bluuebunny/crossref_metadata_2025 huggingface dataset:
Hyperemesis Gravidarum: Can Factors Predict Risk of Readmission? [21L]
Authors: White Sarah , Byrne John , McIntire Donald D. , Nelson David B.
Published: April 2018

INTRODUCTION:

Hyperemesis gravidarum is one of the most common indications for admission in pregnancy. Because some women require re-hospitalization, we hypothesized that the risk for readmission could be identified. The aim of this study was to use patient characteristics and index admission features to determine the risk for readmission.

METHODS:

This was a retrospective cohort study of women admitted with hyperemesis gravidarum at our hospital. Hyperemesis gravidarum was defined as intractable nausea and vomiting with either electrolyte derangement, >10 lb weight loss, or persistent ketonuria suggesting dehydration. Women with alternative etiologies for persistent nausea and vomiting were excluded. Women requiring more than one hospitalization for hyperemesis gravidarum were compared to those with one admission to determine if any factors were associated with readmission during the same pregnancy.

RESULTS:

Between 2009 and 2014, a total of 144 women were admitted with hyperemesis gravidarum that comprised 247 hospital admissions. Fifty-one (35%) women required more than one hospitalization for hyperemesis gravidarum. Factors examined included maternal age, race, parity, habitus, substance use, smoking, and psychiatric illness. None of these features including length of initial hospitalization were found to be associated with the need for readmission. Of those delivered at our hospital, readmission was not associated with differing perinatal outcomes.

CONCLUSION:

More than one-third of women with hyperemesis gravidarum required readmission at our hospital. Factors associated with need for readmission did not include maternal demographic features, substance use, or psychiatric illness. The length of hospitalization for the initial admission also was not associated with later readmission.
Prenatal Dexamethasone to Prevent Newborn Virilization From Fetal CAH: A Cost-Effectiveness Analysis [29L]
Authors: Gabo Virginia , Skeith Ashley E. , Sargent James , Caughey Aaron B.
Published: April 2018

INTRODUCTION:

Congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency can cause virilization in affected females, potentially requiring post-natal surgical correction. Prenatal dexamethasone administration has been shown to reduce incidence and severity of virilization in newborn females. However, diagnostic information regarding fetal CAH status is not available until after critical embryological stages have passed, limiting the effectiveness of the intervention. We designed a model to examine the cost-effectiveness of empiric dexamethasone administration in pregnancies at high-risk for fetal CAH.

METHODS:

A cost-effectiveness model was built using TreeAge Pro and incorporated probabilities, costs, and utilities from the literature. In pregnancies at-risk for CAH, we compared three strategies: empiric initiation of dexamethasone at 6 weeks gestation, conditional dexamethasone administration following a CVS at 10 weeks gestation, and no dexamethasone intervention. The cost-effectiveness threshold was set to $100,000 per quality-adjusted life year (QALY). The model's robustness was assessed with sensitivity analyses.

RESULTS:

In a theoretical cohort of 1,000 women, empiric dexamethasone at 6 weeks gestation lead to 26 fewer affected female neonates requiring surgical intervention. This strategy lead to lower costs and higher QALYs when compared to dexamethasone administration at 10 weeks and no dexamethasone intervention. Because dexamethasone administration was associated with decreased severity and frequency of virilization, it was the cost-effective strategy across a broad range of sensitivity analyses.

CONCLUSION:

In pregnancies at-risk for fetal virilization secondary to CAH, initiation of empiric dexamethasone before 6 weeks gestation was the cost-effective strategy resulting in fewer affected female infants, and fewer surgical corrections.
Pregnancy Outcomes in Women With Current or Previous Cerebrovascular Accident [35L]
Authors: Bushman Elisa T. , Gibbins Karen J. , Silver Robert M.
Published: April 2018

INTRODUCTION:

To describe presence of cerebrovascular accident (CVA) risk factors and obstetric outcomes in women with pregnancy associated stroke (PAS), and to describe management and outcomes of subsequent pregnancies in women with history of CVA.

METHODS:

In a population of 948,074 births women with history of CVA during pregnancy or followed by subsequent pregnancy were identified by ICD-9 and 10 codes. CVA types were categorized as ischemic, hemorrhagic, and transient ischemic event. Major CVA and known pregnancy risk factors for PAS were abstracted. Use of thromboprophylaxis, pregnancy outcomes, and presence of recurrent CVA were abstracted.

RESULTS:

Sixty-one patients were identified with PAS; 51% antepartum and 78% ischemic CVA predominance was found. Thrombophilia was present in 6%, and 27% had concomitant gestational hypertensive disease. Sixty-nine percent of women delivered at term. One hundred two patients were identified with history of CVA (88 patients) or PAS (14 patients) who underwent subsequent pregnancy. Women with previous PAS were more likely to be Hispanic (25% versus 10% P=.024). Thirty-one percent of women with history of PAS received thromboprophylaxis in subsequent pregnancies compared to 61% of women with previous CVA (P=.069). There were six cases of recurrent CVA giving a 5.7% risk of recurrence.

CONCLUSION:

PAS is most commonly ischemic (78%) and is concomitant with hypertensive disease of pregnancy in 27% of cases. Pregnancy outcomes are overall positive if extreme prematurity is avoided. Recurrent CVA occurs in 5.7% of women who pursue future pregnancy, and thus management of these pregnancies remains high risk.
Pregnancy Outcomes in Patients Without Gestational Diabetes Stratified by Maternal Age [39L]
Authors: Hickok Ruth A. , Waites Bethany T. , Walker Allison R. , Caughey Aaron B.
Published: April 2018

INTRODUCTION:

To compare pregnancy outcomes and rates of complications in women without gestational diabetes stratified by maternal age.

METHODS:

We designed a retrospective cohort analysis using data compiled from singleton, non-anomalous gestations in the United States. Using multivariate regression and χ2 tests, we examined maternal and neonatal outcomes stratified by maternal age at time of delivery. Women ages 20–25 severed as reference values. Outcomes examined included preterm delivery, birth weight >4,000 g, small for gestational age, intrauterine fetal demise, neonatal death, cesarean section, abruption, chorioamnionitis, and post-partum hemorrhage. P-value less than 0.05 was considered statistically significant.

RESULTS:

In a population of 1.85 million non-anomalous singleton deliveries, 1,718,481 women without gestational diabetes were identified. Women ≤20 year old had higher rates of preterm deliveries <32 w (OR 1.28; 95% CI 1.20–1.25) compared to women ≥40 (OR 0.95; 95% CI 1.11–1.28). Women 35–40 had increased IUFD (OR 1.68; 95% CI 1.40–2.02). Women 35–40 and ≥40 had higher cesarean section (OR 1.60; 95% CI 1.59–1.62 and OR 1.29; 95% CI 1.26–1.31) and post-partum hemorrhage (OR 1.09; 95% CI 1.05–1.12 and OR 1.10; 95% CI 1.04–1.16) rates. Women ≤20 had lower rates of placental abruption rates (OR 0.98; 95% CI 0.81–0.93) and chorioamnionitis (OR 0.74; 95% CI 0.72–0.77).

CONCLUSION:

Among women without gestational diabetes, younger maternal age is associated with lower risk of cesarean section, placental abruption and chorioamnionitis. Women of advanced maternal age face increased risk for SGA, IUFD, cesarean sections and post-partum hemorrhage. Women at extremes of maternal age have greater risk of preterm delivery and neonatal death.
What Nurses Do
Authors: Kennedy Maureen Shawn
Published: April 2018

Quiet thoughtfulness can be a powerful intervention.
Sexual Harassment in Nursing: A Long-Standing, but Rarely Studied Problem
Authors: Nelson Roxanne
Published: April 2018

The #MeToo and #TimesUp movements have relevance for nurses.
Continuous Negative Abdominal Pressure Reduces Ventilator-induced Lung Injury in a Porcine Model
Authors: Yoshida Takeshi , Engelberts Doreen , Otulakowski Gail , Katira Bhushan , Post Martin , Ferguson Niall D. , Brochard Laurent , Amato Marcelo B. P. , Kavanagh Brian P.
Published: April 2018

Background

In supine patients with acute respiratory distress syndrome, the lung typically partitions into regions of dorsal atelectasis and ventral aeration (“baby lung”). Positive airway pressure is often used to recruit atelectasis, but often overinflates ventral (already aerated) regions. A novel approach to selective recruitment of dorsal atelectasis is by “continuous negative abdominal pressure.”

Methods

A randomized laboratory study was performed in anesthetized pigs. Lung injury was induced by surfactant lavage followed by 1 h of injurious mechanical ventilation. Randomization (five pigs in each group) was to positive end-expiratory pressure (PEEP) alone or PEEP with continuous negative abdominal pressure (−5 cm H2O via a plexiglass chamber enclosing hindlimbs, pelvis, and abdomen), followed by 4 h of injurious ventilation (high tidal volume, 20 ml/kg; low expiratory transpulmonary pressure, −3 cm H2O). The level of PEEP at the start was ≈7 (vs. ≈3) cm H2O in the PEEP (vs. PEEP plus continuous negative abdominal pressure) groups. Esophageal pressure, hemodynamics, and electrical impedance tomography were recorded, and injury determined by lung wet/dry weight ratio and interleukin-6 expression.

Results

All animals survived, but cardiac output was decreased in the PEEP group. Addition of continuous negative abdominal pressure to PEEP resulted in greater oxygenation (Pao
2/fractional inspired oxygen 316 ± 134 vs. 80 ± 24 mmHg at 4 h, P = 0.005), compliance (14.2 ± 3.0 vs. 10.3 ± 2.2 ml/cm H2O, P = 0.049), and homogeneity of ventilation, with less pulmonary edema (≈10% less) and interleukin-6 expression (≈30% less).

Conclusions

Continuous negative abdominal pressure added to PEEP reduces ventilator-induced lung injury in a pig model compared with PEEP alone, despite targeting identical expiratory transpulmonary pressure.
Epithelial Recurrent Erosion Dystrophy Secondary to COL17A1 c.3156C>T Mutation in a Non-white Family
Authors: Vahedi Farnoosh , Chung Doug D. , Gee Katherine M. , Chuephanich Pichaya , Aldave Anthony J.
Published: April 2018

Purpose:

To report the identification of the collagen, type XVII, alpha 1 (COL17A1) c.3156C>T mutation associated with epithelial recurrent erosion dystrophy (ERED) in a Thai family.

Methods:

Slit-lamp examination was performed to determine the affected status of each member of a Thai family, with multiple members demonstrating scattered Bowman layer opacities. After genomic deoxyribonucleic acid (DNA) was isolated from saliva, polymerase chain reaction (PCR) amplification and Sanger sequencing were performed to screen COL17A1 and exons 4 and 12 of the transforming growth factor β–induced gene.

Results:

The 67-year-old proband and her 4 siblings were examined by slit-lamp biomicroscopy, which identified bilateral subepithelial opacities in the proband and in one of the 4 siblings. In both the proband and the affected sister, screening of the COL17A1 gene identified a heterozygous c.3156C>T synonymous mutation that has been previously demonstrated to introduce a cryptic splice donor site, likely leading to aberrant splicing of COL17A1. This mutation was not identified in the unaffected siblings, and no mutations were identified in exons 4 and 12 of the transforming growth factor β–induced gene in any of the screened family members.

Conclusions:

ERED associated with a COL17A1 mutation has been previously reported in only 6 families, all white. Identification of the c.3156C>T mutation, previously identified in 5 of these 6 families, in the Thai family we report indicates conservation of the genetic basis of ERED across different races and underscores the importance of ophthalmologists around the globe being familiar with ERED, which has only recently become a recognized corneal dystrophy.
Outcomes of Thermal Pulsation Treatment for Dry Eye Syndrome in Patients With Sjogren Disease
Authors: Godin Morgan R. , Stinnett Sandra S. , Gupta Preeya K.
Published: April 2018

Purpose:

To evaluate the clinical outcomes of thermal pulsation treatment in patients with meibomian gland dysfunction (MGD) and dry eye secondary to Sjogren disease.

Methods:

Twenty-four eyes from 13 patients with previously diagnosed Sjogren disease who presented to our institution with dry eye symptoms and had thermal pulsation treatment were prospectively followed up. Patients underwent comprehensive slit-lamp examination, including MGD grading, gland oil flow, corneal and conjunctival staining scores, and tear break-up time (TBUT). Tear osmolarity was tested before and after treatment.

Results:

The average patient age was 62.4 years (range, 31–78 yrs); 12 were women and 1 a man. The average meibomian gland oil flow score showed an increase from pretreatment 0.71 to 1.75 at 1 year posttreatment (range 9–15 months) (P = 0.001). The average corneal staining score decreased from a pretreatment grade of 1.04 to a posttreatment grade of 0.36 (P < 0.001). The average conjunctival staining score decreased from a pretreatment grade of 1.5 to a posttreatment grade of 0.48 (P < 0.001). The average tear break-up time improved from 3.8 seconds before treatment to 7.5 seconds after thermal pulsation treatment (P < 0.001). There was no statistically significant change in the tear osmolarity or Ocular Surface Disease Index score.

Conclusions:

Our findings suggest that MGD is an important contributor to dry eye disease in patients with Sjogren disease and should not be overlooked when considering treatment options. Thermal pulsation is a therapeutic option for patients with Sjogren disease who have MGD and dry eye symptoms. After a single treatment, patients exhibited increased oil flow and tear break-up time with an associated decrease in corneal and conjunctival staining.
High-fat diet exacerbates postoperative pain and inflammation in a sex-dependent manner
Authors: Song Zongbin , Xie Wenrui , Strong Judith A. , Berta Temugin , Ulrich-Lai Yvonne M. , Guo Qulian , Zhang Jun-Ming
Published: April 2018

Obesity is often associated with increased pain, but little is known about the effects of obesity and diet on postoperative pain. In this study, effects of diet and obesity were examined in the paw incision model, a preclinical model of postoperative pain. Long–Evans rats were fed high-fat diet (40% calories from butter fat) or low-fat normal chow. Male rats fed high-fat diet starting 6 weeks before incision (a diet previously shown to induce markers of obesity) had prolonged mechanical hypersensitivity and an overall increase in spontaneous pain in response to paw incision, compared with normal chow controls. Diet effects in females were minor. Removing high-fat diet for 2 weeks before incision reversed the diet effects on pain behaviors, although this was not enough time to reverse high-fat diet-induced weight gain. A shorter (1 week) exposure to high-fat diet before incision also increased pain behaviors in males, albeit to a lesser degree. The 6-week high-fat diet increased macrophage density as examined immunohistochemically in lumbar dorsal root ganglion even before paw incision, especially in males, and sensitized responses of peritoneal macrophages to lipopolysaccharide stimuli in vitro. The nerve regeneration marker growth-associated protein 43 (GAP43) in skin near the incision (day 4) was higher in the high-fat diet group, and wound healing was delayed. In summary, high-fat diet increased postoperative pain particularly in males, but some diet effects did not depend on weight gain. Even short-term dietary manipulations, that do not affect obesity, may enhance postoperative pain.
Assessing Information Needs Regarding Metabolic Syndrome Among Gynecological Cancer Survivors
Authors: Jang Insil , Kim Ji-Su , Kim Minhae , Lee Eunkyung
Published: April 2018

Background

Cancer survivors have an increased risk of non–cancer-related deaths, particularly metabolic syndrome (MetS).

Objective

We aimed to assess knowledge deficits regarding metabolism-related diseases among gynecological cancer survivors and the preferred source of health information.

Methods

Using a mixed methods approach, 70 participants responded to a structured modified version of the MetS questionnaire. We conducted 28 semistructured interviews of gynecological cancer survivors with MetS. Responses were independently coded by 2 researchers, including MetS knowledge, behaviors for self-management, and preferred learning methods.

Results

Metabolic syndrome was diagnosed in 17% of the participants. More than 50% of the participants wanted to learn about MetS and requested a consultation with healthcare providers, 70% reported that they had heard of MetS, and 61.4% reported that they had MetS-related knowledge (correct answer rate by MetS-related component, ~50%). The level of MetS-related knowledge was poor in both the quantitative and qualitative data. Most of the participants defined MetS-related self-management health behaviors as regular eating and exercise in their own words. Participants mostly wanted exercise management (29% of the participants), followed by dietary life management (27.4%), stress management (17.4%), weight management (13.7%), definition and diagnostic methods of MetS (9.1%), and smoking and drinking management (3.3%). Participants wished to use a handbook in small groups or receive counseling by healthcare providers.

Conclusion

We observed poor awareness and knowledge level and the need for information regarding MetS among gynecological cancer survivors.

Implications for Practice

An educational handbook or counseling could effectively improve self-management of health-related behaviors.
Effects of Synbiotics on Anthropometric Indices of Obesity in Children
Authors: Kianifar Hamid Reza , Ahanchian Hamid , Safarian Mohammad , Javid Asma , Farsad-Naeimi Alireza , Jafari Seyed Ali , kiani Mohammad Ali , Dahri Monireh
Published: April 2018

A pilot study was done to assess whether synbiotics supplementation could optimize anthropometric indices in Iranian obese children. Participants included 46 overweight or obese children 7 to 13 years of age. The treatment group had a restricted diet, physical activity plan, and a synbiotics capsule per day for 12 weeks. The placebo group received a similar diet, activity plan, and placebo capsules. Body fat and z scores for body mass index showed significant reductions in both groups; however, waist circumference decreased significantly only in the synbiotics group. Between-group comparisons showed no significant differences in any variable. Our findings showed that synbiotics can improve the benefits of lifestyle modifications by decreasing waist circumference in overweight or obese children.
Strategies to Reduce the Risk of Central Line–Associated Bloodstream Infections in Parenteral Nutrition
Authors: Balazh Julia R. , Franck Andrew J.
Published: April 2018

Parenteral nutrition (PN) is a lifesaving or life-sustaining treatment, but complications from its use, including central line–associated bloodstream infections (CLABSIs), necessitate that care be taken to ensure its safety. Our institution developed strategies that aim to incorporate evidence-based practices to reduce the risk of CLABSIs in patients receiving PN. A retrospective evaluation was conducted to assess the implementation of these strategies. Overall, adherence to the risk-reduction strategies was high, and no patients receiving PN experienced CLABSI during the time of the study.
Single-Center Long-Term Analysis of Combined Liver-Lung Transplant Outcomes
Authors: Freischlag Kyle William , Messina Julia , Ezekian Brian , Mulvihill Michael S. , Barbas Andrew , Berg Carl , Sudan Debra , Reynolds John , Hartwig Matthew , Knechtle Stuart
Published: April 2018

Background

Combined lung-liver transplantation (LLT) applies 2 technically challenging transplants in 1 patient with severe 2-organ failure.

Methods

Institutional medical records and United Network for Organ Sharing database were queried for patients at our institution that underwent LLT from 2000 to 2016.

Results

Twelve LLTs were performed from 2000 to 2016 including 9 male and 3 female recipients with a median age of 28.36 years. Indications for lung transplantation were cystic fibrosis (8), idiopathic pulmonary fibrosis (3), and pulmonary fibrosis secondary to hepatopulmonary syndrome (1). Indications for liver transplantation were cystic fibrosis (8), alcoholic cirrhosis (1), idiopathic cirrhosis (2), and alpha-1 antitrypsin deficiency (1). Median forced expiratory volume in 1 second at transplant was 27.8% (±20.38%), and mean Model for End-Stage Liver Disease was 10.5 (±4.68). Median hospital stay was 44.5 days. Seventy-five percent of recipients had 1+ new infection during their transplant hospitalization. Patients experienced 0.68 incidences of acute rejection per year with a 41.7% (95% confidence interval, 21.3%-81.4%) probability of freedom from rejection in the first-year. Patient survival was 100% at 30 days, 91.6% at 1 year, and 71.3% at 3 years. At the time of analysis, 7 of 12 patients were alive, of whom 3 survived over 8 years post-LLT. Causes of death were primary liver graft failure (1), bronchiolitis obliterans syndrome (2), and solid tumor malignancies (2).

Conclusions

Our results indicate that LLT is associated with comparable survival to other LLT series and provides a granular assessment of infectious and rejection rates in this rare population.
An automated, machine learning-based detection algorithm for spike-wave discharges (SWDs) in a mouse model of absence epilepsy
Authors: Pfammatter Jesse A. , Maganti Rama K. , Jones Mathew V.
Published: April 2018

Summary and Keywords

Objective

Manual detection of spike-wave discharges (SWDs) from EEG records is time intensive, costly, and subject to inconsistencies/biases. Additionally, manual scoring often omits information on SWD confidence/intensity which may be important for the investigation of mechanistic-based research questions. Our objective is to develop an automated method for the detection of SWDs in a mouse model of absence epilepsy that is focused on the characteristics of human scoring of pre-selected events to establish a confidence-based, continuous-valued scoring.

Methods

We develop a support vector machine (SVM)-based algorithm for the automated detection of SWDs in the γ2R43Q mouse model of absence epilepsy. The algorithm first identifies putative SWD events using frequency- and amplitude-based peak detection. Four humans scored a set of 2500 putative events identified by the algorithm. Then, using predictors calculated from the wavelet transform of each event and the labels from human scoring, we trained a SVM to classify (SWD/nonSWD) and assign confidence scores to each event identified from 60 24-hour EEG records. We provide a detailed assessment of intra- and inter-rater scoring that demonstrates advantages of automated scoring.

Results

The algorithm scored SWDs along a continuum that is highly correlated with human confidence and that allows us to more effectively characterize ambiguous events. We demonstrate that events along our scoring continuum are temporally and proportionately correlated with abrupt changes in spectral power bands relevant to normal behavioral states including sleep.

Significance

While there are automated and semi-automated methods for the detection of SWDs in humans and rats, we contribute to the need for continued development of SWD detection in mice. Our results demonstrate the value of viewing detection of SWDs as a continuous classification problem to better understand ‘ground truth’ in SWD detection (i.e., the most reliable features agreed upon by humans that also correlate with objective physiological measures).

Key Point Box

Clinicians and researchers may benefit from an automated method of SWD detection that provides a framework for the quantitative description of SWDs and how they relate to other electrographic events.

We present an algorithm for the automated, consistent, and rapid scoring of SWDs that assigns a confidence to detected events that is highly correlated with human scoring confidence.

We characterize the human inter- and intra-rater consistency in the scoring of potential SWD events and compare them with the algorithm.

Events along the scoring continuum generated by the algorithm are temporally and proportionately correlated with changes in spectral power bands relevant to behavioral states including sleep.
Azithromycin resistance through interspecific acquisition of an epistasis dependent efflux pump component and transcriptional regulator in Neisseria gonorrhoeae
Authors: Wadsworth Crista B. , Arnold Brian J. , Abdul Sater Mohamad R. , Grad Yonatan H.
Published: April 2018

Mosaic interspecifically acquired alleles of the multiple transferable resistance (mtr) efflux pump operon correlate with reduced susceptibility to azithromycin in Neisseria gonorrhoeae in epidemiological studies. However, whether and how these alleles cause resistance is unclear. Here, we use population genomics, transformations, and transcriptional analyses to dissect the relationship between variant mtr alleles and azithromycin resistance. We find that the locus encompassing the mtrR transcriptional repressor and the mtrCDE pump is a hotspot of interspecific recombination introducing alleles from N. meningitidis and N. lactamica into N. gonorrhoeae, with multiple rare haplotypes in linkage disequilibrium at mtrD and the mtr promoter region. Transformations demonstrated that resistance is mediated through epistasis between these two loci and that the full length of the mosaic mtrD allele is required. Gene expression profiling revealed the mechanism of resistance in mosaics couples the novel mtrDalleles with promoter mutations enhancing expression of the pump. Overall, our results demonstrate that epistatic interactions at mtr gained from multiple Neisseria has contributed to azithromycin resistance in the gonococcal population.

AUTHOR SUMMARY

Neisseria gonorrhoeae is the sexually transmitted bacterial pathogen responsible for over 100 million cases of gonorrhea worldwide each year. The incidence of reduced susceptibility to the macrolide class antibiotic azithromycin has increased in the past decade; however, a large proportion of the genetic basis of resistance to this drug remains unexplained. Recently, resistance has been shown to be highly associated with mosaic alleles of the multiple transferable resistance (mtr) efflux pump, which have been gained via horizontal gene exchange with other Neisseria. However, if and how these alleles caused resistance was unknown. Here, we demonstrate that resistance has been gained through epistasis between mtrD and the mtr promoter region using evidence from both population genomics and experimental genetic manipulation. Epistasis also acts within the mtrD locus alone, requiring the full length of the gene for phenotypic resistance. Transcriptomic profiling indicates that the mechanism of resistance in mosaics is likely derived from both structural changes to mtrD, coupled with promoter mutations that result in regulatory changes to mtrCDE.
A trade-off between error and synchrony when using temporal codes
Authors: Peterson Erik J , Voytek Bradley
Published: April 2018

Neural oscillations can improve the fidelity of neural coding by grouping action potentials into synchronous windows of activity but this same effect can interfere with coding when action potentials become “over-synchronized”. Diseases ranging from Parkinson’s to epilepsy suggest such over-synchronization can lead to pathological outcomes, but the precise boundary separating healthy from pathological synchrony remains an open theoretical problem. In this paper, we focus on measuring the costs of translating from an aperiodic code to a rhythmic one and use the errors introduced in this translation to predict the rise of pathological results. We study a simple model of entrainment featuring a pacemaker population coupled to biophysical neurons. This model shows that “error” in individual cells’ computations can be traded for population-level synchronization of spike-times. But in this model error and synchronization are not traded linearly, but nonlinearly. The bulk of synchronization happens early with relatively low error. To predict this phenomenon we conceive of “voltage budget analysis”, where small time windows of membrane voltage in single cells can be partitioned into “oscillatory” and “computational”‘ terms. By comparing these terms we discover a set of inequalities that align with an inflection point in the curve of measured errors. In particular, when the entrainment and computational voltage terms are equal, the error curve plateaus. We show this point serves as a reliable natural boundary to define pathological synchrony in neurons. We also derive optimal algorithms for exchanging computational error with population synchrony.

New and Noteworthy. We establish exact conditions for when rhythmic entrainment of precise spike-times in a neural population will improve or harm it’s ability to communicate.
PP2C phosphatases promote autophagy by dephosphorylation of the Atg1 complex
Authors: Memisoglu Gonen , Eapen Vinay V. , Haber James E.
Published: April 2018

Autophagy is orchestrated by the Atg1-Atg13 complex in budding yeast. Under nutrient-rich conditions, Atg13 is maintained in a hyperphosphorylated state by TORC1 kinase. After nutrient starvation, Atg13 is dephosphorylated, triggering Atg1 kinase activity and autophagy induction. The phosphatases that dephosphorylate Atg13 remain uncharacterized. We show that two redundant PP2C phosphatases, Ptc2 and Ptc3, regulate autophagy via dephosphorylating both Atg13 and Atg1. In the absence of these phosphatases, starvation-induced macroautophagy is inhibited, as is the cytoplasm-to-vacuole targeting (Cvt) pathway, and the recruitment of the essential autophagy machinery to phagophore assembly sites (PAS) is impaired. Despite prolongation of the DNA damage-induced checkpoint in ptc2Δ ptc3Δ cells, genotoxin-induced autophagy is also blocked. Creating a genomic atg13-8SA allele under its endogenous promoter, lacking key TORC1 phosphorylation sites, bypasses the autophagy defect in ptc2Δ ptc3Δ strains. Taken together, these results imply that PP2C type phosphatases promote autophagy by regulating Atg1 complex.
Deep learning achieves super-resolution in fluorescence microscopy
Authors: Wang Hongda , Rivenson Yair , Jin Yiyin , Wei Zhensong , Gao Ronald , Günaydin Harun , Bentolila Laurent A. , Ozcan Aydogan
Published: April 2018

Abtsract

We present a deep learning-based method for achieving super-resolution in fluorescence microscopy. This data-driven approach does not require any numerical models of the imaging process or the estimation of a point spread function, and is solely based on training a generative adversarial network, which statistically learns to transform low resolution input images into super-resolved ones. Using this method, we super-resolve wide-field images acquired with low numerical aperture objective lenses, matching the resolution that is acquired using high numerical aperture objectives. We also demonstrate that diffraction-limited confocal microscopy images can be transformed by the same framework into super-resolved fluorescence images, matching the image resolution acquired with a stimulated emission depletion (STED) microscope. The deep network rapidly outputs these super-resolution images, without any iterations or parameter search, and even works for types of samples that it was not trained for.
Human stem cell resources are an inroad to Neandertal DNA functions
Authors: Dannemann Michael , Vernot Benjamin , Pääbo Svante , Kelso Janet , Camp J. Gray
Published: April 2018

Pluripotent stem cells from diverse humans offer the potential to study human functional variation in controlled culture environments. A portion of this variation originates from ancient admixture between modern humans and Neandertals, which introduced alleles that left a phenotypic legacy on individual humans today. Here we show that a large repository of human induced pluripotent stem cells (iPSCs) harbors extensive Neandertal DNA, including most known functionally relevant Neandertal alleles present in modern humans. This resource contains Neandertal DNA that contributes to human phenotypes and diseases, encodes hundreds of amino acid changes, and alters gene expression in specific tissues. Human iPSCs thus provide an opportunity to experimentally explore the Neandertal contribution to present-day phenotypes, and potentially study Neandertal traits.
YAMDA: thousandfold speedup of EM-based motif discovery using deep learning libraries and GPU
Authors: Quang Daniel , Guan Yuanfang , Parker Stephen C.J.
Published: April 2018

Motivation

Motif discovery in large biopolymer sequence datasets can be computationally demanding, presenting significant challenges for discovery in omics research. MEME, arguably one of the most popular motif discovery software, takes quadratic time with respect to dataset size, leading to excessively long runtimes for large datasets. Therefore, there is a demand for fast programs that can generate results of the same quality as MEME.

Results

Here we describe YAMDA, a highly scalable motif discovery software package. It is built on Pytorch, a tensor computation deep learning library with strong GPU acceleration that is highly optimized for tensor operations that are also useful for motifs. YAMDA takes linear time to find motifs as accurately as MEME, completing in seconds or minutes, which translates to speedups over a thousandfold.

Availability

YAMDA is freely available on Github (https://github.com/daquang/YAMDA)

Contact

daquang@umich.edu
Pharmacophore-guided discovery of CDC25 inhibitors causing cell cycle arrest and cell death
Authors: Kabakci Zeynep , Käppeli Simon , Cozza Giorgio , Cantù Claudio , König Christiane , Toggweiler Janine , Gentili Christian , Ribaudo Giovanni , Zagotto Giuseppe , Basler Konrad , Pinna Lorenzo A. , Ferrari Stefano
Published: April 2018

CDC25 phosphatases have a key role in cell cycle transitions and are important targets for cancer therapy. Here, we set out to discover novel CDC25 inhibitors. Using a combination of computational approaches we defined a minimal common pharmacophore in established CDC25 inhibitors and performed a virtual screening of a proprietary library. Taking advantage of the availability of crystal structures for CDC25A and CDC25B and using a molecular docking strategy, we carried out hit expansion/optimization. Enzymatic assays revealed that naphthoquinone scaffolds were the most promising CDC25 inhibitors among selected hits. At the molecular level, the compounds acted through a mixed-type mechanism of inhibition of phosphatase activity, involving reversible oxidation of cysteine residues. In 2D cell cultures, the compounds caused arrest of the cell cycle at the G1/S or at the G2/M transition. Mitotic markers analysis and time-lapse microscopy confirmed that CDK1 activity was impaired and that mitotic arrest was followed by death. Finally, studies on 3D organoids derived from intestinal crypt stem cells of Apc/K-Ras mice revealed that the compounds caused arrest of proliferation.
Crystal structure and theoretical study of N,N-bis[(5-chloro-2-oxo-2,3-dihydrobenzo[d]oxazol-3-yl)methyl]-2-phenylethanamine
Authors: Aydın Abdullah , Soyer Zeynep , Akkurt Mehmet , Büyükgüngör Orhan
Published: April 2018

In the molecular structure of the title compound, C24H19Cl2N3O4, the three C atoms of the central N,N-dimethylmethanamine moiety are bonded to the N atoms of the two 5-chloro-1,3-benzoxazol-2(3H)-one groups and to the methyl C atom of the methylbenzene group. One of the nine-membered 2,3-dihydro-1,3-benzoxazole rings and the phenyl ring are almost parallel to each other, making a dihedral angle of 5.30 (18)°, but they are almost normal to the mean plane of the other nine-membered 2,3-dihydro-1,3-benzoxazole ring, subtending dihedral angles of 89.29 (16) and 85.41 (18)°, respectively. The crystal structure features C—H...O hydrogen bonds and π–π stacking interactions [centroid-to-centroid distances = 3.5788 (19) Å, slippage = 0.438 and 3.7773 (16) Å, and slippage = 0.716 Å].
Crystal structure of octane-1,8-diaminium 4,4′-(diazene-1,2-diyl)dibenzoate monohydrate
Authors: Elkin Igor , Maris Thierry , Christopherson Jan-Constantin , Borchers Tristan H. , Barrett Christopher J.
Published: April 2018

The title salt, C8H22N2
2+·C14H8N2O4
2−·H2O, represents a pseudo-polymer ionic material, resulting from the self-organizing behavior of 4,4′-azinodibenzoate dianions and doubly protonated, 1,8-diaminium-octane cations in aqueous solution. The asymmetric unit consists of two halves of octane 1,8-diaminium cations (the complete cations are both generated by crystallographic inversion symmetry), a 4,4′-azinodibenzoate anion [dihedral angle between the aromatic rings = 10.22 (4)°] and a water molecule of crystallization. One of the cations is in a fully extended linear conformation while the second one has a terminal C—C—C—N gauche conformation. In the crystal, the cations, anions and water molecules are linked into a three-dimensional network via a complex pattern of charge-assisted N—H...O and O—H...O hydrogen bonds.
Crystal structure of difluorido{2-[(4-hydroxyphenyl)diazenyl]-3,5-dimethylpyrrolido}boron
Authors: Feng Huixiao , Yin Zhenming
Published: April 2018

The asymmetric unit of the title azopyrrole-BF2 complex, C12H12BF2N3O, contains two independent molecules, which are linked by an O—H...O hydrogen bond. The dimers are further assembled into a one-dimensional ladder-like structure through O—H...F hydrogen bonds and stabilized by π–π interactions. The ladders are further linked by C—H...π contacts.
2-(3-Chlorophenyl)-3,4-dihydrobenzo[f][1,4]oxazepin-5(2H)-one
Authors: Zhong Ling , Shi Jianyou , Zhong Lei , Wei Xin , Xhang Hongjia , Cheng Liang , Bai Lan
Published: April 2018

In the title compound, C15H12ClNO2, the dihedral angle between the two benzene rings is 73.45 (11)°. The central seven-membered ring is in a psuedo-boat conformation. In the crystal, pairs of molecules are linked by N—H...O hydrogen bonds, forming inversion dimers.
Bis(4-cobaltoceniumyl-1-ferrocenyl-3-methyl-1,2,3-triazolylidene)gold(I) hexafluoridophosphate–trifluoromethanesulfonate (1.2/1.8)
Authors: Vanicek Stefan , Wurst Klaus , Kopacka Holger , Bildstein Benno
Published: April 2018

The title compound, [AuCo2Fe2(C5H5)4(C13H11N3)2](PF6)1.2(CF3SO3)1.8, was synthesized by deprotonation of 4-cobaltoceniumyl-1-ferrocenyl-3-methyl-1,2,3-triazolium hexafluoridophosphate trifluoromethanesulfonate with thallium ethoxide, followed by transmetalation with chlorido(triphenylphosphine)gold(I), crystallizing as orange prisms. It is a unique example of a homoleptic dimetallocenyl-substituted triazolylidene complex.
1,2-Bis(3,5-dimethylphenyl)ethane
Authors: Brieger Lukas , Unkelbach Christian , Strohmann Carsten
Published: April 2018

The title compound, C18H22, is a coupling product of two metallated mesitylene molecules. The dihedral angle between the aromatic rings is 11.10 (5)° and the Car—Cm—Cm—Car (ar = aromatic and m = methylene) torsion angle is 179.60 (14)°. No directional interactions beyond normal van der Waals contacts could be identified in the crystal. To our best knowledge, it is the first known coupling product of metallated mesitylene.
Automatic meeting summarization and topic detection system
Authors: Huang Tai-Chia , Hsieh Chia-Hsuan , Wang Hei-Chia
Published: April 2018

Purpose

Producing meeting documents requires an instantaneous recorder during meetings, which costs extra human resources and takes time to amend the file. However, a high-quality meeting document can enable users to recall the meeting content efficiently. The paper aims to discuss these issues.

Design/methodology/approach

An application based on this framework is developed to help the users find topics and obtain summarizations of meeting contents without extra effort. This app uses the Bluemix speech recognizer to obtain speech transcripts. It then combines latent Dirichlet allocation and a TextTiling algorithm with the speech script of meetings to detect boundaries between different topics and evaluate the topics in each segment. TextTeaser, an open API based on a feature-based approach, is then used to summarize the speech transcripts.

Findings

The results indicate that the summaries generated by the machine are 85 percent similar to the records written by humankind.

Originality/value

To reduce the human effort in generating meeting reports, this paper presents a framework to record and analyze meeting contents automatically by voice recognition, topic detection, and extractive summarization.
The structural characteristics of innovation ecosystem: a fashion case
Authors: Lin Shuyu
Published: April 2018

Purpose

The purpose of this paper is to provide empirical evidence of open innovation mechanism specific to aesthetic innovation. Prior research have drawn its research attention to technological innovation and focussed on the biopharmaceutical and technological sectors as the main research contexts. Thus, to gain a wider picture of the structural characteristics of innovation ecosystem, this paper aims to complement the existing technological-centred literature and provides understanding of aesthetic innovation by focussing on exploring the role of actors and intermediaries in either facilitating or inhibiting innovation in the creative sector.

Design/methodology/approach

This is an exploratory study and the qualitative method was employed. With aim to explore aesthetic innovation in the creative sector, this research grounded its context in the UK designer fashion sector, which is part of the creative industries. Data were collected through a series of semi-structured interviews with respondents being purposely selected so as to ensure representativeness. A wider range of participants within the designer fashion sector was covered. Such multiple-sourced data collection approach allowed this research to triangulate data so that research trustworthiness was enhanced.

Findings

The result suggests the role of a broker in beyond traditionally facilitating knowledge exchange. This paper provides empirical evidence regarding the critical role of a broker in shaping the open innovation mechanism when it comes to aesthetic innovation. A broker in fact occupies a strategic position that allows it to negotiate relationships among the connected organisations and thus to govern the interaction mechanism of the innovation ecosystem as a whole. Given the empowered broker in such setting, the relationship between innovation creators and innovation seekers is controlled by a broker, which leads to risk that an innovation creator may not fully appropriate the value that it creates.

Research limitations/implications

The main limitation of this study is its specific context, that is, the UK designer fashion industry. Such focus limits the scope of generalisation particularly its application to the entire creative sector. Thus, it is suggested that future research may consider to explore other creative industries so that the understanding of the open innovation mechanism from a structural perspective applied to aesthetic innovation can be enhanced.

Originality/value

This paper outlines the structural mechanism of open innovation applied to aesthetic innovation. The result contributes to the literature by complementing the findings derived from technology-centred research. Also, empirical evidence of this study is particularly of value to policy makers in the aspect of creative sector development. The suggested implications provide strategies of innovation ecosystem that could benefit individual actors involved in this open innovation setting and ensure prosper of the sector as a whole.
Growing and aging of entrepreneurial firms
Authors: Thongpapanl Narongsak , Kaciak Eugene , Welsh Dianne H.B.
Published: April 2018

Purpose

The purpose of this paper is to explore whether job rotation strategies and joint reward systems are equally effective in encouraging cross-functional collaboration (CFC) under all organizational contexts, ranging from young and small firms to mature and large ones.

Design/methodology/approach

To ensure a wide applicability of findings in this study, the research model and hypotheses were tested with a sample of 232 Canadian firms active in a variety of industrial sectors. A survey instrument that comprised all the questionnaire items corresponding to the examined constructs is the foundation of the data used in this contribution.

Findings

This study shows that job rotation and joint rewards are strong and positive drivers of interdepartmental collaboration, which subsequently enhance firm performance. However, this illustration must be considered in the context of the firm shaped by its size and age because these two variables strongly and negatively moderate the relationships between CFC and its two antecedents.

Research limitations/implications

The study was limited to Canadian firms only. The manufacturing sector was not differentiated into subsectors, such as technology. Future studies could compare subsectors of manufacturing to see if there is any correlation between types of industries, age, and size.

Originality/value

Not all firms will be able to take advantage of the widely accepted values of job rotation and joint reward systems in generating CFC. Firms, to an extent, appear to be confronted with the liability of aging but not with the liability of smallness.