bluuebunny/crossref_metadata_2025 huggingface dataset:
Clonazepam and clobazam
Authors: Cavanna Andrea E.
Published: June 2018

Clonazepam and clobazam are first-generation antiepileptic drugs characterized by few antiepileptic indications, with good interaction profile in polytherapy. Both clonazepam and clobazam are benzodiazepines with an acceptable behavioural tolerability profile and a good range of psychiatric uses (especially anxiety disorders, alcohol withdrawal, insomnia). Clobazam has an indication for short-term relief (2–4 weeks) of acute anxiety in patients who have not responded to other drugs, with or without insomnia, and without uncontrolled clinical depression. As with all benzodiazepines, caution should be used in consideration of the potential for tolerance and addiction, as well as the risks related to respiratory depression.
Lamotrigine
Authors: Cavanna Andrea E.
Published: June 2018

Lamotrigine is a second-generation antiepileptic drug characterized by a wide range of antiepileptic indications, with an acceptable interaction profile in polytherapy. It has a good behavioural tolerability profile and a wide range of psychiatric uses. In patients with epilepsy, lamotrigine has shown antidepressant properties, as well as mixed effects on anxiety symptoms. Adverse behavioural effects (irritability, agitation, and aggression) are not very common and are usually observed in patients with learning disability. Lamotrigine has a licensed indication for the prevention of depressive episodes associated with bipolar disorder (a widespread use of this antiepileptic drug), whereas it is not indicated for manic phases.
Pregabalin
Authors: Cavanna Andrea E.
Published: June 2018

Pregabalin is a second-generation antiepileptic drug characterized by few antiepileptic indications, with a very good interaction profile in polytherapy. The therapeutic indications of pregabalin for the treatment of epileptic seizures have been largely overshadowed by its widespread use for the treatment of anxiety disorders (especially generalized anxiety disorder and social anxiety disorder) and neuropathic pain (especially post-herpetic neuralgia, diabetic neuropathy, and pain caused by a spinal cord injury). Pregabalin has a very good behavioural tolerability profile and a wide range of psychiatric uses. Specifically, it has a licensed indication for generalized anxiety disorder for which it is currently widely prescribed.
Topiramate
Authors: Cavanna Andrea E.
Published: June 2018

Topiramate is a second-generation antiepileptic drug characterized by a good range of antiepileptic indications, with an acceptable interaction profile in polytherapy. Topiramate has an acceptable behavioural tolerability profile, although it has been associated with a number of negative behavioural effects in patients with epilepsy (in particular depression, irritability, and psychotic symptoms). Identified risk factors for the development of behavioural adverse effects include high starting doses and rapid titration schedules, as well as personal or family history of psychiatric disorders. Topiramate has a restricted range of psychiatric uses , although its clinically significant effect in promoting weight loss in patients with behavioural problems can increase its potential usefulness in psychiatric populations.
Valproate
Authors: Cavanna Andrea E.
Published: June 2018

Valproate is a first-generation antiepileptic drug characterized by a wide range of antiepileptic indications, with an acceptable interaction profile in polytherapy. Valproate has a good behavioural tolerability profile, despite the existence of occasional reports of depression, irritability, and other behavioural symptoms in patients with encephalopathy. Valproate is also characterized by a wide range of psychiatric uses. Most importantly, valproate is an effective mood stabilizser, with a licensed indication for the treatment of acute mania in patients with bipolar affective disorder. Although it has no formal indication, it is also considered as a first-line agent for maintenance treatment in bipolar affective disorder.
Other antiepileptic drugs: rufinamide, lacosamide, perampanel
Authors: Cavanna Andrea E.
Published: June 2018

Rufinamide, lacosamide, and perampanel are third-generation agents licensed for use as antiepileptic drugs in recent years. Clinical experience is still limited, and little is known about their positive and negative psychotropic properties or their implications for the management of behavioural symptoms in patients with epilepsy. There are initial reports of anxiety, depression, irritability, and agitation in patients with epilepsy treated with rufinamide, whereas depression, irritability, agitation, and psychotic symptoms have been reported during lacosamide treatment. There are initial reports of behavioural disturbances (especially depression, anxiety, irritability, and psychosis) in patients with epilepsy treated with perampanel. These effects seem to be dose-related and tend to appear within the first weeks of treatment. Overall, these antiepileptic drugs have no indications for the treatment of psychiatric disorders and there is insufficient experience to draw any conclusion regarding their psychotropic profiles.
Thoracic Spinal Stenosis
Authors: Nagpal Ameet , Wisler Brad
Published: June 2018

Thoracic spinal stenosis is an uncommon pathologic condition of the spine. This chapter reviews its etiology, epidemiology, anatomic features, symptoms, diagnosis, and treatment. Four of the main causes of thoracic spinal stenosis are ossification of the ligamentum flavum, ossification of the posterior longitudinal ligament, thoracic disc herniation, and thoracic spondylosis. Even rarer secondary causes include generalized skeletal disorders, metabolic and endocrine disorders of the spine, neoplastic lesions, and vascular malformations. The chapter presents a brief review of the currently available surgical techniques. An updated review is provided of the literature on non-surgical management of the disease, mainly interventional pain management.
Intercostal Neuralgia and Thoracic Radiculopathy
Authors: Huang Yili , Mehta Neel
Published: June 2018

This chapter on thoracic radiculopathy and intercostal neuralgia examines the challenges and complexities of thoracic neuropathic pain. It reviews the thoracic anatomy and introduces an algorithmic approach to patients who present with thoracic pain syndromes. It outlines the challenges of excluding life-threatening and acute causes of thoracic pain. Common causes of thoracic radiculopathy and intercostal neuralgias are discussed. Diagnostic approaches and treatment options are presented.
Lumbar Facet Arthropathy
Authors: Kapural Leonardo , Badhey Harish , Jolly Suneil
Published: June 2018

Lumbar facet dysfunction is a common cause of low back pain. This syndrome appears to involve anatomic and pathophysiologic degeneration, and the elderly are more commonly affected. This chapter examines the incidence of low back pain related to facet dysfunction. It describes the anatomic and pathophysiologic basis of pain mediated by the lumbar facet. It discusses the anatomic basis for the treatment of lumbar facet pain, with an emphasis on therapies that have a robust evidence base.
Sacroiliac Joint Dysfunction
Authors: Foorsov Victor , Dyara Omar , Bolash Robert , Vrooman Bruce
Published: June 2018

Sacroiliac joint dysfunction is a common cause of chronic low back pain. Certain populations are particularly susceptible to disorders of this unique joint. Anatomically, the joint is complex, and the clinician must understand both intrinsic and extrinsic structures in its vicinity. Unfortunately, there are no particular pathognomonic findings on radiologic imaging. A cluster of physical examination findings has been recognized as demonstrating sacroiliac joint pain. Various treatment options exist in the evidence-based treatment of this condition.
Sacroiliac Joint Fusion: Percutaneous and Open
Authors: Kainth Daraspreet Singh , Dhaliwal Karanpal Singh , Polly David W.
Published: June 2018

Sacroiliac joint (SIJ) pain is the source of back pain in up to 25% of patients presenting with back pain. There is significant individual variation in the anatomy of the sacrum and the lumbosacral junction. SIJ pain is diagnosed with the history and physical examination. SIJ injection of a local anesthetic along with steroids is often used to confirm the diagnosis. Nonoperative treatment includes nonsteroidal anti-inflammatories, physical therapy, joint manipulation therapies, and SIJ injections. SIJ pain can also be successfully treated with radiofrequency ablation in some patients. Surgical treatment includes the open anterior sacroiliac joint fusion technique and minimally invasive techniques. The benefits of minimally invasive SIJ fusion versus open surgery include less blood loss, decreased surgical time, and shorter hospital stay. Further studies are needed to determine the long-term durability of the minimally invasive surgical techniques.
Spinal Tumors: Surgical Considerations and Approaches
Authors: Abu-Bonsrah Nancy , Rory Goodwin C. , Iyer Rajiv R. , Sciubba Daniel M.
Published: June 2018

This chapter examines the preoperative and operative considerations that should influence the management of neoplasms affecting the spinal column. The three broad categories of spinal tumors (extradural, intradural extramedullary, and intramedullary) are described. The patient and tumor subtype factors that can create challenges in the treatment of these patients are discussed. This chapter also covers scoring systems that can help physicians in counseling and management of patients diagnosed with tumors affecting the spinal column. A multidisciplinary approach should be used to ensure that patients with spinal neoplasms receive holistic, comprehensive care.
Ultrasound-Guided Spine Interventions
Authors: Gofeld Michael , Kamel Rami A.
Published: June 2018

This chapter reviews recent advances in ultrasound-guided spine procedures. The evidence-based foundation of these methods is examined and ultrasonography is compared with other imaging techniques. The equipment is briefly described. Ultrasound-guided interventional techniques published in peer-reviewed literature are discussed, with selected techniques described in detail. These techniques are classified regionally beginning with the cervical spine and ending with the sacroiliac joints.
Differential Response of Wheat Cultivars toPseudomonas brassicacearumand Take-All Decline Soil
Authors: Yang Mingming , Mavrodi Dmitri V. , Thomashow Linda S. , Weller David M.
Published: June 2018

2,4-Diacetylphloroglucinol (DAPG)-producing Pseudomonas spp. in the P. fluorescens complex are primarily responsible for a natural suppression of take-all of wheat known as take-all decline (TAD) in many fields in the United States. P. brassicacearum, the most common DAPG producer found in TAD soils in the Pacific Northwest (PNW) of the United States, has biological control, growth promoting and phytotoxic activities. In this study, we explored how the wheat cultivar affects the level of take-all suppression when grown in a TAD soil, and how cultivars respond to colonization by P. brassicacearum. Three cultivars (Tara, Finley, and Buchanan) supported similar rhizosphere population sizes of P. brassicacearum when grown in a TAD soil, however they developed significantly different amounts of take-all. Cultivars Tara and Buchanan developed the least and most take-all, respectively, and Finley showed an intermediate amount of disease. However, when grown in TAD soil that was pasteurized to eliminate both DAPG producers and take-all suppression, all three cultivars were equally susceptible to take-all. The three cultivars also responded differently to the colonization and phytotoxicity of P. brassicacearum strains Q8r1-96 and L5.1-96, which are characteristic of DAPG producers in PNW TAD soils. Compared with cultivar Tara, cultivar Buchanan showed significantly reduced seedling emergence and root growth when colonized by P. brassicacearum, and the response of Finley was intermediate. However, all cultivars emerged equally when treated with a DAPG-deficient mutant of Q8r1-96. Our results indicate that wheat cultivars grown in a TAD soil modulate both the robustness of take-all suppression and the potential phytotoxicity of the antibiotic DAPG.
Planning Study Size Based on Precision Rather Than Power
Authors: Rothman Kenneth J. , Greenland Sander
Published: June 2018

Study size has typically been planned based on statistical power and therefore has been heavily influenced by the philosophy of statistical hypothesis testing. A worthwhile alternative is to plan study size based on precision, for example by aiming to obtain a desired width of a confidence interval for the targeted effect. This article presents formulas for planning the size of an epidemiologic study based on the desired precision of the basic epidemiologic effect measures.
Incidence and Outcomes of Positive Donor Rim Cultures and Infections in the Cornea Preservation Time Study
Authors: Mian Shahzad I. , Aldave Anthony J. , Tu Elmer Y. , Ayres Brandon D. , Jeng Bennie H. , Macsai Marian S. , Nordlund Michael L. , Penta Jeffrey G. , Pramanik Sudeep , Szczotka-Flynn Loretta B. , Ayala Allison R. , Liang Wendi , Maguire Maureen G. , Lass Jonathan H. ,   on behalf of the Cornea Preservation Time Study Group
Published: June 2018

Purpose:

To assess donor rim culture results and outcomes of ocular infections in the Cornea Preservation Time Study (CPTS).

Methods:

Donor corneal rim cultures were optional. Donor characteristics were assessed for association with positive cultures using the Fisher exact test and Poisson regression analyses. Incidence rates of ocular infections were estimated, and 95% confidence intervals were calculated.

Results:

Cultures were performed in 784 (58.9%) of the 1330 cases. For the 0 to 7-day versus 8 to 14-day preservation time groups, respectively, positive fungal growth occurred in 10 of 397 (2.5%) versus 5 of 387 (1.3%) corneas (P = 0.30), whereas positive bacterial cultures occurred in 6 of 397 (1.5%) versus 4 of 387 (1.0%) corneas (P = 0.75). Surgeon-prepared tissue remained a significant risk for positive fungal cultures [relative risk (RR) of surgeon- versus eye-bank-prepared, 2.85; 95% CI (1.02–7.98)], whereas younger donors [RR per year of age, 0.96; 95% CI (0.93–1.00)] and accidental death donors [RR of accident versus disease, 3.71; 95% CI (1.36–10.13)] were at a greater risk for positive bacterial cultures. Fungal infection (Candida glabrata) developed in 1 (6.7%) of 15 recipients with a positive fungal culture, and no recipient infections occurred with positive bacterial culture. With one additional fungal keratitis (Candida albicans) and one bacterial endophthalmitis (E. coli) with no rim culture performed, a total of 2 of 1330 eyes (0.15%) developed fungal and 1/1330 eyes (0.08%) developed bacterial postkeratoplasty infections.

Conclusions:

A longer preservation time was not associated with a higher rate of positive donor rim cultures. The overall rate of infection across the entire cohort was low.
Mental practice for upper limb rehabilitation after stroke: a systematic review and meta-analysis
Authors: Park Si-Woon , Kim Jae-Hyung , Yang Yun-Jung
Published: June 2018

Mental practice (MP) is usually provided in combination with other therapies, and new developments for neurofeedback to support MP have been made recently. The objectives of this study were to evaluate the effectiveness of MP and to investigate the intervention characteristics including neurofeedback that may affect treatment outcome. The Cochrane Central Register of Controlled Trials, PubMed, Embase, KoreaMed, Scopus, Web of Science, PEDro, and CIRRIE were searched from inception to March 2017 for randomized controlled trials to assess the effect of MP for upper limb rehabilitation after stroke. Fugl-Meyer Assessment (FMA) was used as the outcome measure for meta-analysis. Twenty-five trials met the inclusion criteria, and 15 trials were eligible for meta-analysis. Among the trials selected for meta-analysis, MP was added to conventional therapy in eight trials or to modified constraint-induced movement therapy in one trial. The other trials provided neurofeedback to support MP: MP-guided neuromuscular electrical stimulation (NMES) in four trials and MP-guided robot-assisted therapy (RAT) in two trials. MP added to conventional therapy resulted in significantly higher FMA gain than conventional therapy alone. MP-guided NMES showed superior result than conventional NMES as well. However, the FMA gain of MP-guided RAT was not significantly higher than RAT alone. We suggest that MP is an effective complementary therapy either given with neurofeedback or not. Neurofeedback applied to MP showed different results depending on the therapy provided. This study has limitations because of heterogeneity and inadequate quality of trials. Further research is requested.
Resilience Predicts Social Functioning in Clinically Stable Patients With Bipolar Disorder
Authors: Bozikas Vasilis P. , Parlapani Eleni , Ntouros Evangelos , Bargiota Stavroula I. , Floros Georgios , Nazlidou Elena I. , Garyfallos Georgios
Published: June 2018

The current study focused on the association between resilience and social functioning in patients with bipolar disorder (BD). Forty clinically stable patients with BD type I and BD type II, as well as 40 healthy controls, matched for age, sex, and educational background were enrolled. Clinical status was assessed by the Montgomery-Åsberg Depression Rating Scale and the Young Mania Rating Scale. Functioning was evaluated by the Mini International Classification of Functioning, Disability and Health rating of activities and participation in mental illnesses, and the Social and Occupational Functioning Scale. Resilience was measured by the Connor-Davidson Resilience scale. Patients demonstrated significantly lower resilience levels compared with healthy individuals. A stepwise regression analysis indicated that only resilience contributed significantly to social functioning's outcome. Because resilience may constitute a social functioning moderator in clinically stable patients with BD, a paradigm shift toward protective factors could lead to implementation of resilience-oriented interventions designed specifically for patients with BD.
Canine Outreach Promoting Engagement
Authors: Yordy B. Morgan , Pope W. Stuart , Wang Chih-Hsuan
Published: June 2018

Background

Animal-assisted activities (AAAs) show promise in providing emotional and social benefits to older adults and may be used as a tool to promote therapeutic communication between students and cognitively impaired older adults.

Purpose

The purpose was to develop a program incorporating AAAs to enhance social engagement of cognitively impaired older adults in a community respite program and in turn enhance student comfort when caring for this vulnerable population.

Methods

The Dementia Attitudes Scale, a validated tool, was used to measure students’ attitudes before and after AAA intervention. Data were analyzed using repeated-measures analysis of variance.

Results

Students were significantly more comfortable and demonstrated a gain in knowledge after AAAs were included in the community clinical experience.

Conclusions

Incorporating AAAs into student community/service-learning clinical experience improved communication between students and cognitively impaired older adults, improving students’ attitudes when caring for this population.
Ocular Injury Presenting to a Level-III Pediatric Trauma Center
Authors: Schneider Kari , Nguyen-Tran Hai , Segura Bradley J. , Areaux Raymond G. , Nerheim Dan , Louie Jeffrey P.
Published: June 2018

Objective

The purpose of this study is to describe pediatric ocular injuries presenting to a level-III pediatric trauma center and emergency department.

Methods

We performed a retrospective study and identified children from January 1, 2011, to January 1, 2016. Charts were reviewed for any subject, age from newborn to younger than 18 years, based on International Classification of Diseases, ninth and tenth revision, codes for any ocular injury. Data abstraction included age, sex, means of arrival, eye involved, mechanism of injury, type of ocular injury, imaging studies obtained, procedures performed, location of definitive repair (in the operating room or emergency department), and subspecialty services involved.

Results

In the 5-year period, we describe 356 injuries among 278 children. Males had a slightly higher rate of presentation than females (156 and 122, respectively). Forty-three children (15.46%) required repair in the operating room. Dog bites comprised of 7.19% children with outpatient follow-up, one patient (0.36%) eventually developed anophthalmia, and 30 children (10.79%) had long-term ophthalmological sequelae (ie, glaucoma and blindness).

Conclusions

At our institution, a level-III trauma center, we evaluated and managed approximately 1 ocular injury case per week and children required surgical repair in the operating room at a higher rate than higher-level trauma centers. Injuries secondary to dog bites remain a clinically significant etiology.
Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis–Like Lupus Erythematosus
Authors: Tankunakorn Jutamas , Sawatwarakul Sirima , Vachiramon Vasanop , Chanprapaph Kumutnart
Published: June 2018

Background/Objective

Stevens-Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN)–like lupus erythematosus is a hyperacute and life-threatening form of cutaneous lupus erythematosus. Because of its rarity, little is known about this entity. We aimed to evaluate the clinical characteristics, laboratory findings, systemic manifestations, treatments, and outcome of SJS/ TEN-like lupus erythematosus.

Methods

We conducted a chart review study from July 2002 to September 2016 of all patients diagnosed with SJS/TEN-like lupus erythematosus who presented with gradual epidermal necrolysis without clear drug or infectious culprit. We evaluate for clinical features, extracutaneous involvement, Systemic Lupus Erythematosus Disease Activity Index, histologic findings, immunofluorescence pattern, serologic abnormalities, treatment, outcome, and recurrence of SJS/TEN-like lupus erythematosus.

Results

Of 9074 patients diagnosed with cutaneous lupus erythematosus and/or systemic lupus erythematosus, 6 patients justified the diagnosis of SJS/TEN-like lupus erythematosus (5 SJS/TEN-like acute cutaneous lupus erythematosus, 1 TEN-like subacute cutaneous lupus erythematosus), accounting for 0.07%. Fifty percent had epidermal necrolysis as the initial presentation of lupus with a median time from onset of 1.5 months (0–48 months). The median duration between initial rash and epidermal detachment was 4.5 days (3–14 days). All had internal organ involvement (hematologic and renal) and high Systemic Lupus Erythematosus Disease Activity Index score (median, 19.5 [16–24]). Most recovered with systemic corticosteroids, antimalarial drugs, and/or immunosuppressants. None had disease recurrence.

Conclusions

This is the largest single series of patients with SJS/TEN-like lupus erythematosus. Skin damage is an indicator of disease activity, and careful search for extracutaneous involvement to prevent further complications is mandatory.
Fibrinogen Protects Against Barrier Dysfunction Through Maintaining Cell Surface Syndecan-1 In Vitro
Authors: Wu Feng , Kozar Rosemary A.
Published: June 2018

Background:

We have shown that fresh frozen plasma's (FFP) protection of pulmonary endothelial barrier integrity following hemorrhagic shock is due in part to restoration of endothelial syndecan-1. In the present study, we investigated the role of fibrinogen, a major component of FFP, as an endothelial protector and hypothesize that fibrinogen stabilizes cell surface syndecan-1 to restore endothelial barrier integrity.

Methods:

Pulmonary endothelial cells were incubated in FFP, fibrinogen, or lactated Ringers (LR) then immunostained with anti-syndecan-1 or fibrinogen and barrier integrity assessed. In some experiments, cells were exposed to fibrinogen depleted plasma.

Results:

Cell surface syndecan-1 was increased by FFP and fibrinogen compared with LR-treated cells while barrier integrity was augmented by FFP and fibrinogen compared with LR. The physiological concentration of 2.5 mg/mL fibrinogen was sufficient to increase cell surface syndecan-1. Colocalization and co-immunoprecipitation experiments demonstrated that fibrinogen associates with syndecan-1. Fibrinogen-deficient plasma was unable to augment sydnecan-1 immunostaining and lost its endothelial protective effect on barrier integrity.

Conclusion:

These data suggest that in vitro, fibrinogen associated with cell surface syndecan-1 and enhanced endothelial barrier integrity.
Spiking neural networks for computer vision
Authors: Hopkins Michael , Pineda-García Garibaldi , Bogdan Petruţ A. , Furber Steve B.
Published: June 2018

State-of-the-art computer vision systems use frame-based cameras that sample the visual scene as a series of high-resolution images. These are then processed using convolutional neural networks using neurons with continuous outputs. Biological vision systems use a quite different approach, where the eyes (cameras) sample the visual scene continuously, often with a non-uniform resolution, and generate neural spike events in response to changes in the scene. The resulting spatio-temporal patterns of events are then processed through networks of spiking neurons. Such event-based processing offers advantages in terms of focusing constrained resources on the most salient features of the perceived scene, and those advantages should also accrue to engineered vision systems based upon similar principles. Event-based vision sensors, and event-based processing exemplified by the SpiNNaker (Spiking Neural Network Architecture) machine, can be used to model the biological vision pathway at various levels of detail. Here we use this approach to explore structural synaptic plasticity as a possible mechanism whereby biological vision systems may learn the statistics of their inputs without supervision, pointing the way to engineered vision systems with similar online learning capabilities.
Control of gaze in natural environments: effects of rewards and costs, uncertainty and memory in target selection
Authors: Hayhoe Mary M. , Matthis Jonathan Samir
Published: June 2018

The development of better eye and body tracking systems, and more flexible virtual environments have allowed more systematic exploration of natural vision and contributed a number of insights. In natural visually guided behaviour, humans make continuous sequences of sensory-motor decisions to satisfy current goals, and the role of vision is to provide the relevant information in order to achieve those goals. This paper reviews the factors that control gaze in natural visually guided actions such as locomotion, including the rewards and costs associated with the immediate behavioural goals, uncertainty about the state of the world and prior knowledge of the environment. These general features of human gaze control may inform the development of artificial systems.
Not-So-CLEVR: learning same–different relations strains feedforward neural networks
Authors: Kim Junkyung , Ricci Matthew , Serre Thomas
Published: June 2018

The advent of deep learning has recently led to great successes in various engineering applications. As a prime example, convolutional neural networks, a type of feedforward neural network, now approach human accuracy on visual recognition tasks like image classification and face recognition. However, here we will show that feedforward neural networks struggle to learn abstract visual relations that are effortlessly recognized by non-human primates, birds, rodents and even insects. We systematically study the ability of feedforward neural networks to learn to recognize a variety of visual relations and demonstrate that same–different visual relations pose a particular strain on these networks. Networks fail to learn same–different visual relations when stimulus variability makes rote memorization difficult. Further, we show that learning same–different problems becomes trivial for a feedforward network that is fed with perceptually grouped stimuli. This demonstration and the comparative success of biological vision in learning visual relations suggests that feedback mechanisms such as attention, working memory and perceptual grouping may be the key components underlying human-level abstract visual reasoning.
GenomeTrakr proficiency testing for foodborne pathogen surveillance: an exercise from 2015
Authors: Timme Ruth E. , Rand Hugh , Sanchez Leon Maria , Hoffmann Maria , Strain Errol , Allard Marc , Roberson Dwayne , Baugher Joseph D.
Published: June 2018

Pathogen monitoring is becoming more precise as sequencing technologies become more affordable and accessible worldwide. This transition is especially apparent in the field of food safety, which has demonstrated how whole-genome sequencing (WGS) can be used on a global scale to protect public health. GenomeTrakr coordinates the WGS performed by public-health agencies and other partners by providing a public database with real-time cluster analysis for foodborne pathogen surveillance. Because WGS is being used to support enforcement decisions, it is essential to have confidence in the quality of the data being used and the downstream data analyses that guide these decisions. Routine proficiency tests, such as the one described here, have an important role in ensuring the validity of both data and procedures. In 2015, the GenomeTrakr proficiency test distributed eight isolates of common foodborne pathogens to participating laboratories, who were required to follow a specific protocol for performing WGS. Resulting sequence data were evaluated for several metrics, including proper labelling, sequence quality and new single nucleotide polymorphisms (SNPs). Illumina MiSeq sequence data collected for the same set of strains across 21 different laboratories exhibited high reproducibility, while revealing a narrow range of technical and biological variance. The numbers of SNPs reported for sequencing runs of the same isolates across multiple laboratories support the robustness of our cluster analysis pipeline in that each individual isolate cultured and resequenced multiple times in multiple places are all easily identifiable as originating from the same source.
Spontaneous but not voluntary eye blinks during spatial working memory are associated with successful performance
Authors: Lee Andrew S. , Blankson Baaba K. , Manza Peter , O’Rawe Jonathan F. , Evinger Craig , Leung Hoi-Chung
Published: June 2018

Spontaneous eye blink rate (SBR) has been associated with central dopamine (DA) levels, raising the intriguing possibility that SBR is related to cognitive functions dependent on DA, such as spatial working memory (WM). We tested this hypothesis in two behavioral experiments, examining the relationship between SBR, WM load and individual differences in spatial WM performance in 126 young adults. In Experiment 1, we examined the temporal profile of SBR during a spatial delayed recognition task requiring maintenance of 1, 2, 4, 6 or 7 dot locations. We observed a suppression in SBR during dot- and recognition probe-presentation, and a significant increase in SBR afterwards. High performers showed significantly lower SBR than low performers during the first 500 ms of the delay period. In Experiment 2, we used a similar spatial WM task as Experiment 1 to test whether an instructed voluntary blink during the early delay would directly dampen WM performance. While the temporal dynamics of SBR across task events were comparable to Experiment 1, WM performance was not significantly different between the voluntary blink and no blink conditions. Together, these results suggest that spontaneous but not voluntary eye blinking is closely linked to spatial WM, and that lower SBR during WM encoding and early phase of maintenance is associated with better WM task performance.
IQGAP3 Overexpression Correlates with Poor Prognosis and Radiation Therapy Resistance in Breast Cancer
Authors: Hua Xin , Long Zhi-Qing , Zhang Wen-Wen , Lin Chao , Sun Xiao-Qing , Wen Wen , Lu Zi-Jian , Guo Na , He Zhen-Yu , Bing-Song Li , Guo Ling , Lin Huan-Xin
Published: June 2018

Background: IQ motif-containing GTPase activating protein 3 (IQGAP3), the latest found protein of IQGAP family, may act as a crucial factor in the process of cancer development and progression; however, its clinical value in breast cancer remains unestablished so far. Our team explored the correlation between IQGAP3 expression profile and the clinicopathological features in breast cancer. Methods: IQGAP3 levels in breast cancer cell lines and tumor tissues were detected by real-time PCR and western blotting and compared to the normal control groups. Protein expression of IQGAP3 was evaluated immunohistochemically in specimens (archived paraffin embedded) of 257 breast cancer patients. We also analyze the association between IQGAP3 expression and the clinical characters and prognosis. The relationship between IQGAP3 expression and sensitivity to radiation therapy was determined by subgroup analysis. Results: There was significant upregulation of IQGAP3 in breast cancer cell lines and human tumor tissues at both the mRNA and protein level compared to the normal ones. In addition, 110/257 (42.8%) of archived paraffin embedded breast cancer specimens had high protein expression of IQGAP3. High expression of IQGAP3 was significantly related to clinical stage (P=0.001), T category (P=0.002), N category (P=0.001), locoregional recurrence(P=0.002), distant metastasis (P=0.001), and vital status (P=0.001). Univariate and multivariate statistical analysis showed that IQGAP3 was an independent prognostic factor of the whole cohort breast cancer patients (P=0.003, P=0.001). Subgroup analysis revealed IQGAP3 expression correlates with radiation therapy resistance and was also an independent predictor for radiation therapy outcome. Conclusions: Our findings suggest that high IQGAP3 expression predicts poor prognosis and radiation therapy resistance in breast cancer. In addition, IQGAP3 may be a reliable novel biomarker to provide personalized prognostication and identify patients who can profit from more aggressive RT regimen for improving the survival of breast cancer patients.
Dynamics and predicted drug response of a gene network linking dedifferentiation with β-catenin dysfunction in hepatocellular carcinoma
Authors: Gérard Claude , Di-Luoffo Mickaël , Gonay Léolo , Caruso Stefano , Couchy Gabrielle , Loriot Axelle , Tao Junyan , Konobrocka Katarzyna , Cordi Sabine , Monga Satdarshan P. , Hanert Emmanuel , Zucman-Rossi Jessica , Lemaigre Frédéric P.
Published: June 2018

Alterations of individual genes variably affect development of hepatocellular carcinoma (HCC), prompting the need to characterize the function of tumor-promoting genes in the context of gene regulatory networks (GRN). Here, we identify a GRN which functionally links LIN28B-dependent dedifferentiation with dysfunction of CTNNB1 (β-CATENIN). LIN28B and CTNNB1 form a functional GRN with SMARCA4 (BRG1), Let-7b, SOX9, TP53 and MYC. GRN activity is detected in HCC and gastrointestinal cancers; it negatively correlates with HCC prognosis and contributes to a transcriptomic profile typical of the proliferative class of HCC. Using data from The Cancer Genome Atlas and from transcriptomic, transfection and mouse transgenic experiments, we generated and validated a quantitative mathematical model of the GRN. The model predicts how the expression of GRN components changes when the expression of another GRN member varies or is inhibited by a pharmacological drug. The dynamics of GRN component expression reveal distinct cell states that can switch reversibly in normal condition, and irreversibly in HCC. We conclude that identification and modelling of the GRN provides insight into prognosis, mechanisms of tumor-promoting genes and response to pharmacological agents in HCC.
SIV/SHIV-Zika coinfection does not alter disease pathogenesis in adult non-pregnant Rhesus Macaques
Authors: Bidokhti Mehdi R. M. , Dutta Debashis , Madduri Lepakshe S. V. , Woollard Shawna M. , Norgren Robert , Giavedoni Luis , Byrareddy Siddappa N.
Published: June 2018

Due to the large geographical overlap of populations exposed to Zika virus (ZIKV) and human immunodeficiency virus (HIV), understanding disease pathogenesis in such coinfections is urgently needed. We used chronically infected simian immunodeficiency virus and chimeric simian human immunodeficiency virus (SIV/SHIV) macaques and inoculated with ZIKV. Plasma viral loads of both SIV/SHIV and ZIKV showed no significant changes as compared to ZIKV alone-infected animals. Tissue clearance of ZIKV was observed similarly. Furthermore, minimal changes in cytokines/chemokines were observed. Collectively, these data suggest that coinfection may not alter disease pathogenesis and warrants large HIV-ZIKV epidemiological studies to validate these findings.

Author Summary

The co-infection incidence of human immunodeficiency virus (HIV) infection and neglected tropical infectious diseases is increasing due to the large geographical overlap of populations exposed to both of these viruses. Thus, researching on such coinfection is of particular importance. In this study, we investigated HIV-ZIKV coinfection dynamics in adult non-pregnant Rhesus Macaques model chronically infected with simian immunodeficiency virus (SIV) - or chimeric simian human immunodeficiency virus (SHIV). We found that post ZIKV inoculation, plasma viral loads were similar to ZIKV alone infected animals in addition to minimal changes of cytokines. Dynamics of SIV and SHIV also did not change. Tissue clearance of ZIKV was found 67 months later. Our findings provide insights into HIV-ZKIV coinfection to determine the alteration of their pathogenesis.
PennZzz - an algorithm for estimating behavioral states from wrist-worn accelerometery
Authors: McCloskey Richard , Goodman Matthew H. , Grant Sara McHugh , Ghorai Arpita , Gehrman Philip R. , Bućan Maja
Published: June 2018

Sleep is a heterogeneous behavioral state comprised of different stages and interspersed with episodes of wakefulness. Sleep/wake states can be monitored in the sleep laboratory by polysomnography (PSG). However, sleep studies are intrusive, laborious and expensive, and are usually performed over a single night. In contrast, wrist-worn activity-tracking devices (actimeters) are inexpensive, unobtrusive, and can be used to estimate sleep and wake patterns over multiple nights. We designed the PennZzz algorithm to estimate sleep and wake from actimetry data. Results obtained by actimetry-based monitoring in 26 subjects were compared to stages of sleep and wakefulness detected by simultaneous polysomnography. We found that our algorithm identifies PSG-defined wake episodes with a high accuracy (336/431 – 76% of algorithm wake events correspond to true wakefulness). Furthermore, we find that the algorithm is sensitive enough to detect the majority (258/431 – 59%) of true wake episodes occurring after the first NREM1 to NREM2 transition. With correction, algorithm outputs can be used to estimate the total amount of time awake after sleep onset. We further refined this program for application in a high-throughput manner to assess the total amount of sleep, wake, and non-wear during longer recording periods.
Synthesis of three major auxins from glucose in EngineeredEscherichia coli
Authors: Guo Daoyi , Zhang Lihua , Kong Sijia , Liu Zhijie , Chu Xu , Li Xun , Pan Hong
Published: June 2018

Indole-3-acetic acid (IAA) is considered the most common and important naturally occurring auxin in plants and a major regulator of plant growth and development. In addition, phenylacetic acid (PAA) and 4-hydroxyphenylacetic acid (4HPA) can also play a role as auxin in some plants. In recent years, several microbes have been metabolically engineered to produce IAA from L-tryptophan. In this study, we showed that aminotransferasearo8and decarboxylasekdcfromSaccharomyces cerevisiae, and aldehyde dehydrogenasealdHfromEscherichia colihave broad substrate ranges and can catalyze the conversion of three kinds of aromatic amino acids (L-tryptophan, L-tyrosine or L-phenylalanine) to the corresponding IAA, 4HPA and PAA. Subsequently, three de novo biosynthetic pathways for the production of IAA, PAA and 4HPA from glucose were constructed inE. colithrough strengthening the shikimate pathway. This study described here shows the way for the development of agricultural microorganism for biosynthesis of plant auxin and promoting plant growth in the future.
Interactions in self-assembled microbial communities saturate with diversity
Authors: Yu Xiaoqian , Polz Martin F. , Alm Eric J.
Published: June 2018

How the diversity of organisms competing for or sharing resources influences community production is an important question in ecology but has rarely been explored in natural microbial communities. These generally contain large numbers of species making it difficult to disentangle how the effects of different interactions scale with diversity. Here, we show that changing diversity affects measures of community function in relatively simple communities but that increasing richness beyond a threshold has little detectable effect. We generated self-assembled communities with a wide range of diversity by growth of cells from serially diluted seawater on brown algal leachate. We subsequently isolated the most abundant taxa from these communities via dilution-to-extinction in order to compare productivity functions of the entire community to those of individual taxa. To parse the effect of different types of organismal interactions, we developed relative total function (RTF) as an index for positive or negative effects of diversity on community function. Our analysis identified three overall regimes with increasing diversity. At low richness (<12 taxa), potential positive and negative effects of interactions are both weak, while at moderate richness (12-20 taxa), community resource uptake increases but the carbon use efficiency decreases. Finally, beyond 20 taxa, there was no net change in community function indicating a saturation of potential interactions. These data suggest that although more diverse communities had overall greater access to resources, individual taxa within these communities had lower resource availability and reduced carbon use efficiency, indicating that competition due to niche overlap increases with diversity but that these interactions saturate at a specific threshold.
Endothelial Protein C Receptor Could Contribute to Experimental Malaria-Associated Acute Respiratory Distress Syndrome
Authors: Santos Ortolan Luana dos , Sercundes Michelle Klein , Moura Gabriel Candido , de Castro Quirino Thatyane , Debone Daniela , de Sousa Costa Douglas , Murillo Oscar , Marinho Claudio Romero Farias , Epiphanio Sabrina
Published: June 2018

The severity of Plasmodium falciparum malaria is associated with parasite cytoadherence, but there is limited knowledge about the effect of parasite cytoadherence in malaria-associated acute respiratory distress syndrome (ARDS). Our objective was to evaluate the cytoadherence of infected red blood cells (iRBCs) in a murine model of ARDS and to appraise a potential function of endothelial protein C receptor (EPCR) in ARDS pathogenesis. DBA/2 mice infected with P. berghei ANKA were classified as ARDS- or hyperparasitemia (HP)-developing mice according to respiratory parameters and parasitemia. Lungs, blood and bronchoalveolar lavage were collected for gene expression or protein analyses. Primary cultures of microvascular lung endothelial cells from DBA/2 mice were analyzed for iRBC interactions. Lungs from ARDS-developing mice showed evidence of iRBC accumulation along with an increase in EPCR and TNF concentrations. Furthermore, TNF increased iRBC adherence in vitro. Dexamethasone-treated infected mice showed low levels of TNF and EPCR mRNA expression and, finally, decreased vascular permeability, thus protecting mice from ARDS. In conclusion, we identified that increased iRBC cytoadherence in the lungs underlies malaria-associated ARDS in DBA/2-infected mice and that inflammation increased cytoadherence capacity, suggesting a participation of EPCR and a conceivable target for drug development.
OptoGranules reveal the evolution of stress granules to ALS-FTD pathology
Authors: Zhang Peipei , Fan Baochang , Yang Peiguo , Temirov Jamshid , Messing James , Kim Hong Joo , Taylor J. Paul
Published: June 2018

Stress granules are non-membranous assemblies of mRNA and protein that form in response to a variety of stressors. Genetic, pathologic, biophysical and cell biological studies have implicated disturbances in the dynamics of membrane-less organelles, such as stress granules, as a pathobiological component of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD)1–12. This confluence of evidence has inspired the hypothesis that these diseases reflect an underlying disturbance in the dynamics and material properties of stress granules; however, this concept has remained largely untestable in available models of stress granule assembly, which require the confounding variable of exogenous stressors. Here we demonstrate the development and use of a light-inducible stress granule system, termed OptoGranules, which permits discrete, experimental control of the dynamics and material properties of stress granules in living cells in the absence of exogenous stressors. The nucleator in this system is Opto-G3BP1, a light-sensitive chimeric protein assembled from the intrinsically disordered region (IDR) and RNA-binding domain of G3BP1 combined with the light-sensitive oligomerization domain of Arabidopsis thaliana cryptochrome 2 (CRY2) photolyase homology region (PHR). Upon stimulation with blue light, Opto-G3BP1 initiates the rapid assembly of dynamic, cytoplasmic, liquid granules that are composed of canonical stress granule components, including G3BP1, PABP, TIA1, TIAR, eIF4G, eIF3η, ataxin 2, GLE1, TDP-43 and polyadenylated RNA. With this system, we demonstrate that persistent or repetitive assembly of stress granules is cytotoxic and is accompanied by the evolution of stress granules to neuronal cytoplasmic inclusions that recapitulate the pathology of ALS-FTD.
Separable roles for Mec1/ATR in genome maintenance, DNA replication, and checkpoint signaling
Authors: Lanz Michael Charles , Oberly Susannah , Sanford Ethan James , Sharma Sushma , Chabes Andrei , Smolka Marcus Bustamante
Published: June 2018

The Mec1/ATR kinase coordinates multiple cellular responses to replication stress. In addition to its canonical role in activating the checkpoint kinase Rad53, Mec1 also plays checkpoint-independent roles in genome maintenance that are not well understood. Here we used a combined genetic–phosphoproteomic approach to manipulate Mec1 activation and globally monitor Mec1 signaling, allowing us to delineate distinct checkpoint-independent modes of Mec1 action. Using cells in which endogenous Mec1 activators were genetically ablated, we found that expression of “free” Mec1 activation domains (MADs) can robustly activate Mec1 and rescue the severe DNA replication and growth defects of these cells back to wild-type levels. However, unlike the activation mediated by endogenous activator proteins, “free” MADs are unable to stimulate Mec1-mediated suppression of gross chromosomal rearrangements (GCRs), revealing that Mec1's role in genome maintenance is separable from a previously unappreciated proreplicative function. Both Mec1's functions in promoting replication and suppressing GCRs are independent of the downstream checkpoint kinases. Additionally, Mec1-dependent GCR suppression seems to require localized Mec1 action at DNA lesions, which correlates with the phosphorylation of activator-proximal substrates involved in homologous recombination-mediated DNA repair. These findings establish that Mec1 initiates checkpoint signaling, promotes DNA replication, and maintains genetic stability through distinct modes of action.