsense DUOXA2 mutations (p.[Tyr138*];[Tyr246*]). Conclusion: The present case not only illustrates the phenotypic diversity of DUOXA2 mutation carriers but also implies that DUOXA2 is important in prenatal thyroid hormone production.
Why Is the Immunoglobulin Heavy Chain Gene Mutation Status a Prognostic Indicator in Chronic Lymphocytic Leukemia?
Authors: Rozovski Uri , Keating Michael J. , Estrov Zeev
Published: August 2018

The immunoglobulin heavy chain gene (IgHV) mutation status correlates with the clinical outcome of patients with chronic lymphocytic leukemia (CLL) treated with chemoimmunotherapy. Why the survival rate of patients with unmutated IgHV is worse than that of patients with mutated IgHV is unknown. CLL cells with unmutated IgHV were thought to originate from naïve B lymphocytes, whereas CLL cells with mutated IgHV were thought to arise from B cells that have undergone somatic hypermutation (SHM). Cell surface protein expression profile and gene expression studies showing that all CLL cells, regardless of their IgHV mutation status, are of postgerminal center origin, negated this hypothesis. We hereby propose that all CLL cells undergo SHM and their proliferation rate determines their IgHV mutation status. DNA breaks, accumulated during SHM, are restored by various DNA repair mechanisms. In rapidly dividing cells DNA breaks are repaired by the efficient high-fidelity homology-directed DNA repair apparatus, whereas in slowly dividing cells they are repaired by the inefficient low-fidelity nonhomology end-joining repair mechanism. Accordingly, a low IgHV mutation rate is found in rapidly dividing cells whereas a high mutation rate is typically found in slowly dividing cells. Thus, the proliferation rate of CLL cells determines the IgHV mutation status and patients’ clinical outcome.
Association between Atopic Dermatitis and the Metabolic Syndrome: A Systematic Review
Authors: Ali Zarqa , Ulrik Charlotte Suppli , Agner Tove , Thomsen Simon Francis
Published: August 2018

Atopic dermatitis (AD) may be associated with the metabolic syndrome and by that carry an increased risk of cardio­vascular disease. Our objective was to provide an update on current knowledge of the association between AD and metabolic syndrome, including each component of the metabolic syndrome. A systematic literature review was performed to identify studies investigating the association between metabolic syndrome and AD from PubMed, Embase, and the Cochrane Library in accordance with the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines. A total of 14 studies, investigating the association between AD and the metabolic syndrome or AD and components of metabolic syndrome fulfilled the inclusion criteria and were included. It seems unlikely that the association between AD and metabolic syndrome is causal. However, women with AD tended to have components of metabolic syndrome more often than women without AD. There was a positive association between AD and central obesity measured as waist circumference, and this association was stronger for women than men. Despite conflicting results regarding hypertension, the association between hypertension and AD also appeared stronger for women. On the other hand, the association between AD and hyperglycemia appears unlikely, and the association between AD and cholesterol levels was inconsistent. In conclusion, it remains unclear whether AD is a risk factor for metabolic syndrome and its components. However, data indicate that central obesity is associated with AD and that the association is stronger for women than men.
Tryptophan and Kynurenine Metabolites: Are They Related to Depression?
Authors: Pompili Maurizio , Lionetto Luana , Curto Martina , Forte Alberto , Erbuto Denise , Montebovi Franco , Seretti Maria Elena , Berardelli Isabella , Serafini Gianluca , Innamorati Marco , Amore Mario , Baldessarini Ross J. , Girardi Paolo , Simmaco Maurizio
Published: August 2018

Background: Some previous studies found decreased concentrations of L-tryptophan (TRY) and increased L-kynurenine (KYN), or its metabolites, in the body fluids of subjects with major depressive disorder (MDD), sometimes in association with suicidal behavior. Such changes might indicate a shift of TRY away from serotonin production, possibly via the effects of inflammatory peptides which activate indoleamine-2,3-dioxygenase. However, these findings have been inconsistent and require replication. Methods: We used sensitive liquid-chromatography mass spectrometry methods to assay plasma concentrations of TRY, 5-hydroxyindoleacetic acid (5-HIAA), and KYN and its metabolites (anthranilic acid and xanthurenic acid). We compared 49 hospitalized, depressed subjects diagnosed with MDD (n = 37) or bipolar disorder (BD, n = 12), with (n = 22) or without (n = 27) previous suicide attempts, to 78 healthy, ambulatory controls of similar age and sex (total n = 127). Findings: Contrary to expectation, TRY plasma concentrations were higher, KYN plasma concentrations were lower, and their ratio much higher in depressed subjects, with no relationship to suicidal history. Concentrations of 5-HIAA and the kynurenine metabolites did not differ between depressed and healthy subjects. Conclusions: These findings are opposite to expectations and not consistent with a hypothesized increased conversion from TRY to KYN in depressed subjects. In addition, we found no evidence of altered production of serotonin as 5-HIAA concentration was unchanged. None of the observed changes was associated with a history of suicide attempt.
Update on Endoscopic Third Ventriculostomy in Children
Authors: Feng Zhiqiang , Li Qiuping , Gu JianJun , Shen Wenjun
Published: August 2018

Endoscopic third ventriculostomy (ETV) provides a physiological restoration of cerebrospinal fluid and a shunt-free option for hydrocephalus children. Continuous developments in techniques and instruments have improved ETV as the first-line treatment. This paper focuses on the recent advances in surgical techniques, instruments, predictive models, imaging tools, and new cohort studies. The efficacy, safety, indications, and remaining challenges of ETV are discussed. More patients undergo ETV with a better outcome, identifying a new era of hydrocephalus treatment. Deeper understanding of ETV will improve a better shunt-free survival for pediatric hydrocephalus patients.
Bronchial Thermoplasty-Induced Acute Airway Effects Assessed with Optical Coherence Tomography in Severe Asthma
Authors: Goorsenberg Annika W.M. , d’Hooghe Julia N.S. , de Bruin Daniel M. , van den Berk Inge A.H. , Annema Jouke T. , Bonta Peter I.
Published: August 2018

Background: Bronchial thermoplasty (BT) is an endoscopic treatment for severe asthma targeting airway smooth muscle (ASM) with radiofrequent energy. Although implemented worldwide, the effect of BT treatment on the airways is unclear. Optical coherence tomography (OCT) is a novel imaging technique, based on near-infrared light, that generates high-resolution cross-sectional airway wall images. Objective: To assess the safety and feasibility of OCT in severe asthma patients and determine acute airway effects of BT by OCT and compare these to the untreated right middle lobe (RML). Methods: Severe asthma patients were treated with BT (TASMA trial). During the third BT procedure, OCT imaging was performed immediately following BT in the airways of the upper lobes, the right lower lobe treated 6 weeks prior, and the untreated RML. Results: 57 airways were imaged in 15 patients. No adverse events occurred. Three distinct OCT patterns were discriminated: low-intensity scattering pattern of (1) bronchial and (2) peribronchial edema and (3) high-intensity scattering pattern of epithelial sloughing. (Peri)bronchial edema was seen in all BT-treated airways, and less pronounced in only 1/3 of the RML airways. These effects extended beyond the ASM layer and more distal than the directly BT-treated areas and were reduced, but not resolved, after 6 weeks. Epithelial sloughing occurred in 11/14 of the BT-treated airways and was absent in untreated RML airways. Conclusions: Acute BT effects can be safely assessed with OCT and 3 distinct patterns were identified. The acute effects extended beyond the targeted ASM layer and distal of directly BT-treated airway areas, suggesting that BT might also target smaller distal airways.
The Progression of the Stargardt Disease Type 4 (ProgStar-4) Study: Design and Baseline Characteristics (ProgStar-4 Report No. 1)
Authors: Strauss Rupert W. , Muñoz Beatriz , Ahmed Mohamed I. , Bittencourt Millena , Schönbach Etienne M. , Michaelides Michel , Birch David , Zrenner Eberhart , Ervin Ann-Margret , Charbel Issa Peter , Kong Jun , Wolfson Yulia , Shah Mahmood , Bagheri Saghar , West Sheila , Scholl Hendrik P.N. ,   for the ProgStar-4 Study Group
Published: August 2018

Background/Aims: To describe the design and baseline characteristics of patients enrolled in the multicenter, prospective natural history study of Stargardt disease type 4. Methods: Fifteen eligible patients aged 6 years and older at baseline, harboring disease-causing variants in the PROM1 gene, and with specified ocular lesions were enrolled. They were examined at baseline using a standard protocol, with 6 monthly follow-up visits for a 2-year period including best-corrected ETDRS visual acuity, spectral-domain optical coherence tomography, fundus autofluorescence (FAF), mesopic and scotopic microperimetry (MP). Areas of definitely decreased FAF (DDAF) and questionably decreased FAF were outlined and quantified on FAF images. Results: Amongst the 15 patients (29 eyes) that were enrolled at 5 centers in the USA and Europe, 10 eyes (34.5%) had areas of DDAF with an average lesion area of 3.2 ± 3.5 mm2 (range 0.36–10.39 mm2) at baseline. The mean retinal sensitivity of the posterior pole derived from mesopic MP was 8.8 ± 5.8 dB. Conclusions: Data on disease progression in PROM1-related retinopathy from this study will contribute to the characterization of the natural history of disease and the exploration of the utility of several modalities to track progression and therefore to potentially be used in future interventional clinical trials.
Spontaneous Keloids: A Literature Review
Authors: Jfri Abdulhadi , Alajmi Ali
Published: August 2018

Background: Keloids are benign fibroproliferative tumors that extend beyond the original wound. Spontaneous keloids are those that result without a significant history of trauma. There are multiple reported cases in the literature. Objective: This article provides a summary and review of the cases that have been reported with spontaneous keloids and organizes them according to their associated medical conditions. Methods: A literature review was conducted using PubMed and MEDLINE that included all English published cases and case series from May 1955 to February 2018. Results: Spontaneous keloids have been reported mainly in association with syndromes such as Rubinstein-Taybi syndrome, Dubowitz syndrome, Noonan syndrome, Goeminne syndrome, Bethlem myopathy, conjunctivocorneal dystrophy, X-linked recessive polyfibromatosis and a novel X-linked syndrome with flamin A mutation. Furthermore, spontaneous keloids were reported in atopic patients and a couple of patients who are medically healthy. Conclusion: Spontaneous keloids are diagnosed clinically based on the patient’s history, and it is challenging to confirm since they might be triggered by minimal injury or inflammation especially if it is a single lesion. Reported syndromes indicate a genetic possibility in the pathogenesis of spontaneous keloids.
Autophagy and Ubiquitin-Mediated Proteolytic Degradation of PML/Rarα Fusion Protein in Matrine-Induced Differentiation Sensitivity Recovery of ATRA-Resistant APL (NB4-LR1) Cells: in Vitro and in Vivo Studies
Authors: Wu Dijiong  , Shao Keding , Zhou Qihao , Sun Jie , Wang Ziqi , Yan Fei , Liu Tingting , Wu Xiangping , Ye Baodong , Huang He , Zhou Yuhong
Published: August 2018

Background/Aims: Although the cure rate of acute promyelocytic leukemia (APL) has exceeded 90%, the relapse/refractory APL that resistant to all-trans retinoic acid (ATRA) or ATO was still serious concern. Matrine (MAT) could improve the differentiation ability of ATRA-resistant APL cells. This study aimed to explore how the APL-specific fusion protein was degraded in ATRA-resistant APL with the application of MAT and ATRA. Methods: ATRA-sensitive (NB4) and ATRA-resistant (NB4-LR1) cell lines were used. Nitroblue tetrazolium reduction assay and flow cytometry were used to detect the differentiation ability. The activity of ubiquitin-proteasome and autophagy-mediated pathways in both cells treated with ATRA with or without MAT were compared in protein and mRNA level (Western blot analysis, qRT-PCR), the Fluorescent substrate Suc-LLVY-AMC detection was used to detect the activity of proteasome, and electron microscope for observing autophagosome. MG 132(proteasome inhibitor), rapamycin (autophagy activator), hydroxychloroquine (lysosomal inhibitor) and STI571 [retinoic acid receptor alpha (RARα) ubiquitin stabilizer] were used as positive controls. The effect of MAT was observed in vivo using xenografts. Results: MAT improved the sensitivity of NB4-LR1cells to ATRA treatment, which was consistent with the expression of PML-RARα fusion protein. MAT promoted the ubiquitylation level in NB4-LR1. MG 132 induced the decrease in RARα in both cell lines, and hampered the differentiation of NB4 cells. MAT also promoted the autophagy in NB4-LR1 cells, with an increase in microtubule-associated protein 1 light chain3 (LC3)-II and LC3-II/LC3-I ratio and exhaustion of P62. The expression of LC3II increased significantly in the MAT and ATRA + MAT groups in combination with lysosomal inhibitors. A similar phenomenon was observed in mouse xenografts. MAT induced apoptosis and differentiation. Conclusions: Autophagy and ubiquitin-mediated proteolytic degradation of PML/RARα fusion protein are crucial in MAT-induced differentiation sensitivity recovery of NB4-LR1 cells.
The Role of the Acute Octreotide Suppression Test in Detecting Patients with Neuroendocrine Neoplasms
Authors: Kruljac Ivan , Vičić Ivan , Blaslov Kristina , Kolak Zorica , Benković Martina , Kust Davor , Ladika Davidović Blaženka , Tometić Gordan , Penavić Ivan , Dabelić Nina , Vazdar Ljubica , Pavić  Tajana  , Vrkljan Milan
Published: August 2018

Background: Serum chromogranin A (CgA) is routinely used as a biomarker in patients with neuroendocrine neoplasms (NENs). Several conditions and comorbidities may be associated with falsely elevated CgA, often leading to extensive diagnostic evaluation, which may be costly and harmful. The aim of this study was to analyze the effectiveness of the acute octreotide suppression test (AOST) in differentiating falsely elevated serum CgA. Methods: Our prospective study enrolled 45 patients from two different patient cohorts: (1) 29 patients with suspicion or presence of NENs (extensive workup and subsequent biopsy confirmed 16 NENs); (2) 16 consecutive patients admitted via the Emergency Department without NENs (non-NENs). AOST was performed after an overnight fast. Baseline CgA was measured, after which 0.25 mg of octreotide was administered subcutaneously. CgA was measured 3 and 6 h after administration. Results: Baseline CgA levels were similar in NENs and non-NENs. At the end of the AOST, CgA decreased by a median of 83.3% (41.0–127.4) in non-NENs and 13.8% (0.0–43.6) in NENs (p < 0.001). In patients with increased baseline CgA, a decrease in CgA at the 6th hour of < 51.3% had 90.0% sensitivity and 88.9% specificity in detecting NENs. In patients with normal baseline serum CgA, a decrease in CgA at the 3rd hour of < 17.6% had 83.3% sensitivity and 81.8% specificity in detecting patients with NENs. The diagnostic accuracy of the AOST in the entire study population was 86.7%. Conclusions: AOST is a promising tool to increase the diagnostic accuracy of serum CgA.
Motherhood(s) and Polytheisms: Epistemological and Methodological Reflections on the Study of Religions, Gender, and Women
Authors: Guignard Florence Pasche , Pedrucci Giulia
Published: August 2018

Through an approach that combines the academic study of religions with motherhood studies, this article examines rarely considered maternal aspects of Demeter, a goddess of the pantheon of ancient Greek religion. We first discuss theoretical input and concepts drawn from maternal theory that are relevant to uncover innovative lines of research on religious representations and practices in polytheistic systems of the past. In this way we also contribute to broader epistemological reflections in the history and study of religions. Then, considering theHomeric Hymnas well as key ritual elements of theThesmophoriafestival through the lenses of maternal theory, we examine the mother-daughter relationship and the role of the mother as maternal trainer. This concrete case study from the ancient Greek world demonstrates the relevance for historians of religions of considering past polytheistic systems while harnessing the fruitful interdisciplinary potential of maternal theory.
Restraining small decapods and amphipods for in vivo laboratory studies
Authors: Gurkov Anton , Borvinskaya Ekaterina , Shchapova Ekaterina , Timofeyev Maxim
Published: August 2018

During physiological studies, it is often required to restrain a small animal for an experiment, as it is typically challenging to perform in vivo imaging or measurements on freely moving individuals. In this article we describe two widely applicable approaches for repeated restraint of small (approx. 0.5-4 cm) decapods and amphipods that are established in our laboratory: immobilization using gentle gluing and suction. Application of both these approaches as well as their advantages and disadvantages are discussed in detail.
Six new freshwater species of Parvimysis, with notes on breeding biology, statolith composition, and a key to the Mysidae (Mysida) of Amazonia
Authors: Wittmann Karl J.
Published: August 2018

Supplemented descriptions are given for the genus Parvimysis Brattegard, 1969, and its freshwater species P. pisciscibus Henderson & Bamber, 1983, from the Amazon system upstream of the Rio Negro-Solimões confluence. Six new species are described from this range, based on differences regarding eyes, antennae, modified spines in the foregut, fourth male pleopod, and telson. A total of nine freshwater Mysidae species are now known from the Amazon Basin, revealing this system among world’s most species-rich in freshwater mysids. At least five species have the static bodies mineralized with vaterite, a metastable polymorph of crystalline calcium carbonate. The oostegites of at least six Parvimysis species show few setae but are exceptional in exhibiting discoidal structures for the attachment of eggs and larvae. A key to the Mysidae of Amazonia is provided, including keys to all currently known species of Parvimysis and Surinamysis Bowman, 1977.
Simultaneous multitasking behaviour affects feeding efforts of male fiddler crabs (Brachyura, Ocypodidae)
Authors: Tina Fahmida Wazed , Jaroensutasinee Mullica , Jaroensutasinee Krisanadej
Published: August 2018

In animals, both monotasking and multitasking behaviours are observed. Multitasking behaviour helps to increase output quantity, but one activity may distract attention from another, and activities may interact negatively as they compete for the same amount of time available. To test this, we video recorded 23 Austruca bengali (Crane, 1975) males who were ‘feeding only’ (monotasking) and 24 males who were ‘feeding and courting (waving major claws) females’ simultaneously (multitasking). We measured the feeding and waving rates for ‘feeding and waving’ males, and the feeding rate for ‘feeding only’ males. We found that the feeding rate of ‘feeding only’ males was higher, but they reduced their feeding rate when they shared the time for feeding and courting. Moreover, feeding rate was negatively correlated with waving rate for ‘feeding and waving’ males. Our results indicate that courting activity distracted attention from feeding activity, and that activities interacted negatively with each other.
On the identities of Pinnotheres villosissimus Doflein, 1904, P. dofleini Lenz, in Lenz & Strunck, 1914, and P. pilumnoides Nobili, 1906 (Decapoda, Brachyura, Pinnotheridae) from the western Indian Ocean
Authors: Ng Peter K. L.
Published: August 2018

Doflein (1904) accidentally transposed the figures for the third maxillipeds of two species of pinnotherid crabs he described, a mistake which has taxonomic consequences. The species he described, Pinnotheres villosissimus Doflein, 1904, from Sumatra, is here referred to its own genus, Trichobezoares n. gen. The specimen Doflein identified as “Pinnotheres sp.” from South Africa was referred to a new species, Pinnotheres dofleini by Lenz (in Lenz & Strunck, 1914) partly based on Doflein’s (1904) incorrect figure of the third maxilliped. To stabilize the taxonomy of this species, Doflein’s specimen is selected as the lectotype; fixing the species as a member of Afropinnotheres Manning, 1993. Pinnotheres pilumnoides Nobili, 1906 (Djibouti) was differentiated from the taxon T. villosissimus partially on differences in the third maxilliped. It is redescribed, figured and shown to be a second species of Trichobezoares. The correct authorship for the species established in Lenz & Strunck (1914) is also discussed.
Sailing a Ship through Stormy Waters Requires a Compass
Authors: Christiansen Christian Olaf
Published: August 2018

Whereas many scholars have concluded that neoliberalism as well as deregulation was among the key causes of the financial crisis of 2008, much less work has been done on particular reforms and the specific political rhetoric which justified them. This is a comparative study of the political justification of financial deregulation, examining two spectacular cases: the repeal of Glass-Steagall in 1999 and the passing of the Commodity Futures Modernization Act in 2000. There was a widespread, outspoken uncertainty about the consequences of financial deregulation in the 1990s public debates. Building upon Mark Blyth’s seminal work on economic ideas, this article traces the free market ideas and rhetoric that were invoked to reduce this uncertainty about financial derivatives and deregulation, thereby serving as an enabling factor for deregulation.
Abuja Peoples of Nigeria as Indigenous Peoples in International Law
Authors: Barnabas Sylvanus Gbendazhi
Published: August 2018

There is no agreed definition of indigenous peoples (IPs) as the international community has not agreed to any. However, an examination of international instruments and literature on the subject presents a picture. This article examines the definition of IPs and its relevance to Africa. The case study of Abuja, Nigeria is used as a vehicle to challenge the existing descriptions of IPs. It argues that international law should expand its definition of IPs to include collectives of peoples with diverse cultures in Africa. Analogical insights are drawn from international child rights law to advance the argument that international law on IPs’ rights can learn from the evolution of international children’s rights law.
The Value of International Criminal Justice: How Much International Criminal Justice Can the World Afford?
Authors: Ballin Ernst Hirsch
Published: August 2018

International criminal justice, and in particular the icc, has been overburdened by the unrestrained idealism underlying the ambitions inscribed in its fundaments. However, the resulting acts of legal development have not been without value. On the contrary, it is only when idealism sharpens our view on reality that progress can be achieved. Striving to gradually strengthen international criminal justice is therefore worthwhile. Our best bet is to seek to understand where shortcomings in the existing system are grist to the mill for cynicism and to look for opportunities to make international criminal justice more credible in the eyes of victim populations. The question of how much criminal justice the world can afford is the wrong question to ask. Rather, we should be asking whether the international community, if it is still concerned about establishing trust and peace among nations, can afford to do away with international criminal justice.
Maroons in Guyane
Authors: Price Richard
Published: August 2018

This note presents new demographic data on the number and location of “Suriname Maroons” in Guyane (French Guiana), as well as elsewhere in the world. After brief discussion of the methodological challenges of estimating the size of “ethnic” populations in a country whose census prohibits such counts, it shows that about 38 percent of Maroons now live in Guyane and that they form one-third of the total population. It ends by suggesting some implications of this demographic explosion.
Representation of Boreal Winter MJO and Its Teleconnection in a Dynamical Ensemble Seasonal Prediction System
Authors: Kim Hyerim , Lee Myong-In , Kim Daehyun , Kang Hyun-Suk , Hyun Yu-Kyung
Published: August 2018

This study examines the representation of the Madden–Julian oscillation (MJO) and its teleconnection in boreal winter in the Global Seasonal Forecast System, version 5 (GloSea5), using 20 years (1991–2010) of hindcast data. The sensitivity of the performance to the polarity of El Niño–Southern Oscillation (ENSO) is also investigated. The real-time multivariate MJO index of Wheeler and Hendon is used to assess MJO prediction skill while intraseasonal 200-hPa streamfunction anomalies are used to evaluate the MJO teleconnection. GloSea5 exhibits significant MJO prediction skill up to 25 days of forecast lead time. MJO prediction skill in GloSea5 also depends on initial MJO phases, with relatively enhanced (degraded) performance when the initial MJO phase is 2 or 3 (8 or 1) during the first 2 weeks of the hindcast period. GloSea5 depicts the observed MJO teleconnection patterns in the extratropics realistically up to 2 weeks albeit weaker than the observed. The ENSO-associated basic-state changes in the tropics and in the midlatitudes are reasonably represented in GloSea5. MJO prediction skill during the first 2 weeks of the hindcast is slightly higher in neutral and La Niña years than in El Niño years, especially in the upper-level zonal wind anomalies. Presumably because of the better representation of MJO-related tropical heating anomalies, the Northern Hemispheric MJO teleconnection patterns in neutral and La Niña years are considerably better than those in El Niño years.
Pushed and Pulled to the Internet: Self Employment in the Spiritual Marketplace
Authors: Gregory Karen
Published: August 2018

Drawing from participant observation and in-depth interviews, this article illustrates how esoteric practitioners (mainly Tarot card readers) come to see themselves as “self-employed” or entrepreneurs and take up the labor of brand building. These individuals study and use the cards not only as part of a personal “quest” for meaning or experience but also as an attempt to “make a living” from their work. This labor is personal and subjective as well as increasingly digital in nature, occurring through blogs, websites, and other media. Despite the relative ease of Web 2.0 technologies, online brand building poses serious challenges for Tarot readers. In contrast to websites depicting “a best life,” the process of building a personal brand can be fraught with hesitation, speculation, and failure as well as confounded by issues of access to technology. This tension makes many Tarot readers “reluctant entrepreneurs” who feel that they have no choice but to engage with the Internet.
Numerical simulation of airflow characteristics in the spinning zone at starting time of air-jet spinning machine
Authors: Phung Thi Viet Bac , Yoshida Akihiro , Iemoto Yoshiyuki , Uematsu Hideyuki , Tanoue Shuichi
Published: August 2018

To clarify the formation mechanism of a source of yarn and to discuss the effects of supplied air pressure and exhaust air pressure on the fiber suction force and twist torque at the starting time of the spinning process in an air-jet spinning machine, we simulated, numerically, the three-dimensional airflow pattern without fibers in the spinning zone. Results obtained are as follows: High-speed air jetted through the starting nozzles into the yarn duct in the circumferential direction causes a swirl flow in the yarn duct and a negative pressure region near the center axis of the yarn duct. Hence, air and fibers at the fiber inlet are sucked through the processing duct into the yarn duct. A fiber bundle sucked into the yarn duct rotates, owing to the action of the swirl airflow, and twists the fiber bundle in the processing duct, hence generating a source of yarn. The fiber suction force takes a distribution with a peak against the supplied air pressure and is independent of the exhaust air pressure. The fiber twist torque increases monotonously with supplied air pressure.
Determinants of Tourists’ Length of Stay: A Hurdle Count Data Approach
Authors: Boto-García David , Baños-Pino José Francisco , Álvarez Antonio
Published: August 2018

This article analyses tourists’ length of stay in a particular destination using a Hurdle Count Data model that allows us to first identify the determinants of the decision to be a same-day visitor or a tourist, and then to explain the length of stay for tourists. Apart from sociodemographic characteristics, we are interested in the effects of distance, mode of transport, and some relevant destination attributes of the destination such as tranquillity, natural environment, or climate. Another feature this article addresses is how advertising, recommendations, and previous experience at the destination affect both the probability of an overnight stay and the length of the stay. The results indicate that the determinants of the decision to stay overnight and how long to stay are not the same. Besides, a positive previous experience and having seen advertising of the destination positively affect the overnight stay decision and the number of days.
Cytological diagnosis of microfilaria at unusual sites in clinically unsuspected cases: some rare presentations of filariasis
Authors: Bharti Shreekant , Agarwal Neeraj Kumar , Katiyar Richa , Dwivedi Saloni , Shri Mridu
Published: August 2018

Filariasis is a major concern, particularly in endemic regions. The majority of patients harbouring the parasite may remain asymptomatic for years. Here, we present six patients who were sent for routine cytological examination to rule out neoplastic pathology, in whom cytology identified filarial infestation. The main purposes of our paper are to highlight the importance of fine needle aspiration cytology (FNAC), a cheap and quick investigation to detect the microfilaria from tissue swelling and body fluids, and to point out that clinicians practising in endemic regions should always consider filarial infestation in patients presenting with longstanding swelling.