bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cost-effectiveness of a stepwise intervention to promote adherence to cervical cancer screening
Authors: Firmino-Machado João , Soeteman Djøra I , Lunet Nuno 
Published: November 2019

Abstract

Background
Cervical cancer screening is effective in reducing mortality, but adherence is generally low. We aimed to investigate the cost-effectiveness of a stepwise intervention to promote adherence to cervical cancer screening in Portugal.

Methods
We developed a decision tree model to compare the cost-effectiveness of four competing interventions to increase adherence to cervical cancer screening: (i) a written letter (standard-of-care); (ii) automated short message service text messages (SMS)/phone calls/reminders; (iii) automated SMS/phone calls/reminders + manual phone calls; (iv) automated SMS/phone calls/reminders + manual phone calls + face-to-face interviews. The main outcome measure was cost per quality-adjusted life year (QALY) measured over a 5-year time horizon. Costs were calculated from the societal and provider perspectives.

Results
From the societal perspective, the optimal strategy was automated SMS/phone calls/reminders, below a threshold of €8171 per QALY; above this and below €180 878 per QALY, the most cost-effective strategy was automated SMS/phone calls/reminders + manual phone calls and above this value automated SMS/phone calls/reminders + manual phone calls + face-to-face interviews. From the provider perspective, the ranking of the three strategies in terms of cost-effectiveness was the same, for thresholds of €2756 and €175 463 per QALY, respectively.

Conclusions
Assuming a willingness-to-pay threshold of one time the national gross domestic product (€22 398/QALY), automated SMS/phone calls/reminders + manual phone calls is a cost-effective strategy to promote adherence to cervical cancer screening, both from the societal and provider perspectives.
Inactivation of human norovirus and its surrogate by the disinfectant consisting of calcium hydrogen carbonate mesoscopic crystals
Authors: Shimakura Hidekatsu , Gen-Nagata Fumihiro , Haritani Makoto , Furusaki Koichi , Kato Yusei , Yamashita-Kawanishi Nanako , LE Dung T , Tsuzuki Masano , Tohya Yukinobu , Kyuwa Shigeru , Saito Hiroyuki , Horimoto Taisuke , Onodera Takashi , Haga Takeshi 
Published: November 2019

ABSTRACT
Human norovirus is one of the major causes of foodborne gastroenteritis, and it can be easily transmitted from infected person, virus-contaminated foods and environmental surfaces. Effective disinfection method is needed to stop the transmission of human norovirus. CAC-717 is a new disinfectant consisting of calcium hydrogen carbonate mesoscopic crystals. We aimed to evaluate the efficacy of CAC-717 against human norovirus. This study used human norovirus derived from fecal specimens and cultured murine norovirus, which is one of the surrogate viruses for human norovirus. The disinfection effect against murine norovirus was estimated by infectivity assay and transmission electron microscopy. The inactivation effect against human norovirus was assessed by reverse transcription polymerase chain reaction. Disinfection effect of CAC-717 against the infectivity of murine norovirus was shown within 100 s after the CAC-717 treatment, presenting the destruction of viral capsids. The treatment of CAC-717 significantly reduced human norovirus genomic RNA (3.25-log reduction) by the presence of the mesoscopic structure of calcium hydrogen carbonate. CAC-717 stably inactivated human norovirus in stool suspensions. The inactivation effect of CAC-717 against human norovirus was less susceptible to organic substances than sodium hypochlorite. CAC-717 would be a useful alternative for disinfecting human norovirus in contaminated environmental surfaces.
Population structure and toxin gene profiles of Bacillus cereus sensu lato isolated from flour products
Authors: Kindle Patrick , Etter Danai , Stephan Roger , Johler Sophia 
Published: November 2019

ABSTRACT
Data on the occurrence, population structure and toxinogenic potential of Bacillus cereus sensu lato isolated from flour is essential to enable improved risk assessment. We aimed to provide data on the occurrence of B. cereus sensu lato in flour products at retail level. In addition, we screened the isolates for Bacillus thuringiensis and Bacillus cytotoxicus and determined population structure and toxin gene profiles. We screened 89 flour products for presence of B. cereus sensu lato, resulting in 75 positive samples (84%). We were able to show that the population structure of members of the B. cereus group isolated from flour is highly diverse. Isolates were assigned to panC types II (4%), III (21%), IV (39%) and V (36%). Production of parasporal crystals characteristic for Bacillus thuringiensis was detected in seven isolates assigned to panC type III, IV and V. No B. cytotoxicus were detected. Two of the isolates harbored ces encoding cereulide, which causes the emetic syndrome. Various enterotoxin genes were found, with all isolates harboring nhe, 75% of isolates harboring hbl and 51% of the isolates harboring cytK-2. Our findings suggest that toxinogenic B. cereus sensu lato are common in flour products at retail level.
Recurrent pregnancy loss: diagnostic workup after two or three pregnancy losses? A systematic review of the literature and meta-analysis
Authors: van Dijk Myrthe M , Kolte Astrid M , Limpens Jacqueline , Kirk Emma , Quenby Siobhan , van Wely Madelon , Goddijn Mariëtte 
Published: November 2019

Abstract

BACKGROUND
Recurrent pregnancy loss (RPL) occurs in 1–3% of all couples trying to conceive. No consensus exists regarding when to perform testing for risk factors in couples with RPL. Some guidelines recommend testing if a patient has had two pregnancy losses whereas others advise to test after three losses.

OBJECTIVE AND RATIONALE
The aim of this systematic review was to evaluate the current evidence on the prevalence of abnormal test results for RPL amongst patients with two versus three or more pregnancy losses. We also aimed to contribute to the debate regarding whether the investigations for RPL should take place after two or three or more pregnancy losses.

SEARCH METHODS
Relevant studies were identified by a systematic search in OVID Medline and EMBASE from inception to March 2019. A search for RPL was combined with a broad search for terms indicative of number of pregnancy losses, screening/testing for pregnancy loss or the prevalence of known risk factors. Meta-analyses were performed in case of adequate clinical and statistical homogeneity. The quality of the studies was assessed using the Newcastle-Ottawa scale.

OUTCOMES
From a total of 1985 identified publications, 21 were included in this systematic review and 19 were suitable for meta-analyses. For uterine abnormalities (seven studies, odds ratio (OR) 1.00, 95% CI 0.79–1.27, I2 = 0%) and for antiphospholipid syndrome (three studies, OR 1.04, 95% CI 0.86–1.25, I2 = 0%) we found low quality evidence for a lack of a difference in prevalence of abnormal test results between couples with two versus three or more pregnancy losses. We found insufficient evidence of a difference in prevalence of abnormal test results between couples with two versus three or more pregnancy losses for chromosomal abnormalities (10 studies, OR 0.78, 95% CI 0.55–1.10), inherited thrombophilia (five studies) and thyroid disorders (two studies, OR 0.52, 95% CI: 0.06–4.56).

WIDER IMPLICATIONS
A difference in prevalence in uterine abnormalities and antiphospholipid syndrome is unlikely in women with two versus three pregnancy losses. We cannot exclude a difference in prevalence of chromosomal abnormalities, inherited thrombophilia and thyroid disorders following testing after two versus three pregnancy losses. The results of this systematic review may support investigations after two pregnancy losses in couples with RPL, but it should be stressed that additional studies of the prognostic value of test results used in the RPL population are urgently needed. An evidenced-based treatment is not currently available in the majority of cases when abnormal test results are present.
Relationship Between Census Tract–Level Poverty and Domestically Acquired Salmonella Incidence: Analysis of Foodborne Diseases Active Surveillance Network Data, 2010–2016
Authors: Hadler James L , Clogher Paula , Libby Tanya , Wilson Elisha , Oosmanally Nadine , Ryan Patricia , Magnuson Luke , Lathrop Sarah , Mcguire Suzanne , Cieslak Paul , Fankhauser Melissa , Ray Logan , Geissler Aimee , Hurd Sharon 
Published: November 2019

Abstract

Background
The relationships between socioeconomic status and domestically acquired salmonellosis and leading Salmonella serotypes are poorly understood.

Methods
We analyzed surveillance data from laboratory-confirmed cases of salmonellosis from 2010–2016 for all 10 Foodborne Disease Active Surveillance Network (FoodNet) sites, having a catchment population of 47.9 million. Case residential data were geocoded, linked to census tract poverty level, and then categorized into 4 groups according to census tract poverty level. After excluding those reporting international travel before illness onset, age-specific and age-adjusted salmonellosis incidence rates were calculated for each census tract poverty level, overall and for each of the 10 leading serotypes.

Results
Of 52 821geocodable Salmonella infections (&gt;96%), 48 111 (91.1%) were domestically acquired. Higher age-adjusted incidence occurred with higher census tract poverty level (P &lt; .001; relative risk for highest [≥20%] vs lowest [&lt;5%] census tract poverty level, 1.37). Children &lt;5 years old had the highest relative risk (2.07). Although this relationship was consistent by race/ethnicity and by serotype, it was not present in 5 FoodNet sites or among those aged 18–49 years.

Conclusion
Children and older adults living in higher-poverty census tracts have had a higher incidence of domestically acquired salmonellosis. There is a need to understand socioeconomic status differences for risk factors for domestically acquired salmonellosis by age group and FoodNet site to help focus prevention efforts.
Evaluation of phthalazinone phosphodiesterase inhibitors with improved activity and selectivity against Trypanosoma cruzi
Authors: De Araújo Julianna Siciliano , da Silva Patrícia Bernardino , Batista Marcos Meuser , Peres Raiza Brandão , Cardoso-Santos Camila , Kalejaiye Titilola D , Munday Jane C , De Heuvel Erik , Sterk Geert Jan , Augustyns Koen , Salado Irene G , Matheeussen An , De Esch Iwan , De Koning Harry P , Leurs Rob , Maes Louis , Soeiro Maria de Nazaré Correia 
Published: November 2019

Abstract

Background
Chagas’ disease, caused by the protozoan parasite Trypanosoma cruzi, needs urgent alternative therapeutic options as the treatments currently available display severe limitations, mainly related to efficacy and toxicity.

Objectives
As phosphodiesterases (PDEs) have been claimed as novel targets against T. cruzi, our aim was to evaluate the biological aspects of 12 new phthalazinone PDE inhibitors against different T. cruzi strains and parasite forms relevant for human infection.

Methods
In vitro trypanocidal activity of the inhibitors was assessed alone and in combination with benznidazole. Their effects on parasite ultrastructural and cAMP levels were determined. PDE mRNA levels from the different T. cruzi forms were measured by quantitative reverse transcription PCR.

Results
Five TcrPDEs were found to be expressed in all parasite stages. Four compounds displayed strong effects against intracellular amastigotes. Against bloodstream trypomastigotes (BTs), three were at least as potent as benznidazole. In vitro combination therapy with one of the most active inhibitors on both parasite forms (NPD-040) plus benznidazole demonstrated a quite synergistic profile (xΣ FICI = 0.58) against intracellular amastigotes but no interaction (xΣ FICI = 1.27) when BTs were assayed. BTs treated with NPD-040 presented disrupted Golgi apparatus, a swollen flagellar pocket and signs of autophagy. cAMP measurements of untreated parasites showed that amastigotes have higher ability to efflux this second messenger than BTs. NPD-001 and NPD-040 increase the intracellular cAMP content in both BTs and amastigotes, which is also released into the extracellular milieu.

Conclusions
The findings demonstrate the potential of PDE inhibitors as anti-T. cruzi drug candidates.
A preconditioned technique for SH- and Love-wave full-waveform inversion in time domain and crosstalk analysis
Authors: Yan Yingwei , Wang Zhejiang , Li Jing , Huai Nan , Zhang Yujia , Han Fei 
Published: November 2019

AbstractFor the problem of low horizontal resolution in the method of surface wave dispersion analysis, we apply the SH- and Love-wave full-waveforms to achieve 2D and 3D imaging of the subsurface. The gradient obtained by classical full-waveform inversion (FWI) is not scaled with increasing depth. The limited source frequency band, the non-uniform coverage between shot and geophone positions and double scattering are the main reasons for the phenomenon. The Hessian operator of the misfit function can clearly predict the inherent defocusing phenomenon and the artefacts generated by the double scattering in the gradient vector, and the inverse Hessian operator is used as a deconvolution operator to realise gradient preconditioning. We present an expression of the quasi-Hessian operator in SH- and Love-wave FWI based on inverse scattering theory in prestack depth migration, and apply a new preconditioned technique to the fault and large contrast (LC) model reconstruction test. The inverted results show that the new preconditioned technique can greatly improve the imaging accuracy compared with the gradient-based methods of FWI. From single-parameter tests, we can conclude that the quasi-Hessian operator plays roles in illumination compensation and parameter complement estimation in FWI. From the final reconstructed results of a dual-parameter model, we find that the inverted result of the density is slightly closer to the true model than S-wave velocity under the condition of the same comparative distance between the initial and true model, but parametric crosstalk of density is more serious.
Efficient induction of haploid plants in wheat by editing of TaMTL using an optimized Agrobacterium-mediated CRISPR system
Authors: Liu Huiyun , Wang Ke , Jia Zimiao , Gong Qiang , Lin Zhishan , Du Lipu , Pei Xinwu , Ye Xingguo 
Published: November 2019

Abstract
The use of CRISPR/LbCpf1 and CRISPR/xCas9 systems in wheat have not yet been reported. In this study, we compared the efficiencies of three CRISPR editing systems (SpCas9, LbCpf1, and xCas9), and three different promoters (OsU6a, TaU3, and TaU6) that drive single-guide (sg)RNA, which were introduced into wheat via Agrobacterium-mediated transformation. The results indicated that TaU3 was a better choice than OsU6a or TaU6. The editing efficiency was higher using two sgRNAs than one sgRNA, and mutants with a large fragment deletion between the two sgRNAs were produced. The LbCpf1 and xCas9 systems could both be used successfully. Two endogenous genes, TaWaxy and TaMTL, were edited with high efficiency by the optimized SpCas9 system, with the highest efficiency (80.5%) being achieved when using TaU3 and two sgRNAs to target TaWaxy. Rates of seed set in the TaMTL-edited T0 transgenic plants were much lower than that of the wild-type. A haploid induction rate of 18.9% was found in the TaMTL-edited T1 plants using the CRISPR/SpCas9 system. Mutants with reverse insertion of the deleted sequences of TaMTL and TaWaxy between the two sgRNAs were identified in the edited T0 plants. In addition, wheat grains lacking embryos or endosperms were observed in the TaMTL-edited T1 generation.
Deciphering the nature of the pulsar wind nebula CTB 87 with XMM–Newton
Authors: Guest B , Safi-Harb S , MacMaster A , Kothes R , Olmi B , Amato E , Bucciantini N , Arzoumanian Z 
Published: November 2019

ABSTRACT
CTB 87 (G74.9+1.2) is an evolved supernova remnant (SNR) which hosts a peculiar pulsar wind nebula (PWN). The X-ray peak is offset from that observed in radio and lies towards the edge of the radio nebula. The putative pulsar, CXOU J201609.2+371110, was first resolved with Chandra and is surrounded by a compact and a more extended X-ray nebula. Here, we use a deep XMM–Newton observation to examine the morphology and evolutionary stage of the PWN and to search for thermal emission expected from a supernova shell or reverse shock interaction with supernova ejecta. We do not find evidence of thermal X-ray emission from the SNR and place an upper limit on the electron density of 0.05 cm−3 for a plasma temperature kT ∼ 0.8 keV. The morphology and spectral properties are consistent with a ∼20-kyr-old relic PWN expanding into a stellar wind-blown bubble. We also present the first X-ray spectral index map from the PWN and show that we can reproduce its morphology by means of 2D axisymmetric relativistic hydrodynamical simulations.
PRMT1-mediated methylation of the microprocessor-associated proteins regulates microRNA biogenesis
Authors: Spadotto Valeria , Giambruno Roberto , Massignani Enrico , Mihailovich Marija , Maniaci Marianna , Patuzzo Francesca , Ghini Francesco , Nicassio Francesco , Bonaldi Tiziana 
Published: November 2019

AbstractMicroRNA (miRNA) biogenesis is a tightly controlled multi-step process operated in the nucleus by the activity of the Microprocessor and its associated proteins. Through high resolution mass spectrometry (MS)- proteomics we discovered that this complex is extensively methylated, with 84 methylated sites associated to 19 out of its 24 subunits. The majority of the modifications occurs on arginine (R) residues (61), leading to 81 methylation events, while 30 lysine (K)-methylation events occurs on 23 sites of the complex. Interestingly, both depletion and pharmacological inhibition of the Type-I Protein Arginine Methyltransferases (PRMTs) lead to a widespread change in the methylation state of the complex and induce global decrease of miRNA expression, as a consequence of the impairment of the pri-to-pre-miRNA processing step. In particular, we show that the reduced methylation of the Microprocessor subunit ILF3 is linked to its diminished binding to the pri-miRNAs miR-15a/16, miR-17–92, miR-301a and miR-331. Our study uncovers a previously uncharacterized role of R-methylation in the regulation of miRNA biogenesis in mammalian cells.
ATIM-48 (LTBK-05). MULTIDIMENSIONAL PERSONALIZED RESPONSE ASSESSMENT TO MICROGLIA MODULATORS IN GLIOBLASTOMA BIOREACTORS
Authors: Shekarian Tala , Wachnowicz Anna Theresa , Flammer Julia , Paganetti Chiara , Martins Tomas , Muraro Manuele , Schürch Christian Martijn , Hutter Gregor 
Published: November 2019

Abstract

BACKGROUND
Recently, strategies harnessing the non-neoplastic immune tumor microenvironment (iTME), consisting of macrophages and microglia (TAMs), as well as adaptive immune cells have been employed to treat glioblastoma (GBM). To evaluate the effect of local TAM-modulating therapies in combination with T-cell checkpoint inhibitors, we generated 3D GBM perfusion bioreactor cultures from patient-derived samples. We report patient- and tumor region specific responses to microglia modulators and checkpoint inhibitors using multidimensional fluorescent microscopy techniques, and multiplexed cytokine measurements, Subsequently, we aime at identifying responders versus non-responders as well as predictive markers of treatment response.

METHODS
Fresh, neuronavigated GBM biopsies from tumor center and periphery were placed into perfusion bioreactors and cultured for 7 days. Explants were treated with combinations of TAM and T-cell modulating drugs including anti-PD1 and anti-CD47 antibodies and their combination. Tissue was harvested for histology, and supernatants were processed for multiplexed cytokine analysis. Multidimensional CODEX technology analysis using a customized TAM centric 54 marker panel was implemented, and a map of individualized response criteria to specific immunotherapies developed.

RESULTS
Multiplex cytokine analysis showed a dominance of proinflammatory cytokines (CCL2, CCL3, CCL4 and PAI-1) in the periphery of the tumor at baseline. We further observed that the tumor periphery was more responsive to treatments confirming the efficacy of the treatment after tumor resection. Using CODEX, we identified specific cell types responding to the treatment and undergoing phenotypic changes. Moreover, dynamic shifting of T-cell checkpoint expression levels under treatment pointed to potential resistance mechanisms in a subset of tumors. Further, we identified region-specific cytokine release as a response to the treatment in a series of 8 patient-specific explant cultures. In summary, we present an in-depth profiling of the GBM-region specific iTME at baseline and document its dynamic response under innate/adaptive immune modulators using CODEX.

CONCLUSION
The proposed approach serves as a patient-tailored ex vivo “Clinical Trial” by stratifying the individual patient’s iTME response.
Using Latent Class Analysis to Examine Susceptibility to Various Tobacco Products Among Adolescents
Authors: Bold Krysten W , Buta Eugenia , Simon Patricia , Kong Grace , Morean Meghan , Camenga Deepa , Krishnan-Sarin Suchitra 
Published: November 2019

Abstract

Introduction
Most tobacco use is initiated during adolescence and susceptibility is an important predictor of initiation. Research is needed to understand susceptibility across tobacco products among youth to inform prevention efforts.

Aims and Methods
We surveyed 2945 students from four Southeastern Connecticut high schools in 2017. We assessed susceptibility to future use of seven different tobacco products (ie, cigarettes, e-cigarettes, hookah, cigars, cigarillos, blunts, and smokeless tobacco) among youth who had never used a tobacco product. Susceptibility was coded as any response other than “definitely not” to three items assessing (1) curiosity, (2) willingness to experiment with the product in the future, and (3) willingness to try if offered by a friend. Latent class analysis was used to identify patterns of susceptibility across multiple tobacco products and sociodemographic predictors of these classes.

Results
Among n = 1246 youth who had never tried a tobacco product, 51.2% (n = 638) were susceptible to at least one product and 29.1% (n = 363) were susceptible to two or more products (average among susceptible youth: M = 2.4 products, SD = 1.7, range 1–7). Latent class analysis identified three classes: youth who were: (1) susceptible to all products (5.6%), (2) susceptible to e-cigarettes, hookah, and blunts (23.6%), and (3) mostly non-susceptible to all products (70.8%). In a multivariable model, demographic variables and peer tobacco use predicted class membership.

Conclusions
We observed high rates of susceptibility to non-traditional tobacco products among youth, and many youth were susceptible to more than one product. Targeting susceptibility across multiple tobacco products may be important for reducing youth tobacco use.

Implications
Patterns of polytobacco use susceptibility were identified among youth who had never previously used tobacco products. Many youth were susceptible to more than one product and we observed three distinct classes of susceptibility among youth: those who were mostly non-susceptible, those who were susceptible to alternative or non-traditional tobacco products (e-cigarettes, hookah, and blunts), and those who were susceptible to all tobacco products. These findings suggest the importance of addressing susceptibility across multiple tobacco products.