bluuebunny/crossref_metadata_2025_split huggingface dataset:
Fuzzy modeling and global optimization to predict novel therapeutic targets in cancer cells
Authors: Nobile Marco S , Votta Giuseppina , Palorini Roberta , Spolaor Simone , De Vitto Humberto , Cazzaniga Paolo , Ricciardiello Francesca , Mauri Giancarlo , Alberghina Lilia , Chiaradonna Ferdinando , Besozzi Daniela 
Published: November 2019

Abstract

Motivation
The elucidation of dysfunctional cellular processes that can induce the onset of a disease is a challenging issue from both the experimental and computational perspectives. Here we introduce a novel computational method based on the coupling between fuzzy logic modeling and a global optimization algorithm, whose aims are to (1) predict the emergent dynamical behaviors of highly heterogeneous systems in unperturbed and perturbed conditions, regardless of the availability of quantitative parameters, and (2) determine a minimal set of system components whose perturbation can lead to a desired system response, therefore facilitating the design of a more appropriate experimental strategy.

Results
We applied this method to investigate what drives K-ras-induced cancer cells, displaying the typical Warburg effect, to death or survival upon progressive glucose depletion. The optimization analysis allowed to identify new combinations of stimuli that maximize pro-apoptotic processes. Namely, our results provide different evidences of an important protective role for protein kinase A in cancer cells under several cellular stress conditions mimicking tumor behavior. The predictive power of this method could facilitate the assessment of the response of other complex heterogeneous systems to drugs or mutations in fields as medicine and pharmacology, therefore paving the way for the development of novel therapeutic treatments.

Availability and implementation
The source code of FUMOSO is available under the GPL 2.0 license on GitHub at the following URL: https://github.com/aresio/FUMOSO

Supplementary information
Supplementary data are available at Bioinformatics online.
“Living long in India”– India’s progress towards Universal Health Coverage
Authors: Balraj L , Brand H 
Published: November 2019

Abstract

Issue
There are multiple small health insurance schemes throughout India. However, high out-of-pocket (OOP) expenditures, unaffordable and inequitable access to healthcare services still persist. In an attempt to address these issues and achieve Universal Health Coverage (UHC), India launched the healthcare scheme ‘Ayushman Bharat’ (“long live India”) in 2018.

Description
The Ayushman Bharat (AB) scheme has two components which include 1) transforming the existing primary healthcare centers (PHC) under the control of State Governments and 2) the National Health Protection Scheme (NHPS) also known as “ModiCare” - a health insurance. The scheme aims to transform nearly 150.000 PHCs to deliver comprehensive primary healthcare services across the country by 2022. NHPS covers the costs of almost all secondary and many tertiary care procedures of about 40% of the total Indian population. The coverage will be approximately €6.400 per year per beneficiary family; 60% of the costs are borne by the Centre and 40% by the States.

Results
Approximately €127 million have already been allocated by the Centre towards the AB scheme for the fiscal year 2018-19. Till date, around 29 million health insurance cards have been issued, approximately 1,8 million beneficiaries have been admitted and around 15.291 hospitals have been empaneled under NHPS. However, there is no data available validating the usage of the health services yet. Few Indian states are yet to implement the AB scheme.

Lessons
For the first time, attempts have been made to provide affordable healthcare services to the Indian population under a single common initiative. However, the AB scheme fails to cover outpatient health services, which are an important part of OOP expenses in India.

Main message
The effort to launch Ayushman Bharat in a big, democratic and diverse country like India has to be lauded, which not only aims to make healthcare services affordable but also aligns itself to the concept of UHC.
Risk of cardiovascular diseases after breast cancer: an analysis on a cohort of 1.3 million women
Authors: Ricceri F , Calabrese S C , Ferracin E , Di Cuonzo D , Macciotta A , d’Errico A , Franco P F , Numico G , Pagano E , Sacerdote C 
Published: November 2019

Abstract

Background
Breast cancer (BC) is the malignant tumor with the highest incidence in women in the world with an estimate of about 500,000 new cases per year in Europe. Guidelines for BC treatment include surgery followed by radiotherapy, hormonal therapy or chemotherapy. Several studies showed that BC treatment increases the risk of myocardial infarction (MI) while only few studies investigated the risk of stroke after BC.
The aim of the present study was to assess the risk of MI and stroke in BC survivors, taking into account the possible influence of treatments.

Methods
Women included in the study are part of a longitudinal cohort including all residents in the Piedmont region linked to the 2011 census data and followed-up through administrative data on mortality, hospital admissions, drug prescriptions, and outpatient consultations. Validated algorithms to identify BC incident cases and their therapies as well as to identify MI and stroke were applied.
The effect of BC on the risk of MI and stroke was tested using Cox models (adjusted for confounding variables) that allow to account for the competing risks. First, BC patients were compared to healthy women, then BC women that undertwent a specific therapy were compared with both healthy women and other BC patients.

Results
Women with BC showed an increased risk compared to healthy women for both MI (HR: 1.20; 95% CI: 1.05-1.38) and stroke (HR: 1.58; 95%CI: 1.38-1.82). Chemotherapy almost doubled the risk of MI, while radiotherapy did not seem to have a similar effect, even comparing with other BC patients. The high risk of stroke observed comparing BC (any therapy) with healthy women disappeared when comparing specific therapies among BC patients.

Conclusions
Chemotherapy increased the risk of MI in BC patients, while recent radiotherapy strategies had less impact, if any. Moreover, the mechanism for which BC patients have an increased risk of stroke seems not to be related to a late effect of therapies.

Key messages
Breast cancer women are at higher risk of developing cardio and cerebrovascular diseases and this should be taken into account when planning therapies and follow-up surveillance. Despite the increase in quality of the therapeutic approaches for breast cancer patients, chemotherapy increases the risk of myocardial infarction, while radiotherapy dangerousness recently decreased.
An innovative continuing medical education approach of general practitioners on vaccination: ForMéVac
Authors: Guagliardo C , Cortaredona S , Banide M C , Burlot E , Bouvenot J , Jozancy F , Verger P 
Published: November 2019

Abstract

Background
General practitioners (GPs) play a central role in vaccinating the population in France. In a context of mistrust regarding vaccination, and because patients increasingly question their GP about vaccines, we designed the continuing medical education (CME) module in order to 1) reinforce GPs knowledge about vaccination 2) help GPs answer questions most frequently asked by their patients and 3) evaluate the impact of this module on their vaccine prescriptions.

Methods
The CME module lasted 3 hours and focused on MMR, meningitis C and seasonal influenza vaccines; GPs were given confidential feedback information on percentages of their patients vaccinated. We included GPs practicing in Southeastern France and with less than 60% of their child patients (aged between 10 and 34 months) with 2 reimbursements of MMR vaccines (data obtained from the Health Insurance Fund). Eligible GPs were then randomly assigned to three groups: those offered either a face-to-face or e-learning CME module and a control group without CME. We used vaccine reimbursement rates for MMR 2-doses, Meningitis C, seasonal influenza as proxies for vaccine prescription rates, and a difference in differences approach to compare reimbursement rates in the year before the CME session and in the 24 months post-intervention.

Results
Compared to the control group, vaccine reimbursement rates for 2-dose MMR and meningitis C increased by 6% and 4% respectively (p &lt; 0.05) among patients of GPs who participated in the face-to-face CME session (52 GPs, with 1 842 children). For seasonal influenza vaccine, we found a 12% increase in the face-to-face group (p &lt; 0.01). We found no statistically significant increase in the e-learning group (19 GPs, with 674 children) whatever the vaccine.

Conclusions
We found a modest impact of face-to-face CME session with feedback on GPs practices for childhood vaccines and a stronger one for seasonal influenza.

Key messages
The very positive feedback from face-to-face training highlights the fact that this type of training, which bring knowledge on vaccination in general and specific vaccines to GPs, is necessary. We found weak evidence for efficiency of CME sessions associated with audit/feedback to modify GPs practices regarding MMR and meningitis C vaccines.
A content analysis of food advertising in Arab Gulf countries during Ramadan
Authors: Alyousif Zainab , Alkhunain Nahlah , Dahl Wendy J , Mathews Anne E 
Published: November 2019

Abstract
Research has explored the link between exposure to marketing of foods high in energy and low in nutrients, and obesity in Western countries. The prevalence of obesity in Arab Gulf countries is similar to that of Western countries, yet the influence of advertising and frequency of exposure to advertising of foods on subsequent food choices and health is largely unexplored. This project sought to examine the number and quality of foods advertised on television during Ramadan in Arab Gulf countries. Television programming (36 h total), 12 h each for three stations, Alwatan, Dubai and MBC, was recorded. Food and restaurant advertisements (ads) were classified, totaled and analysed for dietary healthfulness using the Model SSCg3d. Of the total ads aired (n = 1473), food and restaurant ads were the most common (20.4%). The ad type and frequency varied among channels with restaurant ads most common on Alwatan, drinks and soda ads on Dubai, and sweet snacks and desserts ads on MBC (p &lt; 0.001). Channels also differed regarding the frequency of dairy food ads (p &lt; 0.001). Most food ads promoted less healthy foods similar to marketing practices in other countries with high rates of obesity. Many ads promoted foods high in energy, saturated fat, sodium and added sugar. This work signals the need to further understand the relationship between advertising of nutrient-poor foods, food behaviours and obesity in Arab Gulf countries and how advertising regulations may address this public health issue.
Homotopy Invariance of Convolution Products
Authors: Sagave Steffen , Schwede Stefan 
Published: November 2019

AbstractThe purpose of this paper is to show that various convolution products are fully homotopical, meaning that they preserve weak equivalences in both variables without any cofibrancy hypothesis. We establish this property for diagrams of simplicial sets indexed by the category of finite sets and injections and for tame $M$-simplicial sets, with $M$ the monoid of injective self-maps of the positive natural numbers. We also show that a certain convolution product studied by Nikolaus and the 1st author is fully homotopical. This implies that every presentably symmetric monoidal $\infty $-category can be represented by a symmetric monoidal model category with a fully homotopical monoidal product.
Candida albicans enhances meropenem tolerance of Pseudomonas aeruginosa in a dual-species biofilm
Authors: Alam Farhana , Catlow Dominic , Di Maio Alessandro , Blair Jessica M A , Hall Rebecca A 
Published: November 2019

Abstract

Background
Pseudomonas aeruginosa is an opportunistic bacterium that infects the airways of cystic fibrosis patients, surfaces of surgical and burn wounds, and indwelling medical devices. Patients are prone to secondary fungal infections, with Candida albicans being commonly co-isolated with P. aeruginosa. Both P. aeruginosa and C. albicans are able to form extensive biofilms on the surfaces of mucosa and medical devices.

Objectives
To determine whether the presence of C. albicans enhances antibiotic tolerance of P. aeruginosa in a dual-species biofilm.

Methods
Single- and dual-species biofilms were established in microtitre plates and the survival of each species was measured following treatment with clinically relevant antibiotics. Scanning electron microscopy and confocal microscopy were used to visualize biofilm structure.

Results
C. albicans enhances P. aeruginosa biofilm tolerance to meropenem at the clinically relevant concentration of 5 mg/L. This effect is specific to biofilm cultures and is dependent upon C. albicans extracellular matrix polysaccharides, mannan and glucan, with C. albicans cells deficient in glycosylation structures not enhancing P. aeruginosa tolerance to meropenem.

Conclusions
We propose that fungal mannan and glucan secreted into the extracellular matrix of P. aeruginosa/C. albicans dual-species biofilms play a central role in enhancing P. aeruginosa tolerance to meropenem, which has direct implications for the treatment of coinfected patients.
World Ecology in Martineau’s and Gaskell’s Colonial Pastorals
Authors: Çelikkol Ayşe 
Published: November 2019

Abstract
The pastoral tends to offer a retreat from modern life, but Harriet Martineau and Elizabeth Gaskell reverse this pattern. They both turn to the colonies to reconcile the pastoral mode with capitalism, and, in their pastoral depictions of colonial life, we witness that mode’s peculiar capacity to narrate what the environmental historian Jason W. Moore calls ‘the capitalist world ecology’ – the globally systemic way of putting nature to work in the service of capitalism. Set in natural environments marked by human influence, the pastoral is a mode that can register economic relations with their ecological dimensions. In Martineau’s Homes Abroad and Cinnamon and Pearls – tales in Illustrations of Political Economy – and Gaskell’s Mary Barton, the pastoral aestheticizes the role that natural environments play in the development of capitalism. Homes Abroad presents peaceful agrarian life in Van Diemen’s Land as a lucrative enterprise in accord with modernization. Turning to Ceylon, Cinnamon and Pearls imagines an organic capitalism in which the celebration of plant life goes hand in hand with emergent property borders. In Mary Barton, the final pastoral setting in Canada is home to peace and progress. The felled trees in that setting signal the appropriation of nature for profit in the timber trade. These works of fiction capture the accumulation of capital in rural and suburban areas, which was historically key to the emergence of capitalism. The pastoral’s ability to depict the capitalist world ecology reflects a preoccupation with historical forces that is already present in the mode’s roots in antiquity.
Observed glitches in 8 young pulsars
Authors: Basu Avishek , Joshi Bhal Chandra , Krishnakumar M A , Bhattacharya Dipankar , Nandi Rana , Bandhopadhay Debades , Char Prasanta , Manoharan P K 
Published: November 2019

Abstract
The abrupt change in the pulse period of a pulsar is called a pulsar glitch. In this paper, we present eleven pulsar glitches detected using the Ooty Radio Telescope (ORT) and the upgraded Giant Metrewave Radio Telescope (uGMRT) in high cadence timing observations of 8 pulsars. The measured relative amplitude of glitches (Δν/ν) from our data ranges from 10−6 to 10−9. Among these glitches, three are new discoveries, being reported for the first time. We also reanalyze the largest pulsar glitch in the Crab pulsar (PSR J0534+2200) by fitting the ORT data to a new phenomenological model including the slow rise in the post-glitch evolution. We measure an exponential recovery of 30 days after the Vela glitch detected on MJD 57734 with a healing factor Q = 5.8 × 10−3. Further, we report the largest glitch (Δν/ν = 3147.9 × 10−9) so far in PSR J1731−4744.
Spectral characteristic of mid-term quasi-periodicities in sunspot data
Authors: Frick P , Sokoloff D , Stepanov R , Pipin V , Usoskin I 
Published: November 2019

ABSTRACTNumerous analyses suggest the existence of various quasi-periodicities in solar activity. The power spectrum of solar activity recorded in sunspot data is dominated by the ∼11-yr quasi-periodicity, known as the Schwabe cycle. In the mid-term range (1 month–11 yr) a pronounced variability known as a quasi-biennial oscillation is widely discussed. In the shorter time-scale a pronounced peak, corresponding to the synodic solar rotation period (∼27 d), is observed. Here we revisit the mid-term solar variability in terms of statistical dynamics of fully turbulent systems, where solid arguments are required to accept an isolated dominant frequency in a continuous (smooth) spectrum. For this, we first undertook an unbiased analysis of the standard solar data, sunspot numbers and the F10.7 solar radio flux index, by applying a wavelet tool, which allows one to perform a frequency–time analysis of the signal. Considering the spectral dynamics of solar activity cycle by cycle, we showed that no single periodicity can be separated, in a statistically significant manner, in the specified range of periods. We examine whether a model of the solar dynamo can reproduce the mid-term oscillation pattern observed in solar data. We found that a realistically observed spectrum can be explained if small spatial (but not temporal) scales are effectively smoothed. This result is important because solar activity is a global feature, although monitored via small-scale tracers like sunspots.
Stellar cosmic rays as an important source of ionisation in protoplanetary disks: a disk mass dependent process
Authors: Rodgers-Lee D , Taylor A M , Downes T P , Ray T P 
Published: November 2019

Abstract
We assess the ionising effect of low energy protostellar cosmic rays in protoplanetary disks around a young solar mass star for a wide range of disk parameters. We assume a source of low energy cosmic rays located close to the young star which travel diffusively through the protoplanetary disk. We use observationally inferred values from nearby star-forming regions for the total disk mass and the radial density profile. We investigate the influence of varying the disk mass within the observed scatter for a solar mass star. We find that for a large range of disk masses and density profiles that protoplanetary disks are “optically thin” to low energy (∼3 GeV) cosmic rays. At R ∼ 10 au, for all of the disks that we consider (Mdisk = 6.0 × 10−4 − 2.4 × 10−2M⊙), the ionisation rate due to low energy stellar cosmic rays is larger than that expected from unmodulated galactic cosmic rays. This is in contrast to our previous results which assumed a much denser disk which may be appropriate for a more embedded source. At R ∼ 70 au, the ionisation rate due to stellar cosmic rays dominates in ∼50% of the disks. These are the less massive disks with less steep density profiles. At this radius there is at least an order of magnitude difference in the ionisation rate between the least and most massive disk that we consider. Our results indicate, for a wide range of disk masses, that low energy stellar cosmic rays provide an important source of ionisation at the disk midplane at large radii (∼70 au).
Pain Care in the Department of Veterans Affairs: Understanding How a Cultural Shift in Pain Care Impacts Provider Decisions and Collaboration
Authors: Mattocks Kristin , Rosen Marc I , Sellinger John , Ngo Tu , Brummett Brad , Higgins Diana M , Reznik Thomas E , Holtzheimer Paul , Semiatin Alicia M , Stapley Todd , Martino Steve 
Published: November 2019

Abstract

Objective
Over the past decade, the Department of Veterans Affairs (VA) has experienced a sizeable shift in its approach to pain. The VA’s 2009 Pain Management Directive introduced the Stepped Care Model, which emphasizes an interdisciplinary approach to pain management involving pain referrals and management from primary to specialty care providers. Additionally, the Opioid Safety Initiative and 2017 VA/Department of Defense (DoD) clinical guidelines on opioid prescribing set a new standard for reducing opioid use in the VA. These shifts in pain care have led to new pain management strategies that rely on multidisciplinary teams and nonpharmacologic pain treatments. The goal of this study was to examine how the cultural transformation of pain care has impacted providers, the degree to which VA providers are aware of pain care services at their facilities, and their perceptions of multidisciplinary care and collaboration across VA disciplines.

Methods
We conducted semistructured phone interviews with 39 VA clinicians in primary care, mental health, pharmacy, and physical therapy/rehabilitation at eight Veterans Integrated Service Network medical centers in New England.

Results
We identified four major themes concerning interdisciplinary pain management approaches: 1) the culture of VA pain care has changed dramatically, with a greater focus on nonpharmacologic approaches to pain, though many “old school” providers continue to prefer medication options; 2) most facilities in this sample have no clear roadmap about which pain treatment pathway to follow, with many providers unaware of what treatment to recommend when; 3) despite multiple options for pain treatment, VA multidisciplinary teams generally work together to ensure that veterans receive coordinated pain care; and 4) veteran preferences for care may not align with existing pain care pathways.

Conclusions
The VA has shifted its practices regarding pain management, with a greater emphasis on nonpharmacologic pain options. The proliferation of nonpharmacologic pain management strategies requires stakeholders to know how to choose among alternative treatments.