bluuebunny/crossref_metadata_2025_split huggingface dataset:
Early relapse of psoriasis after stopping brodalumab: a retrospective cohort study in 77 patients
Authors: Masson Regnault M. , Konstantinou M.‐P. , Khemis A. , Poulin Y. , Bourcier M. , Amelot F. , Bulaï Livideanu C. , Paul C. 
Published: June 2017

AbstractBackgroundBiological agents targeting IL‐17 are very effective for clearing moderate to severe psoriasis. There is limited information regarding the frequency and pattern of psoriasis relapse upon treatment cessation.ObjectiveTo investigate the pattern of psoriasis recurrence in patients who were treated with brodalumab following Amgen's decision to stop the clinical programme in June 2015.Materials and methodsBetween June 2015 and March 2016, we constructed a retrospective multicenter cohort study including patients who were treated with brodalumab in Amgen's protocols after the abrupt interruption of the drug development programme. The relapse was defined as the request of patient to initiate a new treatment after brodalumab withdrawal.ResultsSeventy‐seven patients were followed up. At the time brodalumab treatment was stopped, 67 (87%) patients had reached PASI 90. After brodalumab discontinuation, all 77 patients relapsed after a follow‐up of 9 months. The median time to relapse was 46 days (range 7–224 days). Concerning the type of relapse, 73 patients presented with plaque psoriasis, one patient presented with erythrodermic psoriasis, and three patients experienced pustular psoriasis. In seven patients who had no previous history of psoriatic arthritis (PsA), the relapse of psoriasis was associated with inflammatory joint pain suggestive of PsA. At week 36, eight patients who had a limited relapse were controlled with topical treatment, 43 patients received a biological agent, two patients were included in a clinical trial with an investigational drug and 15 patients were treated with conventional systemic agents.ConclusionAbrupt cessation of brodalumab is associated with a rapid relapse of psoriasis with some patients experiencing a rebound. It seems not advisable to stop treatment with IL‐17 receptor antagonists abruptly even in patients who experience complete clearance of psoriasis.
Global Life Cycle Paper Flows, Recycling Metrics, and Material Efficiency
Authors: Van Ewijk Stijn , Stegemann Julia A. , Ekins Paul 
Published: June 2017

SummaryDespite major improvements in recycling over the last decades, the pulp and paper sector is a significant contributor to global greenhouse gas emissions and other environmental pressures. Further reduction of virgin material requirements and environmental impacts requires a detailed understanding of the global material flows in paper production and consumption. This study constructs a Sankey diagram of global material flows in the paper life cycle, from primary inputs to end‐of‐life waste treatment, based on a review of publicly available data. It then analyzes potential improvements in material flows and discusses recycling and material efficiency metrics. The article argues that the use of the collection rate as a recycling metric does not directly stimulate avoidance of virgin inputs and associated impacts. An alternative metric compares paper for recycling (recovered paper) with total fibrous inputs and indicates that the current rate is at just over half of the technical potential. Material efficiency metrics are found to be more useful if they relate to the reuse potential of wastes. The material balance developed in this research provides a solid basis for further study of global sustainable production and consumption of paper. The conclusions on recycling and efficiency should be considered for improving environmental assessment and stimulating a shift toward resource efficiency and the circular economy.
The Development of Sensitivity to Grammatical Violations in American Sign Language: Native Versus Nonnative Signers
Authors: Novogrodsky Rama , Henner Jon , Caldwell‐Harris Catherine , Hoffmeister Robert 
Published: June 2017

AbstractFactors influencing native and nonnative signers’ syntactic judgment ability in American Sign Language (ASL) were explored for 421 deaf students aged 7;6–18;5. Predictors for syntactic knowledge were chronological age, age of entering a school for the deaf, gender, and additional learning disabilities. Mixed‐effects linear modeling analysis revealed main effects of each predictor and an interaction between signing status and learning disability. The native signers showed typical syntactic development that varied by chronological age, gender, additional learning disabilities, and age of entering a deaf school. In contrast, the syntactic development of nonnative signers was more variable. It was less tightly related to chronological age and more strongly influenced by the age at which they had entered the school where assessment occurred, which was highly related to length of exposure to a sign language.
Security, ethnicity, nationalism
Authors: Neumann Iver B. 
Published: June 2017

AbstractUsing Slavic examples, the article looks at the nationalism/security nexus present today between the birth of ethnicities (early middle ages) and the birth of nationalism (eighteenth century). I discuss how Slavic ethnicity emerged in Greek and Roman security thinking. Others were classified in terms ofethnoiand were then interpellated into this self‐understanding. If ethnicity is an identity for the Other, then nationalism is an identity for the Self. It becomes a security concern not to order the Other polity's identity, as did the Byzantines, but to see to it that groups that may threaten your own nationalism – minorities, imperial subjects – cannot embrace nationalism. The policy of denying nationhood to minorities must be understood amongst other things as security policy. The organic understanding of the nation as young and vital demonstrates a third interstice between security and nationalism. If the young and vital nation is to grow and expand at the expense of the old and tired, then the polity that represents itself as a young and vital nation is by dint of that representation alone a security threat against those that they represent as old and tired. Finally, I discuss how this theme is played out in today's Russia
A Semiparametric Regression Model for Longitudinal Data with Non‐stationary Errors
Authors: Li Rui , Leng Chenlei , You Jinhong 
Published: June 2017

AbstractMotivated by the need to analyze the National Longitudinal Surveys data, we propose a new semiparametric longitudinal mean‐covariance model in which the effects on dependent variable of some explanatory variables are linear and others are non‐linear, while the within‐subject correlations are modelled by a non‐stationary autoregressive error structure. We develop an estimation machinery based on least squares technique by approximating non‐parametric functions via B‐spline expansions and establish the asymptotic normality of parametric estimators as well as the rate of convergence for the non‐parametric estimators. We further advocate a new model selection strategy in the varying‐coefficient model framework, for distinguishing whether a component is significant and subsequently whether it is linear or non‐linear. Besides, the proposed method can also be employed for identifying the true order of lagged terms consistently. Monte Carlo studies are conducted to examine the finite sample performance of our approach, and an application of real data is also illustrated.
Mechanisms underlying vestibulo‐cerebellar motor learning in mice depend on movement direction
Authors: Voges Kai , Wu Bin , Post Laura , Schonewille Martijn , De Zeeuw Chris I. 
Published: June 2017

Key points
Directionality, inherent to movements, has behavioural and neuronal correlates.
Direction of vestibular stimulation determines motor learning efficiency.
Vestibulo‐ocular reflex gain–increase correlates with Purkinje cell simple spike potentiation.
The locus of neural correlates for vestibulo‐ocular reflex adaptation is paradigm specific.
AbstractCompensatory eye movements elicited by head rotation, also known as vestibulo‐ocular reflex (VOR), can be adapted with the use of visual feedback. The cerebellum is essential for this type of movement adaptation, although its neuronal correlates remain to be clarified. In the present study, we show that the direction of vestibular input determines the magnitude of eye movement adaptation induced by mismatched visual input in mice, with larger changes during contraversive head rotation. Moreover, the location of the neural correlate of this changed behaviour depends on the type of paradigm. Gain–increase paradigms induce increased simple spike (SS) activity in ipsilateral cerebellar Purkinje cells (PC), which is in line with eye movements triggered by optogenetic PC activation. By contrast, gain–decrease paradigms do not induce changes in SS activity, indicating that the murine vestibulo‐cerebellar cortical circuitry is optimally designed to enhance ipsiversive eye movements.
Different Resistance Mechanisms for Cadazolid and Linezolid in Clostridium difficile Found by Whole-Genome Sequencing Analysis
Authors: Caspers Patrick , Locher Hans H. , Pfaff Philippe , Diggelmann Sarah , Rueedi Georg , Bur Daniel , Ritz Daniel 
Published: June 2017

ABSTRACT

Cadazolid (CDZ) is a new antibiotic currently in clinical development for the treatment of
Clostridium difficile
infections. CDZ interferes with the bacterial protein synthesis machinery. The aim of the present study was to identify resistance mechanisms for CDZ and compare the results to those obtained for linezolid (LZD) in
C. difficile
by whole-genome sequencing (WGS) of strains generated by
in vitro
passages and to those obtained for LZD-resistant clinical isolates. Clones of
C. difficile
630 selected with CDZ during 46 passages had a maximally 4-fold increase in CDZ MIC, while the LZD MIC for clones selected with LZD increased up to 16-fold. CDZ cross-resistance with LZD was maximally 4-fold, and no cross-resistance with other antibiotics tested was observed. Our data suggest that there are different resistance mechanisms for CDZ and LZD in
C. difficile
. Mutations after passages with CDZ were found in
rplD
(ribosomal protein L4) as well as in
tra
and
rmt
, whereas similar experiments with LZD showed mutations in
rplC
(ribosomal protein L3),
reg
, and
tpr
, indicating different resistance mechanisms. Although high degrees of variation between the sequenced genomes of the clinical isolates were observed, the same mutation in
rplC
was found in two clinical isolates with high LZD MICs. No mutations were found in the 23S rRNA genes, and attempts to isolate the
cfr
gene from resistant clinical isolates were unsuccessful. Analysis of 50% inhibitory concentrations (IC
50
s) determined in
in vitro
transcription/translation assays performed with
C. difficile
cell extracts from passaged clones correlated well with the MIC values for all antibiotics tested, indicating that the ribosomal mutations are causing the resistant phenotype.
Initial Treatment of Cancer Patients with Fluconazole-Susceptible Dose-Dependent Candida glabrata Fungemia: Better Outcome with an Echinocandin or Polyene Compared to an Azole?
Authors: Le Audrey , Farmakiotis Dimitrios , Tarrand Jeffrey J. , Kontoyiannis Dimitrios P. 
Published: June 2017

ABSTRACT

The 28-day crude mortality rate in 68 cancer patients with fluconazole-susceptible dose-dependent
Candida glabrata
fungemia started on treatment (within 48 h after blood culture collection) with an echinocandin or liposomal amphotericin-B was better (30%) than those treated with azole monotherapy (52%) (
P
= 0.07). After adjusting for confounders, azole monotherapy also was associated with worse 28-day survival (hazard ratio, 3.8;
P
= 0.003).
Genomic Analysis of Multidrug-Resistant Escherichia coli from North Carolina Community Hospitals: Ongoing Circulation of CTX-M-Producing ST131-
H
30Rx and ST131-
H
30R1 Strains
Authors: Kanamori Hajime , Parobek Christian M. , Juliano Jonathan J. , Johnson James R. , Johnston Brian D. , Johnson Timothy J. , Weber David J. , Rutala William A. , Anderson Deverick J. 
Published: June 2017

ABSTRACT

Escherichia coli
sequence type 131 (ST131) predominates globally among multidrug-resistant (MDR)
E. coli
strains. We used whole-genome sequencing (WGS) to investigate 63 MDR
E. coli
isolates from 7 North Carolina community hospitals (2010 to 2015). Of these, 39 (62%) represented ST131, including 37 (95%) from the ST131-
H
30R subclone: 10 (27%) from its
H
30R1 subset and 27 (69%) from its
H
30Rx subset. ST131 core genomes differed by a median of 15 (range, 0 to 490) single-nucleotide variants (SNVs) overall versus only 7 within
H
30R1 (range, 3 to 12 SNVs) and 11 within
H
30Rx (range, 0 to 21). The four isolates with identical core genomes were all
H
30Rx. Epidemiological and clinical characteristics did not vary significantly by strain type, but many patients with MDR
E. coli
or
H
30Rx infection were critically ill and had poor outcomes.
H
30Rx isolates characteristically exhibited fluoroquinolone resistance and CTX-M-15 production, had a high prevalence of trimethoprim-sulfamethoxazole resistance (89%),
sul1
(89%), and
dfrA17
(85%), and were enriched for specific virulence traits, and all qualified as extraintestinal pathogenic
E. coli
. The high overall prevalence of CTX-M-15 appeared to be possibly attributable to its association with the ST131-
H
30Rx subclone and IncF[F2:A1:B−] plasmids. Some phylogenetically clustered non-ST131 MDR
E. coli
isolates also had distinctive serotypes/
fimH
types, fluoroquinolone mutations, CTX-M variants, and IncF types. Thus, WGS analysis of our community hospital source MDR
E. coli
isolates suggested ongoing circulation and differentiation of
E. coli
ST131 subclones, with clonal segregation of CTX-M variants, other resistance genes, Inc-type plasmids, and virulence genes.
Micafungin Plasma Levels Are Not Affected by Continuous Renal Replacement Therapy: Experience in Critically Ill Patients
Authors: Vossen M. G. , Knafl D. , Haidinger M. , Lemmerer R. , Unger M. , Pferschy S. , Lamm W. , Maier-Salamon A. , Jäger W. , Thalhammer F. 
Published: June 2017

ABSTRACT

Critically ill patients often experience acute kidney injury and the need for renal replacement therapy in the course of their treatment in an intensive care unit (ICU). These patients are at an increased risk for candidiasis. Although there have been several reports of micafungin disposition during renal replacement therapy, to this date there are no data describing the elimination of micafungin during high-dose continuous venovenous hemodiafiltration with modified AN69 membranes. The aim of this prospective open-label pharmacokinetic study was to assess whether micafungin plasma levels are affected by continuous hemodiafiltration in critical ill patients using the commonly employed AN69 membrane. A total of 10 critically ill patients with micafungin treatment due to suspected or proven candidemia were included in this trial. Prefilter/postfilter micafungin clearance was measured to be 46.0 ml/min (±21.7 ml/min;
n
= 75 individual time points), while hemofilter clearance calculated by the sieving coefficient was 0.0038 ml/min (±0.002 ml/min;
n
= 75 individual time points). Total body clearance was measured to be 14.0 ml/min (±7.0 ml/min;
n
= 12). The population area under the curve from 0 to 24 h (AUC
0–24
) was calculated as 158.5 mg · h/liter (±79.5 mg · h/liter;
n
= 13). In spite of high protein binding, no dose modification is necessary in patients receiving continuous venovenous hemodiafiltration with AN69 membranes. A dose elevation may, however, be justified in certain cases. (This study has been registered at ClinicalTrials.gov under identifier NCT02651038.)
BosR Is A Novel Fur Family Member Responsive to Copper and Regulating Copper Homeostasis in Borrelia burgdorferi
Authors: Wang Peng , Yu Zhuoteng , Santangelo Thomas J. , Olesik John , Wang Yufeng , Heldwein Ekaterina , Li Xin 
Published: June 2017

ABSTRACT

The ferric uptake regulator (Fur) family of DNA-binding proteins represses and/or activates gene transcription via divalent metal ion-dependent signal sensing. The
Borrelia burgdorferi
Fur homologue, also known as
Borrelia
oxidative stress regulator (BosR), promotes spirochetal adaptation to the mammalian host by directly repressing the lipoproteins required for tick colonization and indirectly activating those required for establishing infection in the mammal. Here, we examined whether the DNA-binding activity of BosR was regulated by any of the four most prevalent transition metal ions in
B. burgdorferi
, Mn, Fe, Cu, and Zn. Our data indicated that in addition to a structural site occupied by Zn(II), BosR had two regulatory sites that could be occupied by Zn(II), Fe(II), or Cu(II) but not by Mn(II). While Fe(II) had no effect, Cu(II) and Zn(II) had a dose-dependent inhibitory effect on the BosR DNA-binding activity. Competition experiments indicated that Cu(II) had a higher affinity for BosR than Zn(II) or Fe(II). A BosR deficiency in
B. burgdorferi
resulted in a significant increase in the Cu level but no significant change in the levels of Mn, Fe, or Zn. These data suggest that Cu regulates BosR activity, and BosR in turn regulates Cu homeostasis in
B. burgdorferi
. While this regulatory paradigm is characteristic of the Fur family, BosR is the first one shown to be responsive to Cu(II), which may be an adaptation to the potentially high level of Cu present in the Lyme disease spirochete.

IMPORTANCE
Transition metal ions serve an essential role in the metabolism of all living organisms. Members of the ferric uptake regulator (Fur) family play critical roles in regulating the cellular homeostasis of transition metals in diverse bacteria, and their DNA-binding activity is often regulated by coordination of the cognate divalent metal ions. To date, regulators with metal ion specificity to Fe(II), Mn(II), Zn(II), and Ni(II) have all been described. In this study, we demonstrate that BosR, the sole Fur homologue in
Borrelia burgdorferi
, is responsive to Cu(II) and regulates Cu homeostasis in this bacterium, which may be an adaption to potentially Cu-rich milieu in the Lyme disease spirochete. This study has expanded the repertoire of the Fur family's metal ion specificity.
Abstract MIP-050: NON–CODING GENETIC ABERRATIONS IN HIGH GRADE SEROUS OVARIAN CANCER
Authors: Chaluvally–Raghavan Pradeep 
Published: June 2017

Abstract
BACKGROUND
The 3q26.2 loci amplification is present in a large proportion of high grade serous ovarian cancer (HGSOC) is less frequently curable disease in the clinic. The 3q26.2 loci, which is present in at least 35% of HGSOC, is large and structurally complex suggesting that multiple coding genes of the amplicon contribute to tumor initiation and progression either alone or through cooperative activity. Our high resolution SNP array mapping of 3q26.2 amplicon identified microRNAs miR569 and miR551b are highly amplified in addition to the coding genes in a large set of ovarian cancer samples. Potential role of miR569 and miR551b are not characterized previously in the context of ovarian cancer. Herein our studies provide new mechanisms underlying the oncogenic role of microRNAs amplified in 3q26 in ovarian cancer.
RESULTS
We demonstrated a strong correlation between 3q26.2 amplification and overexpression of miR569 in patient's samples of ovarian cancer. Using target based analysis, AGOCLIP methods, cellular and molecular approaches, we have demonstrated that 3q26 microRNAs altered the expression of TP53INP1, P53AIP1, and STAT3, which are critical regulators of survival and proliferation of ovarian cancer cells. Employing in silico and in vitro experiments, we have showed that miR569 directly targets and inhibited the expression of p53 induced tumor suppressor gene TP53INP1. miRNAs are thought to primarily downregulate the gene expression by binding 3'UTR of target genes. Our recent results identified a novel action of microRNAs, that miR551b can bind to the promoter of STAT3 and activate STAT3 transcription by recruiting transcription factors and RNA–Polymerase–II to the promoter. In sum, the discovery of miRNAs and lncRNAs as potent regulators of RNA stability and translation, dramatically changed our understanding of the mechanisms controlling the gene expression and protein levels. We are expecting that our studies will identify new biomarkers and novel targets for therapy.
Citation Format: Pradeep Chaluvally–Raghavan, PhD. NON–CODING GENETIC ABERRATIONS IN HIGH GRADE SEROUS OVARIAN CANCER [abstract]. In: Proceedings of the 11th Biennial Ovarian Cancer Research Symposium; Sep 12-13, 2016; Seattle, WA. Philadelphia (PA): AACR; Clin Cancer Res 2017;23(11 Suppl):Abstract nr MIP-050.
Abstract MIP-068: TUMOR–PROMOTING EFFECTS OF THE OVARIAN CANCER MUCIN, MUC16, ARE ASSOCIATED WITH SUPPRESSION OF INNATE IMMUNITY
Authors: Felder Mildred , Kapur Arvinder , Rakhmilevich Alexander L. , Qu Xiaoyi , Connor Joseph , Patankar Manish S. 
Published: June 2017

Abstract
The membrane-spanning mucin MUC16 promotes proliferation and metastasis of ovarian cancer cells. Here, we demonstrate that mice implanted with MUC16-knockdown human ovarian tumors show greater than two-fold increase in survival as compared to controls with tumors that express this mucin. While the lower survival of mice bearing MUC16-positive tumors is reportedly attributable to the ability of MUC16 to increase proliferation and metastasis, we also show that murine NK cells and macrophages are more efficient at lysing MUC16-knockdown cells. Macrophages showed infiltration in the MUC16-knockdown tumors but were restricted to the surrounding stroma in MUC16-positive tumors. In vitro cytotoxicity assays with NK cells and macrophages isolated from mice stimulated with agonistic anti-CD40 antibody showed 2-3-fold increased activity against the MUC16-knockdown cells as compared to matching target cells expressing this mucin. Finally, knockdown of MUC16 increased the susceptibility of cancer cells to ADCC and lysis by KS-IL2, an immunocytokine investigated as a treatment for ovarian cancer. Collectively our results support a role for MUC16 in promoting tumor growth. The ability of murine innate cells to selectively target MUC16-knockdown cells indicates that in vivo experiments investigating the biology of this mucin should be interpreted taking into account its immunomodulating activity as well as its growth promoting properties.
Citation Format: Mildred Felder, Arvinder Kapur, Alexander L. Rakhmilevich, Xiaoyi Qu2, Joseph Connor, and Manish S. Patankar. TUMOR–PROMOTING EFFECTS OF THE OVARIAN CANCER MUCIN, MUC16, ARE ASSOCIATED WITH SUPPRESSION OF INNATE IMMUNITY [abstract]. In: Proceedings of the 11th Biennial Ovarian Cancer Research Symposium; Sep 12-13, 2016; Seattle, WA. Philadelphia (PA): AACR; Clin Cancer Res 2017;23(11 Suppl):Abstract nr MIP-068.