bluuebunny/crossref_metadata_2025_split huggingface dataset:
Solutions for management of angiotensin-converting enzyme–induced angioedema in a high risk population: a single center retrospective observational study
Authors: Bastien Alexandra , Townsend Dahlia , Nair Singh , Straker Tracey 
Published: May 2019

Background:There is an increasing rate of angiotensin-converting enzyme (ACE) inhibitor-induced angioedema in the United States which has not plateaued since this side effect was first described in 1980. There are no studies reporting a plateau, decrease in the incidence or decrease in the rate of rise in high risk populations. High risk populations are defined as African Americans, female sex, and age older than 65.Objectives:The objective of this manuscript is to determine the incidence of angioedema in a high risk, urban population over a 7-year period, and to determine impactful solutions on its management by anesthesiologists.Methods:PubMed was queried with the keywords angioedema, ACE inhibitor-induced angioedema, and anesthesiology angioedema management. Subset keyword searches included angioedema incidence and high risk populations, and emergency room anesthesiology angioedema management. Our medical center’s data repository was queried to identify the number of emergency department visits between January 2007 and December 2013. We then queried the database to determine the number of cases that were diagnosed as angioedema. A subset of patients was identified that included all patients that presented with angioedema, and who had a current ACE inhibitor prescription. The medical records of the admitted patients were reviewed to determine whether angioedema was induced by an ACE inhibitor or another etiology. The annual occurrence rates of angioedema and ACE inhibitor-induced angioedema were then calculated. Analysis of the medical records also determined the extent of anesthesiology involvement.Results:There were a total of 478 cases of ACE inhibitor-induced angioedema during the 7-year period. The incidence of ACE inhibitor-induced angioedema rose from 0.17 in 2007 to 0.53 in 2013. There is no evidence of plateau for this rise and current rate of rise appears to be exponential. African Americans, female sex, and age 65 and younger were associated with a greater incidence of ACE inhibitor-induced angioedema. One hundred thirty-three patients that presented to the emergency department with ACE inhibitor-induced angioedema were admitted, and 22 of these patients required intubation. Anesthesiology was consulted 23 times, and performed 14 (63.6%) of the intubations.
Stimulus Unpredictability in Time, Magnitude, and Direction on Accommodation
Authors: Otero Carles , Aldaba Mikel , Díaz-Doutón Fernando , Vera-Diaz Fuensanta A. , Pujol Jaume 
Published: May 2019

SIGNIFICANCE
The effect of predictability in changes of time, magnitude, and direction of the accommodation demand on the accommodation response latency and its magnitude are insignificant, which suggests that repetitive accommodative tasks such as the clinical accommodative facility test may not be influenced by potential anticipation effects.

PURPOSE
The purpose of this study was to investigate the effect of stimulus' time, magnitude, and direction predictability, as well as their interactions, on accommodation latency and response magnitude.

METHODS
Monocular accommodative response and latency were measured in 12 young subjects for nine different conditions where the stimulus accommodative demand changed several times in a steplike fashion for a period of 120 seconds. Each change in accommodative demand could have different time duration (i.e., 1, 2, or 3 seconds), magnitude (1, 2, or 3 diopters), and/or direction (i.e., accommodation or disaccommodation). All conditions were created permuting the factors of time, magnitude, and direction with two levels each: random and not random. The baseline condition was a step signal from 0 to 2 diopters persisting for 2 seconds in both accommodative demands. After each condition, subjects were asked to provide a score from 1 to 5 in their perceived predictability.

RESULTS
Friedman test conducted on the perceived predictability of each condition resulted in statistically significant differences between the nine conditions (χ2 = 56.57, P < .01). However, repeated-measures analysis of variance applied to latency and accommodative response magnitude did not show significant differences (P > .05). In addition, no correlation was found between the perceived predictability scores and both latency and accommodative response magnitudes between the most predictable and the most unpredictable conditions.

CONCLUSIONS
Subjects were able to perceptually notice whether the stimulus was predictable or not, although our results indicate no significant effect of stimuli predictability on either the accommodation latency or its magnitude.
Using the “Sugarcane Chewing” Concept as the Directionality of Motor Neurotizer Selection for Facial Paralysis Reconstruction: Chang Gung Experiences
Authors: Chuang David Chwei-Chin , Lu Johnny Chuieng-Yi , Chang Tommy Nai-Jen , Hamdi Sakarya Ahmet 
Published: May 2019

Background:
Facial paralysis and postparalysis facial synkinesis both cause severe functional and aesthetic deficits. Functioning free muscle transplantation is the authors’ preferred method for reconstructing both deformities.

Methods:
From 1985 to 2017, a total of 392 patients underwent 403 gracilis functioning free muscle transplantations for facial reanimation. Different motor neurotizers were used: cross-face nerve graft (74 percent), spinal accessory nerve (17 percent), and masseter nerve (8 percent). Smile excursion score, cortical adaptation stage, patient questionnaire, Hadlock lip excursion, and the Terzis evaluation systems were used to assess outcomes.

Results:
For smile excursion score, the spinal accessory and masseter nerve groups showed higher scores than the cross-face nerve graft group in the first 2 years, but no difference by 3-year follow-up. For cortical adaptation stage, nearly all cross-face nerve graft patients achieved stage IV or V spontaneity, the spinal accessory nerve group achieved at least stage III (independent) movement, but individuals in the masseter nerve group achieved only stage III or less. The cross-face nerve graft group also achieved higher scores according to the Hadlock system and the Terzis evaluation system compared with the other two groups.

Conclusions:
The concept of “sugarcane chewing” where the sweetness is the least at the tail but the most at the head can be simply applied for surgeons and patients in weighing the benefits and drawbacks during the motor neurotizer selection. Cross-face nerve graft–innervated gracilis is analogous to chewing sugarcane from tail to head; despite lower outcome measures earlier, it yields the highest scores at 3 years postoperatively. Masseter-innervated gracilis is akin to chewing sugarcane from head to tail, with greater outcome scores initially but little improvement at longer follow-up. Spinal accessory–innervated gracilis results fall in between these two groups.

CLINICAL QUESTION/LEVEL OF EVIDENCE:
Therapeutic, IV.
MHC-mismatched Allotransplantation of Induced Pluripotent Stem Cell-derived Cardiomyocyte Sheets to Improve Cardiac Function in a Primate Ischemic Cardiomyopathy Model
Authors: Kashiyama Noriyuki , Miyagawa Shigeru , Fukushima Satsuki , Kawamura Takuji , Kawamura Ai , Yoshida Shohei , Eiraku Seiko , Harada Akima , Matsunaga Keiko , Watabe Tadashi , Toda Koichi , Hatazawa Jun , Sawa Yoshiki 
Published: May 2019

Background.
Although allogeneic-induced pluripotent stem cell (iPSC)-derived cardiomyocytes (CMs) exhibit potential in cardiomyogenesis for heart failure, whether major histocompatibility complex (MHC)-matched allogenic iPSC implantation (MMAI) minimizes immune rejection for cell survival or functional recovery remains unknown. We herein explored whether MMAI with an iPSC-CM sheet is stable for a longer period and therapeutically more effective than MHC-mismatched AI in a primate ischemic cardiomyopathy model.

Methods.
Green fluorescent protein-transfected iPSC-CM sheets, derived from cynomolgus macaques with homozygous MHC haplotypes ‘‘HT1,’’ were transplanted on the left ventricle, generated by ligating the left anterior descending artery for 2 weeks in an ischemic model with or without heterozygous HT1 as MMAI and MHC-mismatched AI. Sham models were made by opening the chest at 14 days after left anterior descending ligation without any treatment.

Results.
Stereomicroscopy revealed that at 4 months after transplantation, green fluorescent protein intensity was higher in the MMAI group than in the MHC-mismatched AI group and the sham group. Immunohistochemistry staining revealed that host immune reaction with CD3-positive cells was stronger in MHC-mismatched AI than in MMAI at 3 months. Cardiac function improved both in MMAI and MHC-mismatched AI at 1 month after transplantation and was preserved until 6 months, whereas in the sham group, functional deterioration progressed over time.

Conclusions.
Although MHC-homo-iPSCs are preferred to avoid immune rejection, MHC-mismatched iPSC-CMs can also induce comparable cardiac functional recovery at late follow-up, suggesting that MHC-mismatched iPSC-based cardiac regenerative therapy with immunosuppressants is a feasible option for treating heart failure in clinical settings.
Defining a Willingness-to-transplant Threshold in an Era of Organ Scarcity: Simultaneous Liver–kidney Transplant as a Case Example
Authors: Cheng Xingxing S. , Goldhaber-Fiebert Jeremy , Tan Jane C. , Chertow Glenn M. , Kim W. Ray , Wall Anji E. 
Published: May 2019

Background.
Organ scarcity continues in solid organ transplantation, such that the availability of organs limits the number of people able to benefit from transplantation. Medical advancements in managing end-stage organ disease have led to an increasing demand for multiorgan transplant, wherein a patient with multiorgan disease receives >1 organ from the same donor. Current allocation schemes give priority to multiorgan recipients compared with single-organ transplant recipients, which raise ethical questions regarding equity and utility.

Methods.
We use simultaneous liver and kidney (SLK) transplant, a type of multiorgan transplant, as a case study to examine the tension between equity and utility in multiorgan allocation. We adapt the health economics willingness-to-pay threshold to a solid organ transplant setting by coining a new metric: the willingness-to-transplant (WTT) threshold.

Results.
We demonstrate how the WTT threshold can be used to evaluate different SLK allocation strategies by synthesizing utility and equity perspectives.

Conclusions.
We submit that this new framework enables us to distill the question of SLK allocation down to: what is the minimum amount of benefit we require from a deceased donor kidney to allocate it for a particular indication? Addressing the above question will prove helpful to devising a rational system of SLK allocation and is applicable to other transplant settings.
Outbreak analytics: a developing data science for informing the response to emerging pathogens
Authors: Polonsky Jonathan A. , Baidjoe Amrish , Kamvar Zhian N. , Cori Anne , Durski Kara , Edmunds W. John , Eggo Rosalind M. , Funk Sebastian , Kaiser Laurent , Keating Patrick , de Waroux Olivier le Polain , Marks Michael , Moraga Paula , Morgan Oliver , Nouvellet Pierre , Ratnayake Ruwan , Roberts Chrissy H. , Whitworth Jimmy , Jombart Thibaut 
Published: May 2019

Despite continued efforts to improve health systems worldwide, emerging pathogen epidemics remain a major public health concern. Effective response to such outbreaks relies on timely intervention, ideally informed by all available sources of data. The collection, visualization and analysis of outbreak data are becoming increasingly complex, owing to the diversity in types of data, questions and available methods to address them. Recent advances have led to the rise ofoutbreak analytics, an emerging data science focused on the technological and methodological aspects of the outbreak data pipeline, from collection to analysis, modelling and reporting to inform outbreak response. In this article, we assess the current state of the field. After laying out the context of outbreak response, we critically review the most common analytics components, their inter-dependencies, data requirements and the type of information they can provide to inform operations in real time. We discuss some challenges and opportunities and conclude on the potential role of outbreak analytics for improving our understanding of, and response to outbreaks of emerging pathogens.This article is part of the theme issue ‘Modelling infectious disease outbreaks in humans, animals and plants: epidemic forecasting and control‘. This theme issue is linked with the earlier issue ‘Modelling infectious disease outbreaks in humans, animals and plants: approaches and important themes’.
Context matters: using reinforcement learning to develop human-readable, state-dependent outbreak response policies
Authors: Probert W. J. M. , Lakkur S. , Fonnesbeck C. J. , Shea K. , Runge M. C. , Tildesley M. J. , Ferrari M. J. 
Published: May 2019

The number of all possible epidemics of a given infectious disease that could occur on a given landscape is large for systems of real-world complexity. Furthermore, there is no guarantee that the control actions that are optimal, on average, over all possible epidemics are also best for each possible epidemic. Reinforcement learning (RL) and Monte Carlo control have been used to develop machine-readable context-dependent solutions for complex problems with many possible realizations ranging from video-games to the game of Go. RL could be a valuable tool to generate context-dependent policies for outbreak response, though translating the resulting policies into simple rules that can be read and interpreted by human decision-makers remains a challenge. Here we illustrate the application of RL to the development of context-dependent outbreak response policies to minimize outbreaks of foot-and-mouth disease. We show that control based on the resulting context-dependent policies, which adapt interventions to the specific outbreak, result in smaller outbreaks than static policies. We further illustrate two approaches for translating the complex machine-readable policies into simple heuristics that can be evaluated by human decision-makers.This article is part of the theme issue ‘Modelling infectious disease outbreaks in humans, animals and plants: epidemic forecasting and control’. This theme issue is linked with the earlier issue ‘Modelling infectious disease outbreaks in humans, animals and plants: approaches and important themes’.
Structural basis for tetherin antagonism as a barrier to zoonotic lentiviral transmission
Authors: Buffalo Cosmo Z. , Stürzel Christina M. , Heusinger Elena , Kmiec Dorota , Kirchhoff Frank , Hurley James H. , Ren Xuefeng 
Published: May 2019

AbstractTetherin is a host defense that physically prevents escape of virions from the plasma membrane. Human tetherin lacks the motif DIWK antagonized by SIV, the antecedent of HIV. Here, we reconstituted the AP-2 clathrin adaptor complex with a simian tetherin and SIV Nef and determined its structure by cryo-EM. Nef refolds the first α-helix of the β2 subunit of AP-2 to a β hairpin, creating a binding site for the DIWK sequence. The tetherin binding site in Nef is distinct from those of MHC-I, CD3, and CD4, but overlaps the site for SERINC5 restricting viral infectivity. The structure explains the dependence of SIVs on the host tetherin DIWK sequence and the consequent barrier to human transmission.
Age at period cessation and trajectories of cardiovascular risk factors across mid and later life: a prospective cohort study
Authors: O’Keeffe Linda M , Kuh Diana , Fraser Abigail , Howe Laura D , Lawlor Debbie A , Hardy Rebecca 
Published: May 2019

SummaryWhat is already known about this topicAge at period cessation is associated with cardiovascular disease. Whether age at period cessation adversely affects change in conventional cardiovascular intermediates from mid to later life is not well understood.What this study addsWomen and clinicians concerned about the impact of type and timing of period cessation on conventional cardiovascular intermediates from midlife should be reassured that the impacts over the long term are small.AbstractObjectiveTo examine the association between age at period cessation (by type of period cessation) and trajectories of anthropometry, blood pressure, lipids and HBA1c from midlife.DesignProspective cohort study of women recruited to the Medical Research Council National Survey of Health and Development (NSHD).SettingPopulation based prospective cohort study.ParticipantsWomen participating in NSHD with a known date of period cessation and at least one measure of each intermediate cardiovascular risk factor.ExposuresAge at period cessation and type of period cessation (hysterectomy compared with natural menopause).OutcomesRepeated measures of systolic blood pressure, diastolic blood pressure, body mass index (BMI) and waist circumference (WC) from 36 to 69 years and repeated measures of triglyceride, low density lipoprotein cholesterol (LDL-c), high density lipoprotein cholesterol (HDL-c) and glycated haemoglobin (HBA1c) from 53 to 69 years.ResultsWe found no evidence that age at period cessation was associated with trajectories of log triglyceride, LDL-c and HDL-c from 53 to 69 years and trajectories of blood pressure from 36 to 69 years, regardless of whether period cessation occurred naturally or due to hysterectomy. While we found some evidence of associations of age at period cessation with log BMI, log WC and log HBA1C, patterns were not consistent and differences were small at age 69 years, with confidence intervals that spanned the null. For instance, the difference in log WC at age 69 per year increase in age at natural menopause was 0.003 (95% confidence interval, −0.0002, 0.01) while the difference per year increase in age at hysterectomy was −0.002 (95% CI, −0.005, 0.001).ConclusionHow and when women experience period cessation is unlikely to adversely affect conventional cardiovascular risk factors across mid and later life. Women and clinicians concerned about the impact of type and timing of period cessation on conventional cardiovascular intermediates from midlife should be reassured that the impacts over the long term are small.
DeepFly3D: A deep learning-based approach for 3D limb and appendage tracking in tethered, adult Drosophila
Authors: Günel Semih , Rhodin Helge , Morales Daniel , Campagnolo João , Ramdya Pavan , Fua Pascal 
Published: May 2019

AbstractStudying how neural circuits orchestrate limbed behaviors requires the precise measurement of the positions of each appendage in 3-dimensional (3D) space. Deep neural networks can estimate 2-dimensional (2D) pose in freely behaving and tethered animals. However, the unique challenges associated with transforming these 2D measurements into reliable and precise 3D poses have not been addressed for small animals including the fly, Drosophila melanogaster. Here we present DeepFly3D, a software that infers the 3D pose of tethered, adult Drosophila—or other animals—using multiple camera images. DeepFly3D does not require manual calibration, uses pictorial structures to automatically detect and correct pose estimation errors, and uses active learning to iteratively improve performance. We demonstrate more accurate unsupervised behavioral embedding using 3D joint angles rather than commonly used 2D pose data. Thus, DeepFly3D enables the automated acquisition of behavioral measurements at an unprecedented level of resolution for a variety of biological applications.
Dynamic DNA structure states interact with the RNA editing enzyme ADAR1 to modulate fear extinction memory
Authors: Marshall Paul R. , Zhao Qiongyi , Li Xiang , Wei Wei , Malathi Abi , Zajaczkowski Esmi , Leighton Laura , Madugalle Sachithrani , Basic Dean , Wang Ziqi , Yin Jiayu , Liau Wei-Siang , Walkley Carl , Bredy Timothy W. 
Published: May 2019

AbstractRNA modification has recently emerged as an important mechanism underlying gene diversity linked to behavioral regulation. The conversion of adenosine to inosine by the ADAR family of enzymes is a particularly important RNA modification as it impacts the physiological readout of protein-coding genes. However, not all variants of ADAR appear to act solely on RNA. ADAR1 binds directly to DNA when it is in a non-canonical, left handed, “Z” conformation, but little is known about the functional relevance of this interaction. Here we report that ADAR1 binds to Z-DNA in an activity-dependent manner and that fear extinction learning leads to increased ADAR1 occupancy at DNA repetitive elements, with targets adopting a Z-DNA structure at sites of ADAR1 recruitment. Knockdown of ADAR1 leads to an inability to modify a previously acquired memory trace and this is associated with a concomitant change in DNA structure and a decrease in RNA editing. These findings suggest a novel mechanism of learning-induced gene regulation whereby ADAR1 physically interacts with Z-DNA in order to mediate its effect on RNA, and both are required for memory flexibility following fear extinction learning.
Diversification or collapse of self-incompatibility haplotypes as outcomes of evolutionary rescue
Authors: Harkness Alexander , Goldberg Emma E. , Brandvain Yaniv 
Published: May 2019

AbstractSelf-incompatibility systems in angiosperms are exemplars of extreme allelic polymorphism maintained by long-term balancing selection. Pollen that shares an allele with the pollen recipient at the self-incompatibility locus is rejected, and this rejection favors rare alleles as well as preventing self-fertilization. Advances in molecular genetics reveal that an ancient, deeply conserved, and well-studied incompatibility system functions through multiple tightly linked genes encoding separate pollen-expressed F-box proteins and pistil-expressed ribonucleases. We show that certain recombinant haplotypes at the incompatibility locus can drive collapse in the number of incompatibility types. We use a modified evolutionary rescue model to calculate the relative probabilities of increase and collapse in number of incompatibility types given the initial collection of incompatibility haplotypes and the population rate of gene conversion. We find that expansion in haplotype number is possible when population size or the rate of gene conversion is large, but large contractions are likely otherwise. By iterating a Markov chain model derived from these expansion and collapse probabilities, we find that a stable haplotype number distribution in the realistic range of 10–40 is possible under plausible parameters. However, small or moderate-sized populations should be susceptible to substantial additional loss of haplotypes beyond those lost by chance during bottlenecks. The same processes that can generate many incompatibility haplotypes in large populations may therefore be crushing haplotype diversity in smaller populations.