bluuebunny/crossref_metadata_2025_split huggingface dataset:
A dimensional approach to assessing psychiatric risk in adults born very preterm
Authors: Kroll Jasmin , Froudist-Walsh Sean , Brittain Philip J. , Tseng Chieh-En J. , Karolis Vyacheslav , Murray Robin M. , Nosarti Chiara 
Published: January 2018

AbstractBackgroundIndividuals who were born very preterm have higher rates of psychiatric diagnoses compared with term-born controls; however, it remains unclear whether they also display increased sub-clinical psychiatric symptomatology. Hence, our objective was to utilize a dimensional approach to assess psychiatric symptomatology in adult life following very preterm birth.MethodsWe studied 152 adults who were born very preterm (before 33 weeks’ gestation; gestational range 24–32 weeks) and 96 term-born controls. Participants’ clinical profile was examined using the Comprehensive Assessment of At-Risk Mental States (CAARMS), a measure of sub-clinical symptomatology that yields seven subscales including general psychopathology, positive, negative, cognitive, behavioural, motor and emotional symptoms, in addition to a total psychopathology score. Intellectual abilities were examined using the Wechsler Abbreviated Scale of Intelligence.ResultsBetween-group differences on the CAARMS showed elevated symptomatology in very preterm participants compared with controls in positive, negative, cognitive and behavioural symptoms. Total psychopathology scores were significantly correlated with IQ in the very preterm group only. In order to examine the characteristics of participants’ clinical profile, a principal component analysis was conducted. This revealed two components, one reflecting a non-specific psychopathology dimension, and the other indicating a variance in symptomatology along a positive-to-negative symptom axis.K-means (k= 4) were used to further separate the study sample into clusters. Very preterm adults were more likely to belong to a high non-specific psychopathology cluster compared with controls.Conclusion and RelevanceVery preterm individuals demonstrated elevated psychopathology compared with full-term controls. Their psychiatric risk was characterized by a non-specific clinical profile and was associated with lower IQ.
Nonholonomic mobile robots' trajectory tracking model predictive control: a survey
Authors: Nascimento Tiago P. , Dórea Carlos E. T. , Gonçalves Luiz Marcos G. 
Published: January 2018

SUMMARYModel predictive control (MPC) theory has gained attention with the recent increase in the processing power of computers that are now able to perform the needed calculations for this technique. This kind of control algorithms can achieve better results in trajectory tracking control of mobile robots than classical control approaches. In this paper, we present a review of recent developments in trajectory tracking control of mobile robot systems using model predictive control theory, especially when nonholonomicity is present. Furthermore, we point out the growth of the related research starting with the boom of mobile robotics in the 90s and discuss reported field applications of the described control problem. The objective of this paper is to provide a unified and accessible presentation, placing the classical model, problem formulations and approaches into a proper context and to become a starting point for researchers who are initiating their endeavors in linear/nonlinear MPC applied to nonholonomic mobile robots. Finally, this work aims to present a comprehensive review of the recent breakthroughs in the field, providing links to the most interesting and successful works, including our contributions to state-of-the-art.
Gene variants and educational attainment in cannabis use: mediating role of DNA methylation
Authors: Gerra Maria Carla , Jayanthi Subramaniam , Manfredini Matteo , Walther Donna , Schroeder Jennifer , Phillips Karran A. , Cadet Jean Lud , Donnini Claudia 
Published: January 2018

AbstractGenetic and sociodemographic risk factors potentially associated with cannabis use (CU) were investigated in 40 cannabis users and 96 control subjects. DNA methylation analyses were also performed to explore the possibility of epigenetic changes related to CU. We conducted a candidate gene association study that included variants involved in the dopaminergic (ANKK1, NCAM1 genes) and endocannabinoid (CNR1, CNR2 gene) pathways. Sociodemographic data included gender, marital status, level of education, and body mass index. We used MeDIP-qPCR to test whether variations in DNA methylation might be associated with CU. We found a significant association between SNP rs1049353 of CNR1 gene (p = 0.01) and CU. Differences were also observed related to rs2501431 of CNR2 gene (p = 0.058). A higher education level appears to decrease the risk of CU. Interestingly, females were less likely to use cannabis than males. There was a significantly higher level of DNA methylation in cannabis users compared to controls in two of the genes tested: hypermethylation at exon 8 of DRD2 gene (p = 0.034) and at the CpG-rich region in the NCAM1 gene (p = 0.0004). Both genetic variants and educational attainment were also related to CU. The higher rate of DNA methylation, evidenced among cannabis users, may be either a marker of CU or a consequence of long-term exposure to cannabis. The identified genetic variants and the differentially methylated regions may represent biomarkers and/or potential targets for designs of pharmacological therapeutic agents. Our observations also suggest that educational programs may be useful strategies for CU prevention.
miR-663 sustains NSCLC by inhibiting mitochondrial outer membrane permeabilization (MOMP) through PUMA/BBC3 and BTG2
Authors: Fiori Micol E. , Villanova Lidia , Barbini Chiara , De Angelis Maria Laura , De Maria Ruggero 
Published: January 2018

AbstractTreatment of lung cancer is an unmet need as it accounts for the majority of cancer deaths worldwide. The development of new therapies urges the identification of potential targets. MicroRNAs’ expression is often deregulated in cancer and their modulation has been proposed as a successful strategy to interfere with tumor cell growth and spread. We recently reported on an unbiased high-content approach to identify miRNAs regulating cell proliferation and tumorigenesis in non-small cell lung cancer (NSCLC). Here we studied the oncogenic role of miR-663 in NSCLC biology and analyzed the therapeutic potential of miR-663 targeting. We found that miR-663 regulates apoptosis by controlling mitochondrial outer membrane permeabilization (MOMP) through the expression of two novel direct targets PUMA/BBC3 and BTG2. Specifically, upon miR-663 knockdown the BH3-only protein PUMA/BBC3 directly activates mitochondrial depolarization and cell death, while BTG2 accumulation further enhances this effect by triggering p53 mitochondrial localization. Moreover, we show that miR-663 depletion is sufficient to elicit cell death in NSCLC cells and to impair tumor growth in vivo.
Mitochondrial glutamine metabolism via GOT2 supports pancreatic cancer growth through senescence inhibition
Authors: Yang Seungyeon , Hwang Sunsook , Kim Minjoong , Seo Sung Bin , Lee Jeong-Hwa , Jeong Seung Min 
Published: January 2018

AbstractCellular senescence, which leads to a cell cycle arrest of damaged or dysfunctional cells, is an important mechanism to restrain the malignant progression of cancer cells. Because metabolic changes underlie many cell-fate decisions, it has been suggested that cell metabolism might play key roles in senescence pathways. Here, we show that mitochondrial glutamine metabolism regulates senescence in human pancreatic ductal adenocarcinoma (PDAC) cells. Glutamine deprivation or inhibition of mitochondrial aspartate transaminase (GOT2) results in a profound induction of senescence and a suppression of PDAC growth. Glutamine carbon flow through GOT2 is required to create NADPH and to maintain the cellular redox state. We found that elevated reactive oxygen species levels by GOT2 knockdown lead to the cyclin-dependent kinase inhibitor p27-mediated senescence. Importantly, PDAC cells exhibit distinct dependence on this pathway, whereas knockdown of GOT2 did not induce senescence in non-transformed cells. The essentiality of GOT2 in senescence regulation of PDAC, which is dispensable in their normal counterparts, may have profound implications for the development of strategies to treat these refractory cancers.
Hepatic SMARCA4 predicts HCC recurrence and promotes tumour cell proliferation by regulating SMAD6 expression
Authors: Chen Zhiao , Lu Xinyuan , Jia Deshui , Jing Ying , Chen Di , Wang Qifeng , Zhao Fangyu , Li Jinjun , Yao Ming , Cong Wenming , He Xianghuo 
Published: January 2018

AbstractHepatocellular carcinoma (HCC) is the most common form of liver cancer and is typically diagnosed at advanced stages. Identification and characterisation of genes within amplified and deleted chromosomal loci can provide new insights into the pathogenesis of cancer and lead to new approaches for diagnosis and therapy. In our previous study, we found a recurrent region of copy number amplification at 19p13.2 in hepatocellular carcinoma (HCC). In the present study, we performed integrated copy number analysis and expression profiling at this locus and a putative cancer gene, SMARCA4/BRG1, was uncovered in this region. BRG1 is a part of the large ATP-dependent chromatin remodelling complex SWI/SNF. The function of BRG1 in various cancers is unclear, including its role in HCC tumorigenesis. Here, we found that BRG1 is upregulated in HCC and that its level significantly correlates with cancer progression in HCC patients. Importantly, we also found that nuclear expression of BRG1 predicts early recurrence for HCC patients. Furthermore, we demonstrated that BRG1 promotes HCC cell proliferation in vitro and in vivo. BRG1 was observed not only to facilitate S-phase entry but also to attenuate cell apoptosis. Finally, we discovered that one of the mechanisms by which BRG1 promotes cell proliferation is the upregulation of SMAD6. These findings highlight the important role of BRG1 in the regulation of HCC proliferation and provide valuable information for cancer prognosis and treatment.
HBV infection potentiates resistance to S-phase arrest-inducing chemotherapeutics by inhibiting CHK2 pathway in diffuse large B-cell lymphoma
Authors: Zhao Xinying , Guo Xudong , Xing Libo , Yue Wenqin , Yin Haisen , He Miaoxia , Wang Jianmin , Yang Jianmin , Chen Jie 
Published: January 2018

AbstractA considerable number of diffuse large B-cell lymphoma (DLBCL) patients are infected with hepatitis B virus (HBV), which is correlated with their poor outcomes. However, the role of HBV infection in DLBCL treatment failure remains poorly understood. Here, our data demonstrated that HBV infection was closely associated with poorer clinical prognosis independent of its hepatic dysfunction in germinal center B-cell type (GCB type) DLBCL patients. Interestingly, we found that DLBCL cells expressing hepatitis B virus X protein (HBX) did not exhibit enhanced cell growth but did show reduced sensitivity to methotrexate (MTX) and cytarabine (Ara-C), which induced S-phase arrest. Mechanism studies showed that HBX specifically inhibited the phosphorylation of checkpoint kinase 2 (CHK2, a key DNA damage response protein). CHK2 depletion similarly conferred resistance to the S-phase arrest-inducing chemotherapeutics, consistent with HBX overexpression in DLBCL cells. Moreover, overexpression of wild-type CHK2 rather than its unphosphorylated mutant (T68A) significantly restored the reduced chemosensitivity in HBX-expressing cells, suggesting that HBV infection conferred resistance to chemotherapeutics that induced S-phase arrest by specifically inhibiting the activation of CHK2 response signaling in DLBCL.
Multiple signaling kinases target Mrc1 to prevent genomic instability triggered by transcription-replication conflicts
Authors: Duch Alba , Canal Berta , Barroso Sonia I. , García-Rubio María , Seisenbacher Gerhard , Aguilera Andrés , de Nadal Eulàlia , Posas Francesc 
Published: January 2018

AbstractConflicts between replication and transcription machineries represent a major source of genomic instability and cells have evolved strategies to prevent such conflicts. However, little is known regarding how cells cope with sudden increases of transcription while replicating. Here, we report the existence of a general mechanism for the protection of genomic integrity upon transcriptional outbursts in S phase that is mediated by Mrc1. The N-terminal phosphorylation of Mrc1 blocked replication and prevented transcription-associated recombination (TAR) and genomic instability during stress-induced gene expression in S phase. An unbiased kinome screening identified several kinases that phosphorylate Mrc1 at the N terminus upon different environmental stresses. Mrc1 function was not restricted to environmental cues but was also required when unscheduled transcription was triggered by low fitness states such as genomic instability or slow growth. Our data indicate that Mrc1 integrates multiple signals, thereby defining a general safeguard mechanism to protect genomic integrity upon transcriptional outbursts.
The sea lamprey germline genome provides insights into programmed genome rearrangement and vertebrate evolution
Authors: Smith Jeramiah J. , Timoshevskaya Nataliya , Ye Chengxi , Holt Carson , Keinath Melissa C. , Parker Hugo J. , Cook Malcolm E. , Hess Jon E. , Narum Shawn R. , Lamanna Francesco , Kaessmann Henrik , Timoshevskiy Vladimir A. , Waterbury Courtney K. M. , Saraceno Cody , Wiedemann Leanne M. , Robb Sofia M. C. , Baker Carl , Eichler Evan E. , Hockman Dorit , Sauka-Spengler Tatjana , Yandell Mark , Krumlauf Robb , Elgar Greg , Amemiya Chris T. 
Published: January 2018

AbstractThe sea lamprey (Petromyzon marinus) serves as a comparative model for reconstructing vertebrate evolution. To enable more informed analyses, we developed a new assembly of the lamprey germline genome that integrates several complementary data sets. Analysis of this highly contiguous (chromosome-scale) assembly shows that both chromosomal and whole-genome duplications have played significant roles in the evolution of ancestral vertebrate and lamprey genomes, including chromosomes that carry the six lamprey HOX clusters. The assembly also contains several hundred genes that are reproducibly eliminated from somatic cells during early development in lamprey. Comparative analyses show that gnathostome (mouse) homologs of these genes are frequently marked by polycomb repressive complexes (PRCs) in embryonic stem cells, suggesting overlaps in the regulatory logic of somatic DNA elimination and bivalent states that are regulated by early embryonic PRCs. This new assembly will enhance diverse studies that are informed by lampreys’ unique biology and evolutionary/comparative perspective.
SlMYB12 Regulates Flavonol Synthesis in Three Different Cherry Tomato Varieties
Authors: Wang Shaoli , Chu Zhaohui , Jia Ru , Dan Fei , Shen Xiangling , Li Yang , Ding Xinhua 
Published: January 2018

AbstractCherry tomato (Lycopersicon esculentum M.) is considered a healthy fruit worldwide due to its wide range of nutrients. Flavonol, one of the major nutrients in cherry tomato, has antioxidant and cell-modulating properties. In this study, we showed a correlation between the expression of SlMYB12 and flavonol content (R2 = 0.922). To characterize the function of SlMYB12, SlMYB12-overexpressing transgenic tomato plants were generated in three different cherry tomato varieties. Significant increases in flavonol content and flavonol biosynthetic gene expression were identified in SlMYB12-overexpressing plants. Therefore, we suggest that SlMYB12 plays a positive role in the flavonol biosynthesis pathway in cherry tomatoes, which further indicates a potential role as a marker in analyzing flavonol content in different cherry tomato varieties.
Distribution and accumulation of dietary ergothioneine and its metabolites in mouse tissues
Authors: Tang Richard Ming Yi , Cheah Irwin Kee-Mun , Yew Terry Shze Keong , Halliwell Barry 
Published: January 2018

AbstractL-ergothioneine (ET) is a diet-derived amino acid that accumulates at high concentrations in animals and humans. Numerous studies have highlighted its antioxidant abilities in vitro, and possible cytoprotective capabilities in vivo. We investigated the uptake and distribution of ET in various organs by a highly sensitive and specific liquid chromatography coupled tandem mass spectrometry (LC-MS/MS) technique, both before and after oral administration of pure ET (35 and 70 mg/kg/day for 1, 7, and 28 days) to male C57BL6J mice. ET primarily concentrates in the liver and whole blood, and also in spleen, kidney, lung, heart, intestines, eye, and brain tissues. Strong correlations were found between ET and its putative metabolites - hercynine, ET-sulfonate (ET-SO3H), and S-methyl ET. Hercynine accumulates in the brain after prolonged ET administration. This study demonstrates the uptake and distribution of ET and provides a foundation for future studies with ET to target oxidative damage in a range of tissues in human diseases.
Necessity of p53-binding to the CDH1 locus for its expression defines two epithelial cell types differing in their integrity
Authors: Oikawa Tsukasa , Otsuka Yutaro , Onodera Yasuhito , Horikawa Mei , Handa Haruka , Hashimoto Shigeru , Suzuki Yutaka , Sabe Hisataka 
Published: January 2018

AbstractTP53 mutation (i.e., loss of normal-p53) may evoke epithelial-mesenchymal transition (EMT), which was previously attributed to loss of certain miRNAs. However, not all epithelial cells undergo EMT upon TP53 mutation, and the p53-miRNA axis may not fully explain p53 function in epithelial integrity. We here show two modes of epithelial integrity: one involves p53-binding to a nucleotide region and the other does not. In the former, p53 binds to the CDH1 (encoding E-cadherin) locus to antagonize EZH2-mediated H3K27 trimethylation (H3K27me3) to maintain high levels of acetylation of H3K27 (H3K27ac). In the latter, the same locus is not highly acetylated at H3K27, and does not allow p53-binding, nor needs to antagonize EZH2. We moreover demonstrated that although the CDH1 locus in the p53-independent cells, but not in fibroblasts, becomes high-H3K27ac by butyrate and allows p53-biniding, their CDH1 expression does not become dependent on p53. Our results identified novel modes of the epithelial integrity, in which the same epithelial-specific gene locus exhibits different requirement for p53 with different histone modifications among different epithelial cells to warrant its expression.
Validierung des Screenings zur komplexen Posttraumatischen Belastungsstörung (SkPTBS) – Revision
Authors: Dorr Florence , Sack Martin , Bengel Jürgen 
Published: January 2018

Zusammenfassung
Hintergrund Zielsetzung war die Weiterentwicklung eines Screeninginstruments zur Diagnostik der komplexen Posttraumatischen Belastungsstörung (kPTBS). Das Screening zur kPTBS (SkPTBS) erfasst a) potenziell traumatische Erfahrungen, b) Risiko- und Schutzfaktoren sowie c) Symptome der kPTBS. Das SkPTBS von Dorr et al. (2016) und wurde entsprechend dem aktuellen ICD-Diagnosevorschlag zur kPTBS überarbeitet wird hier in seiner Revisionsfassung validiert.
Methode Folgen von potenziellen Traumatisierungen wurden bei Patienten der psychosomatischen Rehabilitation und bei Patienten in einer traumatherapeutischen universitären Institutsambulanz erfasst. Die Patienten füllten das Screening zu Beginn ihrer Behandlung aus (N=525, davon n=359 Rehabilitanden und n=157 Patienten in der Ambulanz; mittleres Alter 48 Jahre, 68% Frauen). Die gestellte Diagnose kPTBS sowie Ergebnisse des SKID und des Interviews zur komplexen PTBS (IkPTBS) dienten als primäre Validierungskriterien.
Ergebnisse 88 Patienten (17%) wurden mit kPTBS diagnostiziert. Die Trennschärfe der metrischen Items des SkPTBS war zufriedenstellend. Die interne Konsistenz betrug Cronbachs α=0.91. Die eindimensionale faktorielle Struktur der ersten Auflage des SkPTBS konnte bestätigt werden. Der SkPTBS sagt zuverlässig die Diagnose kPTBS vorher. Sein Gesamtwert korrelierte moderat mit posttraumatischen (IES-15), dissoziativen (DES-Taxon) und depressiven Symptomen (BDI-II, PHQ-9) sowie der globalen Symptombelastung (SCL-90-R). Normen für verschiedene Alters-, Diagnose- und Settinggruppen wurden erstellt.
Schlussfolgerung Mit dem revidierten SkPTBS liegt ein praktikables und ökonomisches Instrument zur Erfassung von Risikopatienten für kPTBS vor. Es wird frei zur Verfügung gestellt und kann zur Diagnostik und Therapieplanung genutzt werden.
From ‘social aid’ to ‘social psychiatry’: mental health and social welfare in post-war Greece (1950s–1960s)
Authors: Kritsotaki Despo 
Published: January 2018

AbstractThe end of World War II and the Civil War (1946–1949) found a great section of the population of Greece struggling with serious economic and social problems, while the next two decades witnessed important socio-economic and cultural changes. Within this context, a group of mental health professionals claimed that their mission was not limited to the treatment of the mentally ill. They founded the Centre for Mental Health and Research and argued that ‘mental hygiene’ could improve the lives of all, relieve social problems and contribute to the modernisation and democratisation of society. During the late 1950s and the 1960s they sought to apply this vision not only in mental health but also in welfare services, the Social Aid Stations in Athens, Piraeus, Thessaloniki and Patrai. The Stations’ clientele originated from the less privileged social strata of these cities and surrounding villages, and requested material and practical assistance, and to a lesser extent, help with emotional and interpersonal problems. Based on unexplored case material, and building on existing literature on social psychiatry and mental hygiene, this paper addresses the gap in our knowledge of the history of mental health-cum-welfare services. It argues that the Stations envisioned and implemented an original combination of mental health and social welfare, which in the late 1950s was perceived as matching the needs and potential of the Greek population, while offering an ideal vehicle for the dissemination of mental hygiene. However, by the mid-1960s the Stations started to focus on mental health, and in the late 1960s the Athens and Patrai Stations were closed down, and the Thessaloniki and Piraeus Stations were turned into Social Psychiatry Services. This paper follows and interprets the shift from psychosocial welfare to social psychiatry, taking into consideration the transformations of Greek society, the specificities of the Stations’ operation and the profile and intentions of the Centre of Mental Health and Research. It asserts that the history of the Stations is significant in helping us understand and rethink the uneasy relationship between the social and the psychological in mental healthcare and social welfare.