bluuebunny/crossref_metadata_2025_split huggingface dataset:
Health IT, hacking, and cybersecurity: national trends in data breaches of protected health information
Authors: Ronquillo Jay G , Erik Winterholler J , Cwikla Kamil , Szymanski Raphael , Levy Christopher 
Published: June 2018

Abstract

Objective
The rapid adoption of health information technology (IT) coupled with growing reports of ransomware, and hacking has made cybersecurity a priority in health care. This study leverages federal data in order to better understand current cybersecurity threats in the context of health IT.

Materials and Methods
Retrospective observational study of all available reported data breaches in the United States from 2013 to 2017, downloaded from a publicly available federal regulatory database.

Results
There were 1512 data breaches affecting 154 415 257 patient records from a heterogeneous distribution of covered entities (P &lt; .001). There were 128 electronic medical record-related breaches of 4 867 920 patient records, while 363 hacking incidents affected 130 702 378 records.

Discussion and Conclusion
Despite making up less than 25% of all breaches, hacking was responsible for nearly 85% of all affected patient records. As medicine becomes increasingly interconnected and informatics-driven, significant improvements to cybersecurity must be made so our health IT infrastructure is simultaneously effective, safe, and secure.
The Future Colorectal Cancer Burden Attributable to Modifiable Behaviors: A Pooled Cohort Study
Authors: Vajdic Claire M , MacInnis Robert J , Canfell Karen , Hull Peter , Arriaga Maria E , Hirani Vasant , Cumming Robert G , Mitchell Paul , Byles Julie E , Giles Graham G , Banks Emily , Taylor Anne W , Shaw Jonathan E , Magliano Dianna J , Marker Julie , Adelstein Barbara-Ann , Gill Tiffany K , Laaksonen Maarit A 
Published: June 2018

Abstract

Background
Previous estimates of the colorectal cancer (CRC) burden attributed to behaviors have not considered joint effects, competing risk, or population subgroup differences.

Methods
We pooled data from seven prospective Australian cohort studies (n = 367 058) and linked them to national registries to identify CRCs and deaths. We estimated the strength of the associations between behaviors and CRC risk using a parametric piecewise constant hazards model, adjusting for age, sex, study, and other behaviors. Exposure prevalence was estimated from contemporary National Health Surveys. We calculated population attributable fractions for CRC preventable by changes to current behaviors, accounting for competing risk of death and risk factor interdependence. Statistical tests were two-sided.

Results
During the first 10 years of follow-up, there were 3471 incident CRCs. Overweight or obesity explained 11.1%, ever smoking explained 10.7% (current smoking 3.9%), and drinking more than two compared with two or fewer alcoholic drinks per day explained 5.8% of the CRC burden. Jointly, these factors were responsible for 24.9% (95% confidence interval [CI] = 19.7% to 29.9%) of the burden, higher for men (36.7%) than women (13.2%, Pdifference < .001). The burden attributed to these factors was also higher for those born in Australia (28.7%) than elsewhere (16.8%, Pdifference = .047). We observed modification of the smoking-attributable burden by alcohol consumption and educational attainment, and modification of the obesity-attributable burden by age group and birthplace.

Conclusions
We produced up-to-date estimates of the future CRC burden attributed to modifiable behaviors. We revealed novel differences between men and women, and other high–CRC burden subgroups that could potentially benefit most from programs that support behavioral change and early detection.
Studying language evolution in the age of big data
Authors: Bhattacharya Tanmoy , Retzlaff Nancy , Blasi Damián E , Croft William , Cysouw Michael , Hruschka Daniel , Maddieson Ian , Müller Lydia , Smith Eric , Stadler Peter F , Starostin George , Youn Hyejin 
Published: June 2018

AbstractThe increasing availability of large digital corpora of cross-linguistic data is revolutionizing many branches of linguistics. Overall, it has triggered a shift of attention from detailed questions about individual features to more global patterns amenable to rigorous, but statistical, analyses. This engenders an approach based on successive approximations where models with simplified assumptions result in frameworks that can then be systematically refined, always keeping explicit the methodological commitments and the assumed prior knowledge. Therefore, they can resolve disputes between competing frameworks quantitatively by separating the support provided by the data from the underlying assumptions. These methods, though, often appear as a ‘black box’ to traditional practitioners. In fact, the switch to a statistical view complicates comparison of the results from these newer methods with traditional understanding, sometimes leading to misinterpretation and overly broad claims. We describe here this evolving methodological shift, attributed to the advent of big, but often incomplete and poorly curated data, emphasizing the underlying similarity of the newer quantitative to the traditional comparative methods and discussing when and to what extent the former have advantages over the latter. In this review, we cover briefly both randomization tests for detecting patterns in a largely model-independent fashion and phylolinguistic methods for a more model-based analysis of these patterns. We foresee a fruitful division of labor between the ability to computationally process large volumes of data and the trained linguistic insight identifying worthy prior commitments and interesting hypotheses in need of comparison.
Gardening in Displacement: The Benefits of Cultivating in Crisis
Authors: Millican Juliet , Perkins Carrie , Adam-Bradford Andrew 
Published: June 2018

AbstractWhile the benefits of gardening to mental health and trauma recovery are well documented, and a number of voluntary organizations have been involved in developing gardens with refugees, as yet there is no clear mandate to allow and mainstream gardening in large-scale refugee camps. This article argues for the importance of this in the planning of camps on the basis that many crises are indeed protracted, that refugees often stay in camps for tens of years rather than months and that gardening has significant environmental, psychological and social benefits, as well as contributing to food sovereignty and sustainable drainage. Drawing on interviews with residents of a refugee camp in northern Iraq, all participants in a camp-based garden competition in 2016 and 2017, this article illustrates the benefits of gardening and argues for their sustained inclusion in camp design.
Cigarette smoke modifies and inactivates SPLUNC1, leading to airway dehydration
Authors: Moore Patrick J. , Reidel Boris , Ghosh Arunava , Sesma Juliana , Kesimer Mehmet , Tarran Robert 
Published: June 2018

ABSTRACTChronic obstructive pulmonary disease (COPD) is a growing cause of morbidity and mortality worldwide. Cigarette smoke (CS) exposure, a major cause of COPD, dysregulates airway epithelial ion transport and diminishes airway surface liquid (ASL) volume. Short palate lung and nasal epithelial clone 1 (SPLUNC1) is secreted into the airway lumen where it maintains airway hydration via interactions with the epithelial Na+ channel (ENaC). Although ASL hydration is dysregulated in CS‐exposed/COPD airways, effects of CS on SPLUNC1 have not been elucidated. We hypothesized that CS alters SPLUNC1 activity, therefore contributing to ASL dehydration. CS exposure caused irreversible SPLUNC1 aggregation and prevented SPLUNC1 from internalizing ENaC and maintaining ASL hydration. Proteomic analysis revealed αβ‐unsaturated aldehyde modifications to SPLUNCL's cysteine residues. Removal of these cysteines prevented SPLUNC1 from regulating ENaC/ASL volume. In contrast, SPX‐101, a peptide mimetic of natural SPLUNC1, that internalizes ENaC, but does not contain cysteines was unaffected by CS. SPX‐101 increased ASL hydration and attenuated ENaC activity in airway cultures after CS exposure and prolonged survival in a chronic airway disease model. These findings suggest that the CS‐induced defects in SPLUNC1 can be circumvented, thus making SPX‐101 a novel candidate for the treatment of mucus dehydration in COPD.—Moore, P. J., Reidel, B., Ghosh, A., Sesma, J., Kesimer, M., Tarran, R. Cigarette smoke modifies and inactivates SPLUNC1, leading to airway dehydration. FASEB J. 32, 6559–6574 (2018). www.fasebj.org
FoxA2 regulates the type II collagen–induced nucleus pulposus–like differentiation of adipose‐derived stem cells by activation of the Shh signaling pathway
Authors: Zhou Xiaopeng , Ma Chiyuan , Hu Bin , Tao Yiqing , Wang Jingkai , Huang Xianpeng , Zhao Tengfei , Han Bin , Li Hao , Liang Chengzhen , Chen Qixin , Li Fangcai 
Published: June 2018

ABSTRACTAdipose tissue–derived stem cell (ADSC)–based therapy is promising for the treatment of intervertebral disc (IVD) degeneration, but the difficulty in inducing nucleus pulposus (NP)–like differentiation limits its clinical applications. Forkhead box (Fox)‐A2 is an essential transcription factor for the formation of a normal NP. We demonstrated that type II collagen stimulates NP‐like differentiation of ADSCs, partly by increasing the expression of FoxA2. We constructed FoxA2‐overexpressing and ‐knockdown ADSCs by using lentiviral vectors. FoxA2 overexpression significantly enhanced NP‐specific gene expression and the synthesis of glycosaminoglycan and collagen, whereas FoxA2 knockdown decreased NP‐like differentiation and the expression of aggrecan and collagen II. The enhanced NP‐like differentiation related to FoxA2 overexpression was partially rescued by an Shh signaling pathway inhibitor. In addition, FoxA2 inhibited the expression of Itg‐α2 and further promoted NP‐like differentiation induced by type II collagen. Furthermore, FoxA2‐overexpressing ADSCs combined with type II collagen hydrogels promoted regeneration of degenerated NP in vivo. Our findings suggest that FoxA2 plays an essential role in the NP‐like differentiation of ADSCs by activating the Shh signaling pathway.—Zhou, X., Ma, C., Hu, B., Tao, Y., Wang, J., Huang, X., Zhao, T., Han, B., Li, H., Liang, C., Chen, Q., Li, F. FoxA2 regulates the type II collagen–induced nucleus pulposus–like differentiation of adipose‐derived stem cells by activation of the Shh signaling pathway. FASEB J. 32, 6582–6595 (2018). www.fasebj.org
Candida albicanshyphal expansion causes phagosomal membrane damage and luminal alkalinization
Authors: Westman Johannes , Moran Gary , Mogavero Selene , Hube Bernhard , Grinstein Sergio 
Published: June 2018

ABSTRACTMacrophages rely on phagosomal acidity to destroy engulfed microorganisms. To survive this hostile response, opportunistic fungi such asCandida albicansdeveloped strategies to evade the acidic environment.C. albicansis polymorphic, able to convert from yeast to hyphae, and this transition is required to subvert the microbicidal activity of the phagosome. However, the phagosomal lumen, which is acidic and nutrient-deprived, inhibits yeast-to-hypha transition. To account for this apparent paradox, it was recently proposed thatC. albicansproduces ammonia that alkalinizes the phagosome, thus facilitating yeast-to-hypha transformation. We re-examined the mechanism underlying phagosomal alkalinization by applying dual-wavelength ratiometric pH measurements. The phagosomal membrane was found to be highly permeable to ammonia, which is therefore unlikely to account for the pH elevation. Instead, we find that yeast-to-hypha transition begins within acidic phagosomes, and that alkalinization is a consequence of proton leakage induced by excessive membrane distension caused by the expanding hypha.IMPORTANCEC. albicansis the most common nosocomial fungal infection, and over three million people acquire life-threatening invasive fungal infections every year. Even if antifungal drugs exist, almost half of these patients will die. Despite this, fungi remain underestimated as pathogens. Our study uses quantitative biophysical approaches to demonstrate that the yeast-to-hypha transition occurs within the nutrient deprived, acidic phagosome and that alkalinization is a consequence, as opposed to the cause of hyphal growth.
Rapid, specific detection and quantification ofYersinia pestisusing a species-specific SNP in the ferric uptake regulator gene (furMAMA)
Authors: Nilsson Pernille , Gurbanov Shair , Easterday W. Ryan 
Published: June 2018

AbstractYersinia pestis, the causative agent of plague, is responsible for about 700 human cases of bubonic and pneumonic plague each year. Yet the disease is far more prevalent within rodent reservoirs than in humans. One of the main means of outbreak prevention is extensive wildlife surveillance, where accurate and rapid detection is essential to prevent spillover into the human population from which, it may otherwise spread more rapidly and over larger distances. Moreover, detection and quantification of the agent aids in investigative studies to understand aspects of the pathogen such as transmission mechanics, pathology, contamination risk and more. Partially based on a previously developed assay by Gabitzsch et al. 2008 we designed a TaqMan®mismatch amplification mutation assay (TaqMAMA) where a primer leverages a species-specific SNP in the chromosomal single copy ferric uptake regulator gene ofYersinia pestis. The assay allows for specific, rapid detection and quantification ofYersinia pestisusing only a single species-specific marker in a highly conserved virulence gene. This low-cost and simple modification of an existing assay eliminates the need for running multiple molecular markers for pathogen detection or performing time-consuming culturing and counting of colonies for quantification.
The dynamics of cortical GABA in human motor learning
Authors: Kolasinski James , Hinson Emily L. , Divanbeighi Zand Amir P. , Rizov Assen , Emir Uzay E. , Stagg Charlotte J. 
Published: June 2018

The ability to learn novel motor skills is both a central part of our daily lives and can provide a model for rehabilitation after a stroke. However, there are still fundamental gaps in our understanding of the physiological mechanisms that underpin human motor plasticity. The acquisition of new motor skills is dependent on changes in local circuitry within the primary motor cortex (M1). This reorganisation has been hypothesised to be facilitated by a decrease in local inhibition via modulation of the neurotransmitter GABA, but this link has not been conclusively demonstrated in humans. Here, we used 7T MR Spectroscopy to investigate the dynamics of GABA concentrations in human M1 during the learning of an explicit, serial reaction time task. We observed a significant reduction in GABA concentration during motor learning that was not seen in an equivalent motor task lacking a learnable sequence, nor during a passive resting task of the same duration. No change in glutamate was observed in any group. Furthermore, baseline M1 GABA was strongly predictive of the degree of subsequent learning, such that greater inhibition was associated with poorer subsequent learning. This result suggests that higher levels of cortical inhibition may present a barrier that must be surmounted in order achieve an increase in M1 excitability, and hence encoding of a new motor skill. These results provide strong support for the mechanistic role of GABAergic inhibition in motor plasticity, raising questions regarding the link between population variability in motor learning and GABA metabolism in the brain.Funding informationJ.K.:Wellcome Trust Sir Henry Wellcome Postdoctoral Fellowship (204696/Z/16/Z). C.J.S.: Wellcome Trust/Royal Society Henry Dale Fellowships (102584/Z/13/Z).
Pulling the covers in electronic health records for an association study with self-reported sleep behaviors
Authors: Rhoades Seth D. , Bastarache Lisa , Denny Joshua C. , Hughey Jacob J. 
Published: June 2018

AbstractThe electronic health record (EHR) contains rich histories of clinical care, but has not traditionally been mined for information related to sleep habits. Here we performed a retrospective EHR study and derived a cohort of 3,652 individuals with self-reported sleep behaviors, documented from visits to the sleep clinic. These individuals were obese (mean body mass index 33.6 kg/m2) and had a high prevalence of sleep apnea (60.5%), however we found sleep behaviors largely concordant with prior prospective cohort studies. In our cohort, average wake time was one hour later and average sleep duration was 40 minutes longer on weekends than on weekdays (p<1·10−12). Sleep duration also varied considerably as a function of age, and tended to be longer in females and in whites. Additionally, through phenome-wide association analyses, we found an association of long weekend sleep with depression, and an unexpectedly large number of associations of long weekday sleep with mental health and neurological disorders (q<0.05). We then sought to replicate previously published genetic associations with morning/evening preference on a subset of our cohort with extant genotyping data (n=555). While those findings did not replicate in our cohort, a polymorphism (rs3754214) in high linkage disequilibrium with a previously published polymorphism nearTARS2was associated with long sleep duration (p<0.01). Collectively, our results highlight the potential of the EHR for uncovering the correlates of human sleep in real-world populations.
Transient and sustained control mechanisms supporting novel instructed behavior
Authors: Palenciano Ana F. , González-García Carlos , Arco Juan E. , Ruz María 
Published: June 2018

AbstractThe success of humans in novel environments is partially supported by our ability to implement new task procedures via instructions. This complex skill has been associated with the activity of control-related brain areas. Current models link fronto-parietal and a cingulo-opercular networks with transient and sustained modes of cognitive control, based on observations during repetitive task settings or rest (Dosenbach et al. 2008). The current study extends this dual model to novel instructed tasks. We employed a mixed design and an instruction-following task to extract phasic and tonic brain signals associated with the encoding and implementation of novel verbal rules. We also performed a representation similarity analysis to capture consistency in task-set encoding within trial epochs. Our findings show that both networks are involved while following novel instructions: transiently, during the implementation of the instruction, and in a sustained fashion, across novel trials blocks. Moreover, the multivariate results showed that task representations in the cingulo-opercular network were more stable than in the fronto-parietal one. Our data extend the dual model of cognitive control to novel demanding situations, highlighting the high flexibility of control-related regions in adopting different temporal profiles.
Essential Roles of theSPPRAFructose-Phosphate Phosphohydrolase Operon in Carbohydrate Metabolism and Virulence Expression byStreptococcus Mutans
Authors: Zeng Lin , Burne Robert A. 
Published: June 2018

AbstractThe dental caries pathogenStreptococcus mutanscan ferment a variety of sugars to produce organic acids. Exposure ofS. mutansto certain non-metabolizable carbohydrates such as xylitol impairs growth and can cause cell death. Recently, the presence of a sugar-phosphate stress inS. mutanswas demonstrated using a mutant lacking 1-phosphofructokinase (FruK) that accumulates fructose-1-phosphate (F-1-P). Here we studied an operon inS. mutans, sppRA, which was highly expressed in thefruKmutant. Biochemical characterization of a recombinant SppA protein indicated that it possessed hexose-phosphate phosphohydrolase activity, with preferences for F-1-P and, to a lesser degree, fructose-6-phosphate (F-6-P). SppA activity was stimulated by Mg2+and Mn2+, but inhibited by NaF. SppR, a DeoR-family regulator, repressed the expression of thesppRAoperon to minimum levels in the absence of the fructose-derived metabolites, F-1-P and likely also F-6-P. Accumulation of F-1-P, as a result of growth on fructose, not only inducedsppAexpression, it significantly altered biofilm maturation through increased cell lysis and enhanced extracellular DNA release. Constitutive expression ofsppA, via a plasmid or by deletingsppR, greatly alleviated fructose-induced stress in afruKmutant, enhanced resistance to xylitol, and reversed effects of fructose on biofilm formation. Finally, by identifying three additional putative phosphatases that are capable of promoting sugar-phosphate tolerance, we show thatS. mutansis capable of mounting a sugar-phosphate stress response by modulating the levels of certain glycolytic intermediates, functions that are interconnected with the ability of the organism to manifest key virulence behaviors.ImportanceStreptococcus mutansis a major etiologic agent for dental caries, primarily due to its ability to form biofilms on tooth surface and to convert carbohydrates into organic acids. We have discovered a two-gene operon inS. mutansthat regulates fructose metabolism by controlling the levels of fructose-1-phosphate, a potential signaling compound that affects bacterial behaviors. With fructose becoming increasingly common and abundant in the human diet, we reveal the ways fructose may alter bacterial development, stress tolerance, and microbial ecology in the oral cavity to promote oral diseases.
Spectrum of Neandertal introgression across modern-day humans indicates multiple episodes of human-Neandertal interbreeding
Authors: Villanea Fernando A. , Schraiber Joshua G. 
Published: June 2018

1AbstractNeandertals and anatomically modern humans overlapped geographically for a period of over 30,000 years following human migration out of Africa. During this period, Neandertals and humans interbred, as evidenced by Neandertal portions of the genome carried by non-African individuals today. A key observation is that the proportion of Neandertal ancestry is ∼12-20% higher in East Asian individuals relative to European individuals. Here, we explore various demographic models that could explain this observation. These include distinguishing between a single admixture event and multiple Neandertal contributions to either population, and the hypothesis that reduced Neandertal ancestry in modern Europeans resulted from more recent admixture with a ghost population that lacked a Neandertal ancestry component (the “dilution” hypothesis). In order to summarize the asymmetric pattern of Neandertal allele frequencies, we compile the joint fragment frequency spectrum (FFS) of European and East Asian Neandertal fragments and compare it to both analytical theory and data simulated under various models of admixture. Using maximum likelihood and machine learning, we found that a simple model of a single admixture does not fit the empirical data, and instead favor a model of multiple episodes of gene flow into both European and East Asian populations. These findings indicate more long-term, complex interaction between humans and Neandertals than previously appreciated.