bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Opp (AmiACDEF) Oligopeptide Transporter Mediates Resistance of Serotype 2 Streptococcus pneumoniae D39 to Killing by Chemokine CXCL10 and Other Antimicrobial Peptides
Authors: Bruce Kevin E. , Rued Britta E. , Tsui Ho-Ching Tiffany , Winkler Malcolm E. 
Published: March 2018

ABSTRACT

Antimicrobial peptides (AMPs), including chemokines, are produced during infections to kill pathogenic bacteria. To fill in gaps in knowledge about the sensitivities of
Streptococcus pneumoniae
and related
Streptococcus
species to chemokines and AMPs, we performed a systematic, quantitative study of inhibition by chemokine CXCL10 and the AMPs LL-37 and nisin. In a standard Tris-glucose buffer (TGS), all strains assayed lacked metabolic activity, as determined by resazurin (alamarBlue) reduction, and were extremely sensitive to CXCL10 and AMPs (50% inhibitory concentration [IC
50
], ∼0.04 μM). In TGS, changes in sensitivities caused by mutations were undetectable. In contrast, strains that retained reductive metabolic activity in a different assay buffer (NPB [10 mM sodium phosphate {pH 7.4}, 1% {vol/vol} brain heart infusion {BHI} broth]) were less sensitive to CXCL10 and AMPs than in TGS. In NPB, mutants known to respond to AMPs, such as Δ
dlt
mutants lacking
d
-alanylation of teichoic acids, exhibited the expected increased sensitivity.
S. pneumoniae
serotype 2 strain D39 was much (∼10-fold) less sensitive to CXCL10 killing in NPB than serotype 4 strain TIGR4, and the sensitivity of TIGR4 was unaffected by the absence of capsule. Candidate screening of strain D39 revealed that mutants lacking Opp (Δ
amiACDEF
) oligopeptide permease were significantly more resistant to CXCL10 than the wild-type strain. This increased resistance could indicate that Opp is a target for CXCL10 binding or that it transports CXCL10 into cells. Finally, Δ
ftsX
or Δ
ftsE
mutants of
Bacillus subtilis
or amino acid changes that interfere with FtsX function in
S. pneumoniae
did not impart resistance to CXCL10, in contrast to previous results for
Bacillus anthracis
, indicating that FtsX is not a general target for CXCL10 binding.

IMPORTANCE
S. pneumoniae
(pneumococcus) is a human commensal bacterium and major opportunistic respiratory pathogen that causes serious invasive diseases, killing millions of people worldwide annually. Because of its increasing antibiotic resistance,
S. pneumoniae
is now listed as a “superbug” for which new antibiotics are urgently needed. This report fills in knowledge gaps and resolves inconsistencies in the scientific literature about the sensitivity of
S. pneumoniae
and related
Streptococcus
pathogens to chemokines and AMPs. It also reveals a new mechanism by which
S. pneumoniae
can acquire resistance to chemokine CXCL10. This mechanism involves the Opp (AmiACDEF) oligopeptide transporter, which plays additional pleiotropic roles in pneumococcal physiology, quorum sensing, and virulence. Taking the results together, this work provides new information about the way chemokines kill pneumococcal cells.
Dynamics of paediatric urogenital schistosome infection, morbidity and treatment: a longitudinal study among preschool children in Zimbabwe
Authors: Osakunor Derick Nii Mensah , Mduluza Takafira , Midzi Nicholas , Chase-Topping Margo , Mutsaka-Makuvaza Masceline Jenipher , Chimponda Theresa , Eyoh Enwono , Mduluza Tariro , Pfavayi Lorraine Tsitsi , Wami Welcome Mkululi , Amanfo Seth Appiah , Murray Janice , Tshuma Clement , Woolhouse Mark Edward John , Mutapi Francisca 
Published: March 2018

BackgroundRecent research has shown that in schistosome-endemic areas preschool-aged children (PSAC), that is, ≤5 years, are at risk of infection. However, there exists a knowledge gap on the dynamics of infection and morbidity in this age group. In this study, we determined the incidence and dynamics of the first urogenital schistosome infections, morbidity and treatment in PSAC.MethodsChildren (6 months to 5 years) were recruited and followed up for 12 months. Baseline demographics, anthropometric and parasitology data were collected from 1502 children. Urinary morbidity was assessed by haematuria and growth-related morbidity was assessed using standard WHO anthropometric indices. Children negative forSchistosoma haematobiuminfection were followed up quarterly to determine infection and morbidity incidence.ResultsAt baseline, the prevalence ofS haematobiuminfection and microhaematuria was 8.5% and 8.6%, respectively. Based on different anthropometric indices, 2.2%–8.2% of children were malnourished, 10.1% underweight and 18.0% stunted. The fraction of morbidity attributable to schistosome infection was 92% for microhaematuria, 38% for stunting and malnutrition at 9%–34%, depending on indices used.S haematobium-positive children were at greater odds of presenting with microhaematuria (adjusted OR (AOR)=25.6; 95% CI 14.5 to 45.1) and stunting (AOR=1.7; 95% CI 1.1 to 2.7). Annual incidence ofS haematobiuminfection and microhaematuria was 17.4% and 20.4%, respectively. Microhaematuria occurred within 3 months of first infection and resolved in a significant number of children, 12 weeks post-praziquantel treatment, from 42.3% to 10.3%; P<0.001.ConclusionWe demonstrated for the first time the incidence of schistosome infection in PSAC, along with microhaematuria, which appears within 3 months of first infection and resolves after praziquantel treatment. A proportion of stunting and malnutrition is attributable toS haematobiuminfection. The study adds scientific evidence to the calls for inclusion of PSAC in schistosome control programmes.
Interagency collaboration models for people with mental ill health in contact with the police: a systematic scoping review
Authors: Parker Adwoa , Scantlebury Arabella , Booth Alison , MacBryde Jillian Catherine , Scott William J , Wright Kath , McDaid Catriona 
Published: March 2018

ObjectiveTo identify existing evidence on interagency collaboration between law enforcement, emergency services, statutory services and third sector agencies regarding people with mental ill health.DesignSystematic scoping review. Scoping reviews map particular research areas to identify research gaps.Data sources and eligibilityASSIA, CENTRAL, the Cochrane Library databases, Criminal Justice Abstracts, ERIC, Embase, MEDLINE, PsycINFO, PROSPERO and Social Care Online and Social Sciences Citation Index were searched up to 2017, as were grey literature and hand searches. Eligible articles were empirical evaluations or descriptions of models of interagency collaboration between the police and other agencies.Study appraisal and synthesisScreening and data extraction were undertaken independently by two researchers. Arksey’s framework was used to collate and map included studies.ResultsOne hundred and twenty-five studies were included. The majority of articles were of descriptions of models (28%), mixed methods evaluations of models (18%) and single service evaluations (14%). The most frequently reported outcomes (52%) were ‘organisational or service level outcomes’ (eg, arrest rates). Most articles (53%) focused on adults with mental ill health, whereas others focused on adult offenders with mental ill health (17.4%). Thirteen models of interagency collaboration were described, each involving between 2 and 13 agencies. Frequently reported models were ‘prearrest diversion’ of people with mental ill health (34%), ‘coresponse’ involving joint response by police officers paired with mental health professionals (28.6%) and ‘jail diversion’ following arrest (23.8%).ConclusionsWe identified 13 different interagency collaboration models catering for a range of mental health-related interactions. All but one of these models involved the police and mental health services or professionals. Several models have sufficient literature to warrant full systematic reviews of their effectiveness, whereas others need robust evaluation, by randomised controlled trial where appropriate. Future evaluations should focus on health-related outcomes and the impact on key stakeholders.
Prognostic value of Ki67 analysed by cytology or histology in primary breast cancer
Authors: Robertson Stephanie , Stålhammar Gustav , Darai-Ramqvist Eva , Rantalainen Mattias , Tobin Nicholas P , Bergh Jonas , Hartman Johan 
Published: March 2018

AimsThe accuracy of biomarker assessment in breast pathology is vital for therapy decisions. The therapy predictive and prognostic biomarkers oestrogen receptor (ER), progesterone receptor, HER2 and Ki67 may act as surrogates to gene expression profiling of breast cancer. The aims of this study were to investigate the concordance of consecutive biomarker assessment by immunocytochemistry on preoperative fine-needle aspiration cytology versus immunohistochemistry (IHC) on the corresponding resected breast tumours. Further, to investigate the concordance with molecular subtype and correlation to stage and outcome.MethodsTwo retrospective cohorts comprising 385 breast tumours with clinicopathological data including gene expression-based subtype and up to 10-year overall survival data were evaluated.ResultsIn both cohorts, we identified a substantial variation in Ki67 index between cytology and histology and a switch between low and high proliferation within the same tumour in 121/360 cases. ER evaluations were discordant in only 1.5% of the tumours. From cohort 2, gene expression data with PAM50 subtype were used to correlate surrogate subtypes. IHC-based surrogate classification could identify the correct molecular subtype in 60% and 64% of patients by cytology (n=63) and surgical resections (n=73), respectively. Furthermore, high Ki67 in surgical resections but not in cytology was associated with poor overall survival and higher probability for axillary lymph node metastasis.ConclusionsThis study shows considerable differences in the prognostic value of Ki67 but not ER in breast cancer depending on the diagnostic method. Furthermore, our findings show that both methods are insufficient in predicting true molecular subtypes.
Educational attainment of children born to mothers with epilepsy
Authors: Lacey Arron S , Pickrell William Owen , Thomas Rhys H , Kerr Mike P , White Cathy P , Rees Mark I 
Published: March 2018

ObjectiveSmall prospective studies have identified that children exposed to valproate in utero have poorer scores on cognitive testing. We wanted to identify whether children exposed to antiepileptic drugs (AEDs) in utero have poorer school performance.MethodsWe used anonymised, linked, routinely collected healthcare records to identify children born to mothers with epilepsy. We linked these children to their national attainment Key Stage 1 (KS1) tests in mathematics, language and science at the age of 7 and compared them with matched children born to mothers without epilepsy, and with the national KS1 results. We used the core subject indicator (CSI) as an outcome measure (the proportion of children achieving a minimum standard in all subjects) and the results in individual subjects.ResultsWe identified 440 children born to mothers with epilepsy with available KS1 results. Compared with a matched control group, fewer children with mothers being prescribed sodium valproate during pregnancy achieved the national minimum standard in CSI (−12.7% less than the control group), mathematics (−12.1%), language (−10.4%) and in science (−12.2%). Even fewer children with mothers being prescribed multiple AEDs during pregnancy achieved a national minimum standard: CSI (by −20.7% less than the control group), mathematics (−21.9%), language (−19.3%) and science (−19.4%). We did not observe any significant difference in children whose mothers were prescribed carbamazepine or were not taking an AED when compared with the control group.ConclusionsIn utero exposure to AEDs in combination, or sodium valproate alone, is associated with a significant decrease in attainment in national educational tests for 7-year-old children compared with both a matched control group and the all-Wales national average. These results give further support to the cognitive and developmental effects of in utero exposure to sodium valproate as well as multiple AEDs, which should be balanced against the need for effective seizure control for women during pregnancy.
Single top partner production at lepton colliders in the left–right twin Higgs model
Authors: Jiang Xingyu , Han Jinzhong , Hou Biaofeng , Yu Chunxu 
Published: March 2018

In the framework of the left–right twin Higgs (LRTH) model, we investigate the single top partner production at lepton colliders. We calculate the production cross-sections of the processes [Formula: see text], [Formula: see text] [Formula: see text] and [Formula: see text] [Formula: see text] at [Formula: see text] TeV, and display some typical differential distributions of the final state particles.
MONETARY POLICY TRANSMISSION IN A MACROECONOMIC AGENT-BASED MODEL
Authors: SCHASFOORT JOERI , GODIN ANTOINE , BEZEMER DIRK , CAIANI ALESSANDRO , KINSELLA STEPHEN 
Published: March 2018

In this paper we explore the variety of monetary policy transmission channels in an agent-based macroeconomic model. We identify eight transmission channels and present a model based on [Caiani et al., J. Econ. Dyn. Contr. 69 (2016) 375–480], extended with an interbank market. We then analyze model simulation results of interest rate shocks in terms of GDP and inflation for four of the transmission channels. We find these effects to be small, in line with the view that monetary policy is a weak tool to control inflation.
Effectiveness of falls prevention intervention programme in community-dwelling older people in Thailand: Randomized controlled trial
Authors: Suttanon Plaiwan , Piriyaprasarth Pagamas , Krootnark Kitsana , Aranyavalai Thanyaporn 
Published: March 2018

Background: Although there is extensive research on falls prevention, most of this knowledge is from western countries, and this may limit its usefulness when implementing in countries with different culture and healthcare systems. Objective: This study evaluated the feasibility and effectiveness of a falls prevention intervention programme for older people in Thailand. Methods: Two hundred and seventy-seven community-dwelling older people were randomized to either an intervention programme which included an education about falls risk management plus a home-based balance exercise delivered by a physiotherapist for four-month duration or control group. Falls, balance, physical activity, and other falls risk factors were measured at baseline and after programme completion. Results: About 90% of the participants in the intervention group completed the programme, with very high adherence to the exercise programme, though poor compliance with the suggestions of other falls risks management. There were no falls or injuries related to the exercise programme reported. There was no significant difference in falls rate between the two groups. Conclusion: This falls prevention program was not effective in reducing falls in community-dwelling older people in Thailand. However, the study provided encouraging evidence that home-based balance exercise could be practically implemented in older people living in communities in Thailand.
Detecting Popular Temporal Modes in Population-scale Unlabelled Trajectory Data
Authors: Xu Fengli , Xia Tong , Cao Hancheng , Li Yong , Sun Funing , Meng Fanchao 
Published: March 2018

With the rapid process of urbanization, revealing the underlying mechanisms behind urban mobility has become a crucial research problem. The movements of urban dwellers are often constituted by their daily routines, and exhibit distinct and contextual temporal modes, i.e., the patterns of individuals allocating their time across different locations. In this paper, we investigate a novel problem of detecting popular temporal modes in population-scale unlabelled trajectory data. Our key finding is that the detected temporal modes capture the semantic feature of human's living style, and is able to unravel meaningful correlations between urban mobility and human behavior.
Specifically, we represent the temporal mode of a trajectory as a partition of the time duration, where the time slices associated with same locations are partitioned into same subsets. Such abstraction decouples the temporal modes from actual physical locations, and allows individuals with similar temporal modes yet completely different physical locations to have similar representations. Based on this insight, we propose a pipeline system composed of three components: 1) noise handler that eliminates the noises in the raw mobility records, 2) representation extractor for temporal modes, and 3) popular temporal modes detector. By applying our system on three real-world mobility datasets, we demonstrate that our system effectively detects the popular temporal modes embedded in population-scale mobility datasets, which is easy to be interpreted and can be justified through the associated PoIs and mobile applications usage. More importantly, our further experiments reveal insightful correlations between the popular temporal modes and individuals' social economic status, i.e. occupation information, which sheds light on the mechanisms behind urban mobility.
Improving CART-Cell Therapy of Solid Tumors with Oncolytic Virus–Driven Production of a Bispecific T-cell Engager
Authors: Wing Anna , Fajardo Carlos Alberto , Posey Avery D. , Shaw Carolyn , Da Tong , Young Regina M. , Alemany Ramon , June Carl H. , Guedan Sonia 
Published: March 2018

Abstract
T cells expressing chimeric antigen receptors (CART) have shown significant promise in clinical trials to treat hematologic malignancies, but their efficacy in solid tumors has been limited. Oncolytic viruses have the potential to act in synergy with immunotherapies due to their immunogenic oncolytic properties and the opportunity of incorporating therapeutic transgenes in their genomes. Here, we hypothesized that an oncolytic adenovirus armed with an EGFR-targeting, bispecific T-cell engager (OAd-BiTE) would improve the outcome of CART-cell therapy in solid tumors. We report that CART cells targeting the folate receptor alpha (FR-α) successfully infiltrated preestablished xenograft tumors but failed to induce complete responses, presumably due to the presence of antigen-negative cancer cells. We demonstrated that OAd-BiTE–mediated oncolysis significantly improved CART-cell activation and proliferation, while increasing cytokine production and cytotoxicity, and showed an in vitro favorable safety profile compared with EGFR-targeting CARTs. BiTEs secreted from infected cells redirected CART cells toward EGFR in the absence of FR-α, thereby addressing tumor heterogeneity. BiTE secretion also redirected CAR-negative, nonspecific T cells found in CART-cell preparations toward tumor cells. The combinatorial approach improved antitumor efficacy and prolonged survival in mouse models of cancer when compared with the monotherapies, and this was the result of an increased BiTE-mediated T-cell activation in tumors. Overall, these results demonstrated that the combination of a BiTE-expressing oncolytic virus with adoptive CART-cell therapy overcomes key limitations of CART cells and BiTEs as monotherapies in solid tumors and encourage its further evaluation in human trials. Cancer Immunol Res; 6(5); 605–16. ©2018 AACR.
Rapid Construction of Antitumor T-cell Receptor Vectors from Frozen Tumors for Engineered T-cell Therapy
Authors: Tsuji Takemasa , Yoneda Akira , Matsuzaki Junko , Miliotto Anthony , Ryan Courtney , Koya Richard C. , Odunsi Kunle 
Published: March 2018

AbstractT cells genetically engineered with tumor antigen–specific T-cell receptor (TCR) genes have demonstrated therapeutic potential in patients with solid tumors. In order to achieve broader application, an efficient method to identify TCR genes for an array of tumor antigens and HLA restriction elements is required. Here, we have developed a method to construct a TCR-expression library from specimens, including frozen tumor biopsies, that contain antigen-specific T cells. TCR-expressing cassettes were constructed and cloned in a retroviral plasmid vector within 24 hours by unbiased PCR amplification of TCR α and β chain variable regions assembled with TCR constant regions. The method was validated by constructing TCR-expressing vectors from tumor antigen–specific T-cell clones and functionally assessing TCR gene–transduced T cells. We applied this method to frozen ovarian tumor specimens that were infiltrated by tumor antigen–specific T cells. The tumor-derived TCR libraries were expressed in peripheral T cells from healthy volunteers and screened for tumor antigen–specific TCR pairs with the use of an MHC/peptide tetramer reagent. Tumor antigen–specific TCR-expressing transgenes were recovered from isolated tetramer-positive T cells. Peripheral T cells that were engineered with library-derived TCR gene showed potent therapeutic antitumor effect in a tumor xenograft model. Our method can efficiently and rapidly provide tumor-specific TCR-expressing viral vectors for the manufacture of therapeutic and personalized antitumor T-cell products. Cancer Immunol Res; 6(5); 594–604. ©2018 AACR.
Pregnancy Outcomes in French Hemodialysis Patients
Authors: Normand Gabrielle , Xu Xiaoli , Panaye Marine , Jolivot Anne , Lemoine Sandrine , Guebre-Egziabher Fitsum , Decullier Evelyne , Bin Sylvie , Doret Muriel , Juillard Laurent 
Published: March 2018

<b><i>Background:</i></b> Pregnancy in hemodialysis (HD) women is a rare event and often associated with maternal and fetal complications. Scarcity of available data from large cohorts impedes fair medical counseling. <b><i>Methods:</i></b> This is a descriptive, retrospective, multi-centric study. Pregnant women on HD during the period from 1985 to 2015 in France were included. The primary outcome was a living infant discharged from hospital, while secondary outcomes included gestational age and birth weight. <b><i>Results:</i></b> We identified 100 pregnancies in 84 women on HD, from 41 centers. Chronic HD was initiated during pregnancy for 17.7% (14/79) of patients explaining a 19.8% prevalence of catheter (19/96) and a preserved residual diuresis for 50% of pregnancy (43/86). Seventy-six (89.4%) women performed daily dialysis during the third trimester (6 times per week). Our primary outcome was met for 78% of newborns with a mean gestational age of 33.2 ± 3.9 weeks and a mean birth weight of 1,719 ± 730 g. <b><i>Conclusions:</i></b> Our study is one of the largest series of ­pregnancies in HD patients. Despite recent progresses, these pregnancies remain at high risk, reinforcing the need for an early nephrologist-obstetrician skilled team co-management.
A escrita na universidade: dificuldades na redação do vestibular e perspectivas para alunos do curso de Direito
Authors: Marquesi Sueli Cristina , Cabral Ana Lúcia Tinoco 
Published: March 2018

Neste artigo, refletimos sobre dificuldades de escrita de alunos ingressantes de uma universidade brasileira. A partir dos dados levantados em resultados de vestibular para curso de Direito e da análise de uma redação, propomos reflexões que orientam o trabalho de escrita na universidade, com vistas à superação das referidas dificuldades. Os procedimentos analíticos que adotamos conjugam noções de plano de texto (ADAM, 2011) e de contexto (VAN DIJK, 2012; 2016), bem como estudos sobre revisão de escrita (PINTO, 2015; HEURLEY, 2006). Para a discussão, recorremos a uma redação retirada de corpus constituído por redações de um processo seletivo de 2017 para o curso de Direito.