bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Promising Antiprion Trimethoxychalcone Binds to the Globular Domain of the Cellular Prion Protein and Changes Its Cellular Location
Authors: Ferreira N. C. , Ascari L. M. , Hughson A. G. , Cavalheiro G. R. , Góes C. F. , Fernandes P. N. , Hollister J. R. , da Conceição R. A. , Silva D. S. , Souza A. M. T. , Barbosa M. L. C. , Lara F. A. , Martins R. A. P. , Caughey B. , Cordeiro Y. 
Published: November 2017

ABSTRACT

The search for antiprion compounds has been encouraged by the fact that transmissible spongiform encephalopathies (TSEs) share molecular mechanisms with more prevalent neurodegenerative pathologies, such as Parkinson's and Alzheimer's diseases. Cellular prion protein (PrP
C
) conversion into protease-resistant forms (protease-resistant PrP [PrP
Res
] or the scrapie form of PrP [PrP
Sc
]) is a critical step in the development of TSEs and is thus one of the main targets in the screening for antiprion compounds. In this work, three trimethoxychalcones (compounds J1, J8, and J20) and one oxadiazole (compound Y17), previously identified
in vitro
to be potential antiprion compounds, were evaluated through different approaches in order to gain inferences about their mechanisms of action. None of them changed PrP
C
mRNA levels in N2a cells, as shown by reverse transcription-quantitative real-time PCR. Among them, J8 and Y17 were effective in real-time quaking-induced conversion reactions using rodent recombinant PrP (rPrP) from residues 23 to 231 (rPrP
23–231
) as the substrate and PrP
Sc
seeds from hamster and human brain. However, when rPrP from residues 90 to 231 (rPrP
90–231
), which lacks the N-terminal domain, was used as the substrate, only J8 remained effective, indicating that this region is important for Y17 activity, while J8 seems to interact with the PrP
C
globular domain. J8 also reduced the fibrillation of mouse rPrP
23–231
seeded with
in vitro
-produced fibrils. Furthermore, most of the compounds decreased the amount of PrP
C
on the N2a cell surface by trapping this protein in the endoplasmic reticulum. On the basis of these results, we hypothesize that J8, a nontoxic compound previously shown to be a promising antiprion agent, may act by different mechanisms, since its efficacy is attributable not only to PrP conversion inhibition but also to a reduction of the PrP
C
content on the cell surface.
Outcomes of Vancomycin plus a β-Lactam versus Vancomycin Only for Treatment of Methicillin-Resistant Staphylococcus aureus Bacteremia
Authors: Truong James , Veillette John J. , Forland Steve C. 
Published: November 2017

ABSTRACT

The objective of this retrospective study was to compare the rates of treatment failure, which was a composite of clinical and microbiologic failure, of patients receiving vancomycin and a β-lactam to those receiving vancomycin only for methicillin-resistant
Staphylococcus aureus
(MRSA) bacteremia. Patients 16 to 89 years of age with MRSA bacteremia admitted to a university-affiliated hospital from 1 January 2014 to 31 December 2016 were screened for study inclusion. Patients were eligible if they received >48 h of vancomycin and a β-lactam (combination group) or vancomycin only (standard group) within 48 h after bacteremia onset. A total of 182 patients were screened: 47 were included in the standard group, and 63 were in the combination group. The combination group had a higher baseline body mass index (29.2 ± 8.0 kg/m
2
versus 25.8 ± 7.1 kg/m
2
,
P
= 0.022), acute physiologic assessment and chronic health evaluation-II (APACHE-II) score (median [interquartile range], 21 [15 to 26] versus 16 [10 to 22],
P
= 0.003), and incidence of septic shock (31.8% versus 14.9%,
P
= 0.047). Using multivariate analysis, combination therapy was the only variable that decreased treatment failures (odds ratio [95% confidence interval], 0.337 [0.142 to 0.997]), while vancomycin MIC > 1 mg/liter and male gender increased treatment failures (4.018 [1.297 to 12.444] and 2.971 [1.040 to 8.488], respectively). The 30-day mortality rates (15.0% versus 14.9%,
P
= 1.000) and the incidence of adverse drug events (19.1% versus 23.4%,
P
= 0.816) were not statistically different between the combination and standard groups. Combination therapy of vancomycin with a β-lactam led to significantly fewer treatment failures than vancomycin monotherapy for MRSA bacteremia.
Activity of Simulated Human Dosage Regimens of Meropenem and Vaborbactam against Carbapenem-Resistant Enterobacteriaceae in an
In Vitro
Hollow-Fiber Model
Authors: Sabet Mojgan , Tarazi Ziad , Rubio-Aparicio Debora , Nolan Thomas G. , Parkinson Jonathan , Lomovskaya Olga , Dudley Michael N. , Griffith David C. 
Published: November 2017

ABSTRACT

The objective of these studies was to evaluate the exposures of meropenem and vaborbactam that would produce antibacterial activity and prevent resistance development in carbapenem-resistant
Klebsiella pneumoniae
carbapenemase (KPC)-producing
Enterobacteriaceae
strains when tested at an inoculum of 10
8
CFU/ml. Thirteen
K. pneumoniae
isolates, three
Enterobacter cloacae
isolates, and one
Escherichia coli
isolate were examined in an
in vitro
hollow-fiber model over 32 h. Simulated dosage regimens of 1 to 2 g of meropenem with 1 to 2 g of vaborbactam, with meropenem administered every 8 h by a 3-h infusion based on phase 1 or phase 3 patient pharmacokinetic data, were studied in the model. A dosage of 2 g of meropenem in combination with 2 g of vaborbactam was bactericidal against
K. pneumoniae
,
E. cloacae
, and
E. coli
strains, with meropenem-vaborbactam MICs of up to 8 mg/liter. When the vaborbactam exposure was adjusted to the levels observed in patients enrolled in phase 3 trials (24-h free AUC, ∼550 mg · h/liter, versus 320 mg · h/liter in the phase 1 studies), 2 g of meropenem with 2 g of vaborbactam was also bactericidal against strains with meropenem-vaborbactam MICs of 16 mg/liter. In addition, this level of vaborbactam also suppressed the development of resistance observed using phase 1 exposures. In this pharmacodynamic model, exposures similar to 2 g of meropenem in combination with 2 g of vaborbactam administered every 8 h by a 3-h infusion in phase 3 trials produced antibacterial activity and suppressed the development of resistance against carbapenem-resistant KPC-producing strains of
Enterobacteriaceae
.
Analysis of the Human Mucosal Response to Cholera Reveals Sustained Activation of Innate Immune Signaling Pathways
Authors: Bourque Daniel L. , Bhuiyan Taufiqur Rahman , Genereux Diane P. , Rashu Rasheduzzaman , Ellis Crystal N. , Chowdhury Fahima , Khan Ashraful I. , Alam Nur Haq , Paul Anik , Hossain Lazina , Mayo-Smith Leslie M. , Charles Richelle C. , Weil Ana A. , LaRocque Regina C. , Calderwood Stephen B. , Ryan Edward T. , Karlsson Elinor K. , Qadri Firdausi , Harris Jason B. 
Published: November 2017

ABSTRACT

To better understand the innate immune response to
Vibrio cholerae
infection, we tracked gene expression in the duodenal mucosa of 11 Bangladeshi adults with cholera, using biopsy specimens obtained immediately after rehydration and 30 and 180 days later. We identified differentially expressed genes and performed an analysis to predict differentially regulated pathways and upstream regulators. During acute cholera, there was a broad increase in the expression of genes associated with innate immunity, including activation of the NF-κB, mitogen-activated protein kinase (MAPK), and Toll-like receptor (TLR)-mediated signaling pathways, which, unexpectedly, persisted even 30 days after infection. Focusing on early differences in gene expression, we identified 37 genes that were differentially expressed on days 2 and 30 across the 11 participants. These genes included the endosomal Toll-like receptor gene
TLR8
, which was expressed in lamina propria cells. Underscoring a potential role for endosomal TLR-mediated signaling
in vivo
, our pathway analysis found that interferon regulatory factor 7 and beta 1 and alpha 2 interferons were among the top upstream regulators activated during cholera. Among the innate immune effectors, we found that the gene for DUOX2, an NADPH oxidase involved in the maintenance of intestinal homeostasis, was upregulated in intestinal epithelial cells during cholera. Notably, the observed increases in
DUOX2
and
TLR8
expression were also modeled
in vitro
when Caco-2 or THP-1 cells, respectively, were stimulated with live
V. cholerae
but not with heat-killed organisms or cholera toxin alone. These previously unidentified features of the innate immune response to
V. cholerae
extend our understanding of the mucosal immune signaling pathways and effectors activated
in vivo
following cholera.
Can physical assessment techniques aid diagnosis in people with chronic fatigue syndrome/myalgic encephalomyelitis? A diagnostic accuracy study
Authors: Hives Lucy , Bradley Alice , Richards Jim , Sutton Chris , Selfe James , Basu Bhaskar , Maguire Kerry , Sumner Gail , Gaber Tarek , Mukherjee Annice , Perrin Raymond N 
Published: November 2017

ObjectiveTo assess five physical signs to see whether they can assist in the screening of patients with chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) and potentially lead to quicker treatment.MethodsThis was a diagnostic accuracy study with inter-rater agreement assessment. Participants recruited from two National Health Service hospitals, local CFS/ME support groups and the community were examined by three practitioners on the same day in a randomised order. Two allied health professionals (AHPs) performed independent examinations of physical signs including: postural/mechanical disturbances of the thoracic spine, breast varicosities, tender Perrin’s point, tender coeliac plexus and dampened cranial flow. A physician conducted a standard clinical neurological and rheumatological assessment while looking for patterns of illness behaviour. Each examination lasted approximately 20 min.ResultsNinety-four participants were assessed, 52 patients with CFS/ME and 42 non-CFS/ME controls, aged 18–60. Cohen’s kappa revealed that agreement between the AHPs was substantial for presence of the tender coeliac plexus (κ=0.65, p<0.001) and moderate for postural/mechanical disturbance of the thoracic spine (κ=0.57, p<0.001) and Perrin’s point (κ=0.56, p<0.001). A McNemar’s test found no statistically significant bias in the diagnosis by the experienced AHP relative to actual diagnosis (p=1.0) and a marginally non-significant bias by the newly trained AHP (p=0.052). There was, however, a significant bias in the diagnosis made by the physician relative to actual diagnosis (p<0.001), indicating poor diagnostic utility of the clinical neurological and rheumatological assessment.ConclusionsUsing the physical signs appears to improve the accuracy of identifying people with CFS/ME and shows agreement with current diagnostic techniques. However, the present study concludes that only two of these may be needed. Examining for physical signs is both quick and simple for the AHP and may be used as an efficient screening tool for CFS/ME. This is a small single-centre study, and therefore, further validation in other centres and larger populations is needed.
Effects of falls prevention interventions on falls outcomes for hospitalised adults: protocol for a systematic review with meta-analysis
Authors: Slade Susan C , Carey David L , Hill Anne-Marie , Morris Meg E 
Published: November 2017

IntroductionFalls are a major global public health problem and leading cause of accidental or unintentional injury and hospitalisation. Falls in hospital are associated with longer length of stay, readmissions and poor outcomes. Falls prevention is informed by knowledge of reversible falls risk factors and accurate risk identification. The extent to which hospital falls are prevented by evidence-based practice, patient self-management initiatives, environmental modifications and optimisation of falls prevention systems awaits confirmation. Published reviews have mainly evaluated community settings and residential care facilities. A better understanding of hospital falls and the most effective strategies to prevent them is vital to keeping people safe.ObjectivesTo evaluate the effectiveness of falls prevention interventions on reducing falls in hospitalised adults (acute and subacute wards, rehabilitation, mental health, operating theatre and emergency departments). We also summarise components of effective falls prevention interventions.Methods and analysisThis protocol has been registered. The systematic review will be informed by Cochrane guidelines and reported according to the Preferred Reporting Items for Systematic review and Meta-Analysis statement. Inclusion criteria: randomised controlled trials, quasi-randomised trials or controlled clinical trials that evaluate falls prevention interventions for use by hospitalised adults or employees. Electronic databases will be searched using key terms including falls, accidental falls, prevention, hospital, rehabilitation, emergency, mental health, acute and subacute. Pairs of independent reviewers will conduct all review steps. Included studies will be evaluated for risk of bias. Data for variables such as age, participant characteristics, settings and interventions will be extracted and analysed with descriptive statistics and meta-analysis where possible. The results will be presented textually, with flow charts, summary tables, statistical analysis (and meta-analysis where possible) and narrative summaries.Ethics and disseminationEthical approval is not required. The systematic review will be published in a peer-reviewed journal and disseminated electronically, in print and at conferences. Updates will guide healthcare translation into practice.Trail registration numberPROSPERO 2017: CRD 42017058887. Available fromhttps://www.crd.york.ac.uk/prospero
Risks for comorbidity in children with atopic disorders: an observational study in Dutch general practices
Authors: Pols David H J , Bohnen Arthur M , Nielen Mark M J , Korevaar Joke C , Bindels Patrick J E 
Published: November 2017

ObjectiveThis study aimed to investigate both atopic and non-atopic comorbid symptoms and diseases in children with physician-diagnosed atopic disorders (atopic eczema, asthma and allergic rhinitis).MethodsAll children aged 0–18 years listed in a nationwide primary care database (the Netherlands Institute for Health Services Research-Primary Care Database) with routinely collected healthcare data in 2014 were selected. Children with atopic disorders were matched on age and gender with non-atopic controls within the same general practice. A total of 404 International Classification of Primary Care codes were examined. Logistic regression analyses were performed to examine the associations between the presence of atopic disorders and (non-)atopic symptoms and diseases by calculating ORs.ResultsHaving one of the atopic disorders significantly increased the risk of having other atopic-related symptoms, even if the child was not registered as having the related atopic disorder. Regarding non-atopic comorbidity, children with atopic eczema (n=15 530) were at significantly increased risk for (infectious) skin diseases (OR: 1.2–3.4). Airway symptoms or (infectious) diseases (OR: 2.1–10.3) were observed significantly more frequently in children with asthma (n=7887). Children with allergic rhinitis (n=6835) had a significantly distinctive risk of ear-nose-throat-related symptoms and diseases (OR: 1.5–3.9). Neither age nor gender explained these increased risks.ConclusionGeneral practitioners are not always fully aware of relevant atopic and non-atopic comorbidity. In children known to have at least one atopic disorder, specific attention is required to avoid possible insufficient treatment and unnecessary loss of quality of life.
Involvement of people with dementia in making decisions about their lives: a qualitative study that appraises shared decision-making concerning daycare
Authors: Groen-van de Ven Leontine , Smits Carolien , de Graaff Fuusje , Span Marijke , Eefsting Jan , Jukema Jan , Vernooij-Dassen Myrra 
Published: November 2017

ObjectiveTo explore how people with dementia, their informal caregivers and their professionals participate in decision making about daycare and to develop a typology of participation trajectories.DesignA qualitative study with a prospective, multiperspective design, based on 244 semistructured interviews, conducted during three interview rounds over the course of a year. Analysis was by means of content analysis and typology construction.SettingCommunity settings and nursing homes in the Netherlands.Participants19 people with dementia, 36 of their informal caregivers and 38 of their professionals (including nurses, daycare employees and case managers).ResultsThe participants’ responses related to three critical points in the decision-making trajectory about daycare: (1) the initial positive or negative expectations of daycare; (2) negotiation about trying out daycare by promoting, resisting or attuning to others; and (3) trying daycare, which resulted in positive or negative reactions from people with dementia and led to a decision. The ways in which care networks proceeded through these three critical points resulted in a typology of participation trajectories, including (1) working together positively toward daycare, (2) bringing conflicting perspectives together toward trying daycare and (3) not reaching commitment to try daycare.ConclusionShared decision making with people with dementia is possible and requires and adapted process of decision making. Our results show that initial preferences based on information alone may change when people with dementia experience daycare. It is important to have a try-out period so that people with dementia can experience daycare without having to decide whether to continue it. Whereas shared decision making in general aims at moving from initial preferences to informed preferences, professionals should focus more on moving from initial preferences to experienced preferences for people with dementia. Professionals can play a crucial role in facilitating the possibilities for a try-out period.
Multi-band terahertz metasurface absorber
Authors: Wang Xuying , Wang Qingmin , Dong Guoyan , Hao Yanan , Lei Ming , Bi Ke 
Published: November 2017

A terahertz metasurface perfect absorber with multi-band performance is demonstrated. The absorber is composed of a ground plane and four split-ring resonators (SRRs) with different dimensions, separated by a dielectric spacer. The numerical simulation results illustrate that the proposed absorber has four distinct absorption peaks at resonance frequencies of 4.24, 5.66, 7.22, and 8.97 THz, with absorption rates of 96.8%, 99.3%, 97.3%, and 99.9%, respectively. Moreover, the corresponding full width at half-maximum (FWHM) values are about 0.27, 0.35, 0.32, and 0.42 THz, respectively, which are much broader than those of previously reported absorbers. Besides, the calculated magnetic field distributions allow us to understand the absorption mechanism in detail. The effects of incident angle and azimuthal angle on the absorber are also investigated. The results show that the proposed absorber is partially sensitive to the incident angle, which makes this design promising for practical applications in terahertz imagers and detectors.
Drug Repositioning Meets Precision in Glioblastoma
Authors: Wick Wolfgang , Kessler Tobias 
Published: November 2017

Abstract
Glioblastoma has a gigantic unmet medical need. Molecular knowledge has evolved substantially, including data on clonal selection with progression. Past trials for all-comers may have produced false negative results. Molecular precision at progression needs workup of new tissue, and revisiting drugs with a focus on brain tumor penetration may yield surprises. Clin Cancer Res; 24(2); 256–8. ©2017 AACR.
See related article by Byron et al., p. 295
Human Papillomavirus Immunity in Oropharyngeal Cancer: Time to Change the Game?
Authors: Laban Simon , Hoffmann Thomas K. 
Published: November 2017

Abstract
For the first time, human papillomavirus (HPV)–specific immunity has been linked directly to the beneficial prognosis of oropharyngeal squamous cell carcinoma (OPSCC). Those patients lacking HPV immunity fare much worse. These results harbor crucial implications for future management of HPV-driven OPSCC as well as for its definition. Clin Cancer Res; 24(3); 505–7. ©2017 AACR.
See related article by Welters et al., p. 634
Contemporary Epidemiology of Heart Failure in Fee-For-Service Medicare Beneficiaries Across Healthcare Settings
Authors: Khera Rohan , Pandey Ambarish , Ayers Colby R. , Agusala Vijay , Pruitt Sandi L. , Halm Ethan A. , Drazner Mark H. , Das Sandeep R. , de Lemos James A. , Berry Jarett D. 
Published: November 2017

Background
To assess the current landscape of the heart failure (HF) epidemic and provide targets for future health policy interventions in Medicare, a contemporary appraisal of its epidemiology across inpatient and outpatient care settings is needed.

Methods and Results

In a national 5% sample of Medicare beneficiaries from 2002 to 2013, we identified a cohort of 2 331 939 unique fee-for-service Medicare beneficiaries ≥65-years-old followed for all inpatient and outpatient encounters over a 10-year period (2004–2013). Preexisting HF was defined by any HF encounter during the first year, and incident HF with either 1 inpatient or 2 outpatient HF encounters. Mean age of the cohort was 72 years; 57% were women, and 86% and 8% were white and black, respectively. Within this cohort, 518 223 patients had preexisting HF, and 349 826 had a new diagnosis of HF during the study period. During 2004 to 2013, the rates of incident HF declined 32%, from 38.7 per 1000 (2004) to 26.2 per 1000 beneficiaries (2013). In contrast, prevalent (preexisting + incident) HF increased during our study period from 162 per 1000 (2004) to 172 per 1000 beneficiaries (2013) (
P
trend
<0.001 for both). Finally, the overall 1-year mortality among patients with incident HF is high (24.7%) with a 0.4% absolute decline annually during the study period, with a more pronounced decrease among those diagnosed in an inpatient versus outpatient setting (
P
interaction
<0.001)

Conclusions
In recent years, there have been substantial changes in the epidemiology of HF in Medicare beneficiaries, with a decline in incident HF and a decrease in 1-year HF mortality, whereas the overall burden of HF continues to increase.