bluuebunny/crossref_metadata_2025 huggingface dataset:
Biphasic Release of the Alarmin High Mobility Group Box 1 Protein Early After Trauma Predicts Poor Clinical Outcome
Authors: Ottestad William , Rognes Ingrid N. , Pischke Soeren E. , Mollnes Tom E. , Andersson Ulf , Eken Torsten
Published: June 2019

Objectives:

The causal role of the prototype alarmin high mobility group box 1 protein in systemic inflammation and remote organ injury after trauma and shock is established in animal models but not in humans. Our aim was therefore to determine high mobility group box 1 protein concentration kinetics with high time resolution during the first hours after trauma in individual patients and investigate the association with outcome.

Design:

Prospective single-center observational study.

Setting:

University hospital Level I trauma center.

Patients:

Convenience recruitment of 136 trauma patients.

Interventions:

None.

Measurements and Main Results:

Total plasma high mobility group box 1 protein levels were analyzed with enzyme-linked immunosorbent assay in repeated samples. Relationships between predefined predictor variables and outcome were examined in multivariable linear regression models. Ventilator-free days was used as primary outcome measure. Two distinct high mobility group box 1 protein release phases were identified. An initial exponential decay phase with half-life 26 minutes was not correlated with outcome. In contrast, a second high mobility group box 1 protein wave peaking 3–6 hours after trauma in the most severely injured and physiologically deranged patients was consistently the most important predictor of outcome in our multivariable models, rendering all other predictor variables insignificant except for smaller contributions from age and sex, and of admission base excess for maximal creatinine concentration.

Conclusions:

High mobility group box 1 protein was released in two consecutive phases. Only the second high mobility group box 1 protein wave was a significant predictor of outcome. Patients with a high high mobility group box 1 protein concentration between 3 and 6 hours after trauma might hypothetically benefit from high mobility group box 1 protein-specific antagonist therapy.
Extracorporeal Membrane Oxygenation for Septic Shock
Authors: Falk Lars , Hultman Jan , Broman Lars Mikael
Published: June 2019

Objectives:

Septic shock carries a high mortality risk. Studies have indicated that patients with septic shock may benefit from extracorporeal membrane oxygenation. In most studies, patients exhibited shock due to myocardial dysfunction rather than distributive/vasoplegic shock. One proposed theory is that venoarterial extracorporeal membrane oxygenation alleviates a failing myocardial function.

Design:

Retrospective observational study.

Setting:

Single-center, high-volume extracorporeal membrane oxygenation unit.

Patients:

All patients treated for septic shock between 2012 and 2017 with an age greater than 18 years old, fulfilling septic shock criteria according to “Sepsis-3” at acceptance for extracorporeal membrane oxygenation, presence of cardiocirculatory failure requiring a support equivalent to a Vasoactive Inotropic Score greater than 50 to reach a mean arterial pressure greater than 65 mm Hg despite adequate fluid resuscitation, were included.

Interventions:

None.

Measurements and Main Results:

Thirty-seven patients, mean age 54.7 years old, were included. Median Simplified Acute Physiology Score-3 score was 86 and Sequential Organ Failure Assessment 16. Twenty-seven patients were submitted to venoarterial and 10 patients to venovenous extracorporeal membrane oxygenation. Hospital survival was 90% for septic shock with left ventricular failure and 64.7% in patients with distributive shock. At long-term follow-up at 46.1 months, total survival was 59.5%. Commencement of venovenous extracorporeal membrane oxygenation and more organ failures at admission showed a less favorable outcome in terms of hospital and long-term survival.

Conclusions:

The current results add not only to the growing evidence of the benefit of venoarterial extracorporeal membrane oxygenation for septic cardiomyopathy but also indicate improved hospital survival in distributive septic shock.
Impact of Critical Care Point-of-Care Ultrasound Short-Courses on Trainee Competence
Authors: Rajamani Arvind , Miu Michelle , Huang Stephen , Elbourne-Binns Henry , Pracher Florian , Gunawan Sutrisno , Lakshmanan Ramanathan , Flynn Gordon , Sasidaran Kandasamy , Subasinghe Shyama , Parmar Jinal , Hyunh Trieu
Published: June 2019

Objectives:

Competence in point-of-care ultrasound is recommended/mandated by several critical care specialties. Although doctors commonly attend point-of-care ultrasound short-courses for introductory training, there is little follow-up data on whether they eventually attain competence. This study was done to determine the impact of point-of-care ultrasound short-courses on point-of-care ultrasound competence.

Design:

Web-based survey.

Setting:

Follow-up after point-of-care ultrasound short-courses in the Asia-Pacific region.

Subjects:

Doctors who attended a point-of-care ultrasound short-course between December 2015 and February 2018.

Interventions:

Each subject was emailed a questionnaire on or after 6 months following their short-course. They were asked if they had performed at least 30 structured point-of-care ultrasound scans and/or reached point-of-care ultrasound competence and their perceived reasons/challenges/barriers. They were also asked if they used point-of-care ultrasound as a clinical diagnostic aid.

Measurements and Main Results:

The response rate was 74.9% (182/243). Among the 182 respondents, only 12 (6.6%) had attained competence in their chosen point-of-care ultrasound modality, attributing their success to self-motivation and time management. For the remaining doctors who did not attain competence (170/182, 93.4%), the common reasons were lack of time, change of priorities, and less commonly, difficulties in accessing an ultrasound machine/supervisor. Common suggestions to improve short-courses included requests for scanning practice on acutely ill ICU patients and prior information on the challenges regarding point-of-care ultrasound competence. Suggestions to improve competence pathways included regular supervision and protected learning time. All 12 credentialled doctors regularly used point-of-care ultrasound as a clinical diagnostic aid. Of the 170 noncredentialled doctors, 123 (72.4%) reported performing unsupervised point-of-care ultrasound for clinical management, either sporadically (42/170, 24.7%) or regularly (81/170, 47.7%).

Conclusions:

In this survey of doctors attending point-of-care ultrasound short-courses in Australasia, the majority of doctors did not attain competence. However, the practice of unsupervised point-of-care ultrasound use by noncredentialled doctors was common. Further research into effective strategies to improve point-of-care ultrasound competence is required.
Müller’s Muscle-conjunctival Resection Combined With Tarsectomy for Treatment of Congenital Ptosis
Authors: Gazit Inbal , Gildener-Leapman Juliana , Or Lior , Burkat Cat N. , Pras Eran , Hartstein Morris E.
Published: June 2019

The authors describe a retrospective case analysis of patients who underwent Müller’s muscle-conjunctival resection combined with tarsectomy, for the treatment of congenital ptosis with moderate-to-good levator function, demonstrates excellent results.

Purpose:

To evaluate the efficacy of Müller’s muscle-conjunctival resection combined with tarsectomy for the treatment of congenital ptosis.

Methods:

A retrospective, noncomparative case series was performed on 38 eyes of 36 patients who underwent Müller’s muscle-conjunctival resection combined with tarsectomy for the treatment of congenital ptosis. Age range was 2–25 years (mean: 7.86 years). Follow-up measurements taken up to 4 years after procedure were compared with baseline values.

Results:

Thirty-six patients presenting with congenital ptosis underwent Müller’s muscle-conjunctival resection combined with tarsectomy. All patients had fair-to-good levator function of 5–10 mm. A mean improvement in the margin reflex distance-1 of 2.79 mm (p value < 0.0001) was noted. All cases except one achieved excellent lid height and postoperative symmetry of the eyelids.

Conclusions:

Müller’s muscle-conjunctival resection combined with tarsectomy is a safe and effective procedure in the treatment of congenital ptosis in patients with moderate-to-good levator function. The surgery is rapid with quick recovery time. No complications were noted.
Impact of Rapid mecA Polymerase Chain Reaction Rapid Diagnostic Testing for Staphylococcus aureus in a Pediatric Setting
Authors: Drwiega Emily N. , Nichols Kristen R. , Israel Emily N. , Knoderer Chad A.
Published: June 2019

Background

Rapid mecA testing, in combination with antimicrobial stewardship intervention, has improved outcomes in adults with Staphylococcus aureus (SA) bacteremia. In pediatric patients, data comparing rapid molecular testing to conventional susceptibility testing for methicillin resistance in SA are limited, and benefits have been observed only in combination with a coordinated real-time antimicrobial stewardship response. The objective of this study was to determine the impact of rapid mecA detection on time to optimal therapy in patients at a pediatric institution without a specific antimicrobial stewardship intervention.

Methods

This was a retrospective cohort study at a freestanding children’s hospital including patients with a blood culture positive for SA. Outcomes before and after the implementation of rapid mecA detection via use of GeneXpert MRSA/SA BC (Cepheid, Sunnyvale, CA) were compared. The primary outcome was time to optimal therapy, which was defined as vancomycin alone for methicillin-resistant SA or nafcillin, oxacillin, or cefazolin alone for methicillin-susceptible SA.

Results

One hundred one patients were included, with 61 patients in the preimplementation period receiving conventional susceptibility testing only and 40 patients in the postimplementation period receiving rapid molecular mecA testing. The median (interquartile range) time (hours) to optimal therapy from culture collection was decreased from 61.5 (47.8–68.1) preimplementation to 42.5 (21.9–56.6; P = 0.003) postimplementation.

Conclusions

Despite lack of a protocol for response to molecular mecA test results, time to optimal therapy and vancomycin use were significantly decreased. Future studies are needed to assess the impact on infection-related outcomes and antibiotic adverse effects.
Not Just a Pill: Toward a Tailored Antismoking Intervention for Respiratory Diseases
Authors: Masiero Marianna , Renzi Chiara , Mazzocco Ketti , Pravettoni Gabriella
Published: June 2019

Tobacco cigarette smoking is a serious epidemic that kills several million people each year. Nevertheless, a significant percentage of patients with respiratory diseases continue to smoke after diagnosis, despite the assistance offered, thus reducing the efficacy of the treatments prescribed by the health providers and dramatically increasing the mortality rate. International guidelines have advocated the importance of including smoking cessation protocols in the management of patients’ respiratory conditions and pointed out the need to deliver integrated and tailored interventions. Consistently with this framework, the commentary proposes a new clinical approach to smoking cessation in patients with respiratory diseases. This approach integrates, according to P5 personalized medicine, pharmacological and psychological aspects affecting smoking behaviors, overcoming the traditional approach mainly based on the pharmacological interventions.
Our Own Worst Enemies
Authors: Edmonson Cole , Zelonka Caroline
Published: June 2019

Nurse bullying is a systemic, pervasive problem that begins well before nursing school and continues throughout a nurse's career. A significant percentage of nurses leave their first job due to the negative behaviors of their coworkers, and bullying is likely to exacerbate the growing nurse shortage. A bullying culture contributes to a poor nurse work environment, increased risk to patients, lower Hospital Consumer Assessment of Healthcare Providers and Systems (HCAHPS) patient satisfaction scores, and greater nurse turnover, which costs the average hospital $4 million to $7 million a year. Addressing nurse bullying begins with acknowledging the problem, raising awareness, mitigating contributing factors, and creating and enforcing a strong antibullying policy. Nurses and stakeholders also must actively work to change the culture, and understand that bullying has no place in the nursing profession or anywhere else in health care.
Clinical and Histopathologic Features of Immune Checkpoint Inhibitor-related Pneumonitis
Authors: Larsen Brandon T. , Chae June M. , Dixit Anuj S. , Hartman Thomas E. , Peikert Tobias , Roden Anja C.
Published: June 2019

Immune checkpoint inhibitors (ICIs) have revolutionized oncology, but are associated with immune-related adverse events. Clinically, pneumonitis is a well-recognized complication, but its histopathologic features are poorly understood. Institutional archives were searched for patients having ICI therapy and subsequent lung tissue sampling. After excluding infectious cases, 9 patients (5 women, median: 59 y) were identified with clinically suspected ICI-related pneumonitis. Clinical history, imaging, and pathology slides were reviewed. Patients received pembrolizumab (6 cases), nivolumab (1), ipilimumab followed by pembrolizumab (1), or pembrolizumab followed by nivolumab (1); the latter experienced pneumonitis with both agents. Treatment duration ranged from 1 to 33 cycles (median: 8). Three patients received concurrent chemotherapy and 1 received radiation; the remainder received ICI monotherapy. Symptoms were nonspecific; 2 patients were asymptomatic. Thoracic imaging showed bilateral ground glass or nodular opacities in all cases, often with pleural effusion. Histologically, organizing pneumonia was seen in 7 patients, all with subclinical or mild disease, admixed with vague non-necrotizing airspace granulomas in 3 cases; all 6 patients with follow-up did well. One patient had acute fibrinous pneumonitis and 1 had diffuse alveolar damage; both died. All 9 cases showed foamy macrophages and pneumocyte vacuolization; 6 had rare eosinophils. ICI-related pneumonitis presents as bilateral ground-glass opacities or nodules, and usually manifests as organizing pneumonia histopathologically, often with vague non-necrotizing airspace granulomas. Foamy macrophages and pneumocyte vacuolization are characteristic and rare eosinophils are often seen. Less commonly, acute fibrinous pneumonitis or diffuse alveolar damage can occur, which may be fatal.
CYSLTR2-mutant Cutaneous Melanocytic Neoplasms Frequently Simulate “Pigmented Epithelioid Melanocytoma,” Expanding the Morphologic Spectrum of Blue Tumors
Authors: Goto Keisuke , Pissaloux Daniel , Paindavoine Sandrine , Tirode Franck , de la Fouchardière Arnaud
Published: June 2019

Recurrent activating Gαq mutations in the spectrum of blue nevi have been well studied. However, the clinicopathologic characteristics of the recently described CYSLTR2-mutant and PLCB4-mutant blue nevi remain limited, owing to their rarity. Herein, we present 7 CYSLTR2-mutant melanocytic neoplasms, including 1 cellular blue nevus, 4 atypical cellular blue nevi, and 2 blue nevus-like melanomas. They occurred on the scalp, breast, flank, forearm, thigh, leg, and ankle of 3 male patients and 4 female patients, with a median age of 43 (25 to 81) years at diagnosis. Five exhibited an exophytic growth, and 6 were heavily pigmented. A fascicular arrangement of medium to large spindle melanocytes was seen in 6 cases, but epithelioid cytology was present in only 2 cases, one of them being focal. A junctional component was present in 3 cases. Immunoreactivity for HMB45 was diffusely present, except in 1 cellular blue nevus. BAP1 nuclear immunoexpression was lost in 1 melanoma case. A canonical CYSLTR2 L129Q hotspot mutation was present in all cases. Altogether, these histopathologic findings suggest that CYSLTR2-mutant melanocytic blue neoplasms frequently exhibit a heavily pigmented exophytic tumor with a silhouette resembling “pigmented epithelioid melanocytoma” rather than usual cellular blue nevus. Moreover, most of these tumors were not clinically recognized as blue nevi and not located in the classic topography of cellular blue nevus aside from the scalp. However, a fascicular arrangement of medium to large-sized spindled melanocytes, as well as a lack of epithelioid or nevoid melanocytes, could be potential diagnostic clues to morphologically distinguish CYSLTR2-mutant tumors from “pigmented epithelioid melanocytoma.”
Use of Platelet-Rich Plasma for the Treatment of Acetabular Labral Tear of the Hip
Authors: De Luigi Arthur Jason , Blatz Daniel , Karam Christopher , Gustin Zachary , Gordon Andrew H.
Published: June 2019

Objective

This study aims to assess whether ultrasound-guided injection of platelet-rich plasma can safely and effectively treat symptoms associated with acetabular hip labral tears.

Design

Institutional review board approval was gained for a prospective study of eight patients (N = 8), who have previously failed conservative management, to receive ultrasound-guided injection of platelet-rich plasma at the site of hip labrum tear. We assessed pain reduction and functional ability at baseline and then 2, 6, and 8 wks after injection, using the visual analog scale and Harris Hip Score, respectively.

Results

Statistically significant differences in Harris Hip Score were seen 2 wks (86.5 ± 10.8, P < 0.01), 6 wks (88.0 ± 10.7) P < 0.01), and 8 wks (92.1 ± 11.6, P < 0.01) after injection as compared with baseline (76.0 ± 13.4). Corresponding improvements were seen in visual analog scale 2 wks (1.0, P < 0.01 at rest, 2.5, P < 0.01 with activity), 6 (0.9, P < 0.01 at rest, 2.3, P < 0.01 with activity), and 8 wks (0.5, P < 0.01 at rest, 1.3, P < 0.01 with activity) compared with baseline (3.8 at rest, 5.4 with activity).

Conclusions

Ultrasound-guided injection of platelet-rich plasma holds promise as an emerging, minimally invasive technique toward symptom relief, reducing pain, and improving function in patients with hip labral tears.
Correlation Between Dual-Energy Computed Tomography Single Scan and Computed Tomography Perfusion for Pancreatic Cancer Patients: Initial Experience
Authors: Bao Jiaqi , Liu Aishi , Zhao Changhong , Hao Fen'e , Su Xiulan , Bao Lili , Zhao Lei
Published: June 2019

Objective

The objective of this study was to evaluate the role and limit of iodine maps by dual-energy computed tomography (CT) single scan for pancreatic cancer.

Methods

Thirty patients with suspected solitary pancreatic cancer were enrolled in this study and underwent CT perfusion and iodine maps. The parameters of pancreatic cancer and normal pancreatic tissue were calculated. Pearson correlation and paired t test were used for evaluating 2 techniques.

Results

Iodine concentration had a moderate positive correlation with blood flow or blood volume (P < 0.05 for both). All values of iodine concentration and blood flow, iodine concentration, and blood volume had significant positive correlations (P < 0.001 for both). The mean effective dose for CT perfusion and iodine maps had significant difference (8.61 ± 0.00 mSv vs 1.13 ± 0.14 mSv, P < 0.001).

Conclusions

Iodine maps had the potential to replace routine CT perfusion for pancreatic cancer with low radiation dose.
Female platelets have distinct functional activity compared with male platelets: Implications in transfusion practice and treatment of trauma-induced coagulopathy
Authors: Coleman Julia R. , Moore Ernest E. , Kelher Marguerite R. , Samuels Jason M. , Cohen Mitchell J. , Sauaia Angela , Banerjee Anirban , Silliman Christopher C. , Peltz Erik D.
Published: June 2019

BACKGROUND

Females are hypercoagulable and have survival benefit in trauma-induced coagulopathy (TIC). The mechanism for this sex-specific hypercoagulability is unknown. Platelets and platelet function are central in providing hemostatic potential and are the largest contributor to clot strength. Ligands (adenosine diphosphate [ADP] and platelet-activating factor [PAF]) bind distinct platelet receptors to potentiate activation and aggregation. We hypothesize that female platelets have a differential response to ADP and PAF, resulting in greater aggregation and activation compared to males, and that estradiol pretreatment of male or female platelets enhances this activity.

METHODS

Platelets were collected from healthy volunteers: premenopausal/postmenopausal females (≤54 years, >54 years) and similarly aged males. Platelet aggregometry and flow cytometry (fibrinogen binding capacity) were examined. After treatment with ADP or PAF, platelet aggregation was assessed with Chronolog and activation assessed by CD41 receptor surface expression using flow cytometry. Aggregation and activation were again assessed after platelet pretreatment with estradiol.

RESULTS

Healthy volunteers included 12 premenopausal and 13 postmenopausal females and 18 similarly aged males. Female platelets (combined premenopausal and postmenopausal) had increased aggregation with ADP stimulation, as compared to male platelets. Male and female platelets had differential fibrinogen receptor expression, with female platelets (combined premenopausal and postmenopausal) demonstrating robust activation with ADP versus male platelets with PAF. In the presence of estradiol incubation, male platelets' activation with PAF approximated that of females (combined premenopausal and postmenopausal) and activation with PAF was enhanced in both male and female platelets.

CONCLUSION

Male and female platelets have differential response to stimuli, suggesting sex-dependent signaling and cellular activation. Female platelets have both increased aggregation and activation potential, and estradiol pretreatment feminizes male platelets to approximate female platelet activation with PAF. These findings offer potential explanation for sex-based differences in hemostatic potential in TIC and question whether donor sex of transfused platelets should be considered in resuscitation. Estradiol may also serve as a novel therapeutic adjunct in TIC.
Detecting adaptive convergent amino acid evolution
Authors: Rey Carine , Lanore Vincent , Veber Philippe , Guéguen Laurent , Lartillot Nicolas , Sémon Marie , Boussau Bastien
Published: June 2019

In evolutionary genomics, researchers have taken an interest in identifying substitutions that subtend convergent phenotypic adaptations. This is a difficult question that requires distinguishing
foreground
convergent substitutions that are involved in the convergent phenotype from
background
convergent substitutions. Those may be linked to other adaptations, may be neutral or may be the consequence of mutational biases. Furthermore, there is no generally accepted definition of convergent substitutions. Various methods that use different definitions have been proposed in the literature, resulting in different sets of candidate foreground convergent substitutions. In this article, we first describe the processes that can generate foreground convergent substitutions in coding sequences, separating adaptive from non-adaptive processes. Second, we review methods that have been proposed to detect foreground convergent substitutions in coding sequences and expose the assumptions that underlie them. Finally, we examine their power on simulations of convergent changes—including in the presence of a change in the efficacy of selection—and on empirical alignments.

This article is part of the theme issue ‘Convergent evolution in the genomics era: new insights and directions'.
Detecting genetic interactions using parallel evolution in experimental populations
Authors: Fisher Kaitlin J. , Kryazhimskiy Sergey , Lang Gregory I.
Published: June 2019

Eukaryotic genomes contain thousands of genes organized into complex and interconnected genetic interaction networks. Most of our understanding of how genetic variation affects these networks comes from quantitative-trait loci mapping and from the systematic analysis of double-deletion (or knockdown) mutants, primarily in the yeast
Saccharomyces cerevisiae
. Evolve and re-sequence experiments are an alternative approach for identifying novel functional variants and genetic interactions, particularly between non-loss-of-function mutations. These experiments leverage natural selection to obtain genotypes with functionally important variants and positive genetic interactions. However, no systematic methods for detecting genetic interactions in these data are yet available. Here, we introduce a computational method based on the idea that variants in genes that interact will co-occur in evolved genotypes more often than expected by chance. We apply this method to a previously published yeast experimental evolution dataset. We find that genetic targets of selection are distributed non-uniformly among evolved genotypes, indicating that genetic interactions had a significant effect on evolutionary trajectories. We identify individual gene pairs with a statistically significant genetic interaction score. The strongest interaction is between genes
TRK1
and
PHO84
, genes that have not been reported to interact in previous systematic studies. Our work demonstrates that leveraging parallelism in experimental evolution is useful for identifying genetic interactions that have escaped detection by other methods.

This article is part of the theme issue ‘Convergent evolution in the genomics era: new insights and directions’.
The role of mutation bias in adaptive molecular evolution: insights from convergent changes in protein function
Authors: Storz Jay F. , Natarajan Chandrasekhar , Signore Anthony V. , Witt Christopher C. , McCandlish David M. , Stoltzfus Arlin
Published: June 2019

An underexplored question in evolutionary genetics concerns the extent to which mutational bias in the production of genetic variation influences outcomes and pathways of adaptive molecular evolution. In the genomes of at least some vertebrate taxa, an important form of mutation bias involves changes at CpG dinucleotides: if the DNA nucleotide cytosine (C) is immediately 5′ to guanine (G) on the same coding strand, then—depending on methylation status—point mutations at both sites occur at an elevated rate relative to mutations at non-CpG sites. Here, we examine experimental data from case studies in which it has been possible to identify the causative substitutions that are responsible for adaptive changes in the functional properties of vertebrate haemoglobin (Hb). Specifically, we examine the molecular basis of convergent increases in Hb–O2affinity in high-altitude birds. Using a dataset of experimentally verified, affinity-enhancing mutations in the Hbs of highland avian taxa, we tested whether causative changes are enriched for mutations at CpG dinucleotides relative to the frequency of CpG mutations among all possible missense mutations. The tests revealed that a disproportionate number of causative amino acid replacements were attributable to CpG mutations, suggesting that mutation bias can influence outcomes of molecular adaptation.

This article is part of the theme issue ‘Convergent evolution in the genomics era: new insights and directions’.
The perils of intralocus recombination for inferences of molecular convergence
Authors: Mendes Fábio K. , Livera Andrew P. , Hahn Matthew W.
Published: June 2019

Accurate inferences of convergence require that the appropriate tree topology be used. If there is a mismatch between the tree a trait has evolved along and the tree used for analysis, then false inferences of convergence (‘hemiplasy’) can occur. To avoid problems of hemiplasy when there are high levels of gene tree discordance with the species tree, researchers have begun to construct tree topologies from individual loci. However, due to intralocus recombination, even locus-specific trees may contain multiple topologies within them. This implies that the use of individual tree topologies discordant with the species tree can still lead to incorrect inferences about molecular convergence. Here, we examine the frequency with which single exons and single protein-coding genes contain multiple underlying tree topologies, in primates and
Drosophila
, and quantify the effects of hemiplasy when using trees inferred from individual loci. In both clades, we find that there are most often multiple diagnosable topologies within single exons and whole genes, with 91% of
Drosophila
protein-coding genes containing multiple topologies. Because of this underlying topological heterogeneity, even using trees inferred from individual protein-coding genes results in 25% and 38% of substitutions falsely labelled as convergent in primates and
Drosophila
, respectively. While constructing local trees can reduce the problem of hemiplasy, our results suggest that it will be difficult to completely avoid false inferences of convergence. We conclude by suggesting several ways forward in the analysis of convergent evolution, for both molecular and morphological characters.

This article is part of the theme issue ‘Convergent evolution in the genomics era: new insights and directions’.
Oxazepam and cognitive reappraisal: a randomised experiment
Authors: Nilsonne Gustav , Tamm Sandra , Golkar Armita , Olsson Andreas , Sörman Karolina , Howner Katarina , Kristiansson Marianne , Ingvar Martin , Petrovic Predrag
Published: June 2019

Background

Cognitive reappraisal is a strategy for emotional regulation, important in the context of anxiety disorders. It is not known whether anxiolytic effects of benzodiazepines affect cognitive reappraisal.

Aims

We aimed to investigate the effect of 25 mg oxazepam on cognitive reappraisal.

Methods

In a preliminary investigation, 33 healthy male volunteers were randomised to oxazepam or placebo, and then underwent an experiment where they were asked to use cognitive reappraisal to upregulate or downregulate their emotional response to images with negative or neutral emotional valence. We recorded unpleasantness ratings, skin conductance, superciliary corrugator muscle activity, and heart rate. Participants completed rating scales measuring empathy (Interpersonal Reactivity Index, IRI), anxiety (State-Trait Anxiety Inventory, STAI), alexithymia (Toronto Alexithymia Scale-20, TAS-20), and psychopathy (Psychopathy Personality Inventory-Revised, PPI-R).

Results

Upregulation to negative-valence images in the cognitive reappraisal task caused increased unpleasantness ratings, corrugator activity, and heart rate compared to downregulation. Upregulation to both negative- and neutral-valence images caused increased skin conductance responses. Oxazepam caused lower unpleasantness ratings to negative-valence stimuli, but did not interact with reappraisal instruction on any outcome. Self-rated trait empathy was associated with stronger responses to negative-valence stimuli, whereas self-rated psychopathic traits were associated with weaker responses to negative-valence stimuli.

Conclusions

While 25 mg oxazepam caused lower unpleasantness ratings in response to negative-valence images, we did not observe an effect of 25 mg oxazepam on cognitive reappraisal.
A Simple Deep Learning Approach for Detecting Duplications and Deletions in Next-Generation Sequencing Data
Authors: Hill Tom , Unckless Robert L.
Published: June 2019

Copy number variants (CNV) are associated with phenotypic variation in several species. However, properly detecting changes in copy numbers of sequences remains a difficult problem, especially in lower quality or lower coverage next-generation sequencing data. Here, inspired by recent applications of machine learning in genomics, we describe a method to detect duplications and deletions in short-read sequencing data. In low coverage data, machine learning appears to be more powerful in the detection of CNVs than the gold-standard methods or coverage estimation alone, and of equal power in high coverage data. We also demonstrate how replicating training sets allows a more precise detection of CNVs, even identifying novel CNVs in two genomes previously surveyed thoroughly for CNVs using long read data.

Available at:https://github.com/tomh1lll/dudeml
The human gut virome is highly diverse, stable and individual-specific
Authors: Shkoporov Andrey N. , Clooney Adam G. , Sutton Thomas D.S. , Ryan Feargal J. , Daly Karen M. , Nolan James A. , McDonnell Siobhan A. , Khokhlova Ekaterina V. , Draper Lorraine A. , Forde Amanda , Guerin Emma , Velayudhan Vimalkumar , Ross R. Paul , Hill Colin
Published: June 2019

The human gut contains a vast array of viruses, mostly bacteriophages. The majority remain uncharacterised and their roles in shaping the gut microbiome and in impacting on human health remain poorly understood. Here we performed a longitudinal focused metagenomic study of faecal bacteriophage populations in healthy adults. Our results reveal high temporal stability and individual specificity of bacteriophage consortia which correlates with the bacterial microbiome. We report the existence of a stable, numerically predominant individual-specific persistent personal virome. Clustering of bacteriophage genomes and de novo taxonomic annotation identified several groups of crAss-like and Microviridae bacteriophages as the most stable colonizers of the human gut. CRISPR-based host prediction highlighted connections between these stable viral communities and highly predominant gut bacterial taxa such as Bacteroides, Prevotella and Faecalibacterium. This study provides insights into the structure of the human gut virome and serves as an important baseline for hypothesis-driven research.
Brain cooling marginally increases maximum thermal tolerance in Atlantic cod
Authors: Jutfelt Fredrik , Roche Dominique G. , Clark Timothy D , Norin Tommy , Binning Sandra A. , Speers-Roesch Ben , Amcoff Mirjam , Morgan Rachael , Andreassen Anna H , Sundin Josefin
Published: June 2019

The physiological mechanisms determining thermal limits in fishes are debated but remain elusive. It has been hypothesised that loss of motor function observed as a loss of equilibrium during an acute thermal challenge is due to direct thermal effects on brain neuronal function. To test this hypothesis, we mounted cooling plates on the head of Atlantic cod(Gadus morhua)and quantified whether local cooling of the brain increased whole-organism critical thermal maxima (CTmax). Brain cooling reduced brain temperature by 2–6°C and increased CTmaxby 0.5–0.7°C relative to instrumented and uninstrumented controls, suggesting that direct thermal effects on brain neurons might contribute to setting upper thermal limits in fish. However, the improvement in CTmaxwith brain cooling was small relative to the difference in brain temperature, demonstrating that other mechanisms (e.g., failure of spinal and peripheral neurons, or muscle) may also contribute to controlling acute thermal tolerance in fishes.

Summary statement

We tested whether brain temperature sets the upper thermal limit in a fish. Selectively cooling the brain during whole-organism thermal ramping marginally increased thermal tolerance.
Recurrent genetic abnormalities in human pluripotent stem cells: definition and routine detection in culture supernatant by targeted droplet digital PCR
Authors: Assou Said , Girault Nicolas , Plinet Mathilde , Bouckenheimer Julien , Sansac Caroline , Combe Marion , Mianné Joffrey , Bourguignon Chloé , Fieldes Mathieu , Ahmed Engi , Commes Thérèse , Boureux Anthony , Lemaître Jean-Marc , De Vos John
Published: June 2019

Genomic integrity of human pluripotent stem cells (hPSCs) is essential for research and clinical applications. However, genetic abnormalities can accumulate during hPSC generation and routine culture and following gene editing. Their occurrence should be routinely monitored, but the current assays to assess hPSC genomic integrity are not fully suitable for suchregular screening. To address this issue, we first carried out a large meta-analysis of all hPSC genetic abnormalities reported in more than 100 publications and identified 738 recurrent genetic abnormalities (i.e., overlapping abnormalities found in at least five distinct scientific publications). We then developed a test based on the droplet digital PCR technology that can potentially detect 94.3% of these hPSC recurrent genetic abnormalities in DNA extracted from culture supernatant samples. This test can be used to routinely screen genomic integrity in hPSCs.
Associations between neonatal cry acoustics and visual attention during the first year
Authors: Kivinummi Aicha , Naithani Gaurav , Tammela Outi , Virtanen Tuomas , Kurkela Enni , Alhainen Miia , Niehaus Dana J. H. , Lachman Anusha , Leppänen Jukka M. , Peltola Mikko J.
Published: June 2019

It has been suggested that early cry parameters are connected to later cognitive abilities. The present study is the first to investigate whether the acoustic features of infant cry are associated with cognitive development already during the first year, as measured by oculomotor orienting and attention disengagement. Cry sounds for acoustic analyses (fundamental frequency; F0) were recorded in two neonatal cohorts at the age of 0-5 days (Tampere, Finland) or at 6 weeks (Cape Town, South Africa). Eye tracking was used to measure oculomotor orienting to peripheral visual stimuli and attention disengagement from central stimuli at 8 months (Tampere) or at 6 months (Cape Town) of age. In the Tampere cohort, a marginal positive correlation between fundamental frequency of cry (F0) and visual attention disengagement was observed; infants with a higher neonatal F0 were slower to shift gaze away from the central stimulus to the peripheral stimulus. However, a similar correlation was not observed in the Cape Town cohort. No associations between F0 and oculomotor orienting were observed in either cohort. We discuss possible factors influencing the discrepancy in results between the cohorts and suggest directions for future research investigating the potential of early cry analysis in predicting later cognitive development.
Dynamic up- and down-regulation of the default (DMN) and extrinsic (EMN) mode networks during alternating task-on and task-off periods
Authors: Hugdahl Kenneth , Beresniewicz Justyna , Kazimierczak Katarzyna , Kompus Kristiina , Westerhausen Rene , Ersland Lars , Grüner Renate , Specht Karsten
Published: June 2019

Using fMRI, Hugdahl et al. (2015) reported the existence of a general-domain cortical network during active task-processing which was non-specific to the cognitive task being processed. They labelled this network the extrinsic mode network (EMN). The EMN would be predicted to be negatively, or anti-correlated with the classic default mode network (DMN), typically observed during periods of rest, such that while the EMN should be down-regulated and the DMN up-regulated in the absence of demands for task-processing, the reverse should occur when demands change from resting to task-processing. This would require alternating periods of task-processing and resting, and analyzing data continuously when demands change from active to passive periods and vice versa. We were particularly interested in how the networks interact in the critical transition points between conditions. For this purpose we used an auditory task with multiple cognitive demands in a standard fMRI block-design. Task-present (ON) blocks were alternated with an equal number of task-absent, or rest (OFF) blocks to capture network dynamics across time and changing environmental demands. To achieve this, we specified the onset of each block, and used a finite-impulse response function (FIR) as basis function for estimation of the fMRI-BOLD response. During active (ON) blocks, the results showed an initial rapid onset of activity in the EMN network, which remained throughout the period, and faded away during the first scan of the OFF-block. During OFF blocks, activity in the DMN network showed an initial time-lag where neither the EMN nor the DMN was active, after which the DMN was up-regulated. Studying network dynamics in alternating passive and active periods may provide new insights into brain network interaction and regulation.
BiosyntheticSPAdes: reconstructing biosynthetic gene clusters from assembly graphs
Authors: Meleshko Dmitry , Mohimani Hosein , Tracanna Vittorio , Hajirasouliha Iman , Medema Marnix H. , Korobeynikov Anton , Pevzner Pavel A.
Published: June 2019

Predicting biosynthetic gene clusters (BGCs) is critically important for discovery of antibiotics and other natural products. While BGC prediction from complete genomes is a well-studied problem, predicting BGCs in fragmented genomic assemblies remains challenging. The existing BGC prediction tools often assume that each BGC is encoded within a single contig in the genome assembly, a condition that is violated for most sequenced microbial genomes where BGCs are often scattered through several contigs, making it difficult to reconstruct them. The situation is even more severe in shotgun metagenomics, where the contigs are often short, and the existing tools fail to predict a large fraction of long BGCs. While it is difficult to assemble BGCs in a single contig, the structure of the genome assembly graph often provides clues on how to combine multiple contigs into segments encoding long BGCs. We describe biosyntheticSPAdes, a tool for predicting BGCs in assembly graphs and demonstrate that it greatly improves the reconstruction of BGCs from genomic and metagenomics data sets.
Targeting SLMAP-ALK—a novel gene fusion in lung adenocarcinoma
Authors: Pagan Carlos , Barua Subit , Hsiao Susan J. , Mansukhani Mahesh , Saqi Anjali , Murty Vundavalli , Fernandes Helen
Published: June 2019

Assessment of ALK gene rearrangements is strongly recommended by the Molecular Testing Guideline for Selection of Lung Cancer Patients proposed by IASLC, AMP, and CAP at the time of diagnosis for patients with advanced stage disease. Non-small-cell lung cancer (NSCLC) with ALK gene rearrangements or the resulting fusion proteins have been, for the most part, successfully targeted with ALK tyrosine kinase inhibitors (TKIs). The most frequent rearrangement, the EML4-ALK oncogenic fusion, has more than 10 distinct variants, each with a discrete breakpoint in EML4. Recent studies have suggested that EML4-ALK variants may have differential responses to TKIs. Additionally, non-EML4-ALK fusions that result from ALK rearrangements with diverse 5′ partners could possibly have varied biologic and clinical implications in their therapeutic responses and outcomes of patients with NSCLC. Existing literature documents at least 20 non-EML4 fusion partners for ALK, and the clinical responsiveness to crizotinib ranges from increased sensitivity to resistance. This underscores the importance of identifying the precise 5′ fusion partner to ALK before initiation of therapy. Herein we report the identification of a novel SLMAP-ALK fusion in a patient with NSCLC.
Focus characterization of the NanoMAX Kirkpatrick–Baez mirror system
Authors: Osterhoff Markus , Robisch Anna-Lena , Soltau Jakob , Eckermann Marina , Kalbfleisch Sebastian , Carbone Dina , Johansson Ulf , Salditt Tim
Published: June 2019

The focusing and coherence properties of the NanoMAX Kirkpatrick–Baez mirror system at the fourth-generation MAX IV synchrotron in Lund have been characterized. The direct measurement of nano-focused X-ray beams is possible by scanning of an X-ray waveguide, serving basically as an ultra-thin slit. In quasi-coherent operation, beam sizes of down to 56 nm (FWHM, horizontal direction) can be achieved. Comparing measured Airy-like fringe patterns with simulations, the degree of coherence |μ| has been quantified as a function of the secondary source aperture (SSA); the coherence is larger than 50% for SSA sizes below 11 µm at hard X-ray energies of 14 keV. For an SSA size of 5 µm, the degree of coherence has been determined to be 87%.
Board independence and information asymmetry: family firms vs non-family firms
Authors: Wu Kean , Sorensen Susan , Sun Li
Published: June 2019

Purpose

The purpose of this paper is to investigate the effect of independent directors in reducing firms’ information asymmetry. Moreover, the authors enrich this investigation by differentiating the effectiveness of independent directors in an intriguing comparative setting of family vs non-family firms. Family firms are used to represent an interesting environment where controlling insiders (i.e. firms’ founding families) have dominant control over corporate decisions. This study addresses the question of whether controlling-insiders dominate independent directors.

Design/methodology/approach

The authors manually collect firms’ founder information to identify family firm status in a sample of S&P 500 firms. Following a large literature in capital market research, the authors proxy information asymmetry by trading volume, bid-ask spread and price volatility. The authors employ multivariate regression with two-stage least square analysis, instrumental variable method, Heckman selection model and Hausman–Taylor model to address the issue of endogenous selection of board of director and family firm status.

Findings

The authors find a negative relation between the board independence and information asymmetry, suggesting independent directors are effective in reducing information asymmetry. Furthermore, the authors find this negative relation is stronger in family firms. These results are robust after controlling for the endogenous issues using various models.

Research limitations/implications

Our results suggest that independent directors in family-controlled firms are more successful in reducing information asymmetry than their counterparts in non-family firms. The authors provide direct evidence to support the existing theoretical arguments from Rediker and Seth (1995) and Anderson and Reeb (2004) that founding families and independent boards might be a powerful combination for aligning the interest of insider and diffused shareholders. The findings ease a prevalent concern that the role of independent directors might be compromised in an environment with controlling shareholders, and advocate regulations promoting board independence for various business practices.

Originality/value

A number of studies concentrate on the practice of corporate disclosure of firm’s performance and governance and how corporate disclosure mitigates information asymmetry (Leuz and Verrecchia, 2000; Ali et al., 2007; Chen et al., 2008). To the best of our knowledge, this study is the first to examine the impact of independent directors in reducing information asymmetry. The research adds to understanding the incentives of board members and supports recent findings that different types of investors have heterogeneous incentives for corporate disclosure (Srinidhi et al., 2014).