bluuebunny/crossref_metadata_2025 huggingface dataset:
Impact of Fibromyalgia on Alpha-2 EEG Power Spectrum in the Resting Condition: A Descriptive Correlational Study
Authors: Villafaina Santos , Collado-Mateo Daniel , Fuentes-García Juan P. , Cano-Plasencia Ricardo , Gusi Narcís
Published: April 2019

Objective. The objective of this prospective cross-sectional study was to analyze the differences between patients with fibromyalgia and non-pain controls in terms of EEG power in the eyes-closed resting state. This study also aims to evaluate potential correlations between EEG power and subjective pain.Methods. The fibromyalgia patients were recruited by the Extremadura Association of Fibromyalgia (AFIBROEX) in Cáceres, Spain. Age- and sex-matched healthy controls (1:1 ratio) were recruited from university facilities and people close to the AFIBROEX by public calls. All underwent EEG during a 1-minute resting period with their eyes closed. The theta, alpha-1, alpha-2, beta-1, beta-2, and beta-3 frequency bands were analyzed by using EEGLAB. Self-reported visual analog scale pain scores were determined just prior to EEG.Results. A total of 62 women participated in the study, 31 of them diagnosed with fibromyalgia and 31 healthy controls. Fibromyalgia group exhibited a significantly lower alpha-2 in C4, T3, P4, Pz, and O2 compared to the healthy controls. Interestingly, pain correlated negatively with alpha-2 in Cz, P4, and Pz only in the fibromyalgia group.Conclusion. The fibromyalgia group exhibited decrease alpha-2 power in central, temporoparietal, and occipital brain areas. Furthermore, higher values of pain correlated with lower level of alpha-2 power in Cz, P4, and Pz. These findings may point the importance of alpha-2 power in pain in women with fibromyalgia.
In Vitro Cultivation of Limbal Epithelial Stem Cells on Surface-Modified Crosslinked Collagen Scaffolds
Authors: Haagdorens Michel , Cėpla Vytautas , Melsbach Eline , Koivusalo Laura , Skottman Heli , Griffith May , Valiokas Ramūnas , Zakaria Nadia , Pintelon Isabel , Tassignon Marie-José
Published: April 2019

Purpose. To investigate the efficacy of recombinant human collagen type I (RHC I) and collagen-like peptide (CLP) hydrogels as alternative carrier substrates for the cultivation of limbal epithelial stem cells (LESC) under xeno-free culture conditions.Methods. Human LESC were cultivated on seven different collagen-derived hydrogels: (1) unmodified RHC I, (2) fibronectin-patterned RHC I, (3) carbodiimide-crosslinked CLP (CLP-12 EDC), (4) DMTMM- (4-(4,6-dimethoxy-1,3,5-triazin-2-yl)-4-methyl-morpholinium-) crosslinked CLP (CLP-12), (5) fibronectin-patterned CLP-12, (6) “3D limbal niche-mimicking” CLP-12, and (7) DMTMM-crosslinked CLP made from higher CLP concentration solution. Cell proliferation, cell morphology, and expression of LESC markers were analyzed. All data were compared to cultures on human amniotic membrane (HAM).Results. Human LESC were successfully cultivated on six out of seven hydrogel formulations, with primary cell cultures on CLP-12 EDC being deemed unsuccessful since the area of outgrowth did not meet quality standards (i.e., inconsistence in outgrowth and confluence) after 14 days of culture. Upon confluence, primary LESC showed high expression of the stem cell marker ΔNp63, proliferation marker cytokeratin (KRT) 14, adhesion markers integrin-β4 and E-cadherin, and LESC-specific extracellular matrix proteins laminin-α1, and collagen type IV. Cells showed low expression of differentiation markers KRT3 and desmoglein 3 (DSG3). Significantly higher gene expression of KRT3 was observed for cells cultured on CLP hydrogels compared to RHC I and HAM. Surface patterning of hydrogels influenced the pattern of proliferation but had no significant effect on the phenotype or genotype of cultures. Overall, the performance of RHC I and DMTMM-crosslinked CLP hydrogels was equivalent to that of HAM.Conclusion. RHC I and DMTMM-crosslinked CLP hydrogels, irrespective of surface modification, support successful cultivation of primary human LESC using a xeno-free cultivation protocol. The regenerated epithelium maintained similar characteristics to HAM-based cultures.
CACNA1C Polymorphism (rs2283291) Is Associated with Schizophrenia in Chinese Males: A Case-Control Study
Authors: Zhu Xiaojing , Li Rixin , Kang Guojun , Kang Qi , Rao Wenwang , Yang Mingjia , Cao Bonan , Zhang Mingyuan , Sun Yaoyao , Wang Yueying , Chen Xin , Yu Yaqin , Yu Qiong
Published: April 2019

Recent research has shown that prenatal famine exposure may be one of the risk factors for schizophrenia and that people born in famine years may be at an increased risk of schizophrenia due to alteration of the DNA methylation of genes. In this study, the association of rs2283291/rs4648635 and the incidence of schizophrenia and prenatal famine exposure at the genetic level were investigated to provide clues to the pathogenesis of schizophrenia. A total of 960 participants were recruited, comprising 473 prenatal famine-exposed individuals (225 patients and 248 controls) and 487 prenatal non-famine-exposed individuals (220 patients and 267 controls). The association of prenatal famine, schizophrenia, and their interaction with DNA methylation levels was analyzed using SPSS and GMDR software. Gender stratification analysis revealed a significant association between the rs2283291 genotype and schizophrenia in male patients (P=0.017), and difference still existed after correction by the Bonferroni method. It was also found that an increasing risk of schizophrenia was associated with rs2283291 in males (OR: 1.62, 95% CI: 1.13-2.33, P=0.0086, AIC=669.7) in an overdominant model. The results of gene-environment interaction and gene-gene interaction revealed no association with the risk of schizophrenia. This study reported for the first time that rs2283291 was associated with schizophrenia in Chinese males.
Selenylation Modification of Atractylodes macrocephala Polysaccharide and Evaluation of Antioxidant Activity
Authors: Hou Ranran , Li Qiu , Liu Jie , Hu Yuanliang
Published: April 2019

The Atractylodes macrocephala polysaccharide (AMP) was extracted by water extracting-alcohol precipitating method and further purified by DEAE column. After that, the polysaccharides were modified by nitric acid-sodium selenite method, and nine kinds of selenizing AMPs (sAMPs) were obtained, namely, from sAMP1 to sAMP9. AMP and sAMP were characterized using FTIR spectrometry. Then their antioxidant activities in vitro were measured by free radical-scavenging test. Among these, sAMP6 presented the strongest antioxidant effect. For the test in vivo, the chickens at day 14 vaccinated with ND vaccine were repeatedly vaccinated at day 28. The chickens in sAMP and AMP were injected respectively with 1 mg of sAMP6 and AMP and, in vaccination control (VC) and BC groups, injected with equal volume of normal saline. Respectively, after the first vaccine, on days 7, 14, 21, and 28, the serum GSH-Px and SOD activities and MDA content were determined. The results suggested that sAMP6 could significantly promote GSH-Px and SOD activities and decrease MDA content. All these results indicated that selenylation modification could significantly enhance the antioxidant activity of AMP.
Spatial Concept Learning: A Spiking Neural Network Implementation in Virtual and Physical Robots
Authors: Cyr André , Thériault Frédéric
Published: April 2019

This paper proposes an artificial spiking neural network (SNN) sustaining the cognitive abstract process of spatial concept learning, embedded in virtual and real robots. Based on an operant conditioning procedure, the robots learn the relationship of horizontal/vertical and left/right visual stimuli, regardless of their specific pattern composition or their location on the images. Tests with novel patterns and locations were successfully completed after the acquisition learning phase. Results show that the SNN can adapt its behavior in real time when the rewarding rule changes.
Determination of Geographical Origin of Wuchang Rice with the Geographical Indicator by Multielement Analysis
Authors: Qian Lili , Zuo Feng , Liu Hongyan , Zhang Caidong , Chi Xiaoxing , Zhang Dongjie
Published: April 2019

The study aims to investigate whether the multielement analysis result can be used as a fingerprint to identify the geographical origin of Wuchang rice. The element contents of rice and soil samples from three regions in China (Wuchang, Qiqihar, and Jiamusi) were analyzed. The concentrations of 16 elements (Na, Mg, Al, K, Ca, V, Mn, Fe, Co, Cu, Zn, As, Rb, Sr, Cd, and Pb) in 194 rice samples and 112 soil samples from the harvest season in 2013 and 2014 were determined. The analysis of variance and linear discriminant analysis were performed to analyze the variation among regions and rice genotypes and classify the geographical origins of rice. Only the element of Cu showed significant differences among different genotypes. In the discriminant analysis, the overall correct identification rates of the rice samples obtained in 2013 and 2014 were, respectively, 96.6% and 89.6% and the overall correct identification rate for Wuchang rice reached 100%.
Efficiency of Sophora flavescens-Fructus Ligustri Lucidi Drug Pairs in the Treatment of Liver Fibrosis Based on the Response Surface Method
Authors: Chu Shuhan , Zhang Hongxu , Ding Lixin
Published: April 2019

The pairing of Sophora flavescens and Fructus Ligustri lucidi is taken from Shi Jinmo Medicine. The idea behind this pairing was inspired by the similarity in pharmacological effects of the two herbal drugs, both of which are known to be effective in the treatment and protection against liver fibrosis. To quantitatively study the extent of the interaction between these drugs and the effect of pairing on the treatment of liver fibrosis, an animal model of liver fibrosis mice was established by intraperitoneal injection of low-dose carbon tetrachloride. The drugs were then administered individually, or in predefined compatibility ratio pairs, by gavage, and the effects on indexes of liver fibrosis were observed. The multisynthetic index method was adopted using Matlab software in order to construct a three-dimensional response surface map of the integration effect and conduct interaction analysis of Sophora flavescens and Fructus Ligustri lucidi. The quadratic surface fitting pattern was designed by quadratic regression to determine the optimal range of each drug. The obtained results show that when the compatibility ratio of Sophora flavescens-Fructus Ligustri lucidi drug pairs is less than or equal to 1:1, their therapeutic effect is enhanced by synergy (interaction value ranging between -0.2 and -1). Overall, the synergy of the high-dose drug pairs is stronger than that of the low-dose drug pairs. The optimal dose ranges are 6~12 g and 8~17 g for Sophora flavescens and Fructus Ligustri lucidi, respectively.
PC-3-Derived Exosomes Inhibit Osteoclast Differentiation by Downregulating miR-214 and Blocking NF-κB Signaling Pathway
Authors: Duan Yang , Tan Zhiwen , Yang Minsheng , Li Jianjun , Liu Chun , Wang Chengqiang , Zhang Fu , Jin Yanglei , Wang Yihan , Zhu Lixin
Published: April 2019

Prostate cancer is a serious disease that can invade bone tissues. These bone metastases can greatly decrease a patient’s quality of life, pose a financial burden, and even result in death. In recent years, tumor cell-secreted microvesicles have been identified and proposed to be a key factor in cell interaction. However, the impact of cancer-derived exosomes on bone cells remains unclear. Herein, we isolated exosomes from prostate cancer cell line PC-3 and investigated their effects on human osteoclast differentiation by tartrate-resistant acid phosphatase (TRAP) staining. The potential mechanism was evaluated by qRT-PCR, western blotting, and microRNA transfection experiments. The results showed that PC-3-derived exosomes dramatically inhibited osteoclast differentiation. Marker genes of mature osteoclasts, including CTSK, NFATc1, ACP5, and miR-214, were all downregulated in the presence of PC-3 exosomes. Furthermore, transfection experiments showed that miR-214 downregulation severely impaired osteoclast differentiation, whereas overexpression of miR-214 promoted differentiation. Furthermore, we demonstrated that PC-3-derived exosomes block the NF-κB signaling pathway. Our study suggested that PC-3-derived exosomes inhibit osteoclast differentiation by downregulating miR-214 and blocking the NF-κB signaling pathway. Therefore, elevating miR-214 levels in the bone metastatic site may attenuate the invasion of prostate cancer.
Analysis of the DD¯⁎K System with QCD Sum Rules
Authors: Di Zun-Yan , Wang Zhi-Gang
Published: April 2019

In this article, we construct the color singlet-singlet-singlet interpolating current with IJP=3/21- to study the DD¯⁎K system through QCD sum rules approach. In calculations, we consider the contributions of the vacuum condensates up to dimension-16 and employ the formula μ=MX/Y/Z2-2Mc2 to choose the optimal energy scale of the QCD spectral density. The numerical result MZ=4.71-0.11+0.19 GeV indicates that there exists a resonance state Z lying above the DD¯⁎K threshold to saturate the QCD sum rules. This resonance state Z may be found by focusing on the channel J/ψπK of the decay B→J/ψππK in the future.
Transcriptional Regulation of Ovarian Steroidogenic Genes: Recent Findings Obtained from Stem Cell-Derived Steroidogenic Cells
Authors: Yazawa Takashi , Imamichi Yoshitaka , Sekiguchi Toshio , Miyamoto Kaoru , Uwada Junsuke , Khan Md. Rafiqul Islam , Suzuki Nobuo , Umezawa Akihiro , Taniguchi Takanobu
Published: April 2019

Ovaries represent one of the primary steroidogenic organs, producing estrogen and progesterone under the regulation of gonadotropins during the estrous cycle. Gonadotropins fluctuate the expression of various steroidogenesis-related genes, such as those encoding steroidogenic enzymes, cholesterol deliverer, and electronic transporter. Steroidogenic factor-1 (SF-1)/adrenal 4-binding protein (Ad4BP)/NR5A1 and liver receptor homolog-1 (LRH-1) play important roles in these phenomena via transcriptional regulation. With the aid of cAMP, SF-1/Ad4BP and LRH-1 can induce the differentiation of stem cells into steroidogenic cells. This model is a useful tool for studying the molecular mechanisms of steroidogenesis. In this article, we will provide insight into the transcriptional regulation of steroidogenesis-related genes in ovaries that are revealed from stem cell-derived steroidogenic cells. Using the cells derived from the model, novel SF-1/Ad4BP- and LRH-1-regulated genes were identified by combined DNA microarray and promoter tiling array analyses. The interaction of SF-1/Ad4BP and LRH-1 with transcriptional regulators in the regulation of ovarian steroidogenesis was also revealed.
Spring Deformation Gauge for Measuring Local Deformations in Triaxial Apparatus
Authors: Ismail Mostafa A. , Ibrahim Yasser E.
Published: April 2019

Local measurement of deformations of a soil specimen has become inevitable for accurate determination of soil stiffness in triaxial tests. Although there are now many devices that can be used to perform this task, each has its own advantages and limitations that render development of new devices with better desirable features. This paper presents an innovative device called spring deformation gauge (SDG) that has many advantages over many of the existing devices and can be readily manufactured in both research and commercial laboratories. The device is based on using a highly flexible, yet very strong metal strip of spring steel secured between two stiff, stainless steel L‐shaped legs; the spring strip is provided with four strain gauges. With this arrangement, local deformation of a specimen is transferred into significant bending in the metal strip and elongation or shortening of the strain gauges. In addition to being very cost effective, the SDG is characterized by the ability to control both range and resolution of measured deformation, its linear output, and a clever pinning mechanism that protects it from being damaged when it goes out of range. Success of the SDG was demonstrated in a true K0 test on carbonate sand.
Expression of Potential Dermal Progenitor Cell Markers in the Tumour and Stroma of Skin Adnexal Malignant and Benign Tumours
Authors: Quist Sven R. , Eckardt Maximilian , Kriesche André , Gollnick Harald P.
Published: April 2019

Stem cells are multipotent cells that maintain the skin epidermis including skin appendages such as hair follicle, sebaceous glands, and sweat glands. There is evidence that reciprocal signalling between the epidermis and the dermis plays an important role in skin development, homeostasis, wound repair, and skin cancer. The origin of skin cancer that derive from skin appendages is still controversial, including basal cell carcinoma and even more of rare tumours such as sebaceous carcinomas and whether those tumours originate from resident tissue stem cells. To investigate whether markers reported to label dermal progenitor cells are preserved in the tumour including the tumour stroma of skin adnexal tumours, we tested 45 human basal cell carcinomas, including superficial, nodular, adenoid, infiltrating, and sclerosing types, and further 38 human tumours of skin appendages including 13 sebaceous adenomas and carcinomas, 20 eccrine sweat gland tumours, and 5 pilomatricomas, syringomas, and hair follicle tumours for the expression of the potential dermal and epidermal cell markers CRABP1, Nestin, and Ephrin B2 and compared these findings with healthy, age-related human epidermis. We detected that CRABP1, Nestin, and Ephrin B2 are expressed in the intratumoural stroma as well as the tumour invasive front of skin tumours of appendages and BCCs.
Performance of the Cold‐Bending Channel‐Angle Buckling‐Restrained Brace under Cyclic Loading
Authors: Wang Kun , Xia Junwu , Chen Xiaomiao , Xu Bo , Liang Xiangzhou , Wang Jian
Published: April 2019

In this study, three restricted cold‐bending channel‐angle buckling‐restrained brace (CCA‐BRB) specimens were experimentally characterised by a low‐reversed cyclic loading test. Three specimens had steel cores with cruciform cross section. Two restraining units were assembled to form an external constraint member, each of which was composed of an equilateral cold‐bending channel and two equilateral cold‐bending angles via welding. A gap or a thin silica gel plate was set between the internal core and the external constraint member to form an unbonded layer. Several evaluation parameters on the seismic performance, hysteretic behaviour, and energy dissipation capability of the CCA‐BRB was investigated, including hysteresis curve, skeleton curve, compression strength adjustment factor, measured and computed stiffness, energy dissipation coefficient, equivalent viscous damping ratio, ductility coefficient, and cumulative plastic deformation. The test results and evaluation indices demonstrated that the hysteretic performance of braces with a rigid connection was stable. A Ramberg–Osgood model and two model parameters were calibrated to predict, with fidelity, the skeleton curve of CCA‐BRB under cyclic load. The initial elastic stiffness of the brace used in practice should contain overall portions of the brace instead of the yielding portion of the brace. Finally, all the tested CCA‐BRBs exhibited a stable energy absorption performance and verified the specimens’ construction was rational.
Ultra-sensitive EGFRT790M Detection as an Independent Prognostic Marker for Lung Cancer Patients Harboring EGFRdel19 Mutations and Treated with First-generation TKIs
Authors: Vendrell Julie A. , Mazieres Julien , Senal Romain , Rouquette Isabelle , Quantin Xavier , Pujol Jean-Louis , Roch Benoit , Bouidioua Abdelali , Godreuil Sylvain , Coyaud Etienne , Brousset Pierre , Solassol Jérôme
Published: April 2019

Purpose:

The detection of preexisting EGFRT790M subclones and the assessment of their clinical significance in the pretreatment of patients with EGFRT790M non–small cell lung cancer (NSCLC) remain unclear.

Experimental Design:

A total of 179 tumor samples from patients treated or not with a first-generation tyrosine kinase inhibitor (TKI) was analyzed. The presence of ultra-low levels of preexisting EGFRT790M mutation was evaluated using ultra-sensitive droplet digital PCR (ddPCR) and the clinical implication of these mutations on first-generation TKI efficiency assessed.

Results:

With a ddPCR linear performance of 0.999 and an analytical sensitivity of approximately 0.001%, we observed a 66% (99/150) overall incidence of ultra-low EGFRT790M mutation. Among 82 patients harboring EGFRactivating mutations, the presence of a preexisting EGFRT790M mutation prior to any treatment was significantly associated with a longer progression-free survival (PFS; P = 0.009; log-rank test). Interestingly, longer PFS was linked to concomitant EGFRdel19 and ultra-low EGFRT790M mutations. Moreover, the presence of both EGFRdel19 and ultra-low EGFRT790M mutations was identified as the best fit for predicting the clinical outcome of patients treated with TKI compared with an ultra-low EGFRT790M mutation status or an activating mutation alone (P = 0.042 and P = 0.0071, respectively).

Conclusions:

We demonstrate that the detection of the ultra-low EGFRT790M mutation in TKI-naïve patients is not a rare event. We suggest that ddPCR should be used in clinical practice to distinguish patients who may respond to first- or third-generation TKIs.
Targeted Inhibition of the Dual Specificity Phosphatases DUSP1 and DUSP6 Suppress MPNST Growth via JNK
Authors: Ramkissoon Annmarie , Chaney Katherine E. , Milewski David , Williams Kyle B. , Williams Rory L. , Choi Kwangmin , Miller Adam , Kalin Tanya V. , Pressey Joseph G. , Szabo Sara , Azam Mohammad , Largaespada David A. , Ratner Nancy
Published: April 2019

Purpose:

In neurofibromatosis type 1 (NF1) and in highly aggressive malignant peripheral nerve sheath tumors (MPNSTs), constitutively active RAS-GTP and increased MAPK signaling are important in tumorigenesis. Dual specificity phosphatases (DUSPs) are negative regulators of MAPK signaling that dephosphorylate p38, JNK, and ERK in different settings. Although often acting as tumor suppressors, DUSPs may also act as oncogenes, helping tumor cells adapt to high levels of MAPK signaling. We hypothesized that inhibiting DUSPs might be selectively toxic to cells from NF1-driven tumors.

Experimental Design:

We examined DUSP gene and protein expression in neurofibroma and MPNSTs. We used small hairpin RNA (shRNA) to knock down DUSP1 and DUSP6 to evaluate cell growth, downstream MAPK signaling, and mechanisms of action. We evaluated the DUSP inhibitor, (E)-2-benzylidene-3-(cyclohexylamino)-2,3-dihydro-1H-inden-1-one (BCI), in MPNST cell lines and in cell-line and patient-derived MPNST xenografts.

Results:

DUSP1 and DUSP6 are expressed in NF1-deleted tumors. Knockdown of DUSP1 and DUSP6, alone or in combination, reduced MPNST cell growth and led to ERK and JNK hyperactivation increasing downstream TP53 and p-ATM. The DUSP inhibitor, BCI, diminished the survival of NF1-deleted Schwann cells and MPNST cell lines through activation of JNK. In vivo, treatment of an established cell-line xenograft or a novel patient-derived xenograft (PDX) of MPNSTs with BCI increased ERK and JNK activation, caused tumor necrosis and fibrosis, and reduced tumor volume in one model.

Conclusions:

Targeting DUSP1 and DUSP6 genetically or with BCI effectively inhibits MPNST cell growth and promotes cell death, in vitro and in xenograft models. The data support further investigation of DUSP inhibition in MPNSTs.
One Clever Macrophage Checkpoint
Authors: Mantovani Alberto , Bonecchi Raffaella
Published: April 2019

Macrophages are a key component of the tumor microenvironment (TME). Blocking Clever-1, a molecule expressed in M2-like macrophages, unleashed macrophage and T-cell–mediated antitumor immunity. Myeloid checkpoints including Clever-1 hold promise as alternative or complementary immunotherapy strategies.

See related article by Viitala et al., p. 3289
EZH2 Inhibitors: Take It EZy, It Is All About Context
Authors: Velcheti Vamsidhar , Wong Kwok-Kin , Saunthararajah Yogen
Published: April 2019

Even in diffuse large B-cell lymphoma (DLBCL), a cancer of professional antigen-presenting cells, response rates to immune checkpoint blockade therapy have been limited. One reason for DLBCL immune evasion is epigenetic repression instead of activation of the antigen-presenting MHC—a dissection of mechanisms underlying this repression suggests an opening for restoring B-cell maturation and, along the way, MHC expression as a novel modality of cytoreducing DLBCL and simultaneously augmenting possibilities for immunotherapy.

See related article by Ennishi et al., p. 546.
Optimization of Medial Forebrain Bundle Stimulation Parameters for Operant Conditioning of Rats
Authors: Kong Chanho , Shin Jaewoo , Koh Chin-Su , Lee Jihyeon , Yoon Min-Sik , Cho Yoon Kyung , Kim Soonyoung , Jun Sang Beom , Jung Hyun Ho , Chang Jin Woo
Published: April 2019

Background: The medial forebrain bundle (MFB) is involved in the integration of pleasure and reward. Previous studies have used various stimulation parameters for operant conditioning, though the effectiveness of these parameters has not been systematically studied. Objectives: The purpose of the present study was to investigate the optimal MFB stimulation parameters for controlling the conditioned behavior of rats. Methods: We evaluated four factors, including intensity, frequency, pulse duration, and train duration, to determine the effect of each on lever pressure applied by animals. We further compared burst and tonic stimulation in terms of learning and performance abilities. Results: The number of lever presses increased with each factor. Animals in the burst stimulation group exhibited more lever presses. Furthermore, the average speed in the 田 maze among burst stimulation group subjects was higher. Conclusion: We determined the optimal parameters for movement control of animals in operant conditioning and locomotor tasks by adjusting various electrical stimulation parameters. Our results reveal that a burst stimulation is more effective than a tonic stimulation for increasing the moving speed and number of lever presses. The use of this stimulation technique also allowed us to minimize the training required to control animal behavior.
Mosaic Trisomy 12 Associated with Overgrowth Detected in Fibroblast Cell Lines
Authors: Gasparini Yanca , Montenegro Marília M. , Novo-Filho Gil M. , Ceroni José R.M. , Honjo Rachel S. , Zanardo Évelin A. , Dias Alexandre T. , Nascimento Amon M. , Costa Taís V.M.M. , Madia Fabrícia A. , Chehimi Samar N. , Damasceno Jullian G. , Kim Chong A. , Kulikowski Leslie D.
Published: April 2019

Mosaic trisomy 12 is a rare anomaly, and only 9 cases of live births with this condition have been reported in the literature. The clinical phenotype is variable, including neuropsychomotor developmental delay, congenital heart disease, microcephaly, cutaneous spots, facial asymmetry, prominent ears, hypotonia, retinopathy, and sensorineural hearing loss. A 2-year-old female presented with neuropsychomotor developmental delay, prominent forehead, dolichocephaly, patchy skin pigmentation, and unexpected overgrowth at birth. Cytogenetic analysis of her peripheral blood showed normal results, suggesting the presence of a chromosomal alteration in other tissues. Further studies using G-banding and FISH performed on fibroblasts from both hyper- and hypopigmented regions identified a 47,XX,+12/46,XX karyotype. To the best of our knowledge, no patients with mosaic trisomy 12 associated with overgrowth have been reported to date. Congenital overgrowth and neonatal overgrowth have been frequently linked to Pallister-Killian syndrome (PKS; OMIM 601803). This case suggests the possibility of an association of genes present in the 12p region with fetal overgrowth, considering that chromosomal duplications could lead to an increase in the production of aberrant transcripts and disturbing gene dosage effects. This case highlights the importance of cytogenetic analysis in different tissues to provide relevant information to the specific genotype/phenotype correlation.
Corneal Perforation after Nd:YAG Capsulotomy: A Case Report and Literature Review
Authors: Khreish Maroun , Hanna Rana , Berkovitz Liron , Tiosano Beatrice
Published: April 2019

Background: Nd:YAG capsulotomy is the treatment of choice for posterior capsular opacification after cataract surgery. We report a case of corneal perforation following Nd:YAG capsulotomy in a patient with systemic scleroderma. Case Presentation: A 69-year-old woman presented with acute onset of blurred vision 2 weeks following Nd:YAG laser capsulotomy for posterior subcapsular opacification. On examination, her best-corrected visual acuity was 1/120, and bio-microscopy revealed a central full-thickness corneal laceration. Conservative treatment consisted of topical ocular antibiotics, cycloplegics, hypotensive drops and a soft therapeutic contact lens. Her final visual acuity improved to 6/18 with resolution of the corneal laceration. Conclusion: The possibility of corneal perforation after Nd-YAG capsulotomy in patients with systemic scleroderma and connective tissue disease should be borne in mind when treating such patients.
A Novel Homozygous AMRH2 Gene Mutation in a Patient with Persistent Müllerian Duct Syndrome
Authors: Fernández-Cancio Mónica , Viswanath Naveen , Puzhankara Ramakrishnan , Valiyaprambil Pavithran Praveen , Mora-Palma Cristina , Camats Núria , Audí Laura , Benito-Sanz Sara
Published: April 2019

Persistent müllerian duct syndrome (PMDS) is characterized by the presence of müllerian duct derivatives in otherwise phenotypically normal males. Homozygous or compound heterozygous alterations in AMH or AMHR2 have been identified in approximately 88% of PMDS cases. We report on a male patient with bilateral undescended gonads, müllerian derivatives, and normal serum AMH levels. A novel homozygous missense mutation, c.119G>C;p.Gly40Ala, in exon 2 of AMHR2 was detected that supported the clinical diagnosis of PMDS.
Precipitating Factors for Diabetic Ketoacidosis among Patients with Type 1 Diabetes Mellitus: The Effect of Socioeconomic Status
Authors: Al-Obaidi Ahmed Hakim , Alidrisi Haider Ayad , Mansour Abbas Ali
Published: April 2019

Background: Diabetic ketoacidosis (DKA) is one of the life-threatening acute complications of diabetes mellitus that mainly occurs in type 1 diabetes mellitus (T1DM). This study aimed to determine the socioeconomic factors associated with DKA in patients with T1DM in Basrah. Methods: A cross-sectional study including patients with T1DM who were admitted due to DKA or any other complaint in any of the teaching hospitals in Basrah, from February to October 2017. Data collection from each patient or their parents using a questionnaire was designed to capture personal, social, and disease-related factors. Results: One hundred forty-seven patients were involved in this study. They were compared with different factors to assess correlations with the risk of DKA. Younger age, underweight, being without a job, low personal and/or mother educational level, travel, home glucose monitoring less than 7 times a week, uncontrolled HbA1c and insulin stoppage as a cause of DKA regardless of the reasons to stop were associated with an increased risk of DKA. On the other hand, own home, availability of a glucometer for checking glucose, basal-bolus insulin regimen, insulin supply, and education at a tertiary center, correct injection technique whoever injected the insulin and dietary adherence, all were associated with a decreased risk of DKA. Other factors like gender, marital status, smoking status, father educational level, residency, income, personal home area, the frequency of HbA1c checking, and family history of diabetes were not associated with a significant effect on the DKA risk. Conclusions: Multiple socioeconomic factors interact to play a vital role in the development of DKA among patients with T1DM in Basrah.
A criação da Biblioteca Pública em 1831
Authors: Galves Marcelo Cheche
Published: April 2019

O texto apresenta informações sobre cultura escrita na capitania/província do Maranhão nas primeiras décadas dos Oitocentos, fundamentadas nos registros de envio de impressos para o Maranhão, preservados pelo Arquivo Nacional da Torre do Tombo e Arquivo Histórico Ultramarino, nas atas do Conselho Presidial (1825-1831) e nos anúncios publicados por jornais maranhenses, entre 1821 e 1834. Em seguida, analisa os registros do jornal O Farol Maranhense referentes à subscrição de dinheiro e livros para criação da Biblioteca Pública, inaugurada em maio de 1831. O objetivo é explorar a demanda por uma biblioteca como componente de expansão da cultura escrita, captada em meio às tensões entre “brasileiros” e “portugueses” na província, agravadas com a chegada da notícia da abdicação de d. Pedro I.
Dual Versus Mono Antiplatelet Therapy in Large Atherosclerotic Stroke
Authors: Kim Dohoung , Park Jong-Moo , Kang Kyusik , Cho Yong-Jin , Hong Keun-Sik , Lee Kyung Bok , Park Tai Hwan , Lee Soo Joo , Kim Jae Guk , Han Moon-Ku , Kim Beom Joon , Lee Jun , Cha Jae-Kwan , Kim Dae-Hyun , Nah Hyun-Wook , Kim Dong-Eog , Ryu Wi-Sun , Kim Joon-Tae , Choi Kang-Ho , Choi Jay Chol , Lee Byung-Chul , Yu Kyung-Ho , Oh Mi Sun , Kim Wook-Joo , Kwon Jee-Hyun , Shin Dong-Ick , Sohn Sung-Il , Hong Jeong-Ho , Lee Ji Sung , Lee Juneyoung , Gorelick Philip B. , Bae Hee-Joon ,   on behalf of Clinical Research Collaboration for Stroke in Korea (CRCS-K) Investigators
Published: April 2019

Background and Purpose—

Two large-scale randomized controlled trials of recurrent stroke prevention suggest that dual antiplatelet therapy with clopidogrel plus aspirin is beneficial for prevention of subsequent ischemic events. There is a paucity of data, however, on the efficacy or effectiveness of such an approach in the treatment of stroke patients with symptomatic large artery atherosclerotic occlusive disease.

Methods—

We used a multicenter stroke registry database (Clinical Research Collaboration for Stroke in Korea) to analyze acute ischemic stroke patients due to large artery atherosclerotic occlusive disease who were treated with aspirin alone or combination of clopidogrel and aspirin from May 2008 to May 2015. The results were analyzed by intention-to-treat, per-protocol, and as-treated methodologies. The primary end point was the 1-year composite outcome of stroke recurrence, myocardial infarction, and all-cause death. To balance the differences between groups, a frailty model using propensity scores and inverse probability of treatment weighting was used.

Results—

A total of 5934 patients with symptomatic large artery atherosclerotic occlusive disease were treated either with clopidogrel plus aspirin (n=2903, 49%) or aspirin (n=3031, 51%). The frequency of the primary outcome was 12% (n=353) in the clopidogrel-aspirin group and 14% (n=410) in the aspirin group. The hazards of the primary outcome with combination over aspirin only were significantly reduced in the per-protocol and as-treated analyses (hazard ratio, 0.71; 95% CI, 0.57–0.88;
P
=0.002 and hazard ratio, 0.81; 95% CI, 0.69–0.96;
P
=0.02, respectively), but there was borderline significance in the intention-to-treat analysis (hazard ratio, 0.86; 95% CI, 0.74–1.01;
P
=0.06). Combination therapy was beneficial for all-cause death in all analyses but did not reduce recurrent stroke.

Conclusions—

Compared with patients receiving aspirin monotherapy, the primary outcome seemed to occur less frequently in patients receiving dual antiplatelet therapy, which is explained mainly by the decrease of all-cause death. Since this is a nonrandomized, retrospective, observational study, our study should be cautiously interpreted.
Evolved Open-Endedness, Not Open-Ended Evolution
Authors: Pattee Howard H. , Sayama Hiroki
Published: April 2019

Open-endedness is often considered a prerequisite property of the whole evolutionary system and its dynamical behaviors. In the actual history of evolution on Earth, however, there are many examples showing that open-endedness is rather a consequence of evolution. We suggest that this view, which we call evolved open-endedness (EOE), be incorporated more into research on open-ended evolution. This view should allow for systematic investigation of more nuanced, more concrete research questions about open-endedness and its relationship with adaptation and sustainability.
Two Modes of Evolution: Optimization and Expansion
Authors: Rasmussen Steen , Sibani Paolo
Published: April 2019

We document and discuss two different modes of evolution across multiple systems, optimization and expansion. The former suffices in systems whose size and interactions do not change substantially over time, while the latter is a key property of open-ended evolution, where new players and interaction types enter the game. We first investigate systems from physics, biology, and engineering and argue that their evolutionary optimization dynamics is the cumulative effect of multiple independent events, or quakes, which are uniformly distributed on a logarithmic time scale and produce a decelerating fitness improvement when using the appropriate independent variable. The appropriate independent variable can be physical time for a disordered magnetic system, the number of generations for a bacterial system, or the number of produced units for a particular technological product. We then derive and discuss a simple microscopic theory that explains the nature of the involved optimization processes, and provide simulation results as illustration. Finally, we explore the evolution of human culture and technology, using empirical economic data as a proxy for human fitness. Assuming the overall dynamics is a combined optimization and expansion process, the two processes can be separated and quantified by superimposing the mathematical form of an optimization process on the empirical data and thereby transforming the independent variable. This variable turns out to increase faster than any exponential function of time, a property likely due to strong historical changes in the web of human interactions and to the associated increase in the amount of available knowledge. A microscopic theory for this time dependence remains, however, a challenging open problem.
The MODES Toolbox: Measurements of Open-Ended Dynamics in Evolving Systems
Authors: Dolson Emily L. , Vostinar Anya E. , Wiser Michael J. , Ofria Charles
Published: April 2019

Building more open-ended evolutionary systems can simultaneously advance our understanding of biology, artificial life, and evolutionary computation. In order to do so, however, we need a way to determine when we are moving closer to this goal. We propose a set of metrics that allow us to measure a system's ability to produce commonly-agreed-upon hallmarks of open-ended evolution: change potential, novelty potential, complexity potential, and ecological potential. Our goal is to make these metrics easy to incorporate into a system, and comparable across systems so that we can make coherent progress as a field. To this end, we provide detailed algorithms (including C++ implementations) for these metrics that should be easy to incorporate into existing artificial life systems. Furthermore, we expect this toolbox to continue to grow as researchers implement these metrics in new languages and as the community reaches consensus about additional hallmarks of open-ended evolution. For example, we would welcome a measurement of a system's potential to produce major transitions in individuality. To confirm that our metrics accurately measure the hallmarks we are interested in, we test them on two very different experimental systems: NK landscapes and the Avida digital evolution platform. We find that our observed results are consistent with our prior knowledge about these systems, suggesting that our proposed metrics are effective and should generalize to other systems.
Phylogenetic relationships among extinct and extant turtles: the position of Pleurodira and the effects of the fossils on rooting crown-group turtles
Authors: Sterli Juliana
Published: April 2019

The origin and evolution of the crown-group of turtles (Cryptodira + Pleurodira) is one of the most interesting topics in turtle evolution, second perhaps only to the phylogenetic position of turtles among amniotes. The present contribution focuses on the former problem, exploring the phylogenetic relationships of extant and extinct turtles based on the most comprehensive phylogenetic dataset of morphological and molecular data analyzed to date. Parsimony analyses were conducted for different partitions of data (molecular and morphological) and for the combined dataset. In the present analysis, separate analyses of the molecular data always retrieve Pleurodira allied to Trionychia. Separate analysis of the morphological dataset, by contrast, depicts a more traditional arrangement of taxa, with Pleurodira as the sister group of Cryptodira, being Chelonioidea the most basal cryptodiran clade. The simultaneous analysis of all available data retrieves all major extant clades as monophyletic, except for Cryptodira given that Pleurodira is retrieved as the sister group of Trionychia. The paraphyly of Cryptodira is an unorthodox result, and is mainly caused by the combination of two factors. First, the molecular signal allies Pleurodira and Trionychia. Second, the morphological data with extinct taxa locates the position of the root of crown-group Testudines in the branch leading to Chelonioidea. This study highlights major but poorly explored topics of turtle evolution: the alternate position of Pleurodira and the root of crown turtles. The diversification of crown turtles is characterized by the presence of long external branches and short internal branches (with low support for the internal nodes separating the major clades of crown turtles), suggesting a rapid radiation of this clade. This rapid radiation is also supported by the fossil record, because soon after the appearance of the oldest crown-group turtles (Middle-Late Jurassic of Asia) the number and diversity of turtles increases remarkably. This evolutionary scenario of a rapid diversification of modern turtles into the major modern lineages is likely the reason for the difficulty in determining the interrelationships and the position of the root of crown-group turtles.
Phylogeography, genetic diversity and structure of the poecilosclerid sponge Phorbas fictitius at oceanic islands
Authors: Xavier Joana R. , van Soest Rob W.M. , Breeuwer A.J. , Martins António M.F. , Menken Steph B.J.
Published: April 2019

In this study we assessed the sequence variation in the I3-M11 partition of the mtDNA cytochrome c oxidase subunit I gene (COI) in ten populations of the Atlanto-Mediterranean demosponge Phorbas fictitius (Porifera: Poecilosclerida) at two spatial scales: a regional scale comparing mainland (Iberian) and insular (Macaronesian) populations, and a local (Archipelagic) scale focusing on different island populations of the Azores archipelago. A multiple approach combining diversity measures, FST estimates, phylogenetic inference and nested clade phylogeographic analysis was used to assess the genetic structure and elucidate the evolutionary history of this species. Genetic differentiation, based of FST estimates, was found among most populations at both scales revealing highly structured populations. This results of a presumably low dispersal potential and bathymetric range of the species, and the geographical isolation of the studied populations. However we found evidence of long distance dispersal events between some populations. Phylogenetic and network analyses indicate a separation of insular (Macaronesian) and mainland (Iberian) clades with only two haplotypes shared between these areas. The high genetic diversity and prevalence of ancestral haplotypes suggest the Macaronesian islands as the likely place of origin of this species with posterior expansion to mainland locations via current-mediated dispersal of larvae or sponge fragments. This study adds to the growing evidence of structured populations in the marine realm and highlights the importance of the Macaronesian islands on the evolutionary history of the Northeast Atlantic marine biota.
The subjective nature of Linnaean categories and its impact in evolutionary biology and biodiversity studies
Authors: Laurin Michel
Published: April 2019

Absolute (Linnaean) ranks are essential to rank-based nomenclature (RN), which has been used by the vast majority of systematists for the last 150 years. They are widely recognized as being subjective among taxonomists, but not necessarily in other fields. For this reason, phylogenetic nomenclature (PN) and other alternative nomenclatural systems have been developed. However, reluctance to accept alternative nomenclatural systems and continued use of higher taxa of a given Linnaean category in comparative analyses presumably reflect a lack of appreciation of the deleterious effects of the subjective nature of Linnaean categories in other biological fields, such as conservation and evolutionary biology. To make that point clearer, evolutionary models under which such categories would be natural are presented and are shown to be highly unrealistic and to lack empirical support. Under all realistic evolutionary models, ranking of taxa into Linnaean categories is highly subjective. Solutions that could make taxonomic ranks objective are surveyed. A review of the literature illustrates two problems created by the use of Linnaean categories in comparative or evolutionary studies, namely suboptimal taxonomic sampling schemes in studies of character evolution, and unreliable biodiversity assessment drawn on the basis of counting higher taxa (taxon surrogacy).
Searching for cryptic species in Erpobdella octoculata (L.) (Hirudinea: Clitellata): discordance between the results of genetic analysis and cross-breeding experiments
Authors: Koperski Paweł , Milanowski Rafał , Krzyk Agnieszka
Published: April 2019

The main aim of this study was to reveal reproduction barriers and potentially cryptic radiation within the very common and morphologically variable leech species - Erpobdella octoculata (L., 1758). The differences in reproductive success of the morphological forms were compared experimentally. The data based on the results of field sampling and analysis of ITS and COI sequences is also presented. The results of the analysis of DNA sequences clearly show lack of reproduction barriers between the analysed morphological forms. Subtle differences in DNA sequences between individuals, found with the use of the arbitrary primers method, seem to be related mainly to geographical distance between sub-populations. On the basis of these results, E. octoculata should be treated as one, valid species, in spite of its great morphological variability. However, experimentally confirmed differences in reproductive success of individuals belonging to morphologically divergent forms may be explained by the presence of reproductive barriers between them. Visible incongruity between the results of DNA sequences and the experimental results is not easy to explain - this question definitely needs further studies. Different percentages of morphological forms noted in field samples, suggests an adaptive value for divergent colour patterns in different habitats. Such differences may be a result of diverse mortality of individuals differing in colour dwelling on different bottom substrate, caused by predation by benthivorous fish.