bluuebunny/crossref_metadata_2025_split huggingface dataset:
Assessment of Lymph Node Stromal Cells as an Underlying Factor in Age-Related Immune Impairment
Authors: Masters April R , Hall Alexxus , Bartley Jenna M , Keilich Spencer R , Lorenzo Erica C , Jellison Evan R , Puddington Lynn , Haynes Laura 
Published: February 2019

Abstract
Aging negatively impacts immunity, resulting in inefficient responses to vaccinations and infections. Fibroblastic reticular cells (FRCs) are the major stromal cell subset in lymph nodes (LNs) and play an intricate role in the orchestration and control of adaptive immune responses. Although stromal cells have a major impact on immune responses, the impact of aging on LN stromal cells remains unclear. Quantitative analysis of LN stromal cells by flow cytometry revealed that there are no significant differences in the number of stromal cells in young and aged LN at steady state but after influenza infection aged FRCs have delayed expansion as a result of reduced proliferation. Aged LNs also produce reduced levels of homeostatic chemokines, which correlates with reduced homing of naive T cells. Image analysis reveals that young and aged T-cell zone FRCs have similar morphology at steady state and after infection. Furthermore, aged FRCs did not appear to be a contributing factor in the reduced proliferation of young T cells transferred into aged LNs after influenza infection. These results demonstrate that aging alters LN stromal cell response to challenge and these age-related changes may be an underlying contributor to impaired immune responses in the elderly people.
Disaster Planning and Research Continuity in Responsible Animal Research
Authors: Petervary Nicolette , Pullium Jennifer K 
Published: February 2019

AbstractDisaster preparedness for research facilities can be a daunting task. The purpose of this review is to introduce basic preparedness concepts and terminology so that facilities may begin to develop customized plans for their specific needs. Regulatory requirements are reviewed and an overview of the Incident Command System, National Preparedness System Planning Frameworks, and fundamental terms is provided. Important concepts for successful planning are then explored. Good planning involves fostering a culture of preparedness, resilience, and understanding the interactions and partnerships with other groups that are essential for core functions and incident response. Methods to gain institutional support and set up an advisory committee are examined in detail. Next, the steps to develop and carry out a plan are outlined. Risk assessments using an all hazards approach and tools such as risk indices and risk matrices are explained, and tips to design and test plans, train personnel, and evaluate improvement are discussed. Finally, special challenges unique to animal research facilities are considered along with ways to address them. Examples and information are drawn from a wide variety of organizations both to underscore themes common to all preparedness plans and to introduce new concepts that may be adapted for use in research institutions.
Psychiatric Neuroethics
Authors: Glannon Walter 
Published: February 2019

Abstract
This book is an analysis and discussion of questions at the intersection of psychiatry, neuroscience, philosophy, and law that have arisen from advances in psychiatric research and clinical psychiatric practice in the last 30 years. Are psychiatric disorders diseases of the brain, caused by dysfunctional neural circuits and neurotransmitters? What role do genes, neuroendocrine and neuroimmune interactions, and a person’s response to the environment play in the development of these disorders? How do different explanations of the etiology and pathophysiology of mental illness influence diagnosis, prognosis, and decisions about treatment? How do psychiatric disorders affect consciousness and agency? Could the presumed salutary effects of neural interventions for pathological thought and behavior change one’s mental states in undesirable ways? What are the social justice issues regarding access to treatment and experimental and innovative interventions for treatment-refractory conditions? What are the obligations of clinicians and researchers to patients and research subjects in psychiatry? Could the interests of society in preventing recidivism and public harm override the cognitive liberty of criminal offenders with a psychiatric disorder to refuse a therapeutic intervention in the brain? Would it be rational for a person with a chronic treatment-resistant disorder to request euthanasia or assisted suicide to end his suffering? Could psychiatric disorders be predicted and prevented? The book examines these questions in a comprehensive, systematic, and thematically integrated way. It is written for a multidisciplinary audience, including psychiatrists, neurologists, neurosurgeons, philosophers, psychologists, legal theorists, and informed lay readers.
Introduction
Authors: Glannon Walter 
Published: February 2019

Abstract
This Introduction describes the book as an analysis and discussion of questions at the intersection of psychiatry, philosophy and law that have arisen from advances in psychiatric research and practice in the last 30 years. After pointing out the extent to which mental illness constitutes the global burden of disease, it outlines a paradigm for major psychiatric conditions as diseases of the brain and mind consisting in a biopsychosocial model in which the DSM-5 and RDoC are complementary frameworks. The Introduction explains psychiatric disorders as disorders of consciousness, memory and will, examines invasive and non-invasive treatments for them, how these treatments affect autonomous agency and the obligations of researchers to subjects participating in psychiatric research. In addition, it explores ethical and legal issues in brain interventions for psychopathy, arguments for and against euthanasia and assisted suicide for psychiatric disorders and how to prevent them.
Prediction and prevention
Authors: Glannon Walter 
Published: February 2019

Abstract
This chapter considers reasons for and against intervening with psychotropic drugs during the prodromal phase of disease. It also discusses how the identification of biomarkers for psychiatric disorders in childhood or adolescence might predict who would be at risk of developing these disorders. Biomarkers could indicate which interventions could reduce this risk or eliminate it altogether. But there are questions about their predictive value. Abnormal neuroimmune and neuroendocrine interactions may disrupt normal rates of synaptic pruning and myelination in childhood and adolescence and increase the risk of schizophrenia and other disorders with an onset in adolescence or early adulthood. Immune-modulating drugs could reverse this process, but require careful weighing of potential benefits and risks. The chapter also discusses different interventions before birth that might prevent people from having a psychiatric disorder after birth.
Epilogue: Psychiatry, neuroscience, philosophy
Authors: Glannon Walter 
Published: February 2019

Abstract
This Epilogue summarizes the main points of the book's eight chapters. It emphasizes a biopsychosocial model for understanding, treating and possibly psychiatric disorders. It also points out that major forms of mental illness are disorders of this brain as well as disorders of the mind and the person relations to others and the world. Advances in neuroscience may lead to better explanations of the pathophysiology of psychiatric disorders and their philosophical implications. But these advances may not completely account for the experience of living with these disorders. Given the global burden of disease from mental illness, it should receive priority in medical research over other types of disease to improve the quality of life of the people affected by it.
Immunotherapy is associated with improved survival and decreased neurologic death after SRS for brain metastases from lung and melanoma primaries
Authors: Lanier Claire M , Hughes Ryan , Ahmed Tamjeed , LeCompte Michael , Masters Adrianna H , Petty William J , Ruiz Jimmy , Triozzi Pierre , Su Jing , O’Neill Stacy , Watabe Kuonosuke , Cramer Christina K , Laxton Adrian W , Tatter Stephen B , Wang Ge , Whitlow Christopher , Chan Michael D 
Published: February 2019

Abstract

Background
The effect of immunotherapy on brain metastasis patients remains incompletely understood. Our goal was to evaluate its effect on survival, neurologic death, and patterns of failure after stereotactic radiosurgery (SRS) without prior whole-brain radiation therapy (WBRT) in patients with lung and melanoma primaries metastatic to the brain.

Methods
We performed a retrospective analysis of 271 consecutive lung or melanoma patients treated with upfront SRS for brain metastases between 2013 and 2018. Of these patients, 101 (37%) received immunotherapy and 170 (63%) did not. Forty-three percent were treated with nivolumab. Thirty-seven percent were treated with pembrolizumab. Fifteen percent were treated with ipilimumab. One percent were treated with a combination of nivolumab and ipilimumab. One percent were treated with atezolizumab. Three percent were treated with another immunotherapy regimen. Survival was estimated by the Kaplan–Meier method and cumulative incidences of neurologic death, and local and distant brain failure were estimated using death as a competing risk.

Results
The median overall survival (OS) of patients treated with immunotherapy vs without was 15.9 (95% CI: 13.3 to 24.8) vs 6.1 (95% CI: 5.1 to 8.8) months (P < .01). The 1-year cumulative incidence of neurologic death was 9% in patients treated with immunotherapy vs 23% in those treated without (P = .01), while nonneurologic death was not significantly different (29% vs 41%, P = .51). Median brain metastasis velocity (BMV) did not differ between groups, and rates of salvage SRS and WBRT were similar.

Conclusions
The use of immunotherapy in patients with lung cancer or melanoma metastatic to the brain treated with SRS is associated with improved OS and decreased incidence of neurologic death.
Willingness to Participate in Passive Mobile Data Collection
Authors: Keusch Florian , Struminskaya Bella , Antoun Christopher , Couper Mick P , Kreuter Frauke 
Published: February 2019

Abstract
The rising penetration of smartphones now gives researchers the chance to collect data from smartphone users through passive mobile data collection via apps. Examples of passively collected data include geolocation, physical movements, online behavior and browser history, and app usage. However, to passively collect data from smartphones, participants need to agree to download a research app to their smartphone. This leads to concerns about nonconsent and nonparticipation. In the current study, we assess the circumstances under which smartphone users are willing to participate in passive mobile data collection. We surveyed 1,947 members of a German nonprobability online panel who own a smartphone using vignettes that described hypothetical studies where data are automatically collected by a research app on a participant’s smartphone. The vignettes varied the levels of several dimensions of the hypothetical study, and respondents were asked to rate their willingness to participate in such a study. Willingness to participate in passive mobile data collection is strongly influenced by the incentive promised for study participation but also by other study characteristics (sponsor, duration of data collection period, option to switch off the app) as well as respondent characteristics (privacy and security concerns, smartphone experience).
Cortical zeta-inhibitory peptide injection reduces local sleep need
Authors: Carroll Caitlin M , Hsiang Harrison , Snyder Sam , Forsberg Jade , Dash Michael B 
Published: February 2019

Abstract
Local sleep need within cortical circuits exhibits extensive interregional variability and appears to increase following learning during preceding waking. Although the biological mechanisms responsible for generating sleep need are unclear, this local variability could arise as a consequence of wake-dependent synaptic plasticity. To test whether cortical synaptic strength is a proximate driver of sleep homeostasis, we developed a novel experimental approach to alter local sleep need. One hour prior to light onset, we injected zeta-inhibitory peptide (ZIP), a pharmacological antagonist of protein kinase Mζ, which can produce pronounced synaptic depotentiation, into the right motor cortex of freely behaving rats. When compared with saline control, ZIP selectively reduced slow-wave activity (SWA; the best electrophysiological marker of sleep need) within the injected motor cortex without affecting SWA in a distal cortical site. This local reduction in SWA was associated with a significant reduction in the slope and amplitude of individual slow waves. Local ZIP injection did not significantly alter the amount of time spent in each behavioral state, locomotor activity, or EEG/LFP power during waking or REM sleep. Thus, local ZIP injection selectively produced a local reduction in sleep need; synaptic strength, therefore, may play a causal role in generating local homeostatic sleep need within the cortex.
Genetic lesioning of histamine neurons increases sleep–wake fragmentation and reveals their contribution to modafinil-induced wakefulness
Authors: Yu Xiao , Ma Ying , Harding Edward C , Yustos Raquel , Vyssotski Alexei L , Franks Nicholas P , Wisden William 
Published: February 2019

Abstract
Acute chemogenetic inhibition of histamine (HA) neurons in adult mice induced nonrapid eye movement (NREM) sleep with an increased delta power. By contrast, selective genetic lesioning of HA neurons with caspase in adult mice exhibited a normal sleep–wake cycle overall, except at the diurnal start of the lights-off period, when they remained sleepier. The amount of time spent in NREM sleep and in the wake state in mice with lesioned HA neurons was unchanged over 24 hr, but the sleep–wake cycle was more fragmented. Both the delayed increase in wakefulness at the start of the night and the sleep–wake fragmentation are similar phenotypes to histidine decarboxylase knockout mice, which cannot synthesize HA. Chronic loss of HA neurons did not affect sleep homeostasis after sleep deprivation. However, the chronic loss of HA neurons or chemogenetic inhibition of HA neurons did notably reduce the ability of the wake-promoting compound modafinil to sustain wakefulness. Thus, part of modafinil’s wake-promoting actions arise through the HA system.
Design of a comprehensive microfluidic and microscopic toolbox for the ultra-wide spatio-temporal study of plant protoplasts development and physiology
Authors: Sakai K. , Charlot F. , Le Saux T. , Bonhomme S. , Nogué F. , Palauqui J.C. , Fattaccioli J. 
Published: February 2019

ABSTRACTBackgroundOne of the main features of plant cells is their strong plasticity, and their propensity to regenerate an organism from a single cell. Plant protoplasts are basic plant cells units in which the pecto-cellulosic cell wall has been removed, but the plasma membrane is intact. One of the main features of plant cells is their strong plasticity, which in some species, can be very close from what is defined as cell totipotency. Methods and differentiation protocols used in plant physiology and plant biology usually involve macroscopic vessels and containers that make difficult, for example, to follow the fate of the same protoplast all along its full development cycle, but also to perform continuous studies of the influence of various gradients in this context. These limits have hampered the precise study of regeneration processes.ResultsHerein, we present the design of a comprehensive, physiologically relevant, easy-to-use and low-cost microfluidic and microscopic setup for the monitoring of Physcomitrella patens (P. patens) growth and development on a long-term basis. The experimental solution we developed is made of two parts (i) a microfluidic chip composed of a single layer of about a hundred flow-through microfluidic traps for the immobilization of protoplasts, and (ii) a low-cost, light-controlled, custom-made microscope allowing the continuous recording of the moss development in physiological conditions.We validated the experimental setup with three proofs of concepts: (i) the kinetic monitoring of first division steps and cell wall regeneration, (ii) the influence of the photoperiod on growth of the protonemata, and (iii) finally the induction of leafy buds using a phytohormone, cytokinin.ConclusionsWe developed the design of a comprehensive, physiologically relevant, easy-to-use and low-cost experimental setup for the study of P. patens development in a microfluidic environment. This setup allows imaging of P. patens development at high resolution and over long time periods.
Fine-scale family structure shapes influenza transmission risk in households: insights from a study of primary school students in Matsumoto city, 2014/15
Authors: Endo Akira , Uchida Mitsuo , Kucharski Adam J. , Funk Sebastian 
Published: February 2019

AbstractBackgroundHouseholds are important settings for the transmission of seasonal influenza. Previous studies found that the per-person risk of within-household transmission decreases with household size. However, more detailed heterogeneities driven by household composition and contact patterns have not been studied.MethodsWe employed a mathematical model which accounts for infections both from outside and within the household. The model was applied to citywide primary school surveillance data of seasonal influenza in 2014/15 season in Matsumoto city, Japan. We compared a range of models to estimate the structure of household transmission.ResultsFamilial relationship and household composition strongly influenced the transmission patterns of seasonal influenza in households. Children had substantially high risk of infection from outside the household (up to 20%) compared with adults (1-3%). Intense transmission was observed within-generation (between children/parents/grandparents) and also between mother and child, with transmission risks typically ranging around 5-20% depending on the pair and household composition.ConclusionsWe characterised heterogeneity in household transmission patterns of influenza. Children were identified as the largest source of secondary transmission, with family structure influencing infection risk. This suggests that vaccinating children would have stronger secondary effects on transmission than would be assumed without taking into account transmission patterns within the household.
A Brownian ratchet model explains the biased sidestepping movement of single-headed kinesin-3 KIF1A
Authors: Mitra A. , Suñé M. , Diez S. , Sancho J. M. , Oriola D. , Casademunt J. 
Published: February 2019

AbstractThe kinesin-3 motor KIF1A is involved in long-ranged axonal transport in neurons. In order to ensure vesicular delivery, motors need to navigate the microtubule lattice and overcome possible roadblocks along the way. The single-headed form of KIF1A is a highly diffusive motor that has been shown to be a prototype of Brownian motor by virtue of a weakly-bound diffusive state to the microtubule. Recently, groups of single-headed KIF1A motors were found to be able to sidestep along the microtubule lattice, creating left-handed helical membrane tubes when pulling on giant unilamellar vesicles in vitro. A possible hypothesis is that the diffusive state enables the motor to explore the microtubule lattice and switch protofilaments, leading to a left-handed helical motion. Here we study microtubule rotation driven by single-headed KIF1A motors using fluorescene-interference contrast (FLIC) microscopy. We find an average rotational pitch of ≃ 1.4 μm which is remarkably robust to changes in the gliding velocity, ATP concentration and motor density. Our experimental results are compared to stochastic simulations of Brownian motors moving on a two-dimensional continuum ratchet potential, which quantitatively agree with the FLIC experiments. We find that single-headed KIF1A sidestepping can be explained as a consequence of the intrinsic handedness and polarity of the microtubule lattice in combination with the diffusive mechanochemical cycle of the motor.
An actin-based protrusion originating from a podosome-enriched region initiates macrophage fusion
Authors: Faust James J. , Balabiyev Arnat , Heddleston John M. , Podolnikova Nataly P. , Page Baluch D. , Chew Teng-Leong , Ugarova Tatiana P. 
Published: February 2019

AbstractMacrophage fusion resulting in the formation of multinucleated giant cells occurs in a variety of chronic inflammatory diseases, yet the mechanism responsible for initiating macrophage fusion is unknown. Here, we used live cell imaging to show that actin-based protrusions at the leading edge initiate macrophage fusion. Phase contrast video microscopy demonstrated that in the majority of events, short protrusions (3 ± 1 μm) between two closely apposed cells initiated fusion, but occasionally we observed long protrusions (16 ± 7 μm). Using macrophages isolated from LifeAct mice and imaging with lattice light sheet microscopy, we further found that fusion-competent actin-based protrusions formed at sites enriched in podosomes. Inducing fusion in mixed populations of GFP- and mRFP-LifeAct macrophages showed rapid spatial overlap between GFP and RFP signal at the site of fusion. Cytochalasin B strongly reduced fusion and when rare fusion events occurred, protrusions were not observed. Fusion of macrophages deficient in Wiskott-Aldrich syndrome protein and Cdc42, key molecules involved in the formation of actin-based protrusions and podosomes, was also impaired bothin vitroandin vivo. Finally, inhibiting the activity of the Arp2/3 complex decreased fusion and podosome formation. Together these data indicate that an actin-based protrusion formed at the leading edge initiates macrophage fusion.
AMMISOFT for AMMI Analysis with Best Practices
Authors: Gauch Hugh G. , Moran David R. 
Published: February 2019

ABSTRACTThe Additive Main effects and Multiplicative Interaction (AMMI) model has been used extensively for analysis of multi-environment yield trials for two main purposes: understanding complex genotype-by-environment interactions and increasing accuracy. A 2013 paper in Crop Science presented a protocol for AMMI analysis with best practices, which has four steps: (i) analysis of variance, (ii) model diagnosis, (iii) mega-environment delineation, and (iv) agricultural recommendations. This preprint announces free open-source software, called AMMISOFT, which makes it easy to implement this protocol and thereby to accelerate crop improvement.
Experimental Evolution of the Megaplasmid pMPPla107 in Pseudomonas stutzeri Enables Identification of Genes Contributing to Sensitivity to an Inhibitory Agent
Authors: Smith Brian A. , Dougherty Kevin , Clark Meara , Baltrus David A. 
Published: February 2019

ABSTRACTHorizontally transferred elements such as plasmids can, at times, burden host cells with various metabolic and fitness costs. Our previous work demonstrated that acquisition of the Pseudomonas syringae megaplasmid pMPPla107 causes sensitivity to a growth inhibiting substance that is produced in cultures during growth under standard laboratory conditions. After 500 generations of laboratory passage of P. stutzeri lines containing pMPPla107, two out of six independent lines displayed resistance to this inhibitory agent. We therefore sequenced the genomes of isolates from each independent evolutionary line to identify the genetic basis of this resistance phenotype through comparative genomics. Our analysis demonstrates that two different compensatory mutations on the megaplasmid ameliorate the sensitivity phenotype: 1) a large deletion of approximately 368kb in pMPPla107 and 2) a SNP in the gene we name skaA for Supernatant Killing Activity. These results provide further evidence that costs associated with horizontal gene transfer can be compensated through single mutational events and emphasize the power of experimental evolution and resequencing to better understand the genetic basis of evolved phenotypes.