bluuebunny/crossref_metadata_2025_split huggingface dataset:
A High-Resolution View of Adaptive Event Dynamics in a Plasmid
Authors: Mei Han , Arbeithuber Barbara , Cremona Marzia A , DeGiorgio Michael , Nekrutenko Anton 
Published: September 2019

AbstractCoadaptation between bacterial hosts and plasmids frequently results in adaptive changes restricted exclusively to host genome leaving plasmids unchanged. To better understand this remarkable stability, we transformed naïve Escherichia coli cells with a plasmid carrying an antibiotic-resistance gene and forced them to adapt in a turbidostat environment. We then drew population samples at regular intervals and subjected them to duplex sequencing—a technique specifically designed for identification of low-frequency mutations. Variants at ten sites implicated in plasmid copy number control emerged almost immediately, tracked consistently across the experiment’s time points, and faded below detectable frequencies toward the end. This variation crash coincided with the emergence of mutations on the host chromosome. Mathematical modeling of trajectories for adaptive changes affecting plasmid copy number showed that such mutations cannot readily fix or even reach appreciable frequencies. We conclude that there is a strong selection against alterations of copy number even if it can provide a degree of growth advantage. This incentive is likely rooted in the complex interplay between mutated and wild-type plasmids constrained within a single cell and underscores the importance of understanding of intracellular plasmid variability.
Benefit-Finding Intervention Delivered Individually to Alzheimer Family Caregivers: Longer-Term Outcomes of a Randomized Double-Blind Controlled Trial
Authors: Cheng Sheung-Tak , Mak Emily P M , Kwok Timothy , Fung Helene , Lam Linda C W 
Published: September 2019

Abstract

Objectives
To examine the longer-term effects of benefit-finding on caregivers’ depressive symptoms (primary outcome), and global burden, role overload, psychological well-being, and positive aspects of caregiving (secondary outcomes).

Method
Ninety-six Hong Kong Chinese caregivers of relatives with Alzheimer’s disease were randomly assigned to receive the benefit-finding intervention (BFT) or one of the two control conditions, namely, simplified psychoeducation (lectures only; SIM-PE) or standard psychoeducation (STD-PE). Caregivers received four biweekly one-to-one interventions of 3 hours each at their own homes. We focused on outcomes measured at 4- and 10-month follow-ups. The trajectories of intervention effects were modeled by BFT × time and BFT × time2 interaction terms.

Results
Mixed-effects regression showed significant BFT × time2 interaction effects on depressive symptoms against both control conditions, suggesting diminishing BFT effects over time. Z tests showed that, compared with controls, BFT participants reported substantial reductions in depressive symptoms at 4-month follow-up (d = −0.85 and −0.75 vs. SIM-PE and STD-PE, respectively). For depressive symptoms measured at 10-month follow-up, BFT was indistinguishable from STD-PE, whereas a moderate effect was observed in comparison with SIM-PE (d = −0.52). Moreover, positive aspects of caregiving, but not other secondary outcomes, continued to show intervention effect up to 10-month follow-up.

Discussion
Benefit-finding is an efficacious intervention for depressive symptoms in Alzheimer caregivers, with strong effects in the medium-term post-intervention and possible moderate effects in the longer-term post-intervention.
The Roles of Marital Dissolution and Subsequent Repartnering on Loneliness in Later Life
Authors: Wright Matthew R , Hammersmith Anna M , Brown Susan L , Lin I-Fen 
Published: September 2019

Abstract

Objectives
Loneliness in later life is associated with poorer health and higher risk of mortality. Our study assesses whether gray divorced adults report higher levels of loneliness than the widowed and whether social support or repartnership offset loneliness.

Method
Using data from the 2010 and 2012 Health and Retirement Study, we estimated ordinary least squares regression models for women (n = 2,362) and men (n = 1,127) to examine differences in loneliness by dissolution pathway (i.e., divorce versus widowhood), accounting for social support and repartnership.

Results
Divorced men were lonelier than their widowed counterparts. Although social support reduced loneliness among men, the difference between the divorced and widowed persisted. Repartnership assuaged men’s loneliness and reduced the variation between divorced and widowed men. Among women, the results did not reveal differences in loneliness for the divorced and widowed although social support and repartnership linked to less loneliness.

Discussion
Later-life marital dissolutions increasingly occur through divorce rather than spousal death. Some older adults go on to form new partnerships. Our findings demonstrate the importance of gerontological research widening the lens beyond widowhood to consider the ramifications of later-life divorce and repartnership for well-being.
The Cost-effectiveness of Initial Immunomodulators or Infliximab Using Modern Optimization Strategies for Crohn’s Disease in the Biosimilar Era
Authors: Vasudevan Abhinav , Ip Francis , Liew Danny , Van Langenberg Daniel R 
Published: September 2019

Abstract

Background
Treatment cost, efficacy, and safety are integral considerations when optimizing management of Crohn’s disease (CD). This study assessed the cost-effectiveness of initial immunomodulator and anti–tumor necrosis factor (anti-TNF) agents for the treatment of CD from a US third-party perspective, incorporating current treatment algorithms, optimization strategies, and reduced costs availed by biosimilars.

Method
A 1-year Markov model was developed to simulate the cost and quality-adjusted life-years (QALYs) of initial azathioprine, infliximab, and combination therapy for moderate to severe CD. Treatment was changed based on tolerability and clinical disease activity at 3-monthly intervals. Efficacy data were based on published literature.

Results
Initial azathioprine had the lowest cost and utility ($35,337 and 0.63 QALYs), whereas combination therapy was the costliest yet conferred the highest health benefits ($57,638 and 0.67 QALYs). The incremental cost-effectiveness of infliximab and combination therapy compared with azathioprine were both in excess of $500,000 per QALY gained. Initial azathioprine remained the most cost-effective treatment on sensitivity analysis compared with infliximab and combination therapy, with 90% reductions in anti-TNF therapy costs and a 5-year time horizon, although combination therapy had an acceptable cost-effectiveness when costs were reduced in the extended model. Initial infliximab, ustekinumab, and vedolizumab were dominated by combination therapy.

Conclusions
In the biosimilar era, initial azathioprine with escalation to infliximab appeared more cost-effective in the short term compared with infliximab or combination therapy, although initial combination therapy yields acceptable ICERs in the long term with continued reductions in anti-TNF therapy costs and will likely be the preferred treatment strategy in the future.
Between hard and soft thresholding: optimal iterative thresholding algorithms
Authors: Liu Haoyang , Foygel Barber Rina 
Published: September 2019

AbstractIterative thresholding algorithms seek to optimize a differentiable objective function over a sparsity or rank constraint by alternating between gradient steps that reduce the objective and thresholding steps that enforce the constraint. This work examines the choice of the thresholding operator and asks whether it is possible to achieve stronger guarantees than what is possible with hard thresholding. We develop the notion of relative concavity of a thresholding operator, a quantity that characterizes the worst-case convergence performance of any thresholding operator on the target optimization problem. Surprisingly, we find that commonly used thresholding operators, such as hard thresholding and soft thresholding, are suboptimal in terms of worst-case convergence guarantees. Instead, a general class of thresholding operators, lying between hard thresholding and soft thresholding, is shown to be optimal with the strongest possible convergence guarantee among all thresholding operators. Examples of this general class includes $\ell _q$ thresholding with appropriate choices of $q$ and a newly defined reciprocal thresholding operator. We also investigate the implications of the improved optimization guarantee in the statistical setting of sparse linear regression and show that this new class of thresholding operators attain the optimal rate for computationally efficient estimators, matching the Lasso.
Cohort selection for clinical trials: n2c2 2018 shared task track 1
Authors: Stubbs Amber , Filannino Michele , Soysal Ergin , Henry Samuel , Uzuner Özlem 
Published: September 2019

AbstractObjectiveTrack 1 of the 2018 National NLP Clinical Challenges shared tasks focused on identifying which patients in a corpus of longitudinal medical records meet and do not meet identified selection criteria.Materials and MethodsTo address this challenge, we annotated American English clinical narratives for 288 patients according to whether they met these criteria. We chose criteria from existing clinical trials that represented a variety of natural language processing tasks, including concept extraction, temporal reasoning, and inference.ResultsA total of 47 teams participated in this shared task, with 224 participants in total. The participants represented 18 countries, and the teams submitted 109 total system outputs. The best-performing system achieved a micro F1 score of 0.91 using a rule-based approach. The top 10 teams used rule-based and hybrid systems to approach the problems.DiscussionClinical narratives are open to interpretation, particularly in cases where the selection criterion may be underspecified. This leaves room for annotators to use domain knowledge and intuition in selecting patients, which may lead to error in system outputs. However, teams who consulted medical professionals while building their systems were more likely to have high recall for patients, which is preferable for patient selection systems.ConclusionsThere is not yet a 1-size-fits-all solution for natural language processing systems approaching this task. Future research in this area can look to examining criteria requiring even more complex inferences, temporal reasoning, and domain knowledge.
Discretionary Authority and Prioritizing in Government Agencies
Authors: Schinkel Maarten Pieter , Tóth Lukáš , Tuinstra Jan 
Published: September 2019

AbstractGovernment agencies have a certain freedom to choose among different possible courses of action. This article studies agency decision making on priorities in a principal–agent framework with multiple tasks. Agency leadership has discretion over part of the agency’s budget to incentivize staff in the pickup of cases. The head is concerned not only with society’s benefits from the agency’s overall performance, but also with the organization’s public image. Based on their talent and the contracts offered by the head, staff officials choose which type of task to pursue: complex major cases with an uncertain outcome or basic minor and simple cases with a higher probability of success. We show how the size of the agency’s discretionary budget influences both the scale and type of tasks it will engage in. Small changes in the budget can cause extensive restructuring from major to minor tasks, or vice versa, causing social welfare jumps. The mechanism provides overhead authorities with some control over the priorities of supposedly independent agencies. It applies generally to government bureaus with the formal and informal discretion to choose their tasks. Antitrust authorities serve as one illustration of implications for institutional design.
An Old Disease Comes Back: Reporting 2 Cases of Neonatal Measles
Authors: Capasso Letizia , Lepore Lorenza , Lo Vecchio Andrea , Caprio Maria Grazia , Vallone Gianfranco , Raimondi Francesco 
Published: September 2019

Abstract
We report two cases of neonatal measles (one congenital and one post natal infection) admitted to our neonatal intensive care unit and discuss the management. This report intend to keep alert against measles and point out the risk for susceptible pregnant women and their offspring in countries with reduction of coverage from anti measles vaccine.
CRISPR/Cas9-mediated targeted mutagenesis for functional genomics research of crassulacean acid metabolism plants
Authors: Liu Degao , Chen Mei , Mendoza Brian , Cheng Hua , Hu Rongbin , Li Linling , Trinh Cong T , Tuskan Gerald A , Yang Xiaohan 
Published: September 2019

Abstract
Crassulacean acid metabolism (CAM) is an important photosynthetic pathway in diverse lineages of plants featuring high water-use efficiency and drought tolerance. A big challenge facing the CAM research community is to understand the function of the annotated genes in CAM plant genomes. Recently, a new genome editing technology using CRISPR/Cas9 has become a more precise and powerful tool than traditional approaches for functional genomics research in C3 and C4 plants. In this study, we explore the potential of CRISPR/Cas9 to characterize the function of CAM-related genes in the model CAM species Kalanchoë fedtschenkoi. We demonstrate that CRISPR/Cas9 is effective in creating biallelic indel mutagenesis to reveal previously unknown roles of blue light receptor phototropin 2 (KfePHOT2) in the CAM pathway. Knocking out KfePHOT2 reduced stomatal conductance and CO2 fixation in late afternoon and increased stomatal conductance and CO2 fixation during the night, indicating that blue light signaling plays an important role in the CAM pathway. Lastly, we provide a genome-wide guide RNA database targeting 45 183 protein-coding transcripts annotated in the K. fedtschenkoi genome.
Frequency and Evolution of New Postoperative Enhancement on 3 Tesla Intraoperative and Early Postoperative Magnetic Resonance Imaging
Authors: Miskin Nityanand , Unadkat Prashin , Carlton Michael E , Golby Alexandra J , Young Geoffrey S , Huang Raymond Y 
Published: September 2019

Abstract

BACKGROUND
Intraoperative magnetic resonance imaging (IO-MRI) provides real-time assessment of extent of resection of brain tumor. Development of new enhancement during IO-MRI can confound interpretation of residual enhancing tumor, although the incidence of this finding is unknown.

OBJECTIVE
To determine the frequency of new enhancement during brain tumor resection on intraoperative 3 Tesla (3T) MRI. To optimize the postoperative imaging window after brain tumor resection using 1.5 and 3T MRI.

METHODS
We retrospectively evaluated 64 IO-MRI performed for patients with enhancing brain lesions referred for biopsy or resection as well as a subset with an early postoperative MRI (EP-MRI) within 72 h of surgery (N = 42), and a subset with a late postoperative MRI (LP-MRI) performed between 120 h and 8 wk postsurgery (N = 34). Three radiologists assessed for new enhancement on IO-MRI, and change in enhancement on available EP-MRI and LP-MRI. Consensus was determined by majority response. Inter-rater agreement was assessed using percentage agreement.

RESULTS
A total of 10 out of 64 (16%) of the IO-MRI demonstrated new enhancement. Seven of 10 patients with available EP-MRI demonstrated decreased/resolved enhancement. One out of 42 (2%) of the EP-MRI demonstrated new enhancement, which decreased on LP-MRI. Agreement was 74% for the assessment of new enhancement on IO-MRI and 81% for the assessment of new enhancement on the EP-MRI.

CONCLUSION
New enhancement occurs in intraoperative 3T MRI in 16% of patients after brain tumor resection, which decreases or resolves on subsequent MRI within 72 h of surgery. Our findings indicate the opportunity for further study to optimize the postoperative imaging window.
Prospects of Photo- and Thermoacoustic Imaging in Neurosurgery
Authors: Ravina Kristine , Lin Li , Liu Charles Y , Thomas Debi , Hasson Denise , Wang Lihong V , Russin Jonathan J 
Published: September 2019

Abstract
The evolution of neurosurgery has been, and continues to be, closely associated with innovations in technology. Modern neurosurgery is wed to imaging technology and the future promises even more dependence on anatomic and, perhaps more importantly, functional imaging. The photoacoustic phenomenon was described nearly 140 yr ago; however, biomedical applications for this technology have only recently received significant attention. Light-based photoacoustic and microwave-based thermoacoustic technologies represent novel biomedical imaging modalities with broad application potential within and beyond neurosurgery. These technologies offer excellent imaging resolution while generally considered safer, more portable, versatile, and convenient than current imaging technologies. In this review, we summarize the current state of knowledge regarding photoacoustic and thermoacoustic imaging and their potential impact on the field of neurosurgery.
Selective Dorsal Root Rhizotomy for Spastic Cerebral Palsy: A Longitudinal Case-Control Analysis of Functional Outcome
Authors: Iorio-Morin Christian , Yap Rita , Dudley Roy W R , Poulin Chantal , Cantin Marie-Andrée , Benaroch Thierry E , Farmer Jean-Pierre 
Published: September 2019

Abstract

BACKGROUND
The benefit of selective dorsal rhizotomies (SDR) on motor function relative to the cerebral palsy (CP) natural history remains unknown.

OBJECTIVE
To determine the functional benefit of SDR over the longitudinal CP natural history.

METHODS
Retrospective, single-center, case-control study of patients post-SDR after 1990. Inclusion criteria were the following: diagnosis of spastic CP, at least 1 preoperative and 1 postoperative Gross Motor Function Measure (GMFM-88), at least 1 yr of postoperative follow-up. GMFM-88 assessments were performed at 1, 2, 3, 5, 10, and 15 yr postoperatively and converted to GMFM-66. Cases were stratified by preoperative Gross Motor Function Classification System (GMFCS) and matched against their expected natural history using published reference centiles. After age 12, our cohort and matched controls were also fitted to published nonlinear mixed models of GMFM-66 evolution over time.

RESULTS
Analysis included 190 patients. Median follow-up, 5.3 yr (range: 1-16.9), median age at surgery, 4.6 yr, and 81.6% of patients grouped as GMFCS II or III pre-op. SDR patients performed statistically significantly better than their expected natural history (P < .0005). At 21 yr old, a modeled benefit of 8.435 was observed for GMFCS I (P = .0051), 0.05 for GMFCS II (P = .9647), 6.31 for GMFCS III (P < .0001), and 1.191 for GMFCS IV patients (P = .0207).

CONCLUSION
These results support the use of SDR in carefully selected spastic CP children.
Freedom and Obligation
Authors: Haji Ishtiyaque 
Published: September 2019

Abstract
This chapter first summarizes the responsibility dilemma—responsibility is incompatible with both determinism and its falsity—and then outlines the homologous obligation dilemma. It primarily focuses on showing that obligation requires alternative possibilities: an obligation for one to do something presupposes that one can do, and one can refrain from doing, it. Four principles undergird the view that obligation entails avoidability: (i) If one ought to do something, then one can do it; (ii) if it is impermissible for one to do something, then one can do it; (iii) one ought to do something if, and only if, it is impermissible for one not to do it; and (iv) if it is impermissible for one to do something, there is something else one can do, which is obligatory for one. A formidable analysis of the concept of obligation validates these principles.
China and the Era of Industrial Citizenship
Authors: Andreas Joel 
Published: September 2019

AbstractChapter 1 develops a theoretical framework, involving industrial citizenship and autonomy, to analyze authority relations in workplaces. In factories, as in states, citizenship is the essential prerequisite for democratic participation; if workers’ jobs are not secure and they are not recognized as legitimate stakeholders, they cannot claim rights to participate in decision-making and hold factory leaders accountable. To effectively participate, however, also requires autonomy, that is, the freedom to manage your own work, express opinions, and organize collectively. Both citizenship and autonomy are continuous variables, combinations of which produce four ideal types: market despotism (weak citizenship and little autonomy), individual autonomy (weak citizenship but substantial autonomy), paternalism (strong citizenship but little autonomy), and workplace democracy (strong citizenship and substantial autonomy). During the postwar decades, when workers in many countries enjoyed relatively strong industrial citizenship, workplace democracy was on the agenda, even if it was rarely accomplished in practice.
Russia, the Former Soviet Republics, and Europe Since 1989
Authors: Graney Katherine 
Published: September 2019

Abstract
Nearly three decades after the fall of the Berlin Wall, early hopes for the integration of the post-Soviet states into a “Europe whole and free” seem to have been decisively dashed. Europe itself is in the midst of a multifaceted crisis that threatens the considerable gains of the postwar liberal European experiment. This book provides a panoramic view of the process of “Europeanization” in Russia and all fourteen of the other former Soviet republics since 1989, in a study that is both theoretically grounded (with five chapters that discuss the historical and contemporary meanings of “Europe” in its cultural-civilizational, political, and security guises) and empirically rich (with case studies that examine the question of Europeanization in Russia and each of the other fourteen ex-Soviet republics). It argues that deeply rooted ideas about Europe’s cultural-civilizational primacy and about who “belongs” in Europe, and who doesn’t—and who might be able to “become European” someday, and who definitely cannot—to influence both internal politics in contemporary Europe and the processes of Europeanization in Russia and the former Soviet Union. From the “European dreams” of people in Ukraine and Georgia, who continue to see Europe as a beacon of liberal values, democratic institutions, and economic prosperity, to Russia’s efforts to weaken the postwar European order by presenting an alternative, more ethnonationalist, realist, and revanchist view of “Europe,” it demonstrates the necessity and utility of viewing contemporary Eurasian politics as a struggle over the meaning and practices of “Europeanness.”
When the Drop Broke the Pop Song
Authors: Sloan Nate , Harding Charlie , Gottlieb Iris 
Published: September 2019

Abstract
Rihanna and Calvin Harris ushered in the first major revision to conventional pop form in decades when they inserted a new musical section borrowed from electronic dance music (EDM) into their hit “We Found Love,” discussed in Chapter 4. The song ratchets up intensity like a rollercoaster by migrating the “build and drop” approach of EDM into pop. The sections are two sides of the same coin: the build generates pent-up energy and the drop releases it, all but requiring listeners to bounce up and down in fifteen seconds of ecstatic joy. It is hard to say whether the pop drop is a permanent change or a passing fad, but the result in “We Found Love” is a song that generates a feeling of ecstatic liberation not only through a pounding beat and celebratory lyrics, but also through its denial of formal expectation.