bluuebunny/crossref_metadata_2025_split huggingface dataset:
Neoadjuvant (Chemo)radiotherapy With Total Mesorectal Excision Only Is Not Sufficient to Prevent Lateral Local Recurrence in Enlarged Nodes: Results of the Multicenter Lateral Node Study of Patients With Low cT3/4 Rectal Cancer
Authors: Ogura Atsushi , Konishi Tsuyoshi , Cunningham Chris , Garcia-Aguilar Julio , Iversen Henrik , Toda Shigeo , Lee In Kyu , Lee Hong Xiang , Uehara Keisuke , Lee Peter , Putter Hein , van de Velde Cornelis J.H. , Beets Geerard L. , Rutten Harm J.T. , Kusters Miranda ,   on behalf of the Lateral Node Study Consortium
Published: November 2018

Purpose Improvements in magnetic resonance imaging (MRI), total mesorectal excision (TME) surgery, and the use of (chemo)radiotherapy ([C]RT) have improved local control of rectal cancer; however, we have been unable to eradicate local recurrence (LR). Even in the face of TME and negative resection margins (R0), a significant proportion of patients with enlarged lateral lymph nodes (LLNs) suffer from lateral LR (LLR). Japanese studies suggest that the addition of an LLN dissection (LLND) could reduce LLR. This multicenter pooled analysis aims to ascertain whether LLNs actually pose a problem and whether LLND results in fewer LLRs. Patients and Methods Data from 1,216 consecutive patients with cT3/T4 rectal cancers up to 8 cm from the anal verge who underwent surgery in a 5-year period were collected. LLND was performed in 142 patients (12%). MRIs were re-evaluated with a standardized protocol to assess LLN features. Results On pretreatment MRI, 703 patients (58%) had visible LLN, and 192 (16%) had a short axis of at least 7 mm. One hundred eight patients developed LR (5-year LR rate, 10.0%), of which 59 (54%) were LLRs (5-year LLR rate, 5.5%). After multivariable analyses, LLNs with a short axis of at least 7 mm resulted in a significantly higher risk of LLR (hazard ratio, 2.060; P = .045) compared with LLNs of less than 7 mm. In patients with LLNs at least 7 mm, (C)RT plus TME plus LLND resulted in a 5-year LLR of 5.7%, which was significantly lower than that in patients who underwent (C)RT plus TME (5-year LLR, 19.5%; P = .042). Conclusion LLR is still a significant problem after (C)RT plus TME in LLNs with a short axis at least 7 mm on pretreatment MRI. The addition of LLND results in a significantly lower LLR rate.
Role of Donor Clonal Hematopoiesis in Allogeneic Hematopoietic Stem-Cell Transplantation
Authors: Frick Mareike , Chan Willy , Arends Christopher Maximilian , Hablesreiter Raphael , Halik Adriane , Heuser Michael , Michonneau David , Blau Olga , Hoyer Kaja , Christen Friederike , Galan-Sousa Joel , Noerenberg Daniel , Wais Verena , Stadler Michael , Yoshida Kenichi , Schetelig Johannes , Schuler Esther , Thol Felicitas , Clappier Emmanuelle , Christopeit Maximilian , Ayuk Francis , Bornhäuser Martin , Blau Igor Wolfgang , Ogawa Seishi , Zemojtel Tomasz , Gerbitz Armin , Wagner Eva M. , Spriewald Bernd M. , Schrezenmeier Hubert , Kuchenbauer Florian , Kobbe Guido , Wiesneth Markus , Koldehoff Michael , Socié Gérard , Kroeger Nicolaus , Bullinger Lars , Thiede Christian , Damm Frederik 
Published: November 2018

Purpose Clonal hematopoiesis of indeterminate potential (CHIP) occurs in the blood of approximately 20% of older persons. CHIP is linked to an increased risk of hematologic malignancies and of all-cause mortality; thus, the eligibility of stem-cell donors with CHIP is questionable. We comprehensively investigated how donor CHIP affects outcome of allogeneic hematopoietic stem-cell transplantation (HSCT). Methods We collected blood samples from 500 healthy, related HSCT donors (age ≥ 55 years) at the time of stem-cell donation for targeted sequencing with a 66-gene panel. The effect of donor CHIP was assessed on recipient outcomes, including graft-versus-host disease (GVHD), cumulative incidence of relapse/progression (CIR/P), and overall survival (OS). Results A total of 92 clonal mutations with a median variant allele frequency of 5.9% were identified in 80 (16.0%) of 500 donors. CHIP prevalence was higher in donors related to patients with myeloid compared with lymphoid malignancies (19.2% v 6.3%; P ≤ .001). In recipients allografted with donor CHIP, we found a high cumulative incidence of chronic GVHD (cGVHD; hazard ratio [HR], 1.73; 95% CI, 1.21 to 2.49; P = .003) and lower CIR/P (univariate: HR, 0.62; 95% CI, 0.40 to 0.97; P = .027; multivariate: HR, 0.63; 95% CI, 0.41 to 0.98; P = .042) but no effect on nonrelapse mortality. Serial quantification of 25 mutations showed engraftment of 24 of 25 clones and disproportionate expansion in half of them. Donor-cell leukemia was observed in two recipients. OS was not affected by donor CHIP status (HR, 0.88; 95% CI, 0.65 to 1.321; P = .434). Conclusion Allogeneic HSCT from donors with CHIP seems safe and results in similar survival in the setting of older, related donors. Future studies in younger and unrelated donors are warranted to extend these results. Confirmatory studies and mechanistic experiments are warranted to challenge the hypothesis that donor CHIP might foster cGVHD development and reduce relapse/progression risk.
Cullin-3–KCTD10-mediated CEP97 degradation promotes primary cilium formation
Authors: Nagai Tomoaki , Mukoyama Sachiho , Kagiwada Harumi , Goshima Naoki , Mizuno Kensaku 
Published: November 2018

ABSTRACT
Primary cilia are antenna-like sensory organelles that transmit various extracellular signals. Ciliogenesis requires the removal of CP110 and its interactor CEP97 from the mother centriole for initiating ciliary axoneme extension, but the underlying mechanism remains unknown. Here we show that, upon serum starvation, CEP97 is partially degraded by the ubiquitin-proteasome system. CEP97 was polyubiquitylated in serum-starved cells, and overexpression of a non-ubiquitylatable CEP97 mutant effectively blocked CP110 removal and ciliogenesis induced by serum-starvation. Through several screening steps, we identified the cullin-3–RBX1–KCTD10 complex as the E3 ligase that mediates CEP97 degradation and removal from the mother centriole. Depletion of each component of this E3 complex caused aberrant accumulation of CEP97 on the centrosome, suppressed the removal of CEP97 and CP110 from the mother centriole, and impaired ciliogenesis. Moreover, KCTD10 was specifically localized to the mother centriole. These results suggest that CEP97 degradation by the cullin-3–RBX1–KCTD10 complex plays a crucial role in serum-starvation-induced CP110 removal and ciliogenesis.
Elongated mitochondrial constrictions and fission in muscle fatigue
Authors: Lavorato Manuela , Loro Emanuele , Debattisti Valentina , Khurana Tejvir S. , Franzini-Armstrong Clara 
Published: November 2018

ABSTRACT
Mitochondria respond to stress and undergo fusion and fission at variable rates, depending on cell status. To understand mitochondrial behavior during muscle fatigue, we investigated mitochondrial ultrastructure and expression levels of a fission- and stress-related protein in fast-twitch muscle fibers of mice subjected to fatigue testing. Mice were subjected to running at increasing speed until exhaustion at 45 min–1 h. In further experiments, high-intensity muscle stimulation through the sciatic nerve simulated the forced treadmill exercise. We detected a rare phenotype characterized by elongated mitochondrial constrictions (EMCs) connecting two separate segments of the original organelles. EMCs are rare in resting muscles and their frequency increases, albeit still at low levels, in stimulated muscles. The constrictions are accompanied by elevated phosphorylation of Drp1 (Dnm1l) at Ser 616, indicating an increased translocation of Drp1 to the mitochondrial membrane. This is indicative of a mitochondrial stress response, perhaps leading to or facilitating a long-lasting fission event. A close apposition of sarcoplasmic reticulum (SR) to the constricted areas, detected using both transmission and scanning electron microscopy, is highly suggestive of SR involvement in inducing mitochondrial constrictions.
Localization of all four ZnT zinc transporters in Dictyostelium and impact of ZntA and ZntB knockout on bacteria killing
Authors: Barisch Caroline , Kalinina Vera , Lefrançois Louise H. , Appiah Joddy , López-Jiménez Ana T. , Soldati Thierry 
Published: November 2018

ABSTRACT
Professional phagocytes have developed an extensive repertoire of autonomous immunity strategies to ensure killing of bacteria. Besides phagosome acidification and the generation of reactive oxygen species, deprivation of nutrients and the lumenal accumulation of toxic metals are essential to kill ingested bacteria or inhibit the growth of intracellular pathogens. Here, we used the soil amoeba Dictyostelium discoideum, a professional phagocyte that digests bacteria for nutritional purposes, to decipher the role of zinc poisoning during phagocytosis of nonpathogenic bacteria and visualize the temporal and spatial dynamics of compartmentalized, free zinc using fluorescent probes. Immediately after particle uptake, zinc is delivered to phagosomes by fusion with ‘zincosomes’ of endosomal origin, and also by the action of one or more zinc transporters. We localized the four Dictyostelium ZnT transporters to endosomes, the contractile vacuole and the Golgi complex, and studied the impact of znt knockouts on zinc homeostasis. We show that zinc is delivered into the lumen of Mycobacterium smegmatis-containing vacuoles, and that Escherichia coli deficient in the zinc efflux P1B-type ATPase ZntA are killed faster than wild-type bacteria.
CAP1-mediated actin cycling via ADF/cofilin proteins is essential for asymmetric division in mouse oocytes
Authors: Jin Zhe-Long , Jo Yu-Jin , Namgoong Suk , Kim Nam-Hyung 
Published: November 2018

ABSTRACT
Dynamic reorganization of the actin cytoskeleton is fundamental to a number of cellular events, and various actin-regulatory proteins modulate actin polymerization and depolymerization. Adenylyl cyclase-associated proteins (CAPs), highly conserved actin monomer-binding proteins, have been known to promote actin disassembly by enhancing the actin-severing activity of the ADF/cofilin protein family. In this study, we found that CAP1 regulated actin remodeling during mouse oocyte maturation. Efficient actin disassembly during oocyte maturation is essential for asymmetric division and cytokinesis. CAP1 knockdown impaired meiotic spindle migration and asymmetric division, and resulted in an accumulation of excessive actin filaments near the spindles. In contrast, CAP1 overexpression reduced actin mesh levels. CAP1 knockdown also rescued a decrease in cofilin family protein overexpression-mediated actin levels, and simultaneous expression of human CAP1 (hCAP1) and cofilin synergistically decreased cytoplasmic actin levels. Overexpression of hCAP1 decreased the amount of phosphorylated cofilin, indicating that CAP1 facilitated actin depolymerization via interaction with ADF/cofilin during mouse oocyte maturation. Taken together, our results provide evidence for the importance of dynamic actin recycling by CAP1 and cofilin in the asymmetric division of mouse female gametes.
This article has an associated First Person interview with the first author of the paper.
Case Report: Dentigerous cyst marsupialization for a child with Hunter’s syndrome
Authors: Sabry Shaimaa , Moheb Dalia , El Shahawy Osama 
Published: November 2018

Hunter’s syndrome or mucopolysaccharidosis (MPS) type II is an inherited disorder caused by enzyme iduronate-2-sulfatase deficiency. It is characterized by involvement of the nervous, cardiovascular, respiratory, and musculoskeletal systems, along with numerous oral manifestations. This is a case report of an eight year-old girl diagnosed with Hunter’s syndrome, who was referred to the Pediatric Dentistry Department, Faculty of Dentistry, Cairo University with a chief complaint of hard swelling related to the lower left posterior area. Radiographic examination revealed well defined corticated radiolucency surrounding an unerupted lower left first molar. Aspiration was done and cytopathologic examination revealed cystic fluid mixed with blood. The case was diagnosed as a dentigerous cyst. Cyst marsupialization was done under general anaesthesia. From this case report we concluded that in Hunter’s syndrome patients more conservative approaches are more valuable. Regular dental follow up is advised to maintain good oral hygiene, and to detect any complications as early as possible.
Asset Growth, Profitability, and Investment Opportunities
Authors: Cooper Ilan , Maio Paulo 
Published: November 2018

We show that recent prominent equity factor models are to a large degree compatible with the Intertemporal CAPM (ICAPM) framework. Factors associated with alternative profitability measures forecast the equity premium in a way that is consistent with the ICAPM. Several factors based on firms’ asset growth predict a significant decline in stock market volatility, thus being consistent with their positive prices of risk. The investment-based factors are also strong predictors of an improvement in future economic activity. The time-series predictive ability of most equity state variables is not subsumed by traditional ICAPM state variables. Importantly, factors that earn larger risk prices tend to be associated with state variables that are more correlated with future investment opportunities or economic activity. Moreover, these risk price estimates can be reconciled with plausible risk-aversion parameter estimates. Overall, the ICAPM can be used as a common theoretical background for recent multifactor models. This paper was accepted by Karl Diether, finance.
INCOME AND QUALITY OF LIFE INFLUENCE ON CITIZENS' PARTICIPATION IN ACTIVITIES OF LOCAL GOVERNMENTS IN LATVIA
Authors: Šavriņa Baiba , Seimuškāne Lilita 
Published: November 2018

The aim of the paper is to analyse the factors influencing the citizen participation in activities of local governments in relation to quality of life in Latvia. The use of the CLEAR model, elaborated by a group of British researchers under guidance of Gerry Stoker, shows the possibilities of participation and engagement of citizens based on theoretical aspects. Latvia, as a member state of the EU, needs to develop and to involve more citizens in different social activities, since it has comparatively small experience in democratic processes due to its past of 50 years being a part of another country — the Soviet Union. The opportunities to participate in the European Parliament’s election and to promote the resolution of common issues or questions specific for the country can be one of the ways for expressing life priorities. Historical heritage is still influencing the priorities of population, such as changes in income level and possibilities to increase the quality of life, have a strong impact on the perception of citizens. By using the concept of a welfare state and a welfare economy, it is possible to explain the enlargement of areas of citizens’ interaction. Unbalanced regional development with a huge impact on the capital city in the national economy and in the number of inhabitants concentrated in Rīga that amounts to a third of the total population with important differences in income level and quality of life has profound influence on other regions and the interests of inhabitants to participate in local governmental activities. The factors, which affect this engagement, are analysed by using primary and secondary data. The main conclusions are: 1) there is more active citizens participating in the activities of local government than in the election of the European Parliament due to faster and more visible results in solving problems, 2) the global financial crisis strongly affected the participation level, the changes of economic conjuncture have an important impact on the participation of citizens 3) imbalance in regional development is reflected by the level of participation, since there is a higher level of participation in economically favourable regions.
PREEMINENT SOUTH-DANUBIAN ROMANIANS: ANDREI ŞAGUNA AND EFTIMIE MURGU
Authors: Iulian Raluca Iulia 
Published: November 2018

At the end of the First World War in 1918, after the break-up of the Habsburg Empire, several national states were constituted, reconstituted or completed. Among them, Romania realized the Great Union on December 1, 1918 by unification with Transylvania and Bessarabia. This was the realization of an ideal pursued for centuries by the Romanian people despite historical vicissitudes. The purpose of the paper is to highlight the special contributions of two personalities, South-Danubian Romanians that stand out in the social, religious, political and economic life in Transylvania and in the rest of the Habsburg Empire in the 19th century, thus creating the prerequisites for the Great Union. The method we used in our research was the direct analysis of various materials such as studies, basic documents, and historical texts concerning the South-Danubian Romanians. Andrei Şaguna, one of the greatest Romanian Orthodox hierarchs, re-established the old Orthodox Metropolitan Church of Transylvania in Alba Iulia. He also activated in the political field especially during the revolutionary year 1848, promoting the rights of Romanians in the Habsburg Empire and strengthening their national identity. Andrei Şaguna also developed the Romanian education system. Eftimie Murgu, emblematic fighter for the rights and the liberties of Romanians in Transylvania, professor and lawyer, revived the flame of national consciousness in the Romanian historical provinces. He has a great contribution in the affirmation of the Latin origin of the Romanian people, and of its national identity. Andrei Şaguna and Eftimie Murgu had an decisive contribution to the preparation of the unification of the country, one as a priest and the other as a civilian.
THE ATTITUDES OF STUDENTS IN BULGARIA AND THE CZECH REPUBLIC TOWARDS PEOPLE WITH SPECIAL EDUCATIONAL NEEDS
Authors: Ruseva Margarita , Kazashka Vesela 
Published: November 2018

The paper is covering a survey aimed to find out what is the publicity and the interest of society in people with disabilities, what is the public attitude of students towards this stigmatized group of people, are there any already formed stereotypes and positive stigmas of the people with disabilities, how to achieve their overall integration into society, i.e. starting from the family, through university and finally at work. We carried out surveys (questionnaires) among students from the Czech Republic and Republic of Bulgaria, as for this purpose we interviewed 100 students from both countries.This work reviews the concept of a relation between people with disabilities and the students, and the positive attitude of the latter for the purpose of integration into society. This survey uses several statistical methods. This fact increases its value and in great extent increases the possibilities of obtaining adequate and credible results. As a result of the survey, we determined the following: Direct contact with people with special educational needs is more influential both for people with disabilities and for the change of attitudes towards them. Overcoming the problem with the socialization and realization of the people with disabilities, both in public and personal aspect are a positive stigma which is a motivator and generator of new attitudes. Positive stigma, positive examples and direct contact are catalysts of the social processes related to people with disabilities and stimulate attitudes of the society and the individual.
NEGLECT OF SENIORS AS A FORM OF DOMESIC VIOLENCE
Authors: Tittlová Marcela 
Published: November 2018

The neglect of seniors is new and more current problem in society nowadays. Originally. Domestic violence in criminological sources was limited just on violence against women, later child victims was emerged. Quite late relating to documents adopted by European Union (Opinion of the European Economic and Social Committee on ‘Elder abuse’ in 2008) the problem of domestic violence has extended on seniors as another category of possible victims. The submitted report addresses the current and new phenomenon which requires consistent criminological behaviour as the basis for possible solutions in the legal order. Neglect of seniors, as new social phenomenon, requires rigorous examination in the light of the area of this term, as well as causes for which it occurs. The originators of this negative social phenomenon are considered to be not only children and grandchildren, but in some cases also subject (institutions) which are obliged to provide care for seniors on a contractual basis or ex lege. The forms of neglect are based on general knowledge about domestic violence and are not beyond the framework of this phenomenon. Otherwise it is for the causes which are ground for violent behaviour of seniors because of necessity to be found in originators of violent forms of behaviour. Such causes include economic (financial, property) reason, as well as overworking, stress, lack of time on the side of the aggressors covering the lack of interest to care of the senior. The consequences of this violent behavior are very serious in the case of seniors because of the physical, psychological and financial possibilities of seniors often do not allow them to help and care any other way. The neglect of seniors is consistently showing very high latency. Only its versatile examination (criminological, legal and in terms of victims) can lead to effective control of this kind of crime. As a new social phenomenon, it is only very rarely determined in available sources, which is the reason why there is only a minimal amount of knowledge about the neglect of seniors. This negative phenomenon is needed to be thoroughly explored, which is the basis for its solution.