bluuebunny/crossref_metadata_2025_split huggingface dataset:
InvestigatingBordetella pertussiscolonisation and immunity: protocol for an inpatient controlled human infection model
Authors: de Graaf Hans , Gbesemete Diane , Gorringe Andrew R. , Diavatopoulos Dimitri A. , Kester Kent E. , Faust Saul N. , Read Robert C. 
Published: October 2017

IntroductionWe summarise an ethically approved protocol for the development of an experimental human challenge colonisation model. GloballyBordetella pertussisis one of the leading causes of vaccine-preventable death. Many countries have replaced whole cell vaccines with acellular vaccines over the last 20 years during which pertussis appears to be resurgent in a number of countries in the developed world that boast high immunisation coverage. The acellular vaccine provides relatively short-lived immunity and, in contrast to whole cell vaccines, may be less effective against colonisation and subsequent transmission. To improve vaccine strategies, a greater understanding of humanB. pertussiscolonisation is required. This article summarises a protocol and does not contain any results.Methods and analysisA controlled human colonisation model will be developed over two phases. In phase A, a low dose of the inoculum will be given intranasally to healthy participants. This dose will be escalated or de-escalated until colonisation is achieved in approximately 70% (95% CI 47% to 93%) of the exposed volunteers without causing disease. The colonisation period, shedding and exploratory immunology will be assessed during a 17-day inpatient stay and follow-up over 1 year. The dose of inoculum that achieves 70% colonisation will then be confirmed in phase B, comparing healthy participants exposed toB. pertussiswith a control group receiving a sham inoculum.Ethics and disseminationThis study has been approved by the ethical committee reference: 17/SC/0006, 24 February 2017. Findings will be published in peer-reviewed open access journals as soon as possible.
Descriptive study of female roller derby athletes' beliefs about risk factors for injury in roller derby
Authors: Cathorall Michelle L , Punches Megan 
Published: October 2017

ObjectivesTo examine skaters’ beliefs about risk factors related to roller derby injuries.DesignQualitative study based on semistructured focus group discussions with female roller derby skaters.MethodsSkaters with varying levels of experience and injury history were invited to participate in focus group discussions. Semistructured focus group discussions were based on the question ‘What factors do you believe contribute to roller derby injuries?’. Analysis of the data were organised into themes, summarised and interpreted, separated based on being an intrinsic or extrinsic factor and then reorganised by frequency of citation. Focus groups continued until no new themes were added to the data.ResultsThe factors discussed by derby skaters were divided into intrinsic and extrinsic factors. The most common intrinsic factors cited were behavioural and psychological, ‘knowing one’s body’ and internal pressure related to ‘not letting team down’. The most cited extrinsic factors were ‘unmatched skill level’ and ‘poor quality’ equipment.ConclusionsFemale roller derby skaters contribute the greatest injury risk to new skaters not knowing their body and experienced skaters not considering new skaters skill levels. Knowing the factors that skaters perceive as increasing injury risk may contribute to interventions to decrease the frequency and severity of injuries. New findings include behavioural, psychological and social factors related to injury risk. Important considerations for healthcare providers treating roller derby skaters include the psychological and social factors that affect injury.
Augmented 3D venous navigation for neuroendovascular procedures
Authors: Blanc Raphaël , Fahed Robert , Roux Pascal , Smajda Stanislas , Ciccio Gabriele , Desilles Jean-Philippe , Redjem Hocine , Mazighi Mikael , Baharvahdat Humain , Piotin Michel 
Published: October 2017

BackgroundEndovascular venous access is increasingly used for the treatment of many cerebrovascular diseases. The quality of venous roadmapping through arterial injection can be problematic because of contrast media dilution, slow flow velocity, and unilateral opacification of the venous system.ObjectiveTo describe our experience with the VesselNavigator (Philips Healthcare, Best, The Netherlands) in performing live 3D roadmapping for intracranial venous procedures.Material and methodsLive 3D roadmapping is an image-processing technique that allows dynamic roadmapping of vessels with immediate adaptation to the C-arm movements without the need for contrast injection. For this purpose, 3D MR venography is overlaid on live fluoroscopy images after semiautomatic coregistration. The technique was applied to cases of idiopathic venous stenosis and arteriovenous fistula.ResultsThe process of coregistration was performed by the principal operator in <5 min, just before the treatment. The accuracy was controlled peroperatively and was judged satisfactory. Three illustrative cases demonstrate the use of this software for venous navigation and pressure measurement (case 1), venous stenting (case 2), and transvenous embolization of a carotid-cavernous fistula (case 3).ConclusionOur preliminary experience suggests that it is a feasible and safe technique for intracranial venous navigation and procedures. The potential lowering of overall radiation dose and contrast media use needs to be verified with further studies.
Switching biological disease-modifying antirheumatic drugs in patients with axial spondyloarthritis: results from a systematic literature review
Authors: Navarro-Compán Victoria , Plasencia-Rodríguez Chamaida , de Miguel Eugenio , Diaz del Campo Petra , Balsa Alejandro , Gratacós Jordi 
Published: October 2017

ObjectivesFirst, to investigate if switching biological disease-modifying antirheumatic drugs (bDMARDs) after the failure to prior bDMARD is efficacious in patients with axial spondyloarthritis (axSpA). Second, to evaluate the influence on this efficacy of (1) the reason to discontinue prior tumour necrosis factor inhibitor (TNFi), (2) changing the type of TNFi and (3) changing the target.MethodsA systematic literature review until January 2017 was performed using Medline, EMBASE and Cochrane databases. Longitudinal studies assessing clinical response after switching bDMARDs in patients with axSpA were analysed.ResultsIn total, 9 studies out of 1862 retrieved citations were included. Overall, the level of evidence was poor. In these studies, all patients received a TNFi as first bDMARD, 1956 patients switched to a second bDMARD (97% TNFi and 3% interleukin-17 inhibitors (IL-17i)) and 170 to a third bDMARD (all TNFi). Clinical response (Bath Ankylosing Spondylitis Disease Activity Index 50) after a second TNFi was achieved by 25%–56% of patients compared with 50%–72% after the first TNFi. Also, 47% of patients switching to IL-17i after a TNFi responded (Assessment of SpondyloArthritis international Society 40) compared with 66% in those who received IL-17i as first line. The response after switching was not influenced by the reason to discontinue, type of prior TNFi or changing the target.ConclusionsIn patients with axSpA, switching to a second bDMARD (a TNFi or IL-17i) after prior TNFi is efficacious. Nevertheless, the clinical response is lower than the observed in patients naive to bDMARD. So far, the reason to discontinue prior bDMARD or the type of bDMARD has not been identified as predictor of response. Published evidence for switching to a third bDMARD is lacking.
High prevalence of high-risk HPV genotypes other than 16 and 18 in cervical cancers of Curaçao: implications for choice of prophylactic HPV vaccine
Authors: Hooi Desiree J , Lissenberg-Witte Birgit I , de Koning Maurits N C , Pinedo Herbert M , Kenter Gemma G , Meijer Chris JLM , Quint Wim G 
Published: October 2017

BackgroundCuraçao is a Dutch-Caribbean Island located in a high-risk area for cervical cancer.Prior to introduction of a prophylactic human papillomavirus (HPV) vaccine, knowledge of the prevalence of high-risk HPV vaccine genotypes (HPV16, 18, 31, 33, 45, 52 and 58) in cervical (pre)cancer is required.ObjectiveTo investigate the prevalence of HPV genotypes in invasive cervical cancers (ICC) and cervical intraepithelial neoplasia (CIN) grade 1, 2 and 3 in Curaçao.MethodsParaffin-embedded blocks of 104 cervical cancers (89 squamous, 15 adenocarcinoma), 41 CIN3, 39 CIN2 and 40 CIN1 lesions were analysed for the presence of HPV. Sections were stained by H&E for histopathological evaluation, and DNA was extracted using proteinase K. HPV genotypes were detected using Short PCR Fragment (SPF10) PCR DNA enzyme immunoassay and a Line Probe Assay (LiPA25) .ResultsHPV was found in 92 (88.5%) ICC; 87 (94.6%) had a single HPV infection and 86 (93.5%) were high-risk human papillomavirus (hrHPV)-type positive.The three most common HPV types in ICC were 16 (38.5%), 18 (13.5%) and 45 (6.7%), covering 58.7%.HrHPV vaccine genotypes 16, 18, 31, 35, 45, 52 and 58 were responsible for 73.1% of ICC. For precancerous lesions, the HPV attribution was 85.4% for CIN3, 66.7% for CIN2% and 42.5% for CIN1.ConclusionsOur study, the largest in the Caribbean region in (pre)cancer, shows that the prevalence of HPV-type 16 and 18 in cervical cancer is lower compared with the world population but no differences in prevalence of these two HPV types are seen in precancerous lesions.When considering HPV vaccination in Curaçao, the relatively high contribution of non-HPV 16/18 genotypes in ICC should be taken into account.
Towards ubiquitous indoor spatial awareness on a worldwide scale
Authors: Elhamshary Moustafa , Youssef Moustafa 
Published: October 2017

While a remarkable effort has been put in developing indoor spatial awareness systems, they are still isolated efforts that are tailored to specific deployments. A truly ubiquitous indoor spatial awareness system is envisioned to be deployed on a large scale worldwide, with minimum overhead, and to work with the heterogeneous IoT devices. Such a system will enable a wide set of new applications including worldwide seamless direction finding between indoor locations, anywhere anytime health monitoring, enhanced first responders' safety, and providing richer context for indoor mobile computing applications.
In this paper, we describe our vision and work towards achieving ubiquitous indoor spatial awareness systems as well as the open challenges that need to be addressed to materialize this dream.
Macrophage depletion using clodronate liposomes decreases tumorigenesis and alters gut microbiota in the AOM/DSS mouse model of colon cancer
Authors: Bader Jackie E. , Enos Reilly T. , Velázquez Kandy T. , Carson Meredith S. , Nagarkatti Mitzi , Nagarkatti Prakash S. , Chatzistamou Ioulia , Davis J. Mark , Carson James A. , Robinson Cory M. , Murphy E. Angela 
Published: October 2017

We examined the role of macrophages in inflammation associated with colorectal cancer (CRC). Given the emerging evidence on immune-microbiota interactions in CRC, we also sought to examine the interaction between macrophages and gut microbiota. To induce CRC, male C57BL/6 mice ( n = 32) received a single injection of azoxymethane (AOM), followed by three cycles of dextran sodium sulfate (DSS)-supplemented water in weeks 1, 4, and 7. Prior to the final DSS cycle ( week 7) and twice weekly until euthanasia, mice ( n = 16/group) received either 200 μl ip of clodronate-filled liposomes (CLD) or phosphate-buffered saline (PBS) encapsulated liposomes to deplete macrophages. Colon tissue was analyzed for polyp burden, macrophage markers, transcription factors, and inflammatory mediators. Stool samples were collected, and DNA was isolated and subsequently sequenced for 16S rRNA. Clodronate liposomes decreased tumor number by ∼36% and specifically large (≥1 mm) tumors by ∼36% ( P < 0.05). This was consistent with a decrease in gene expression of EMR1 in the colon tissue and polyp tissue as well as expression of select markers associated with M1 (IL-6) and M2 macrophages (IL-13, IL-10, TGFβ, CCL17) in the colon tissue ( P < 0.05). Similarly, there was a decrease in STAT3 and p38 MAPK and ERK signaling in colon tissue. Clodronate liposomes increased the relative abundance of the Firmicutes phylum ( P < 0.05) and specifically Lactobacillaceae and Clostridiaceae families, which have been associated with reduced CRC risk. Overall, these data support the development of therapeutic strategies to target macrophages in CRC and provide support for further evaluation of immune-microbiota interactions in CRC. NEW & NOTEWORTHY We found that macrophage depletion during late-stage tumorigenesis is effective at reducing tumor growth. This was associated with a decrease in macrophage markers and chemokines in the colon tissue and a decrease in transcription factors that are linked to colorectal cancer. The macrophage-depleted group was found to have an increased abundance of Firmicutes, a phylum with documented anti-tumorigenic effects. Overall, these data support the development of therapeutic strategies to target macrophages in colorectal cancer.
Aging is associated with increased propensity for central apnea during NREM sleep
Authors: Chowdhuri Susmita , Pranathiageswaran Sukanya , Loomis-King Hillary , Salloum Anan , Badr M. Safwan 
Published: October 2017

The reason for increased sleep-disordered breathing with predominance of central apneas in the elderly is unknown. We hypothesized that the propensity to central apneas is increased in older adults, manifested by a reduced carbon-dioxide (CO2) reserve in older compared with young adults during non-rapid eye movement sleep. Ten elderly and 15 young healthy adults underwent multiple brief trials of nasal noninvasive positive pressure ventilation during stable NREM sleep. Cessation of mechanical ventilation (MV) resulted in hypocapnic central apnea or hypopnea. The CO2 reserve was defined as the difference in end-tidal CO2 ([Formula: see text]) between eupnea and the apneic threshold, where the apneic threshold was [Formula: see text] that demarcated the central apnea closest to the eupneic [Formula: see text]. For each MV trial, the hypocapnic ventilatory response (controller gain) was measured as the change in minute ventilation (V̇e) during the MV trial for a corresponding change in [Formula: see text]. The eupneic [Formula: see text] was significantly lower in elderly vs. young adults. Compared with young adults, the elderly had a significantly reduced CO2 reserve (−2.6 ± 0.4 vs. −4.1 ± 0.4 mmHg, P = 0.01) and a higher controller gain (2.3 ± 0.2 vs. 1.4 ± 0.2 l·min−1·mmHg−1, P = 0.007), indicating increased chemoresponsiveness in the elderly. Thus elderly adults are more prone to hypocapnic central apneas owing to increased hypocapnic chemoresponsiveness during NREM sleep. NEW & NOTEWORTHY The study describes an original finding where healthy older adults compared with healthy young adults demonstrated increased breathing instability during non-rapid eye movement sleep, as suggested by a smaller carbon dioxide reserve and a higher controller gain. The findings may explain the increased propensity for central apneas in elderly adults during sleep and potentially guide the development of pathophysiology-defined personalized therapies for sleep apnea in the elderly.
Multiple coupled resonances in the human vascular tree: refining the Westerhof model of the arterial system
Authors: Schumacher Gerhard , Kaden Jens J. , Trinkmann Frederik 
Published: October 2017

The human arterial vascular tree can be described by multicompartment models using electrical components. First introduced in the 1960s by Noordergraaf and Westerhof, these hardware-based approaches required several simplifications. We were able to remove the restrictions using modern software simulation tools and improve overall model quality considerably. Whereas the original Westerhof model consisted of 121 Windkessel elements, the refined model has 711 elements and gives realistic pulse waveforms of the aorta and brachial and radial arteries with realistic blood pressures. Moreover, novel insights concerning the formation of the physiological aortic-to-radial transfer function were gained. Its being potentially due to the coupling of many small resonant elements gives new impetus to the discussion of arterial pressure wave reflection. The individualized transfer function derived from our improved model incorporates distinct patient characteristics and can potentially be used for estimation of central blood pressure values. NEW & NOTEWORTHY We were able to find an individualized transfer function giving realistic pulse waveforms and blood pressures using a multicompartment model of the arterial system. Based on the hardware-built Westerhof approach, several simplifications initially introduced in the 1960s could be reversed using software simulation. Overall model quality was improved considerably, and multiple coupled resonances were identified as potential explanation for the formation of the aortic-to-radial transfer function, giving new impetus to the discussion of arterial pressure wave reflection.
A dual-axis rotation rule for updating the head direction cell reference frame during movement in three dimensions
Authors: Page Hector J. I. , Wilson Jonathan J. , Jeffery Kate J. 
Published: October 2017

In the mammalian brain, allocentric (Earth-referenced) head direction, called azimuth, is encoded by head direction (HD) cells, which fire according to the facing direction of the animal’s head. On a horizontal surface, rotations of the head around the dorsoventral (D-V) axis, called yaw, correspond to changes in azimuth and elicit appropriate updating of the HD “compass” signal to enable large-scale navigation. However, if the animal moves through three-dimensional (3D) space then there is no longer a simple relationship between yaw rotations and azimuth changes, and so processing of 3D rotations is needed. Construction of a global 3D compass would require complex integration of 3D rotations, and also a large neuronal population, most neurons of which would be silent most of the time since animals rarely sample all available 3D orientations. We propose that, instead, the HD system treats the 3D space as a set of interrelated 2D surfaces. It could do this by updating activity according to both yaw rotations around the D-V axis and rotations of the D-V axis around the gravity-defined vertical axis. We present preliminary data to suggest that this rule operates when rats move between walls of opposing orientations. This dual-axis rule, which we show is straightforward to implement using the classic one-dimensional “attractor” architecture, allows consistent representation of azimuth even in volumetric space and thus may be a general feature of mammalian directional computations even for animals that swim or fly.NEW & NOTEWORTHY Maintaining a sense of direction is complicated when moving in three-dimensional (3D) space. Head direction cells, which update the direction sense based on head rotations, may accommodate 3D movement by processing both rotations of the head around the axis of the animal’s body and rotations of the head/body around gravity. With modeling we show that this dual-axis rule works in principle, and we present preliminary data to support its operation in rats.
Metabolite Profiling Reveals the Glutathione Biosynthetic Pathway as a Therapeutic Target in Triple-Negative Breast Cancer
Authors: Beatty Alexander , Fink Lauren S. , Singh Tanu , Strigun Alexander , Peter Erik , Ferrer Christina M. , Nicolas Emmanuelle , Cai Kathy Q. , Moran Timothy P. , Reginato Mauricio J. , Rennefahrt Ulrike , Peterson Jeffrey R. 
Published: October 2017

Abstract
Cancer cells can exhibit altered dependency on specific metabolic pathways and targeting these dependencies is a promising therapeutic strategy. Triple-negative breast cancer (TNBC) is an aggressive and genomically heterogeneous subset of breast cancer that is resistant to existing targeted therapies. To identify metabolic pathway dependencies in TNBC, we first conducted mass spectrometry–based metabolomics of TNBC and control cells. Relative levels of intracellular metabolites distinguished TNBC from nontransformed breast epithelia and revealed two metabolic subtypes within TNBC that correlate with markers of basal-like versus non-basal–like status. Among the distinguishing metabolites, levels of the cellular redox buffer glutathione were lower in TNBC cell lines compared to controls and markedly lower in non-basal–like TNBC. Significantly, these cell lines showed enhanced sensitivity to pharmacologic inhibition of glutathione biosynthesis that was rescued by N-acetylcysteine, demonstrating a dependence on glutathione production to suppress ROS and support tumor cell survival. Consistent with this, patients whose tumors express elevated levels of γ-glutamylcysteine ligase, the rate-limiting enzyme in glutathione biosynthesis, had significantly poorer survival. We find, further, that agents that limit the availability of glutathione precursors enhance both glutathione depletion and TNBC cell killing by γ-glutamylcysteine ligase inhibitors in vitro. Importantly, we demonstrate the ability to this approach to suppress glutathione levels and TNBC xenograft growth in vivo. Overall, these findings support the potential of targeting the glutathione biosynthetic pathway as a therapeutic strategy in TNBC and identify the non-basal-like subset as most likely to respond. Mol Cancer Ther; 17(1); 264–75. ©2017 AACR.
Prediction for Intravenous Immunoglobulin Resistance by Using Weighted Genetic Risk Score Identified From Genome-Wide Association Study in Kawasaki Disease
Authors: Kuo Ho-Chang , Wong Henry Sung-Ching , Chang Wei-Pin , Chen Ben-Kuen , Wu Mei-Shin , Yang Kuender D. , Hsieh Kai-Sheng , Hsu Yu-Wen , Liu Shih-Feng , Liu Xiao , Chang Wei-Chiao 
Published: October 2017

Background—
Intravenous immunoglobulin (IVIG) is the treatment of choice in Kawasaki disease (KD). IVIG is used to prevent cardiovascular complications related to KD. However, a proportion of KD patients have persistent fever after IVIG treatment and are defined as IVIG resistant.

Methods and Results—

To develop a risk scoring system based on genetic markers to predict IVIG responsiveness in KD patients, a total of 150 KD patients (126 IVIG responders and 24 IVIG nonresponders) were recruited for this study. A genome-wide association analysis was performed to compare the 2 groups and identified risk alleles for IVIG resistance. A weighted genetic risk score was calculated by the natural log of the odds ratio multiplied by the number of risk alleles. Eleven single-nucleotide polymorphisms were identified by genome-wide association study. The KD patients were categorized into 3 groups based on their calculated weighted genetic risk score. Results indicated a significant association between weighted genetic risk score (groups 3 and 4 versus group 1) and the response to IVIG (Fisher’s exact
P
value 4.518×10
−
03
and 8.224×10
−
10
, respectively).

Conclusions—
This is the first weighted genetic risk score study based on a genome-wide association study in KD. The predictive model integrated the additive effects of all 11 single-nucleotide polymorphisms to provide a prediction of the responsiveness to IVIG.