bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mechanical property alterations across the cerebral cortex due to Alzheimer’s disease
Authors: Hiscox Lucy V , Johnson Curtis L , McGarry Matthew D J , Marshall Helen , Ritchie Craig W , van Beek Edwin J R , Roberts Neil , Starr John M 
Published: December 2019

AbstractAlzheimer’s disease is a personally devastating neurodegenerative disorder and a major public health concern. There is an urgent need for medical imaging techniques that better characterize the early stages and monitor the progression of the disease. Magnetic resonance elastography (MRE) is a relatively new and highly sensitive MRI technique that can non-invasively assess tissue microstructural integrity via measurement of brain viscoelastic mechanical properties. For the first time, we use high-resolution MRE methods to conduct a voxel-wise MRE investigation and state-of-the-art post hoc region of interest analysis of the viscoelastic properties of the cerebral cortex in patients with Alzheimer’s disease (N = 11) compared with cognitively healthy older adults (N = 12). We replicated previous findings that have reported significant volume and stiffness reductions at the whole-brain level. Significant reductions in volume were also observed in Alzheimer’s disease when white matter, cortical grey matter and subcortical grey matter compartments were considered separately; lower stiffness was also observed in white matter and cortical grey matter, but not in subcortical grey matter. Voxel-based morphometry of both cortical and subcortical grey matter revealed localized reductions in volume due to Alzheimer’s disease in the hippocampus, fusiform, middle, superior temporal gyri and precuneus. Similarly, voxel-based MRE identified lower stiffness in the middle and superior temporal gyri and precuneus, although the spatial distribution of these effects was not identical to the pattern of volume reduction. Notably, MRE additionally identified stiffness deficits in the operculum and precentral gyrus located within the frontal lobe; regions that did not undergo volume loss identified through voxel-based morphometry. Voxel-based-morphometry and voxel-based MRE results were confirmed by a complementary post hoc region-of-interest approach in native space where the viscoelastic changes remained significant even after statistically controlling for regional volumes. The pattern of reduction in cortical stiffness observed in Alzheimer’s disease patients raises the possibility that MRE may provide unique insights regarding the neural mechanisms which underlie the development and progression of the disease. The measured mechanical property changes that we have observed warrant further exploration to investigate the diagnostic usefulness of MRE in cases of Alzheimer’s disease and other dementias.
Management of pulmonary arterial hypertension in patients aged over 65 years
Authors: Sitbon Olivier , Howard Luke 
Published: December 2019

AbstractHistorically, pulmonary arterial hypertension (PAH) has been considered a disease of young adults, but over the last three decades, the average age at diagnosis has increased, presenting clinicians with some unique challenges. Clinical symptoms of PAH, including shortness of breath and reduced functional capacity, are not specific for the disease and may be present in older patients because of their age or as a result of comorbid conditions. Eliminating other causes for these symptoms can delay PAH diagnosis and initiation of PAH-specific treatment compared with younger patients. Currently, there are no specific guidelines relating to PAH in older patients and existing guidelines for identifying patients at potential risk of PAH may not be appropriate for patients aged over 65 years. Even though older patients tend to be diagnosed with more advanced symptoms, and evidence suggests that they are less responsive to PAH-specific therapies, treatment is often less aggressive than in younger patients. Even after adjusting for age, survival rates remain disproportionately lower in the older vs. younger PAH populations. Specific guidelines for diagnosis and treatment of older patients with PAH are needed to improve care and outcomes in this growing population. This review aims to assess the challenges associated with diagnosing and managing PAH in older patients, based on literature searches, authors’ experiences, and expert opinions.
The revised definition of pulmonary hypertension: exploring the impact on patient management
Authors: Simonneau Gérald , Hoeper Marius M 
Published: December 2019

Abstract
At the 6th World Symposium on Pulmonary Hypertension (PH), it was proposed that the mean pulmonary arterial pressure (mPAP) threshold used to define PH should be lowered from ≥25 mmHg to &gt;20 mmHg. The rationale for this change is that the ≥25 mmHg threshold is arbitrary, whereas the revised threshold is based on scientific evidence. For the definition of all forms of pre-capillary PH, the inclusion of a pulmonary vascular resistance (PVR) ≥3 Wood Units was also proposed, placing greater emphasis on an elevated PVR to identify pulmonary vascular disease. Here, we discuss the possible impact of the revised definition of PH on future clinical management. This change may facilitate earlier PH detection, particularly in at-risk patient groups that are already undergoing screening programmes, e.g. those with systemic sclerosis or mutations associated with PH. As an mPAP above the upper limit of normal (&gt;20 mmHg) but &lt;25 mmHg is associated with increased risk of morbidity and mortality compared with a normal mPAP, early identification of patients in this group is important to enable close monitoring and timely treatment initiation once clinically indicated. Treatments currently approved for PH are not necessarily suitable for patients with an mPAP 21–24 mmHg, as the management of this group has not been widely examined. The revised definition may facilitate inclusion of these patients in prospective trials, allowing the evaluation of appropriate management strategies.
Pulmonary arterial hypertension populations of special interest: portopulmonary hypertension and pulmonary arterial hypertension associated with congenital heart disease
Authors: Savale Laurent , Manes Alessandra 
Published: December 2019

AbstractGuidelines exist for management of pulmonary arterial hypertension (PAH), but information is limited for certain patient subgroups, including adults with portopulmonary hypertension (PoPH) or with PAH associated with congenital heart disease (PAH-CHD). This article discusses screening, clinical management, and prognosis in PoPH and PAH-CHD and, as such, considers the most recent clinical data and expert advice. A multidisciplinary consultation and follow-up by specialists are crucial for management of both PoPH and PAH-CHD, but each condition presents with unique challenges. Development of PoPH most commonly occurs among patients with liver cirrhosis. Initially, patients may be asymptomatic for PoPH and, if untreated, survival with PoPH is generally worse than with idiopathic PAH (IPAH), so early identification with screening is crucial. PoPH can be managed with PAH-specific pharmacological therapy, and resolution is possible in some patients with liver transplantation. With PAH-CHD, survival rates are typically higher than with IPAH but vary across the four subtypes: Eisenmenger syndrome, systemic-to-pulmonary shunts, small cardiac defects, and corrected defects. Screening is also crucial and, in patients who undergo correction of CHD, the presence of PAH should be assessed immediately after repair and throughout their long-term follow-up, with frequency of assessments determined by the patient’s characteristics at the time of correction. Early screening for PAH in patients with portal hypertension or CHD, and multidisciplinary management of PoPH or PAH-CHD are important for the best patient outcomes.
Educational differences in acute infectious diseases in the Netherlands: results from a nationwide health survey
Authors: de Gier Brechje , Houben - van Herten Marieke , Uiters Ellen , Hahné Susan J M 
Published: December 2019

AbstractBackgroundIt is unclear to what extent socioeconomic inequalities exist in common infectious diseases in high-income countries. We aimed to explore educational differences in five common acute infectious diseases in adults in the Netherlands.MethodsAs part of a year-round repeated cross-sectional health survey, adults aged 25 and older were asked if they had experienced acute upper or lower respiratory tract infections, acute otitis media, urinary tract infections or gastro-enteritis in the two previous months. If so, participants were asked whether they had consulted their general practitioner and if they had been unable to perform their normal daily activities. These outcomes were analyzed per highest attained level of education.ResultsData of 18 629 survey respondents were used in the analyses. People with a low educational level had lower odds of upper respiratory tract infections (OR 0.88, 95% CI 0.81–0.95), but higher odds of lower respiratory tract infections (OR 1.57, 95% CI 1.16–2.11). After adjustment for several covariates, the differences in upper respiratory tract infections remained statistically significant (aOR 0.84, 95% CI 0.77–0.91). The educational differences in lower respiratory tract infections were mitigated by adjusting for chronic diseases and health behaviours. For all infectious diseases, the likelihood of general practitioner consultation was highest for the lower educated group. Inability to work or perform normal daily activities due to an infectious disease was similar across all levels of education.ConclusionThis study shows that educational differences in incidence and care seeking behaviours exist for common acute infectious diseases in the Netherlands.
Migrant Advocacy under Austerity: Transforming Solidarity in the Greek-Refugee Regime
Authors: Pendakis Katherine L 
Published: December 2019

AbstractWith the United Nations High Commissioner for Refugees’ declaration of an emergency in 2016, Thessaloniki’s refugee regime began to develop rapidly. Local non-governmental organizations (NGOs) were transformed from underfunded initiatives to institutions managing large budgets and requiring staff with intercultural competencies and experience with migrant populations. For this, they turned to the ‘lost generation’— Greek youth who had come of age during the economic crisis and who had formed close relationships with migrants through political mobilizations and local solidarity networks that had sprung up in response to widespread austerity. In this article, I ask: How is the conversion of young ‘radicals’ from ‘anti-state’ activist networks into NGO representatives achieved? How does this transition impact former activists’ relationships with migrants and how do former activists make sense of this change? What, if anything, makes this a ‘Thessaloniki story’? My argument is three-fold. First, the conversion of activists into NGO representatives is made possible by a combination of young people’s exclusion from economic opportunities and the state’s disciplining of forms of solidarity that exist outside of the refugee regime. Second, the refugee regime converts solidarity established through political struggle into a form of human capital that affords former activists social mobility. Existing solidarity between former activists and migrants is undermined as a result. Third, on account of their new role as gatekeepers in NGOs, former activists struggle to offer a compelling narrative of continuity with their left-wing identity and their politicized commitment to migrants. In doing so, they rely on identifiable forms of boundary work and justification.
Lethality caused by ADP-glucose accumulation is suppressed by salt-induced carbon flux redirection in cyanobacteria
Authors: Díaz-Troya Sandra , Roldán Miguel , Mallén-Ponce Manuel J , Ortega-Martínez Pablo , Florencio Francisco J 
Published: December 2019

Abstract
Cyanobacteria are widely distributed photosynthetic organisms. During the day they store carbon, mainly as glycogen, to provide the energy and carbon source they require for maintenance during the night. Here, we generate a mutant strain of the freshwater cyanobacterium Synechocystis sp. PCC 6803 lacking both glycogen synthases. This mutant has a lethal phenotype due to massive accumulation of ADP-glucose, the substrate of glycogen synthases. This accumulation leads to alterations in its photosynthetic capacity and a dramatic decrease in the adenylate energy charge of the cell to values as low as 0.1. Lack of ADP-glucose pyrophosphorylase, the enzyme responsible for ADP-glucose synthesis, or reintroduction of any of the glycogen synthases abolishes the lethal phenotype. Viability of the glycogen synthase mutant is also fully recovered in NaCl-supplemented medium, which redirects the surplus of ADP-glucose to synthesize the osmolite glucosylglycerol. This alternative metabolic sink also suppresses phenotypes associated with the defective response to nitrogen deprivation characteristic of glycogen-less mutants, restoring the capacity to degrade phycobiliproteins. Thus, our system is an excellent example of how inadequate management of the adenine nucleotide pools results in a lethal phenotype, and the influence of metabolic carbon flux in cell viability and fitness.
Search for the optical counterpart of the GW170814 gravitational wave event with the VLT Survey Telescope
Authors: Grado A , Cappellaro E , Covino S , Getman F , Greco G , Limatola L , Yang S , Amati L , Benetti S , Branchesi M , Brocato E , Botticella M , Campana S , Cantiello M , Dadina M , D’Ammando F , De Cesare G , D’Elia V , Della Valle M , Iodice E , Longo G , Mapelli M , Masetti N , Nicastro L , Palazzi E , Possenti A , Radovich M , Rossi A , Salvaterra R , Stella L , Stratta G , Testa V , Tomasella L 
Published: December 2019

ABSTRACT
We report on the search for the optical counterpart of the gravitational event GW170814, which was carried out with the VLT Survey Telescope (VST) by the GRAvitational Wave Inaf TeAm. Observations started 17.5 h after the Laser Interferometer Gravitational-wave Observatory (LIGO) and Virgo alert and we covered an area of 99 deg2 that encloses $\sim 77{{\ \rm per\ cent}}$ and $\sim 59{{\ \rm per\ cent}}$ of the initial and refined localization probability regions, respectively. A total of six epochs were secured over nearly two months. The survey reached an average limiting magnitude of 22 AB mag in the r band. After assuming the model described in Perna, Lazzati & Farr, that derives as possible optical counterpart of a BBH (binary black hole) event a transient source declining in about one day, we have computed a survey efficiency of about $5{{\ \rm per\ cent}}$. This paper describes the VST observational strategy and the results obtained by our analysis pipelines developed to search for optical transients in multi-epoch images. We report the catalogue of the candidates with possible identifications based on light-curve fitting. We have identified two dozens of SNe, nine AGNs, and one QSO. Nineteen transients characterized by a single detection were not classified. We have restricted our analysis only to the candidates that fall into the refined localization map. None out of 39 left candidates could be positively associated with GW170814. This result implies that the possible emission of optical radiation from a BBH merger had to be fainter than r ∼ 22 (Loptical ∼ 1.4 × 1042 erg s−1) on a time interval ranging from a few hours up to two months after the gravitational wave event.
Effect of turbulent pressure on the origin of low-frequency quasi-periodic oscillations in rotating black holes
Authors: Mondal Santanu 
Published: December 2019

ABSTRACT
Quasi-periodic oscillation (QPO), particularly of low frequency (LF), is a very obvious feature of outbursting black hole candidates. The association of QPOs in a specific spectral state and their transition with states make them a key ingredient in understanding the underlying physical processes that produce them. Observations have revealed that generally, in the hard spectral state of the outburst, the size of the Compton cloud is relatively bigger, which produces low-frequency QPOs (LFQPOs). In progressive days increased cooling shrinks the area of the cloud, the inner edge of the disc comes close to the black holes, and produces higher frequency QPOs. However, rotating black holes with higher spin values are likely to produce LFQPOs even if their inner edge of the disc is closer to the hole. Here, for the first time, we address the issue, solving hydrodynamic flow equations in the presence of qualitative turbulent pressure and cooling in pseudo-Kerr geometry. Increasing turbulence slackens the infalling flow, thus the infall time becomes longer, producing LFQPOs. Our study discovers that the effect of turbulence modifies LFQPOs value significantly, by a factor of a few lower throughout the angular momentum distribution of the flow. We find a strong correlation between the turbulence and the spin parameter of the hole. Finally, we discuss the observed results in light of the present solution.
Can close-in giant exoplanets preserve detectable moons?
Authors: Sucerquia Mario , Ramírez Vanesa , Alvarado-Montes Jaime A , Zuluaga Jorge I 
Published: December 2019

ABSTRACT
Exoplanet discoveries have motivated numerous efforts to find unseen populations of exomoons, yet they have been unsuccessful. A plausible explanation is that most discovered planets are located on close-in orbits, which would make their moons prone to tidal evolution and orbital detachment. In recent models of tidally driven migration of exomoons, evolving planets might prevent what was considered their most plausible fate (i.e. colliding against their host planet), favouring scenarios where moons are pushed away and reach what we define as the satellite tidal orbital parking distance ($a_{\rm \mathrm{stop}}$), which is often within the critical limit for unstable orbits and depends mainly on the system’s initial conditions: mass ratio, semimajor axes, and rotational rates. Using semi-analytical calculations and numerical simulations, we calculate $a_{\rm \mathrm{stop}}$ for different initial system parameters and constrain the transit detectability of exomoons around close-in planets. We found that systems with Mm/Mp ≥ 10−4, which are less likely to form, are also stable and detectable with present facilities (e.g. Kepler and TESS) through their direct and secondary effects in planet + moon transit, as they are massive, oversized, and migrate slowly. In contrast, systems with lower moon-to-planet mass ratios are ephemeral and hardly detectable. Moreover, any detection, confirmation, and full characterization would require both the short cadence capabilities of TESS and high photometric sensitivity of ground-based observatories. Finally, despite the shortage of discovered long-period planets in currently available data bases, the tidal migration model adopted in this work supports the idea that they are more likely to host the first detectable exomoon.
Information theoretic bounds on cosmic string detection in CMB maps with noise
Authors: Ciuca Razvan , Hernández Oscar F 
Published: December 2019

ABSTRACT
We use a convolutional neural network to study cosmic string detection in cosmic microwave background (CMB) flat sky maps with Nambu–Goto strings. On noiseless maps, we can measure string tensions down to order 10−9, however when noise is included we are unable to measure string tensions below 10−7. Motivated by this impasse, we derive an information theoretic bound on the detection of the cosmic string tension Gμ from CMB maps. In particular, we bound the information entropy of the posterior distribution of Gμ in terms of the resolution, noise level and total survey area of the CMB map. We evaluate these bounds for the ACT, SPT-3G, Simons Observatory, Cosmic Origins Explorer, and CMB-S4 experiments. These bounds cannot be saturated by any method.
Subtle structural alterations in G-quadruplex DNA regulate site specificity of fluorescence light-up probes
Authors: Kumar Rajendra , Chand Karam , Bhowmik Sudipta , Das Rabindra Nath , Bhattacharjee Snehasish , Hedenström Mattias , Chorell Erik 
Published: December 2019

AbstractG-quadruplex (G4) DNA structures are linked to key biological processes and human diseases. Small molecules that target specific G4 DNA structures and signal their presence would therefore be of great value as chemical research tools with potential to further advance towards diagnostic and therapeutic developments. However, the development of these types of specific compounds remain as a great challenge. In here, we have developed a compound with ability to specifically signal a certain c-MYC G4 DNA structure through a fluorescence light-up mechanism. Despite the compound's two binding sites on the G4 DNA structure, only one of them result in the fluorescence light-up effect. This G-tetrad selectivity proved to originate from a difference in flexibility that affected the binding affinity and tilt the compound out of the planar conformation required for the fluorescence light-up mechanism. The intertwined relation between the presented factors is likely the reason for the lack of examples using rational design to develop compounds with turn-on emission that specifically target certain G4 DNA structures. However, this study shows that it is indeed possible to develop such compounds and present insights into the molecular details of specific G4 DNA recognition and signaling to advance future studies of G4 biology.
Co-use and Mixing Tobacco With Cannabis Among Ontario Adults
Authors: Jayakumar Navitha , Chaiton Michael , Goodwin Renee , Schwartz Robert , O’Connor Shawn , Kaufman Pamela 
Published: December 2019

Abstract

Introduction
The legalization of nonmedical cannabis in 2018 may have important implications for tobacco use in Canada. There is a risk of renormalizing tobacco use with co-use of tobacco and cannabis introducing nontobacco users to tobacco. Co-use is the use of both substances by the same individual at the same time or on different occasions, as well as mixed together. This study assessed the prevalence of co-use and mixing of tobacco and cannabis among Ontario adults and the characteristics of the users.

Aims and Methods
Data from the 1996 to 2017 cycles of the Centre for Addiction and Mental Health Monitor (n = 4481) were used to examine trends in prevalence and the proportion of Ontario adults co-using and mixing tobacco and cannabis. Logistic regression was used to study associations between user characteristics and co-use and mixing.

Results
Co-use of cigarettes and cannabis among cannabis users declined from 59.8% in 1996 to 41.7% in 2017. Past-year e-cigarette use was the only predictor of co-use. From 2015 to 2017, 31.1% (95% confidence interval 27.0, 35.9) of Ontario adults who used cannabis reported mixing it with tobacco in the past year. Being white, past-year e-cigarette use, having moderate or high nicotine dependence, and having moderate or high risk for cannabis problems were significant predictors of mixing among cannabis users.

Conclusion
Given the well-established negative health effects associated with tobacco use, alongside a growing evidence base for negative health effects of cannabis smoking, co-use and mixing could pose a considerable public health concern in the context of legalization.

Implications
Considerable effort has been expended to reduce tobacco smoking. However, current efforts to reduce tobacco smoking may be diminished since this study found the prevalence of mixing tobacco and cannabis among cannabis users in Ontario to be higher than expected. Mixing tobacco and cannabis may introduce nontobacco smokers to tobacco, exposing them to health risks associated with both cannabis and tobacco smoke. Therefore, there is a need to monitor changes in tobacco use and understanding implications for tobacco control and cessation programs within the changing environment of cannabis legalization in Canada and other jurisdictions.