bluuebunny/crossref_metadata_2025_split huggingface dataset:
Phenotype–Genotype Correlation in Children with Neurofibromatosis Type 1
Authors: Vaessen Sandrine , Bulk Saskia , Harvengt Julie , Misson Jean-Paul , Barrea Christophe 
Published: February 2018

AbstractNeurofibromatosis type 1 (NF1) is a common autosomal dominant disorder with an incidence of ∼1 in 4,000 live births. Neurofibromin, the gene product, is ubiquitously expressed at high levels in the nervous system and functions as a tumor suppressor. Haploinsufficiency of neurofibromin through mutation leads to an increased risk of developing benign and malignant tumors in affected individuals. Although NF1 has complete penetrance, it displays considerable inter- and intrafamilial variability in phenotypic expression which poses disease prediction and management problems. Some NF1 genotype–phenotype correlations have been described. To evaluate the genetic component of variable expressivity in NF1, we examined the phenotypic correlations between affected relatives in 52 NF1 patients from 45 families.
Mucosal-Associated Invariant T Cells in Chronic Inflammatory Liver Disease
Authors: Bolte Fabian , Rehermann Barbara 
Published: February 2018

AbstractThe broadening field of microbiome research has led to a substantial reappraisal of the gut–liver axis and its role in chronic liver disease. The liver is a central immunologic organ that is continuously exposed to food and microbial-derived antigens from the gastrointestinal tract. Mucosal-associated invariant T (MAIT) cells are enriched in the human liver and can be activated by inflammatory cytokines and microbial antigens. In chronic inflammatory liver disease, MAIT cells are depleted suggesting an impaired MAIT cell-dependent protection against bacterial infections.
Auswahl klinischer und diagnostischer Ergebnisse bei entzündlichen Gelenkerkrankungen
Authors: Detert Jacqueline 
Published: February 2018

ZusammenfassungZahlreiche Fortschritte in der Grundlagenforschung, in der Diagnostik und Therapie in den letzten Jahren führen dazu, dass Patienten mit einer entzündlichen Gelenkerkrankung eine Remission bzw. niedrigstmögliche Krankheitsaktivität, Lebensqualität, einen Erhalt ihrer Arbeitsfähigkeit als auch das Beibehalten der sozialen Integration beibehalten. Diese Erfolge werden schrittweise versucht, auf andere Autoimmunerkrankungen zu übertragen. Es zeigt sich gerade auf dem Gebiet der Medikamentenentwicklung jedoch immer wieder, dass es sich um pathogenetisch unterschiedlich verursachte Erkrankungen handelt und Therapieerfolge nicht immer gleichermaßen erreichbar sind. Jedoch sind inzwischen zahlreiche Medikamente zur Behandlung der entzündlichen Gelenkerkrankungen verfügbar, weitere werden derzeit intensiv in klinischen Studien geprüft bzw. sind zur Zulassungsentscheidung bei den Aufsichtsbehörden registriert. So sind auch in den nächsten Jahren weitere Therapiemöglichkeiten zu erwarten. Die rheumatoide Arthritis ist ein Beispiel dieser Erfolgsgeschichte, so dass inzwischen sogar die Frage diskutiert wird, ob diese Erkrankung präventiv zu behandeln und somit die Manifestation der Erkrankung zu stoppen ist. Diese Übersicht vermittelt eine Auswahl aktueller Forschungsergebnisse und Medikamentenentwicklungen bei entzündlichen Gelenkerkrankungen.
Posttraumatische Rehabilitation von Patienten aus dem rheumatischen Formenkreis
Authors: Ulmar Benjamin , Dorn Tobias , Dimitrov Nikolay , Mandache Alin-Ionud , Rehart Stefan , Sell Stefan 
Published: February 2018

Zusammenfassung„Rheumatiker“ haben ein erhöhtes Frakturrisiko. Die chirurgische Versorgung eines akuten Traumas bzw. der eingetretenen Traumafolgen ist aufgrund der schlechten ossären und weichteiligen Gewebestrukturen anspruchsvoll. Das Risiko für perioperative Komplikationen ist erhöht. Die Behandlung von „Rheumatikern“ nach Trauma ist komplex und erfordert eine individuelle multimodale Rehabilitation in spezialisierten Einrichtungen, welche die muskulo-skelettale und systemische Manifestation der Grunderkrankung und der additiv vorliegenden Traumafolgen adressieren kann.
Impact of Green Tea Catechin ECG and Its Synthesized Fluorinated Analogue on Prostate Cancer Cells and Stimulated Immunocompetent Cells
Authors: Stadlbauer Sven , Steinborn Carmen , Klemd Amy , Hattori Fumihiko , Ohmori Ken , Suzuki Keisuke , Huber Roman , Wolf Philipp , Gründemann Carsten 
Published: February 2018

AbstractAmong the known or suspected risk factors, inflammation plays an important role in infectious and non-infectious pathways leading to cancer. Green tea polyphenols have been associated with reducing inflammation and protection against carcinogenesis, especially in prostate cancer. While most of the research in this field, so far, has focussed on epigallocatechin-3-O-gallate only, we studied epicatechin-3-O-gallate, the second most abundant green tea polyphenol with essential therapeutic potential, to obtain a more detailed understanding of its anti-tumor and anti-inflammatory action. Furthermore, to improve the bioactivity of (−)-epicatechin-3-O-gallate, we synthesized a difluoro analogue, called (−)-5,7-difluoro-epicatechin-3-O-gallate. Both compounds reduced cell proliferation of human primary inflammatory lymphocytes in an apoptosis-specific fashion, while (−)-5,7-difluoro-epicatechin-3-O-gallate had a significantly higher activity compared to the natural product (−)-epicatechin-3-O-gallate. Treatment of low-metastatic LNCaP and high-metastatic PC-3 prostate cancer cells with (−)-epicatechin-3-O-gallate and (−)-5,7-difluoro-epicatechin-3-O-gallate demonstrated a dose-dependent inhibition of cell viability in the low micromolar range. These effects suggest that (−)-epicatechin-3-O-gallate and the more effective (−)-5,7-difluoro-epicatechin-3-O-gallate could be therapeutically used to inhibit tumorigenesis during initiation, promotion, and progression by diminishing the amount of inflammation due to a reduction of inflammatory lymphocytes. Further studies are needed to prove this in in vivo experiments.
Upgraded curriculum? An analysis of knowledge boundaries in teaching under the Swedish subject‐based curriculum*
Authors: Adolfsson Carl-Henrik 
Published: February 2018

ABSTRACTThis article offers a contribution to the current debate about knowledge and the curriculum, especially initiated by social realist writers. The enacted Swedish subject‐based curriculum for compulsory schooling is examined and is also used as a significant case with the aim of discussing practical implications of social realist claims regarding knowledge and the curriculum. Video‐recorded lessons from grade six in six different Swedish schools, in combination with teacher interviews, are explored within the scope of a curriculum theory framework with the purpose of illuminating dominant patterns of knowledge boundaries and knowledge conceptions. The study shows how the Swedish subject‐based curriculum frames teaching in a direction where a disciplinary knowledge conception with fixed knowledge boundaries predominates over other knowledge forms. The subject‐based curriculum also appears to produce an ‘overloading’ of content, which implies that pupils’ questions and experiences are avoided and dismissed in the teaching practice.
Spontaneous topological charging of tactoids in a living nematic
Authors: Genkin Mikhail M , Sokolov Andrey , Aranson Igor S 
Published: February 2018

Abstract
Living nematic is a realization of an active matter combining a nematic liquid crystal with swimming bacteria. The material exhibits a remarkable tendency towards spatio-temporal self-organization manifested in formation of dynamic textures of self-propelled half-integer topological defects (disclinations). Here we report on the study of such living nematic near normal inclusions, or tactoids, naturally realized in liquid crystals close to the isotropic-nematic (I–N) phase transition. On the basis of the computational analysis, we have established that tactoid’s I–N interface spontaneously acquire negative topological charge which is proportional to the tactoid’s size and depends on the concentration of bacteria. The observed negative charging is attributed to the drastic difference in the mobilities of +1/2 and −1/2 topological defects in active systems. The effect is described in the framework of a kinetic theory for point-like weakly-interacting defects with different mobilities. Our dedicated experiment fully confirmed the theoretical prediction. The results hint into new strategies for control of active matter.
Speciation of heavy metals Cu, Ni and Zn by modified BCR sequential extraction procedure in sediments from Banten Bay, Banten Province, Indonesia
Authors: Lestari  , Budiyanto F , Hindarti D 
Published: February 2018

Abstract
Banten Bay is categorized as a marine area that is busy with marine tourism activities, settlements and also industries. One potential impact of the condition is the occurrence of pollution from both industrial and domestic sources, erosion and sedimentation in the coastal environment. Samples were collected from 25 representative stations in April 2016. Chemical speciation of three heavy metals (Cu, Ni, and Zn) was studied using a modified sequential extraction procedure proposed by the European Standard, Measurements and Testing (SM&T) program, formerly the Community Bureau of Reference (BCR). The aims of this study are to determine geochemical speciation of 4 bounds of metal: acid-soluble, reducible, oxidizable and residual, and to assess their impacts in the sediments of Banten Bay, Indonesia. The result shows that the percentage of Copper (45.90-83.75%), Nickel (18.28-65.66%), and Zinc (30.45-79.51%) were mostly accumulated in residual fraction of the total concentrations. The Risk Assessment Code (RAC) reveals that about 0-7.07% of Copper and 1.11-24.35 % of Zinc at sites exist in exchangeable fraction and therefore, they are in low risk category. While 7.34-34.90 of Ni at sites exists in exchangeable fraction and therefore, it is in medium risk category to aquatic environment.
MARSI: metabolite analogues for rational strain improvement
Authors: Cardoso João G R , Zeidan Ahmad A , Jensen Kristian , Sonnenschein Nikolaus , Neves Ana Rute , Herrgård Markus J 
Published: February 2018

Abstract

Summary
Metabolite analogues (MAs) mimic the structure of native metabolites, can competitively inhibit their utilization in enzymatic reactions, and are commonly used as selection tools for isolating desirable mutants of industrial microorganisms. Genome-scale metabolic models representing all biochemical reactions in an organism can be used to predict effects of MAs on cellular phenotypes. Here, we present the metabolite analogues for rational strain improvement (MARSI) framework. MARSI provides a rational approach to strain improvement by searching for metabolites as targets instead of genes or reactions. The designs found by MARSI can be implemented by supplying MAs in the culture media, enabling metabolic rewiring without the use of recombinant DNA technologies that cannot always be used due to regulations. To facilitate experimental implementation, MARSI provides tools to identify candidate MAs to a target metabolite from a database of known drugs and analogues.

Availability and implementation
The code is freely available at https://github.com/biosustain/marsi under the Apache License V2. MARSI is implemented in Python.

Supplementary information
Supplementary data are available at Bioinformatics online.
Schlafen-8 is essential for lymphatic endothelial cell activation in experimental autoimmune encephalomyelitis
Authors: Nakagawa Katsuhiro , Matsuki Takanori , Zhao Liang , Kuniyoshi Kanako , Tanaka Hiroki , Ebina Isao , Yoshida Kenta J , Nabeshima Hiroshi , Fukushima Kiyoharu , Kanemaru Hisashi , Yamane Fumihiro , Kawasaki Takahiro , Machida Tomohisa , Naito Hisamichi , Takakura Nobuyuki , Satoh Takashi , Akira Shizuo 
Published: February 2018

Abstract
Schlafen-8 (Slfn8) is a member of the Schlafen family of proteins, which harbor helicase domains and are induced by LPS and interferons. It has been reported that the Schlafen family are involved in various cellular functions, including proliferation, differentiation and regulation of virus replication. Slfn8 has been implicated in T-cell differentiation in the thymus. However, the roles of Slfn8 in the immune system remains unclear. In this study, we generated Slfn8 knockout mice (Slfn8−/−) and investigated the immunological role of Slfn8 using the T-cell-mediated autoimmune model experimental autoimmune encephalomyelitis (EAE). We found that the clinical score was reduced in Slfn8−/− mice. IL-6 and IL-17A cytokine production, which are associated with EAE onset and progression, were decreased in the lymph nodes of Slfn8−/− mice. Immune cell populations in Slfn8−/− mice, including macrophages, neutrophils, T cells and B cells, did not reveal significant differences compared with wild-type mice. In vitro activation of Slfn8−/− T cells in response to TCR stimulation also did not reveal significant differences. To confirm the involvement of non-hematopoietic cells, we isolated CD45− CD31+ endothelial cells and CD45−CD31− gp38+ fibroblastic reticular cells by FACS sorting. We showed that the levels of IL-6 and Slfn8 mRNA in CD45− CD31+ endothelial cells were increased after EAE induction. In contrast, the level of IL-6 mRNA after EAE induction was markedly decreased in CD31+ endothelial cells from Slfn8−/− mice. These results indicate that Slfn8 may play a role in EAE by regulating inflammation in endothelial cells.
The Effects of Mismatches between Survey Question Stems and Response Options on Data Quality and Responses
Authors: Smyth Jolene D , Olson Kristen 
Published: February 2018

AbstractSeveral questionnaire design texts emphasize a dual role of question wording: the wording needs to express what is being measured and tell respondents how to answer. Researchers tend to focus heavily on the first of these goals, but sometimes overlook the second, resulting in question wording that does not match the response options provided (i.e., mismatches). Common examples are yes/no questions with ordinal or nominal response options, open-ended questions with closed-ended response options, and check-all-that apply questions with forced-choice response options. A slightly different type of mismatch utilizes a question stem that can be read as asking for two different types of answers with no indication of which type should be provided. In this paper, we report the results of twenty-two experimental comparisons of data quality indicators (i.e., item nonresponse and response time) and response distributions across matched and mismatched versions of questions from a postal mail survey and a telephone survey. We find that mismatched items generally have lower data quality than matched items and that substantive results differ significantly across matched and mismatched designs, especially in the telephone survey. The results suggest that researchers should be wary of mismatches and should strive for holistic design.
Sidney Lumet
Authors: Rapf Joanna E. 
Published: February 2018

Sidney Lumet (b. 1924–d. 2011) was adamantly anti-auteurist, always emphasizing the collaborative nature of making movies (he avoided the words “film” and “cinema” as pretentious). He was that rare director who refused the possessory credit, “a film by . . .” which may be the reason he lacks the name recognition of a Spielberg, Scorsese, or Coppola. However, his movies are among the classics of the second half of the twentieth century, including his first feature, the courtroom drama Twelve Angry Men. Lumet explores such diverse topics as the story of a holocaust survivor in The Pawnbroker; corruption in the New York police department in Serpico, and Prince of the City. Others include a thwarted bank robbery by a bisexual Vietnam veteran in Dog Day Afternoon; the power of television in the prescient Network; and medical malpractice and the Catholic Church in The Verdict. He made over forty features and was nominated by the Motion Picture Academy for Best Director four times and once for screenwriting. In 2005, he finally received a long overdue Oscar for Lifetime Achievement. He began his career as a child actor in New York, the son of Baruch Lumet, a well-known Yiddish actor. His Broadway debut was in Sidney Kingsley’s Dead End in 1935, and he continued to perform regularly on and off Broadway as a child. Again portraying a slum kid, he starred in the film One Third of a Nation, directed by Dudley Murphy in 1939. Perhaps because of his own acting experience, actors loved working with him and appreciated his sensitivity to their needs. In 1941, he joined the Army Signal Corps. After World War II, he founded an off-Broadway acting group and began directing. However, it was the so-called Golden Age of television that really gave him his start as a director, and he credits those television years with teaching him how to shoot quickly and efficiently, how to edit in the camera, and how to use lenses to help tell a story. Besides his skill as a technician, Lumet also brought to his early television projects his humanity and ongoing concern for social justice. He was fascinated by the human cost involved in following passions and commitments, as well as the cost those passions and commitments inflict on others. This concern is at the core of most of his movies, exploring the complexities of human behavior. Human Rights First, a nonprofit, nonpartisan organization based in New York City and Washington, has honored the humanitarian impact of his career by creating the “Sidney Lumet Award for Integrity in Entertainment” to pay tribute to works of popular culture that advance understanding of pressing human rights issues.
EFFICACY AND SAFETY OUTCOMES OF INTRAVITREAL AFLIBERCEPT FOCUSING ON PATIENTS WITH DIABETIC MACULAR EDEMA FROM JAPAN
Authors: Terasaki Hiroko , Shiraki Kunihiko , Ohji Masahito , Metzig Carola , Schmelter Thomas , Zeitz Oliver , Sowade Olaf , Kobayashi Masato , Vitti Robert , Berliner Alyson , Shiraga Fumio 
Published: February 2018

Purpose:
To evaluate the efficacy and safety of intravitreal aflibercept injection (IAI) in Japanese patients with diabetic macular edema (DME).

Methods:
VIVID-DME was a Phase 3 study comprising patients with DME randomized 1:1:1 to IAI 2 mg every 4 weeks (2q4), IAI 2 mg every 4 weeks until Week 16 then 8-week dosing (2q8), and laser. A total of 403 patients (76 Japanese) were included in this study. VIVID-Japan (72; all Japanese patients) was a nonrandomized, open-label study comprising Japanese patients with DME receiving IAI 2q4 until Week 16, then 2q8. Primary efficacy endpoint (Week 52) of VIVID-DME was mean change from baseline in best-corrected visual acuity; VIVID-Japan evaluated safety and tolerability.

Results:
Mean change in best-corrected visual acuity (letters) for 2q4, 2q8, and laser groups was +10.6, +10.9, and +1.2 and +9.8, +9.5, and +1.1 in the non-Japanese and Japanese populations of VIVID-DME, respectively. In VIVID-Japan, it was +9.3 for IAI 2q8. Intravitreal aflibercept injection also provided consistently greater benefits for anatomical outcomes versus laser. Adverse events were consistent with the known safety profile of IAI.

Conclusion:
In Japanese patients with DME, IAI treatment was superior to laser for visual and anatomical outcomes and resulted in efficacy and safety outcomes similar to those in a non-Japanese patient population.
ROUTINE FUNDUS SCREENING OF FAMILIES OF CHILDREN WITH RETINOBLASTOMA
Authors: Kaliki Swathi , Gupta Rathi Shweta , Patel Anamika 
Published: February 2018

Purpose:
To discuss the importance of routine ophthalmic examination of parents and siblings of retinoblastoma (RB) patients.

Methods:
Prospective nonrandomized observational/interventional case series of consecutive families of 131 RB patients.

Results:
Routine ophthalmic examination of families (parents and siblings) of 131 consecutive newly diagnosed RB patients, including 262 parents and 23 siblings, revealed spontaneously regressed RB in at least 1 parent of 10 (8%) patients and active RB in at least 1 sibling of 3 (2%) patients. Of the 10 parents with spontaneously regressed RB, the lesions were unilateral (n = 7) or bilateral (n = 3). The regression patterns (n = 13) were comparable with postirradiation regression patterns Type 1 (n = 3), Type 2 (n = 2), Type 3 (n = 2), and Type 4 (n = 3), and spontaneous phthisis bulbi (n = 3). Fundus screening of siblings revealed active RB in at least 1 sibling of 3 (2%) patients. Of these 3 siblings, 2 had unilateral and 1 had bilateral disease. The mean age at detection of RB was 15 months (median, 6 months; range, 2–36 months). The disease was unilateral in 2 and bilateral in 1 patient. Based on International Classification of Intraocular Retinoblastoma, the tumors (n = 4) were classified as Group A (n = 2) and Group B (n = 2).

Conclusion:
Routine fundus screening of siblings allows for early detection of RB in otherwise asymptomatic children. Detection of spontaneously regressed RB in parents may act as a surrogate marker for germline RB1 mutation and is helpful in genetic counseling.
Autoantibodies against N-methyl-d-aspartate receptor 1 in health and disease
Authors: Ehrenreich Hannelore 
Published: February 2018

Purpose of review
Humoral autoimmunity has gained highest interest in neurology and psychiatry. Despite numerous recent articles on this hot topic, however, the biological significance of natural autoantibodies (AB) and the normal autoimmune repertoire of mammals remained quite obscure. AB may contribute to disorder-relevant phenotypes and are even believed to induce diseases themselves, but the circumstances under which AB become pathogenic are not fully understood. This review will focus on the highly frequent AB against the N-methyl-d-aspartate receptor 1 (NMDAR1-AB) as an illustrating example and provide a critical overview of current work (please note that the new nomenclature, GluN1, is disregarded here for consistency with the AB literature). In particular, it will demonstrate how little is known at this point and how many conclusions are drawn based on small numbers of individuals, fragmentary experimental approaches or missing controls.

Recent findings
NMDAR1-AB were investigated by clinicians world-wide with numerous small studies and case reports appearing yearly. Many publications were on ‘anti-NMDAR encephalitis’ cases or tried to separate those from other NMDAR1-AB associated conditions. Original exclusivity claims (e.g. electroencephalogram, EEG or functional magnetic resonance imaging, fMRI findings) turned out not to be exclusive for ‘anti-NMDAR encephalitis’. Systematic analyses of representative NMDAR1-AB positive sera of all immunoglobulin (Ig) classes showed comparable distribution of different epitopes, often polyspecific/polyclonal, across health and disease. Sophisticated imaging tools provided findings on synapse trafficking changes induced by NMDAR1-AB from psychotic subjects but still lack epitope data to support any claimed disorder link. Persistently high titers of NMDAR1-AB (IgG) in immunized mice with open blood–brain barrier (BBB)-induced psychosis-like symptoms but failed to induce inflammation in the brain. Knowledge on peripheral NMDAR, for example in the immune system, and on potential inducers of NMDAR1-AB is only slowly increasing.

Summary
The present knowledge on the (patho) physiological role of NMDAR1-AB is very limited and still characterized by adamant rumors. Much more experimental work and more solid and informative clinical reports, including large numbers of subjects and adequate control groups, follow-up investigations and interdisciplinary approaches will be necessary to obtain a better understanding of the significance of humoral autoimmunity in general (in focus here: NMDAR1-AB) and its disease-relevance in particular.