bluuebunny/crossref_metadata_2025 huggingface dataset:
Trends and Outcomes of Management of Mandibular Fractures
Authors: Hassanein Ahmed Gaber
Published: March 2019

Introduction:

the diversity of the causes of trauma produces different patterns of fractures depending on sociodemographics, lifestyle, industry, and outdoor activities. Mandibular fractures (MFs) are the commonest facial fractures. Reconstruction aims to restore the preinjury anatomy and function as much as possible.

Aim of the study:

to evaluate the demographics, etiologies, patterns, treatment modalities and outcomes of management of MFs in southern Egypt.

Patients and Methods:

records of 1371 patients with MFs were reviewed to study the incidence, causes, patterns, treatment modalities and outcomes of surgical management.

Results:

the study included 1152 (84.03%) males and 219 (15.97%) females. The second and third decades were the most vulnerable groups. Isolated MFs appeared in 75.49% of patients while in the others either zygoma and/or maxilla were affected. The commonest causes were road traffic accidents (66.89%) and fall from height (15.1%). The body was the commonest involved region (30.98%), followed by parasymphyseal region (24.33%). In 66.16% of patients, the treatment was open reduction and internal fixation while in 22.17%, closed reduction and intermaxillary fixation were used. 20.24% of the cases had 1 or more postoperative complications, mainly temporomandibular joint dysfunction in 64 cases, malocclusion in 58 cases, and paresthesia in 42 cases.

Conclusion:

the MFs are common in the youth. The road traffic accidents are the most common etiology. This can be reduced by simple measures like compulsory seat belts and wearing the helmet. Open reduction and internal fixation is the commonest treatment modality.
Medication-Related Osteonecrosis of the Jaw: The Use of Leukocyte-Platelet-Rich Fibrin as an Adjunct in the Treatment
Authors: Valente Nicola Alberto , Chatelain Sibylle , Alfonsi Fortunato , Mortellaro Carmen , Barone Antonio
Published: March 2019

Medication-related osteonecrosis of the jaw are bone exposures in the maxillofacial region that does not heal after 8 weeks from the observation of a health care provider in patients with history of the intake of antiresorptive agents and no previous irradiation of the craniofacial region. Initially attributed only to the intake of bisphosphonates they have later been associated also with the intake of other classes of antiresorptive medications.

This retrospective study analyzed records from patients with documented medication-related osteonecrosis of the jaws treated in our unit. Clinical data, comorbidities and concurrent medications, treatment outcome information such us number of repeated treatments needed, antibiotic used, type of treatment adopted were recorded. Baseline demographics for the included records of 15 patients (mean age: 64 years) revealed a treatment success rate of 73.3% (mean observation period: 42.2 months), failure rate of 26.6%, dental extraction trigger rate of 33.3%, and a spontaneous trigger rate of 40%.

Zolendronate and denosumav were the medications most frequently associated with the upset of medication-related osteonecrosis of the jaw (60% of the sample). In 8 cases out of the 11 that were successful, the surgical treatment had to be repeated more than once. Leukocyte-platelet-rich fibrin led to the resolution of 11 of the 14 cases in which it was used.
Endoscopic Medial Maxillectomy With Preservation of Inferior Turbinate: Assessing Results by Acoustic Rhinometry
Authors: Gras-Cabrerizo Juan R. , Martel-Martin Maria , Montserrat-Gili Joan R. , Pardo-Muñoz Laura , Prats-Morera Laura , Ademá-Alcover Joan M. , Massegur-Solench Humbert
Published: March 2019

Background:

The aim of this study is to demonstrate the effectiveness of the Endoscopic Medial Maxillectomy technique with the preservation of the nasal anatomy and function of the inferior turbinate.

Methods:

From January 2005 to December 2016, the authors performed 27 Endoscopic Medial Maxillectomy with preservation of inferior turbinate on 26 patients. The most frequent pathologies diagnosed were inverted papillomas (13/27) and antrochoanal polyps (7/27). There were 21 primary lesions and 6 patients had been previously treated. There were 19 males and 7 females. On 11 patients the authors could perform an acoustic rhinometry at 4 months postoperatively.

Results:

The authors did not find any recurrences. In all cases the authors note the presence of the C-notch being the narrowest area of the nasal cavity, on both the surgical and nonsurgical nasal fossa. The mean area for the C-notch in the nonsurgical nasal cavities was 0.50 cm2 (0.18–0.82) and it was 0.57 cm2 (0.08–1.06) in the surgical nasal cavities. The increase of the C-notch after nasal decongestion was 0.10 cm2 in nonsurgical cavities and it was 0.03 cm2 in the surgical cavities. The mean distance for the C-notch was 2.18 cm and 2.36 cm before and after nasal decongestion in the nonsurgical fossae. In the surgical cavities were 2.31 and 2.37  cm respectively.

Conclusions:

The authors’ rhinometrics data suggest that Endoscopic Medial Maxillectomy with preservation of inferior turbinate is an effective technique that preserves the anatomic structure and the functions of the inferior turbinate after its resection and reposition.
A Simulation-Based Pilot Study of a Mobile Application (NRP Prompt) as a Cognitive Aid for Neonatal Resuscitation Training
Authors: Chan Natalie H. , Mistry Niraj , Campbell Douglas M.
Published: March 2019

Introduction

Despite standardized neonatal resuscitation program (NRP) training, retention and adherence to the NRP algorithm remain a challenge. Cognitive aids can potentially improve acquisition and application of NRP knowledge and skills. The objective of this study was to determine whether an interactive mobile application providing audiovisual prompts, NRP Prompt, can help novice NRP providers learn the NRP algorithm more effectively and therefore improve their NRP performance.

Methods

First- and second-year residents from family medicine and obstetrics and gynecology attending NRP training were randomized into intervention and control groups. Resident pairs used standard visual aids with NRP Prompt (intervention) or visual aids only (control) in two simulated neonatal resuscitation training sessions with each resident taking turns as a team leader. Pairs were then evaluated in a third simulation that was video recorded, where neither group used cognitive aids. The primary outcome was comparing resuscitation performance. Secondary outcomes included the following: times to positive-pressure ventilation, intubation, and chest compressions.

Results

Thirty-nine residents participated, of which 18 received the intervention. Neonatal resuscitation program performance scores did not significantly differ (P = 0.69). Wilcoxon rank-sum tests showed no significant differences in secondary outcomes of times to positive-pressure ventilation (P = 0.43), intubation (P = 0.44), or chest compressions (P = 0.35).

Conclusions

Training using NRP Prompt did not improve performance scores in simulated neonatal resuscitations immediately after training. Potential reasons include voice prompts in their current format being distracting and lack of customizability to user preferences. Future development of prompting applications should apply a user-centered design approach to optimize the ability to meet end-user needs.
Long-term prescription opioid utilization, substance use disorders, and opioid overdoses after adolescent trauma
Authors: Bell Teresa M. , Raymond Jodi , Vetor Ashley , Mongalo Alejandro , Adams Zachary , Rouse Thomas , Carroll Aaron
Published: March 2019

BACKGROUND

Injured adolescents have a 56% increased risk of developing a substance use disorder (SUD) within 3 years of their injury. The transition from medical prescription opioid use to nonmedical use in adolescent trauma patients has not been longitudinally studied long-term. The aim of this study is to describe 5-year patterns of opioid use in a cohort of injured adolescents as well as the proportion of patients experiencing overdose and SUD diagnoses.

METHODS

Our retrospective cohort study consisted of 736 patients aged 12 years to 18 years who were admitted for trauma from 2011 to 2013. We examined up to 5 years of regional health information exchange data containing information on prescription fills as well as diagnoses from inpatient, outpatient, and emergency department encounters.

RESULTS

At 1 year, over 20% of adolescents filled more than two opioid prescriptions after being discharged for their injury; and at 4 years, over 13% had received more than eight opioid fills. Over the 5-year period, 11% received an opioid antagonist injection, 14% received an SUD diagnosis, and 8% had an overdose diagnosis. Relatively few patients had diagnoses for other mental health conditions including depression (5.5%), posttraumatic stress disorder (2.1%), and chronic pain (3.6%).

CONCLUSION

Opioid usage remains high for multiple years in a subset of the adolescent trauma population. Mental health diagnosis rates were substantially lower in injured adolescents than what has been reported in adults. However, overdose and SUD diagnoses occur in over 1 in 10 adolescents within 5 years of their injury.

LEVEL OF EVIDENCE

Prognostic and epidemiological study, level IV.
Earlier time to hemostasis is associated with decreased mortality and rate of complications: Results from the Pragmatic Randomized Optimal Platelet and Plasma Ratio trial
Authors: Chang Ronald , Kerby Jeffrey D. , Kalkwarf Kyle J. , Van Belle Gerald , Fox Erin E. , Cotton Bryan A. , Cohen Mitchell J. , Schreiber Martin A. , Brasel Karen , Bulger Eileen M. , Inaba Kenji , Rizoli Sandro , Podbielski Jeanette M. , Wade Charles E. , Holcomb John B.
Published: March 2019

BACKDROP

Clinicians intuitively recognize that faster time to hemostasis is important in bleeding trauma patients, but these times are rarely reported.

METHODS

Prospectively collected data from the Pragmatic Randomized Optimal Platelet and Plasma Ratios trial were analyzed. Hemostasis was predefined as no intraoperative bleeding requiring intervention in the surgical field or resolution of contrast blush on interventional radiology (IR). Patients who underwent an emergent (within 90 minutes) operating room (OR) or IR procedure were included. Mixed-effects Poisson regression with robust error variance (controlling for age, Injury Severity Score, treatment arm, injury mechanism, base excess on admission [missing values estimated by multiple imputation], and time to OR/IR as fixed effects and study site as a random effect) with modified Bonferroni corrections tested the hypothesis that decreased time to hemostasis was associated with decreased mortality and decreased incidence of acute kidney injury (AKI), acute respiratory distress syndrome (ARDS), multiple-organ failure (MOF), sepsis, and venous thromboembolism.

RESULTS

Of 680 enrolled patients, 468 (69%) underwent an emergent procedure. Patients with decreased time to hemostasis were less severely injured, had less deranged base excess on admission, and lower incidence of blunt trauma (all p < 0.05). In 408 (87%) patients in whom hemostasis was achieved, every 15-minute decrease in time to hemostasis was associated with decreased 30-day mortality (RR, 0.97; 95% confidence interval [CI], 0.94–0.99), AKI (RR, 0.97; 95% CI, 0.96–0.98), ARDS (RR, 0.98; 95% CI, 0.97–0.99), MOF (RR, 0.94; 95% CI, 0.91–0.97), and sepsis (RR, 0.98; 95% CI, 0.96–0.99), but not venous thromboembolism (RR, 0.99; 95% CI, 0.96–1.03).

CONCLUSION

Earlier time to hemostasis was independently associated with decreased incidence of 30-day mortality, AKI, ARDS, MOF, and sepsis in bleeding trauma patients. Time to hemostasis should be considered as an endpoint in trauma studies and as a potential quality indicator.

LEVEL OF EVIDENCE

Therapeutic/care management, level III.
An analysis of pediatric trauma center undertriage in a mature trauma system
Authors: Rogers Amelia T. , Horst Michael A. , Vernon Tawnya M. , Gaines Barbara A. , Bradburn Eric H. , Cook Alan D. , Jammula Shreya , Rogers Frederick B.
Published: March 2019

BACKGROUND

Improved mortality as a result of appropriate triage has been well established in adult trauma and may be generalizable to the pediatric trauma population as well. We sought to determine the overall undertriage rate (UTR) in the pediatric trauma population within Pennsylvania (PA). We hypothesized that a significant portion of pediatric trauma population would be undertriaged.

METHODS

All pediatric (age younger than 15) admissions meeting trauma criteria (International Classification of Diseases, Ninth Revision: 800–959) from 2003 to 2015 were extracted from the Pennsylvania Health Care Cost Containment Council (PHC4) database and the Pennsylvania Trauma Systems Foundation (PTSF) registry. Undertriage was defined as patients not admitted to PTSF-verified pediatric trauma centers (n = 6). The PHC4 contains inpatient admissions within PA, while PTSF only reports admissions to PA trauma centers. ArcGIS Desktop was used for geospatial mapping of undertriage.

RESULTS

A total of 37,607 cases in PTSF and 63,954 cases in PHC4 met criteria, suggesting UTR of 45.8% across PA. Geospatial mapping reveals significant clusters of undertriage regions with high UTR in the eastern half of the state compared to low UTR in the western half. High UTR seems to be centered around nonpediatric facilities. The UTR for patients with a probability of death 1% or less was 39.2%.

CONCLUSION

Undertriage is clustered in eastern PA, with most areas of high undertriage located around existing trauma centers in high-density population areas. This pattern may suggest pediatric undertriage is related to a system issue as opposed to inadequate access.

LEVEL OF EVIDENCE

Retrospective study, without negative criteria, Level III.
The changing concepts in the neuropathology of acquired demyelinating central nervous system disorders
Authors: Lassmann Hans
Published: March 2019

Purpose of review

Research on multiple sclerosis (MS) pathogenesis and therapy is to a large extent driven by results obtained in experimental autoimmune encephalomyelitis (EAE). This approach provided deep insights into the mechanism of brain inflammation and immune mediated tissue injury and, thus, most of our currently established therapies for MS patients have been developed with profound contributions of experimental autoimmune research. Recent data, which are summarized in this review article, however, show important differences between EAE and MS.

Recent findings

EAE models perfectly reproduce a disease, now called myelin oligodendrocyte glycoprotein (MOG) antibody-associated inflammatory demyelinating disease, which, however, is different from classical MS. In MS, the inflammatory reaction in the brain is dominated by CD8+ T-lymphocyte and CD20+ B cells. Demyelination in MS appears to be triggered by soluble factors, produced by T cells and/or B cells, which are different from anti-MOG antibodies seen in EAE, and induce widespread MS like primary demyelination and tissue damage associated with oxidative injury, mitochondrial damage and subsequent ‘virtual’ hypoxia.

To define the antigenic target of the inflammatory reaction, the nature of the inflammatory response and the mechanisms of tissue injury are key topics of ongoing MS research.
Emerging treatments for cluster headache: hopes and disappointments
Authors: Magis Delphine
Published: March 2019

Purpose of review

Cluster headache stands among the worst debilitating pain conditions. Available treatments for cluster headache have often disabling side effects, are not tolerated, or are ineffective. The management of drug-refractory chronic forms is challenging. New treatments are warranted and reported here.

Recent findings

In cluster headache acute treatment, delivery systems like Demand Valve Oxygen or nonrebreather-type masks could enhance the effectiveness of inhaled oxygen therapy. Noninvasive vagus nerve stimulation relieves cluster headache pain at short-term in episodic patients. Sphenopalatine ganglion stimulation combines acute and preventive properties in subsets of patients and is of interest in selected refractory chronic forms. In cluster headache prevention, ‘hypothalamic’ deep brain stimulation is being refined using slightly different stereotactic coordinates or lower risk methods like endoventricular stimulation. Anti-CGRP monoclonal antibodies provide interesting results in episodic cluster headache, have a good safety profile, but do not appear effective in chronic cluster headache.

These novel approaches provide additional alternatives to conventional cluster headache management, but results obtained in chronic forms are often disappointing. Research on cluster headache is often hampered by the lack of awareness in the medical world and by the relatively low prevalence of cluster headache compared with migraine. However, common features shared by these two primary headaches could help developing disease-specific therapies.
An Option to Consider for Alternating Hemiplegia of Childhood: Aripiprazole
Authors: Dundar Nihal Olgac , Cavusoglu Dilek , Kaplan Yusuf Cem , Hasturk Mehmet Oytun
Published: March 2019

Alternating hemiplegia of childhood (AHC) is an infrequent neurological disorder characterized by recurrent transient attacks of hemiplegia that last minutes to days and impress either side of the body, dystonic or tonic attacks, and nystagmus. Cognitive or neurological deficits with progressive course are another findings. Epileptic seizures may occur in some patients. We report the medical treatment in a case of AHC in a-12-year-old male patient with convulsions. The patient did not respond to available therapies for AHC, except for aripiprazole. After the initiation of aripiprazole therapy, duration and frequency of hemiplegia episodes were decreased. Also, he is currently seizure-free with topiramate treatment for 3 months. On follow-up, a compound heterozygous ATP1A3 mutation c.868C > T (p.R290C)/c.684 + 1G > A was determined. Aripiprazole may reduce the attacks of AHC, which are resistant to other available therapies.
Origins and evolution of CRISPR-Cas systems
Authors: Koonin Eugene V. , Makarova Kira S.
Published: March 2019

CRISPR-Cas, the bacterial and archaeal adaptive immunity systems, encompass a complex machinery that integrates fragments of foreign nucleic acids, mostly from mobile genetic elements (MGE), into CRISPR arrays embedded in microbial genomes. Transcripts of the inserted segments (spacers) are employed by CRISPR-Cas systems as guide (g)RNAs for recognition and inactivation of the cognate targets. The CRISPR-Cas systems consist of distinct adaptation and effector modules whose evolutionary trajectories appear to be at least partially independent. Comparative genome analysis reveals the origin of the adaptation module from casposons, a distinct type of transposons, which employ a homologue of Cas1 protein, the integrase responsible for the spacer incorporation into CRISPR arrays, as the transposase. The origin of the effector module(s) is far less clear. The CRISPR-Cas systems are partitioned into two classes, class 1 with multisubunit effectors, and class 2 in which the effector consists of a single, large protein. The class 2 effectors originate from nucleases encoded by different MGE, whereas the origin of the class 1 effector complexes remains murky. However, the recent discovery of a signalling pathway built into the type III systems of class 1 might offer a clue, suggesting that type III effector modules could have evolved from a signal transduction system involved in stress-induced programmed cell death. The subsequent evolution of the class 1 effector complexes through serial gene duplication and displacement, primarily of genes for proteins containing RNA recognition motif domains, can be hypothetically reconstructed. In addition to the multiple contributions of MGE to the evolution of CRISPR-Cas, the reverse flow of information is notable, namely, recruitment of minimalist variants of CRISPR-Cas systems by MGE for functions that remain to be elucidated. Here, we attempt a synthesis of the diverse threads that shed light on CRISPR-Cas origins and evolution.

This article is part of a discussion meeting issue ‘The ecology and evolution of prokaryotic CRISPR-Cas adaptive immune systems’.
Competition between mobile genetic elements drives optimization of a phage-encoded CRISPR-Cas system: insights from a natural arms race
Authors: McKitterick Amelia C. , LeGault Kristen N. , Angermeyer Angus , Alam Munirul , Seed Kimberley D.
Published: March 2019

CRISPR-Cas systems function as adaptive immune systems by acquiring nucleotide sequences called spacers that mediate sequence-specific defence against competitors. Uniquely, the phage ICP1 encodes a Type I-F CRISPR-Cas system that is deployed to target and overcome PLE, a mobile genetic element with anti-phage activity inVibrio cholerae. Here, we exploit the arms race between ICP1 and PLE to examine spacer acquisition and interference under laboratory conditions to reconcile findings from wild populations. Natural ICP1 isolates encode multiple spacers directed against PLE, but we find that single spacers do not interfere equally with PLE mobilization. High-throughput sequencing to assay spacer acquisition reveals that ICP1 can also acquire spacers that target theV. choleraechromosome. We find that targeting theV. choleraechromosome proximal to PLE is sufficient to block PLE and is dependent on Cas2-3 helicase activity. We propose a model in which indirect chromosomal spacers are able to circumvent PLE by Cas2-3-mediated processive degradation of theV. choleraechromosome before PLE mobilization. Generally, laboratory-acquired spacers are much more diverse than the subset of spacers maintained by ICP1 in nature, showing how evolutionary pressures can constrain CRISPR-Cas targeting in ways that are often not appreciated throughin vitroanalyses.

This article is part of a discussion meeting issue ‘The ecology and evolution of prokaryotic CRISPR-Cas adaptive immune systems’.
Aquaculture as a source of empirical evidence for coevolution between CRISPR-Cas and phage
Authors: Hoikkala Ville , Almeida Gabriel M. F. , Laanto Elina , Sundberg Lotta-Riina
Published: March 2019

So far, studies on the bacterial immune system CRISPR-Cas and its ecological and evolutionary effects have been largely limited to laboratory conditions. While providing crucial information on the constituents of CRISPR-Cas, such studies may overlook fundamental components that affect bacterial immunity in natural habitats. Translating laboratory-derived predictions to nature is not a trivial task, owing partly to the instability of natural communities and difficulties in repeated sampling. To this end, we review how aquaculture, the farming of fishes and other aquatic species, may provide suitable semi-natural laboratories for examining the role of CRISPR-Cas in phage/bacterium coevolution. Existing data from disease surveillance conducted in aquaculture, coupled with growing interest towards phage therapy, may have already resulted in large collections of bacterium and phage isolates. These data, combined with premeditated efforts, can provide empirical evidence on phage–bacterium dynamics such as the bacteriophage adherence to mucus hypothesis, phage life cycles and their relationship with CRISPR-Cas and other immune defences. Typing of CRISPR spacer content in pathogenic bacteria can also provide practical information on diversity and origin of isolates during outbreaks. In addition to providing information of CRISPR functionality and phage–bacterium dynamics, aquaculture systems can significantly impact perspectives on design of phage-based disease treatment at the current era of increasing antibiotic resistance.

This article is part of a discussion meeting issue ‘The ecology and evolution of prokaryotic CRISPR-Cas adaptive immune systems’.
Editing the microbiome the CRISPR way
Authors: Ramachandran Gayetri , Bikard David
Published: March 2019

Our bodies are colonized by a complex ecosystem of bacteria, unicellular eukaryotes and their viruses that together play a major role in our health. Over the past few years tools derived from the prokaryotic immune system known as CRISPR-Cas have empowered researchers to modify and study organisms with unprecedented ease and efficiency. Here we discuss how various types of CRISPR-Cas systems can be used to modify the genome of gut microorganisms and bacteriophages. CRISPR-Cas systems can also be delivered to bacterial population and programmed to specifically eliminate members of the microbiome. Finally, engineered CRISPR-Cas systems can be used to control gene expression and modulate the production of metabolites and proteins. Together these tools provide exciting opportunities to investigate the complex interplay between members of the microbiome and our bodies, and present new avenues for the development of drugs that target the microbiome.

This article is part of a discussion meeting issue ‘The ecology and evolution of prokaryotic CRISPR-Cas adaptive immune systems’.
Mice Against Ticks: an experimental community-guided effort to prevent tick-borne disease by altering the shared environment
Authors: Buchthal Joanna , Evans Sam Weiss , Lunshof Jeantine , Telford Sam R. , Esvelt Kevin M.
Published: March 2019

Mice Against Ticks is a community-guided ecological engineering project that aims to prevent tick-borne disease by using CRISPR-based genome editing to heritably immunize the white-footed mice (Peromyscus leucopus) responsible for infecting many ticks in eastern North America. Introducing antibody-encoding resistance alleles into the local mouse population is anticipated to disrupt the disease transmission cycle for decades. Technology development is shaped by engagement with community members and visitors to the islands of Nantucket and Martha's Vineyard, including decisions at project inception about which types of disease resistance to pursue. This engagement process has prompted the researchers to use only white-footed mouse DNA if possible, meaning the current project will not involve gene drive. Instead, engineered mice would be released in the spring when the natural population is low, a plan unlikely to increase total numbers above the normal maximum in autumn. Community members are continually asked to share their suggestions and concerns, a process that has already identified potential ecological consequences unanticipated by the research team that will likely affect implementation. As an early example of CRISPR-based ecological engineering, Mice Against Ticks aims to start small and simple by working with island communities whose mouse populations can be lastingly immunized without gene drive.

This article is part of a discussion meeting issue ‘The ecology and evolution of prokaryotic CRISPR-Cas adaptive immune systems’.
Genome-wide correlation analysis suggests different roles of CRISPR-Cas systems in the acquisition of antibiotic resistance genes in diverse species
Authors: Shehreen Saadlee , Chyou Te-yuan , Fineran Peter C. , Brown Chris M.
Published: March 2019

CRISPR-Cas systems are widespread in bacterial and archaeal genomes, and in their canonical role in phage defence they confer a fitness advantage. However, CRISPR-Cas may also hinder the uptake of potentially beneficial genes. This is particularly true under antibiotic selection, where preventing the uptake of antibiotic resistance genes could be detrimental. Newly discovered features within these evolutionary dynamics are anti-CRISPR genes, which inhibit specific CRISPR-Cas systems. We hypothesized that selection for antibiotic resistance might have resulted in an accumulation of anti-CRISPR genes in genomes that harbour CRISPR-Cas systems and horizontally acquired antibiotic resistance genes. To assess that question, we analysed correlations between the CRISPR-Cas, anti-CRISPR and antibiotic resistance gene content of 104 947 reference genomes, including 5677 different species. In most species, the presence of CRISPR-Cas systems did not correlate with the presence of antibiotic resistance genes. However, in some clinically important species, we observed either a positive or negative correlation of CRISPR-Cas with antibiotic resistance genes. Anti-CRISPR genes were common enough in four species to be analysed. In
Pseudomonas aeruginosa
, the presence of anti-CRISPRs was associated with antibiotic resistance genes. This analysis indicates that the role of CRISPR-Cas and anti-CRISPRs in the spread of antibiotic resistance is likely to be very different in particular pathogenic species and clinical environments.

This article is part of a discussion meeting issue ‘The ecology and evolution of prokaryotic CRISPR-Cas adaptive immune systems’.
Have It, Know It, but Don’t Show It: Examining Physiological Arousal, Anxiety, and Facial Expressions over the Course of a Social Skills Intervention for Autistic Adolescents
Authors: Jain Niharika , Ahamed Sheikh Iqbal , Bozdag Serdar , Dolan Bridget K. , McVey Alana J. , Willar Kirsten S. , Pleiss Sheryl S. , Murphy Christina C. , Casnar Christina L. , Potts Stephanie , Cibich Daniel , Nelsen-Freund Kylie , Fernandez Dana , Hernandez Illeana , Van Hecke Amy Vaughan
Published: March 2019

Facial expressions provide a nonverbal mechanism for social communication, a core challenge for autistic people. Little is known regarding the association between arousal, self-report of anxiety, and facial expressions among autistic adolescents. Therefore, this study investigated session-by-session facial expressions, self-report of anxiety, and physiological arousalviaElectrodermal Activity (EDA), of 12 autistic male adolescents in a didactic social skills intervention setting. The goals of this study were threefold: 1) identify physiological arousal levels (“have-it”), 2) examine if autistic adolescents’ facial expressions indicated arousal (“show-it”), and 3) determine whether autistic adolescents were self-aware of their anxiety (“know-it”). Our results showed that autistic adolescents’ self-rated anxiety was significantly associated with peaks in EDA. Both machine learning algorithms and human participant-based methods, however, had low accuracy in predicting autistic adolescents’ arousal state from facial expressions, suggesting that autistic adolescent’s facial expressions did not coincide with their arousal. Implications for understanding social communication difficulties among autistic adolescents, as well as future targets for intervention, are discussed. This project is registered with ClinicalTrials.gov, Identifier:NCT02680015.
Computational and experimental insights into the chemosensory navigation ofAedes aegyptimosquito larvae
Authors: Lutz Eleanor K. , Grewal Tjinder S. , Riffell Jeffrey A.
Published: March 2019

Mosquitoes are prolific disease vectors that affect public health around the world. Although many studies have investigated search strategies used by host-seeking adult mosquitoes, little is known about larval search behavior. Larval behavior affects adult body size and fecundity, and thus the capacity of individual mosquitoes to find hosts and transmit disease. Understanding vector survival at all life stages is crucial for improving disease control. In this study we use experimental and computational methods to investigate the chemical ecology and search behavior ofAedes aegyptimosquito larvae. We show that larvae do not respond to several olfactory cues used by adultAe. aegyptito assess larval habitat quality, but perceive microbial RNA as a potent foraging attractant. Second, we demonstrate thatAe. aegyptilarvae use a strategy consistent with chemokinesis, rather than chemotaxis, to navigate chemical gradients. Using computational modeling, we further show that chemokinesis is more efficient than chemotaxis for avoiding repellents in ecologically relevant larval habitat sizes. Finally, we use experimental observations and computational analyses to demonstrate that larvae respond to starvation pressure by optimizing exploration behavior. Our results identify key characteristics of foraging behavior in a disease vector mosquito, including the identification of a surprising foraging attractant and an unusual behavioral mechanism for chemosensory preference. In addition to implications for better understanding and control of disease vectors, this work establishes mosquito larvae as a tractable model for chemosensory behavior and navigation.
Extraordinary claims require extraordinary evidence in the case of asserted mtDNA biparental inheritance
Authors: Salas Antonio , Schönherr Sebastian , Bandelt Hans-Jürgen , Gómez-Carballa Alberto , Weissensteiner Hansi
Published: March 2019

A breakthrough article published in PNAS by Luo et al. (2018) challenges a central dogma in biology which states that the mitochondrial DNA (mtDNA) is inherited exclusively from the mother. By sequencing the mitogenomes of several members of three independent families, the authors inferred an unprecedented pattern of biparental inheritance that requires the participation of an autosomal nuclear factor in the molecular process. However, a comprehensive analysis of their data reveals a number of issues that must be carefully addressed before challenging the current paradigm. Unfortunately, the methods section lacks any description of sample management, validation of their results in independent laboratories was deficient, and the reported findings have been observed at a frequency at complete variance with established evidence. Moreover, the remarkably high (and unusually homogeneous) levels of heteroplasmy reported can be readily detected using classical techniques for DNA sequencing. By reassessing the raw sequencing data with an alternative computational pipeline, we report strong correlation to the NextGENe results provided by the authors on a per sample base. However, the sequencing replicates from the same donors show aberrations in the variants detected that need further investigation to exclude contributions from other sources or methodological artifacts. Finally, applying the principle ofreductio ad absurdum, we demonstrate that the nuclear factor invoked by the authors would need to be extraordinarily complex and precise in order to preclude linear accumulation of mtDNA lineages across generations. We discuss alternate scenarios that explain findings of the same nature as reported by Luo et al., in the context ofin-vitrofertilization and therapeutic mtDNA replacement ooplasmic transplantation.
Carrion flies as sentinels for monitoring rabbit calicivirus activity in Australia
Authors: Hall Robyn N , Huang Nina , Roberts John , Strive Tanja
Published: March 2019

Rabbit caliciviruses are an essential tool for managing wild rabbit populations in Australia. Our understanding of rabbit calicivirus epidemiology in Australia currently depends on members of the public submitting liver samples from dead rabbits through a monitoring program called Rabbitscan. However, many wild rabbits die in inaccessible locations or are scavenged before sampling can occur, leading to considerable sampling bias. In this study we screened field-caught carrion flies for the presence of rabbit caliciviruses to monitor virus circulation patterns in the landscape, with an aim to establish a less biased epidemiological surveillance tool. Carrion flies were collected from two study sites over a 22 month period and these samples were used to optimise and validate molecular testing methods in this sample type for the currently circulating rabbit calicivirus variants. Virus was clearly detectable in field-caught carrion flies using optimised SYBR-green RT-qPCR and RT-PCR assays. However, variant identification was frequently hindered by the low virus loads present in carrion fly samples and spurious RT-PCR amplification. This was overcome by frequent sampling, which effectively acts as replicate sampling to verify inconclusive results. There was good correlation between virus detections in carrion flies and in samples recovered from wild rabbits, both temporally and for virus variant identification. The methods reported here provide a robust and efficient additional surveillance tool to monitor rabbit calicivirus activity at a landscape scale, which in turn can help to guide more effective rabbit management programs.
Codon Bias Confers Stability to mRNAs via ILF2 in Humans
Authors: Hia Fabian , Yang Sheng Fan , Shichino Yuichi , Yoshinaga Masanori , Murakawa Yasuhiro , Vandenbon Alexis , Fukao Akira , Fujiwara Toshinobu , Landthaler Markus , Natsume Tohru , Adachi Shungo , Iwasaki Shintaro , Takeuchi Osamu
Published: March 2019

Codon bias has been implicated as one of the major factors contributing to mRNA stability in yeast. However, the effects of codon-bias on mRNA stability remain unclear in humans. Here we show that human cells possess a mechanism to modulate RNA stability through a unique codon bias different from that of yeast. Bioinformatics analysis showed that codons could be clustered into two distinct groups – codons with G or C at the third base position (GC3) and codons with either A or T at the third base position (AT3); the former stabilizing while the latter destabilizing mRNA. Quantification of codon bias showed that increased GC3 content entails proportionately higher GC content. Through bioinformatics, ribosome profiling andin vitroanalysis, we show that decoupling of the effects of codon bias reveals two modes of mRNA regulation, GC3- and GC-content dependent. Employing an immunoprecipitation-based strategy, we identified ILF2 as an RNA binding protein that differentially regulates global mRNA abundances based on codon bias. Our results demonstrate that codon bias is a two-pronged system that governs mRNA abundance.
Identifying suitableListeria innocuastrains as surrogates forListeria monocytogenesfor horticultural products
Authors: Mohan Vathsala , Wibisono Reginald , de Hoop Lana , Summers Graeme , Fletcher Graham C
Published: March 2019

We conducted a laboratory-based study testing nineListeria innocuastrains independently and a cocktail of 11Listeria monocytogenesstrains. The aim was to identify suitableL. innocuastrain(s) to modelL. monocytogenesin inactivation experiments. Three separate inactivation procedures and a hurdle combination of the three were employed: thermal inactivation (55°C), UV-C irradiation (245 nm) and chemical sanitiser (Tsunami™ 100, a mixture of acetic acid, peroxyacetic acid and hydrogen peroxide). The responses were strain dependent in the case ofL. innocuawith different strains responding differently to different regimes.L. innocuaisolates generally responded differently to theL. monocytogenescocktail and had different responses among themselves. In the thermal inactivation treatment, inactivation of all strains including theL. monocytogenescocktail plateaued after 120 minutes. Chemical sanitiser, inactivation could be achieved at concentrations of 10 and 20 ppm with inactivation increasing with contact time up to 8 minutes, beyond which there was no significant benefit. Although most of theL. innocuastrains in the study responded similarly toL. monocytogeneswhen subjected to a single inactivation treatment, when the treatments were applied as hurdle, allL. innocuastrains except PFR16D08 were more sensitive than theL. monocytogenescocktail. PFR16D08 almost matched the resistance of theL. monocytogenescocktail but was much more resistant to the individual treaments. A cocktail of twoL. innocuastrains (PFR 05A07 and PFR 05A10) had the closest responses to the hurdle treatment to those of theL. monocytogenescocktail and is therefore recommended for hurdle experiments.

Importance

Owing to researcher safety risks it is often difficult to use actual pathogens, such asListeria monocytogenes, to explore different inactivation procedures under field conditions. Organisms that are closely related to the pathogen but without its virulence are therefore used as surrogates for the actual pathogen. However, this assumes that the surrogate will behave in a similar manner to the pathogen and it is difficult to predict the responses of the surrogate compared to the actual pathogen. This study compares the responses of individual and combined “cocktails” of strains of non-pathogenicListeria innocuato different inactivation procedures when compared to the response of a cocktail ofL. monocytogenes. Our study highlights the importance of evaluating a number of strains when choosing surrogates.
First record of the endophytic bacteria ofDeschampsia antarcticaE. Desv. from two distant localities of the maritime Antarctica
Authors: Podolich O. , Parnikoza I. , Voznyuk T. , Zubova G. , Zaets I. , Miryuta N. , Myryuta G. , Poronnik O. , Kozeretska I. , Kunakh V. , Pirttila A.M. , Kozyrovska N.
Published: March 2019

The vascular plantDeschampsia antarcticasamples were collected for endophytic bacteria study from two regions in the maritime Antarctic 400 km distant from one another: Point Thomas oasis (King George Island) and Argentine Islands (Galindez Island). The endophytes were isolated from roots and leaves ofD. antarctica, cultivated and identified by using a partial sequencing of the 16S rRNA gene served as a phylomarker. Endophyte isolates from two sites of Galindez Island were represented mainly byPseudomonasspecies and byGammaproteobacteria, FirmicutesandActinobacteria. The vast majority of the isolates had specific for endophytes cellulase and pectinase activities, however,Bacillusspp. did not express both activities. A group-specific PCR screening at the four sites of Galindez Island and two sites of King George Island, indicatedAlphaproteobacteria, Betaproteobacteria, Gammaproteobacteria, Firmicutes, Cytophaga-FlavobacteriaandActinobacteria.Notably, the number of endophytic bacteria taxa was significantly larger in leaves than in roots of plants.
Meningitis pathogens evade immune responses by thermosensing
Authors: Eichner Hannes , Spelmink Laura , Pathak Anuj , Henriques-Normark Birgitta , Loh Edmund
Published: March 2019

Bacterial meningitis is a major cause of death and disability in children worldwide. Two human restricted pathogens, Streptococcus pneumoniae and Haemophilus influenzae, are the major causative agents of bacterial meningitis, attributing to 200,000 deaths annually. These pathogens are often part of the nasopharyngeal microflora of healthy carriers. However, what factors elicit them to disseminate and cause invasive diseases remain unknown. Elevated temperature and fever are hallmarks of inflammation triggered by infections and can act as warning signal to these pathogens. Here, we investigate whether these pathogens could sense environmental temperature to evade host complement-mediated killing. We show that expression of two vital virulence factors and vaccine components, the capsule and factor H binding proteins, are temperature dependent. We identify and characterize four novel RNA thermosensors in S. pneumoniae and H. influenzae within their 5′-untranslated regions of genes, responsible for capsular biosynthesis and production of factor H binding proteins. Our data further demonstrate that these pathogens have co-evolved thermosensing abilities independently with unique RNA sequences, but distinct secondary structures, to evade the human immune system.

Author Summary

Streptococcus pneumoniae and Haemophilus influenzae are bacteria that reside in the upper respiratory tract. This harmless colonization may progress to severe and often lethal septicaemia and meningitis, but molecular mechanisms that control why these pathogens invade the circulatory system remain largely unknown. Here we show that both S. pneumoniae and H. influenzae can evade complement killing by sensing the temperature of the host. We identify and characterize four novel RNA thermosensors in S. pneumoniae and H. influenzae within their respective 5′-untranslated regions of genes, influencing capsular biosynthesis and production of factor H binding proteins. Moreover, we show that these RNA thermosensors evolved independently with exclusive unique RNA sequences to sense the temperature in the nasopharynx and in other body sites to avoid immune killing. Our finding that regulatory RNA senses temperatures and directly regulate expression of two important virulence factors and vaccine components of S. pneumoniae and H. influenzae, is most important for our understanding of bacterial pathogenesis and for vaccine development. Our work could pave the way for similar studies in other important bacterial pathogens and enables clinicians and microbiologists to adjust their diagnostic techniques, and treatments to best fit the condition of the patients.
Global biogeographical regions reveal a signal of past human impacts
Authors: Rueda Marta , González-Suárez Manuela , Revilla Eloy
Published: March 2019

Ecologists have long documented that the world’s biota is spatially organized in regions with boundaries shaped by processes acting on geological and evolutionary timescales. Although growing evidence suggests that human impact has been key in how biodiversity is currently assembled, its role as a driver of the geographical organization of biodiversity remains unclear. Here, we quantify the relative importance of human land use from ∼5000 years ago to predict the current assemblage of terrestrial mammals in biogeographical regions across the Earth. Results show that past anthropogenic land use has left an imprint on the taxonomic differentiation of some of the largest biogeographical realms, whereas land use at present stands out as a driver of the taxonomic differences between medium-sized subregions, i.e., within and among continents. Our findings highlight the far-reaching effect that past anthropogenic actions have had on the organization of biodiversity globally.
Encoding Variability: When Pattern Reactivation Does Not Benefit Context Memory
Authors: Sievers Carolin , Smith Fraser W. , Saada Janak , Simons Jon S. , Renoult Louis
Published: March 2019

A growing body of evidence suggests that neural pattern reactivation supports successful memory formation across multiple study episodes. Previous studies investigating the beneficial effects of repeated encoding typically presented the same stimuli repeatedly under the same encoding task instructions. In contrast, repeating stimuli in different contexts is associated with superior item memory, but poorer memory for contextual features varying across repetitions. In the present functional magnetic-resonance imaging (fMRI) study, we predicted dissociable mechanisms to underlie the successful formation of context memory when the context in which stimuli are repeated is either held constant or varies at each stimulus presentation. Twenty participants studied names of famous people four times, either in the same task repeatedly, or in four different encoding tasks. This was followed by a surprise recognition memory test, including a source judgement about the encoding task. Behaviourally, different task encoding compared to same task encoding was associated with fewer correct context memory judgements but also better item memory, as reflected in fewer misses. Searchlight representational similarity analysis revealed fMRI pattern reactivation in the posterior cingulate cortex to be higher for correct compared to incorrect source memory judgements in the same task condition, with the opposite pattern being observed in the different task condition. It was concluded that higher levels of pattern reactivation in the posterior cingulate cortex index generalisation across context information, which in turn may improve item memory performance during encoding variability but at the cost of contextual features.