bluuebunny/crossref_metadata_2025 huggingface dataset:
Generation, implementation, and appraisal of an N-gram-based stemming algorithm
Authors: Pande Bhagwati P , Tamta Pawan , Dhami Hoshiyar S
Published: November 2018

A language-independent stemmer has always been looked for. Single N-gram tokenization technique works well; however, it often generates stems that start with intermediate characters, rather than initial ones. We present a novel technique that takes the concept of N-gram stemming one step ahead and compare our method with an established algorithm in the field, say, Porter’s stemmer for English, Spanish, and Portuguese languages. Results indicate that our N-gram stemmer is comparable with the Porter’s linguistic stemmer.
What is a Case-Control Study?
Authors: Dupépé Esther B , Kicielinski Kimberly P , Gordon Amber S , Walters Beverly C
Published: November 2018

Case-control (case-control, case-controlled) studies are beginning to appear more frequently in the neurosurgical literature. They can be more robust, if well designed, than the typical case series or even cohort study to determine or refine treatment algorithms. The purpose of this review is to define and explore the differences between case-control studies and other so-called nonexperimental, quasiexperimental, or observational studies in determining preferred treatments for neurosurgical patients.
Blockchain technology: development and prospects
Authors: Zhao Weijie
Published: November 2018

It has been more than 10 years since Satoshi Nakamoto published his famous paper entitled ‘Bitcoin: a peer-to-peer electronic cash system’, which set the foundation of blockchain technology. Accompanied by the price volatility of bitcoins from 2017 to 2018, blockchain has been a hot word on the internet, and particularly hot in China. Blockchain offers a distributed and secure system for data storage and value transactions. Its applications are springing up in multiple fields.

The Chinese government is considering these trends with great caution. Initial coin offering has been banned in China since September 2017. By contrast, an official white paper on China's blockchain technology, which was released in May 2018, said that blockchain technology will be widely applied in the real economy of China within 3 years. In a recent panel discussion held by National Science Review, experts talked about related topics. Their opinions may provide a quick view of the future development of blockchain in China and abroad.

Jing Chen

Assistant Professor of Computer Science Department, Stony Brook University and Chief Scientist at Algorand LLC, USA

Xiaotie Deng

Professor of School of Electronics Engineering and Computer Science, Peking University, China

Guohua Gan

Vice President of Beijing Tai Cloud Technology Corp., China

Xiaoyun Wang

Professor of Institute of Advanced Study, Tsinghua University, China

Zhiming Zheng

Professor of School of Mathematics and Systems Science, Beihang University, China

Lei Guo (Chair)

Professor of Academy of Mathematics and Systems Science, Chinese Academy of Sciences, China
Systems Biology and Machine Learning in Plant–Pathogen Interactions
Authors: Mishra Bharat , Kumar Nilesh , Mukhtar M. Shahid
Published: November 2018

Systems biology is an inclusive approach to study the static and dynamic emergent properties on a global scale by integrating multiomics datasets to establish qualitative and quantitative associations among multiple biological components. With an abundance of improved high throughput -omics datasets, network-based analyses and machine learning technologies are playing a pivotal role in comprehensive understanding of biological systems. Network topological features reveal most important nodes within a network as well as prioritize significant molecular components for diverse biological networks, including coexpression, protein–protein interaction, and gene regulatory networks. Machine learning techniques provide enormous predictive power through specific feature extraction from biological data. Deep learning, a subtype of machine learning, has plausible future applications because a domain expert for feature extraction is not needed in this algorithm. Inspired by diverse domains of biology, we here review classic systems biology techniques applied in plant immunity thus far. We also discuss additional advanced approaches in both graph theory and machine learning, which may provide new insights for understanding plant–microbe interactions. Finally, we propose a hybrid approach in plant immune systems that harnesses the power of both network biology and machine learning, with a potential to be applicable to both model systems and agronomically important crop plants.
Characterization and Pathogenicity of Botryosphaeriaceae Species Obtained from Avocado Trees with Branch Canker and Dieback and from Avocado Fruit with Stem End Rot in Chile
Authors: Valencia Ana L. , Gil Pilar M. , Latorre Bernardo A. , Rosales I. Marlene
Published: November 2018

Several species of the Botryosphaeriaceae family have been associated with branch canker, dieback, and stem end rot in avocado (Persea americana Mill.). In Chile, the incidence of diseases affecting the avocado tree increased from 2011 to 2016, which coincided with a severe drought that affected avocado production. Moreover, distant countries importing avocados from Chile also reported an increase of stem end rot of ripe avocados. Therefore, the aims of this study were to identify the pathogen species associated with branch canker, dieback, and stem end rot of avocado in Chile and to study their pathogenicity. This study was conducted between 2015 and 2016 in ‘Hass’ avocado orchards located in the main avocado-producing regions in Chile. A diverse collection of fungal species was recovered from both necrotic woody tissue and necrotic tissue on harvested ripe fruit. On the basis of morphology and phylogenetic analyses of the internal transcribed spacer region (ITS1-5.8S-ITS2) and the translation elongation factor 1-α (TEF1-α) gene, eight species in the Botryosphaeriaceae family were identified: Diplodia mutila, D. pseudoseriata, D. seriata, Dothiorella iberica, Lasiodiplodia theobromae, Neofusicoccum australe, N. nonquaesitum, and N. parvum. For each of these species, pathogenicity studies were conducted on 1-year-old healthy Hass avocado plants. All isolates produced brown gum exudate and caused necrosis in the vascular system 3 weeks after inoculation. N. nonquaesitum, N. parvum, and D. pseudoseriata were the most virulent species. Necrotic lesions and cavities with white mycelia near the peduncle union were observed on Hass avocado fruit inoculated postharvest. L. theobromae, N. australe, and N. parvum were significantly more virulent than the other tested species in the Botryosphaeriaceae family. This study identified and characterized the pathogenicity of Botryosphaeriaceae species in Chile, which will prove useful to future research on these pathogens directed at establishing effective control strategies in avocado.
Diverting dementia
Authors: Ritsema Tamara S.
Published: November 2018

As the population ages, more adults in the United States are living with dementia. Younger family members often are concerned that they too may develop dementia, but the general public is largely unaware that strategies exist to slow or delay onset of dementia. In fact, by implementing a number of healthful strategies throughout their lifespans, patients may be able to reduce the likelihood of developing dementia or at least delay its onset. These strategies include eating a high-quality diet; keeping physically, socially, and intellectually active; preventing or treating hearing loss; avoiding obesity, hypertension, and diabetes; and avoiding or stopping tobacco smoking. This article reviews the recent scientific literature for dementia risk-reduction strategies and offers suggestions to healthcare professionals who wish to help their patients stave off cognitive loss.
Orthopaedic surgery resident consultations at a level I trauma center
Authors: Snoap Tyler , Walbridge Joseph , Albright Patrick , Weistroffer Joseph , Kenter Keith
Published: November 2018

Background:

The responsibilities of an on-call orthopaedic surgery resident has been minimally described in the literature. The most common diagnoses, procedures, and surgical cases that occur during an on-call shift would be of interest to an incoming resident. This study was designed to provide insight as to the knowledge and skills necessary to be a competent orthopaedic surgery resident on call.

Methods:

An electronic databank was created for the on-call residents to prospectively log inpatient and emergency department consultations at a level I trauma center over a 3-month period. Pertinent information was gathered about each consultation such as the diagnosis, treatment required in the emergency department or formal operative suite, type of anesthetic used to complete a reduction or procedure if necessary, duration of consultation, and more.

Results:

Over 500 consults were recorded during the collection period. The top three most common diagnoses included distal radial and/or distal ulnar fracture (8.2%), hand laceration (8.0%), and compression, burst, transverse process, or fracture dislocation of the spine (5.7%). The top three most common procedures or reductions performed in the emergency department included closed reduction of a fracture (38.9%), irrigation and debridement (24.0%), and closed reduction of a fracture dislocation or isolated dislocation (15.7%).

Conclusions:

This is the first study to evaluate the most common diagnoses and procedures encountered by orthopaedic residents on call at a level I trauma center. The results of the study can be utilized by orthopaedic program directors and department chairs, residents in training, and medical students.
Current topics in women’s sports medicine: evaluation and treatment of the female athlete
Authors: Tanaka Miho J.
Published: November 2018

The passing of Title IX in 1972 has led to a rapid increase in the number of female athletes, and with this, the field of women’s sports medicine has continued to grow. As the number and type of female athletes continue to increase, our role as sports medicine surgeons is to meet the needs of this rapidly changing field by improving our knowledge of the injuries, treatments, and outcomes that are specific to this population. Our understanding of injury prevention and long-term outcomes after anterior cruciate ligament injuries is still evolving, yet this is a clear area for future study in female athletes. The role of gender in concussions and its relationship to musculoskeletal injuries continues to be explored. The unique element of pregnancy in athletes, which is gaining increasing attention, leads to a greater need for multidisciplinary care. Because of this, close collaboration with specialists who can augment our knowledge of the treatment of sports medicine conditions and maintaining awareness of the rapidly changing field of women’s sports medicine will allow us to continually improve care for female athletes.
Facilitators and Barriers to Reducing Emergency Department Admissions for Chest Pain: A Qualitative Study
Authors: Lin Michelle P. , Natsui Shaw , Sinnette Corine , Ball Alexis , Weissman Joel S. , Schuur Jeremiah D.
Published: November 2018

Background:

Chest pain of possible cardiac etiology is a leading reason for emergency department (ED) visits and hospitalizations nationwide. Evidence suggests outpatient management is safe and effective for low-risk patients; however, ED admission rates for chest pain vary widely. To identify barriers and facilitators to outpatient management after ED visits, we performed a multicenter qualitative study of key stakeholders.

Methods and Results:

We identified Massachusetts hospitals with below-average admission rates for adult ED chest pain visits from 2010 to 2011. We performed a qualitative case study of 27 stakeholders across 4 hospitals to identify barriers and facilitators to outpatient management. Clinicians cited ability to coordinate follow-up care, including stress testing and cardiology consultation, as key facilitators of ED discharge. When these services are unavailable, or inconsistently available, they present a barrier to outpatient management. Clinicians identified pressure to maintain throughput and the lack of observation units as barriers to ED discharge. At 3 of 4 hospitals without observation units, clinicians did not use clinical protocols to guide the admission decision. At the site with a dedicated ED observation unit, low ED admission rates were attributed to clinician adherence to clinical protocols.

Conclusions:

In conclusion, most participants have not adopted protocols focused on reducing variation in ED chest pain admissions. Robust systems to ensure follow-up care after ED visits may reduce admission rates by mitigating the perceived risk of discharging ED patients with chest pain. Greater use of observation protocols may promote adoption of clinical guidelines and reduce admission rates.
OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY CHANGES AFTER SUBTHRESHOLD MICROPULSE YELLOW LASER IN DIABETIC MACULAR EDEMA
Authors: Vujosevic Stela , Gatti Valentina , Muraca Andrea , Brambilla Marco , Villani Edoardo , Nucci Paolo , Rossetti Luca , De Cilla' Stefano
Published: November 2018

Purpose:

To assess changes on optical coherence tomography (OCT) angiography in diabetic macular edema (DME) treated with subthreshold micropulse yellow laser (SMPL) over a period of 6 months.

Methods:

Thirty-five eyes (35 consecutive patients) with treatment-naive DME prospectively underwent (at baseline, 3 and 6 months) best-corrected visual acuity, swept-source OCT angiography/OCT, and fundus autofluorescence. Following parameters were evaluated on OCT angiography in the superficial capillary plexus (SCP) and deep capillary plexus (DCP): the area of foveal avascular zone, number of microaneurysms (MA), area of cysts, and presence of capillary network alterations. Microaneurysm change was also evaluated in 15 fellow eyes, not needing treatment over 6 months. Vessel and perfusion densities were evaluated in the SCP, DCP, and choriocapillaris, with image J. Retina thickness, number of hyperreflective retinal spots, and external limiting membrane integrity were evaluated on OCT. All measurements were performed by two masked graders, independently.

Results:

All patients had diabetes mellitus Type 2 (mean age, 69.4 ± 10.9 years; duration of diabetes mellitus, 15.7 ± 8.7 years; and HbA1c 7.7 ± 1.2%). Mean best-corrected visual acuity at baseline was 69.7 ± 12.0 letters ETDRS, 72.7 ± 10.7 at 3 months (gain 3.1 ± 4.3, P = 0.0049) and 74.3 ± 9.5 at 6 months (gain 4.6 ± 7.2, P < 0.0001). Foveal avascular zone area decreased in the DCP at 6 months (P = 0.01). Area of cysts decreased in the SCP at 3 months and 6 months (P = 0.038; P = 0.049), and in the DCP at 6 months (P = 0.0071). Number of MA decreased at 6 months in the SCP (P = 0.0007) and at 3 months and 6 months in the DCP (P = 0.048; P < 0.0001) in treated eyes. No significant change in number of MA was found in nontreated eyes. There was no statistically significant change in any other OCT angiography/OCT parameter.

Conclusion:

Subthreshold micropulse yellow laser induces more pronounced changes in the DCP than in the SCP in DME. These changes occurred as early as 3 months after treatment. The evaluation of specific parameters in the DCP may help in determining treatment response.
Cross-Country Transportation Efficacy and Clinical Outcomes of Preloaded Large-Diameter Ultra-Thin Descemet Stripping Automated Endothelial Keratoplasty Grafts
Authors: Parekh Mohit , Ruzza Alessandro , Steger Bernhard , Willoughby Colin E. , Rehman Salwah , Ferrari Stefano , Ponzin Diego , Kaye Stephen B. , Romano Vito
Published: November 2018

Purpose:

To evaluate the clinical outcomes of preloaded large-diameter ultra-thin grafts for Descemet stripping automated endothelial keratoplasty (UT-DSAEK) after cross-country shipment.

Methods:

A laboratory study in an eye bank and a clinical cohort study in an academic tertiary care center were performed. UT-DSAEK (9.5 mm diameter) grafts (n = 7) were prepared, loaded into a commercial device (iGlide; Eurobio, Les Ulis, France), preserved for 4 days at room temperature in transport medium, and analyzed. In a retrospective study, preloaded tissues (n = 39) for clinical use were prepared, transported from Italy to the United Kingdom, and surgically delivered into the eyes of patients undergoing UT-DSAEK. Central and peripheral endothelial cell density (ECD) and viability were measured before and after loading and storage of the grafts in the laboratory study. Clinically, best-corrected visual acuity, ECD before and at final follow-up, dislocation rate, primary graft failure, and surgical time were recorded.

Results:

In the laboratory study, postcut central graft thickness was 93.3 ± 17.2 μm. ECD and cell mortality did not change significantly before and after preservation (P = 0.8). Cell loss after 4 days of preservation was 1.7% ± 1.6%. Clinically, 39 eyes of 39 patients at final follow-up showed a mean central graft thickness of 88 ± 22 μm and a best-corrected visual acuity of 0.34 ± 0.24 logMAR. Nine of 39 cases (23%) needed rebubbling, and 28% cell loss was observed at final follow-up.

Conclusions:

Large-diameter UT-DSAEK grafts can be prepared and preloaded in the eye bank using the iGlide and transported to the surgical center facilitating surgery for patients undergoing UT-DSAEK, potentially reducing tissue wastage, surgical time, and costs related to surgery.
Multidisciplinary Approach to Improve Sepsis Outcomes
Authors: MacMillan Andrew , Rudinsky David , Han Gena , Elliott John O. , Jordan Kim
Published: November 2018

Severe sepsis and septic shock cause significant morbidity and mortality with health care costs approximating $17 billion annually. The Surviving Sepsis Campaign 2012 recommended time-sensitive care bundles to improve outcomes for patients with sepsis. At our community teaching hospital, a review of sepsis management for patients admitted to a medical intensive care unit (ICU) between December 2015 and March 2016 found 70.8% compliance with timing of lactate draw, 65.3% compliance for blood cultures, and 51.4% compliance with antibiotic administration recommendations. Thus, a quality improvement initiative to improve detection and time to bundle completion for ICU-level patients was designed. Previous studies suggest that utilization of sepsis alert systems and sepsis response teams in the emergency department setting is associated with improved compliance with recommended sepsis bundles and improved hospital mortality. Therefore, a “sepsis alert” protocol was implemented that used both an electronic alert and an overhead team alert that mobilized nursing, pharmacy, phlebotomy, and a senior internal medicine resident to bedside. In addition, a template to document sepsis diagnosis and bundle adherence was created. After implementation, we noted improvement in appropriately timed serum lactate, 88.6% versus 70.8% (p = .008) with no significant improvements in blood cultures, antibiotic administration, or mortality.
Examining the Competency of Recent Graduates of an Orthotics and Prosthetics Training Program
Authors: Boe Bronwen E. , Gardner Aimee K.
Published: November 2018

Introduction

The purpose of this study was to assess perceived competence of graduates of an orthotic and prosthetic (O&P) master's program.

Method

Recent graduates and their supervisors completed a survey adapted from the American Board for Certification in Orthotics, Prosthetics & Pedorthics (ABC) Practice.

Analysis of Certified Practitioners in the Disciplines of Orthotics and Prosthetics, with each group rating graduate ability to independently perform 66 items along the categories of the following: “patient assessment,” “formulation of treatment plan,” “implementation of treatment plan,” “follow-up of treatment plan,” “practice management,” and “promotion of professional practice” on a 1-to-7 scale (1, unable to perform independently; 7, can independently perform). Supervisors also indicated the extent to which graduates met expectations of competency. Basic descriptive and independent-sample t-tests were used to analyze data.

Results

Overall competency mean was 5.78 ± 1.01 for graduates (n = 25; 74% response rate) and 5.39 ± 0.74 for supervisors (n = 16; 53% response rate). Means for each category were similar between groups. Implementation of the treatment plan had the most items with significant differences between groups. These differences emerged in tasks related to patient shape capture method and device setup. All supervisors agreed that graduate competency met expectations or was exceptional.

Conclusions

Both graduates and supervisors agree on high levels of competency across all competency areas defined by certification bodies. Opportunities exist to enhance curricula related to implementation of treatment plan.
Gastrointestinal hormones and regulation of gastric emptying
Authors: Camilleri Michael
Published: November 2018

Purpose of review

This review examines the hormonal regulation of gastric emptying, a topic of increasing relevance, given the fact that medications that are analogs of some of these hormones or act as agonists at the hormonal receptors, are used in clinical practice for optimizing metabolic control in the treatment of type 2 diabetes and in obesity.

Recent findings

The major effects on gastric emptying result from actions of incretins, particularly gastric inhibitory polypeptide, glucagon-like peptide-1, and peptide tyrosine–tyrosine, the duodenal and pancreatic hormones, motilin, glucagon, and amylin, and the gastric orexigenic hormones, ghrelin and motilin. All of these hormones delay gastric emptying, except for ghrelin and motilin which accelerate gastric emptying. These effects on gastric emptying parallel the effects of the hormones on satiation (by those retarding emptying) and increase appetite by those that accelerate emptying. Indeed, in addition to the effects of these hormones on hypothalamic appetite centers and glycemic control, there is evidence that some of their biological effects are mediated through actions on the stomach, particularly with the glucagon-like peptide-1 analogs or agonists used in treating obesity.

Effects of gastrointestinal hormones on gastric emptying are increasingly recognized as important mediators of satiation and postprandial glycemic control.
Evolution of a Schmorl’s Node and a Degenerative Osteophyte on Sequential 68Ga-DOTATATE PET/CT Scans
Authors: Hod Nir , Levin Daniel , Anconina Reut , Benkovich Elya , Ezroh Kazap Dina , Lantsberg Sophie
Published: November 2018

Schmorl's node (SN) arises from the herniation of the nucleus pulposus of the disc through the cartilaginous endplate into the body of the vertebra. Our report describes a patient with carcinoid tumor who underwent a series of 68Ga-DOTATATE PET/CT scans for follow-up, demonstrating gradually increasing focal vertebral uptake in absence of CT abnormality, suspicious for a metastasis. Both CT and MRI eventually revealed classical findings of a SN. Also observed in the same vertebra is a degenerative osteophyte showing intense 68Ga-DOTATATE uptake. This interesting case shows 2 benign spinal lesions, which potentially can simulate bone metastasis in patients with neuroendocrine tumors.
Synchronous Metastatic Breast Carcinoma and Parathyroid Adenoma on 18F-FDG PET/CT and 99mTc-Sestamibi Imaging
Authors: Singh Harkamal , Wale Daniel J. , Wong Ka Kit , Gross Milton D. , Viglianti Benjamin L.
Published: November 2018

In addition to nuclear cardiac and breast imaging, 99mTc-sestamibi scintigraphy is often used to localize parathyroid adenomas. 18F- fluorodeoxyglucose (FDG) PET is heavily utilized in oncology, although its use in identifying parathyroid adenomas is limited. We describe a case of a 57-year-old woman who underwent parathyroid scintigraphy and 18F-FDG PET/CT in the same week due to hyperparathyroidism and an enlarging breast mass, respectively. A right paratracheal mediastinal mass that otherwise would be suspicious for nodal metastases by CT alone was correctly identified to be an ectopic parathyroid adenoma using a combination of the nuclear medicine studies performed.
Patterns of Cortical Visual Field Defects From Embolic Stroke Explained by the Anastomotic Organization of Vascular Microlobules
Authors: Horton Jonathan C. , Adams Daniel L.
Published: November 2018

The cerebral cortex is supplied by vascular microlobules, each comprised of a half dozen penetrating arterioles that surround a central draining venule. The surface arterioles that feed the penetrating arterioles are interconnected via an extensively anastomotic plexus. Embolic occlusion of a small surface arteriole rarely produces a local infarct, because collateral blood flow is available through the vascular reticulum. Collateral flow also protects against infarct after occlusion of a single penetrating arteriole. Cortical infarction requires blockage of a major arterial trunk, with arrest of blood flow to a relatively large vascular territory. For striate cortex, the major vessels compromised by emboli are the inferior calcarine and superior calcarine arteries, as well as the distal branches of the middle cerebral artery. Their vascular territories have a fairly consistent relationship with the retinotopic map. Consequently, occlusion by emboli results in stereotypical visual field defects. The organization of the arterial supply to the occipital lobe provides an anatomical explanation for a phenomenon that has long puzzled neuro-ophthalmologists, namely, that of the myriad potential patterns of cortical visual field loss, only a few are encountered commonly from embolic cortical stroke.
Diagnostic outcomes of exome gene panel sequencing in patients with unusual syndromic cleft lip/palate phenotypes
Authors: Jabalameli Reza
Published: November 2018

Orofacial clefting (OFC) is a common craniofacial birth defect that has a prevalence of 1.2 in 1,000 live births. Syndromic OFC in which patients present with additional developmental deficits are identified to have a strong genetic component. We applied exome gene panel sequencing in a cohort of 14 Colombian patients identified at Operation Smile in Bogota, Colombia, with syndromic orofacial clefting phenotypes and additional features initially suggesting Aarskog-Scott syndrome (AAS). Gene panel sequencing failed to identify any causal variants in the FGD1 gene which underlies this condition, but variants in a number of genes suggest alternative clinical diagnoses across five patients (~36%). The novel variants identified here maps to developmentally important genes including SRCAP, OFD1, NIPBL, GRIN2A and KMT2D6. Our result demonstrates the extensive heterogeneity underlying OFC and emphasises the need for systematic phenotyping of patients with rare conditions. Gene panel sequencing has the potential to cost-effectively resolve ambiguous clinical diagnoses, but rigorous attention should be paid to gene coverage as our results suggest highly variable read depths across individual gene exons and this may reduce the quality of variant calls at specific locations.
Predicting the fundamental thermal niche of crop pests and diseases in a changing world: a case study on citrus greening
Authors: Taylor Rachel A. , Ryan Sadie J. , Lippi Catherine A. , Hall David G. , Narouei-Khandan Hossein A. , Rohr Jason R. , Johnson Leah R.
Published: November 2018

Predicting where crop pests and diseases can occur, both now and in the future under different climate change scenarios, is a major challenge for crop management. One solution is to estimate the fundamental thermal niche of the pest/disease to indicate where establishment is possible. Here we develop methods for estimating and displaying the fundamental thermal niche of pests and pathogens and apply these methods to Huanglongbing (HLB), a vector-borne disease that is currently threatening the citrus industry worldwide.

We derive a suitability metric based on a mathematical model of HLB transmission between tree hosts and its vectorDiaphorina citri, and incorporate the effect of temperature on vector traits using data from laboratory experiments performed at different temperatures. We validate the model using data on the historical range of HLB.

Our model predicts that transmission of HLB is possible between 16°C and 33°C with peak transmission at ~25°C. The greatest uncertainty in our suitability metric is associated with the mortality of the vectors at peak transmission, and fecundity at the edges of the thermal range, indicating that these parameters need further experimental work.

We produce global thermal niche maps by plotting how many months each location is suitable for establishment of the pest/disease. This analysis reveals that the highest suitability for HLB occurs near the equator in large citrus-producing regions, such as Brazil and South-East Asia. Within the northern hemisphere, the Iberian peninsula and California are HLB suitable for up to 7 months of the year and are free of HLB currently.

Policy implications. The thermal niche map indicates the places at greatest risk of HLB establishment should the disease enter these regions. This indicates where surveillance should be focused to prevent establishment. Our mechanistic method can be used to predict new areas for HLB transmission under different climate change scenarios and is easily adapted to other vector-borne diseases.
Memory in trait macroevolution
Authors: Goldberg Emma E. , Foo Jasmine
Published: November 2018

The history of a trait within a lineage may influence its future evolutionary trajectory, but macroevolutionary theory of this process is not well developed. For example, consider the simple binary trait of living in cave versus surface habitat. The longer a species has been cave-dwelling, the more may accumulated loss of vision, pigmentation, and defense restrict future adaptation if the species encounters the surface environment. However, the Markov model of discrete trait evolution that is widely adopted in phylogenetics does not allow the rate of cave-to-surface transition to decrease with longer duration as a cave-dweller. Here, we describe three models of evolution that remove this ‘memory-less’ constraint, using a renewal process to generalize beyond the typical Poisson process of discrete trait macroevolution. We then show how the two-state renewal process can be used for inference, and we investigate the potential of phylogenetic comparative data to reveal different influences of trait duration, or ‘memory’ in trait evolution. We hope that such approaches may open new avenues for modeling trait evolution and for broad comparative tests of hypotheses that some traits become entrenched.
Inference of Differential Gene Regulatory Networks Based on Gene Expression and Genetic Perturbation Data
Authors: Zhou Xin , Cai Xiaodong
Published: November 2018

Motivation

Gene regulatory networks (GRNs) of the same organism can be different under different conditions, although the overall network structure may be similar. Understanding the difference in GRNs under different conditions is important to understand condition-specific gene regulation. When gene expression and other relevant data under two different conditions are available, they can be used by an existing network inference algorithm to estimate two GRNs separately, and then to identify the difference between the two GRNs. However, such an approach does not exploit the similarity in two GRNs, and may sacrifice inference accuracy.

Results

In this paper, we model GRNs with the structural equation model (SEM) that can integrate gene expression and genetic perturbation data, and develop an algorithm named fused sparse SEM (FSSEM), to jointly infer GRNs under two conditions, and then to identify difference of the two GRNs. Computer simulations demonstrate that the FSSEM algorithm outperforms the approach that estimates two GRNs separately. Analysis of a gene expression and SNP dataset of lung cancer and normal lung tissues with FSSEM inferred a GRN largely agree with the known lung GRN reported in the literature, and it identified a differential GRN, whose genes with largest degrees were reported to be implicated in lung cancer. The FSSEM algorithm provides a valuable tool for joint inference of two GRNs and identification of the differential GRN under two conditions.

Availability

The software package for the FSSEM algorithm is available at https://github.com/Ivis4ml/FSSEM.git

Contact

x.cai@miami.edu
An Analysis of Characterized Plant Sesquiterpene Synthases
Authors: Durairaj Janani , Girolamo Alice Di , Bouwmeester Harro J , de Ridder Dick , Beekwilder Jules , van Dijk Aalt DJ
Published: November 2018

Plants exhibit a vast array of sesquiterpenes, C15 hydrocarbons which often function as herbivore-repellents or pollinator-attractants. These in turn are produced by a diverse range of sesquiterpene synthases. A comprehensive analysis of these enzymes in terms of product specificity has been hampered by the lack of a centralized resource of sufficient functionally annotated sequence data. To address this, we have gathered 262 plant sesquiterpene synthase sequences with experimentally characterized products. The annotated enzyme sequences allowed for an analysis of terpene synthase motifs, leading to the extension of one motif and recognition of a variant of another. In addition, putative terpene synthase sequences were obtained from various resources and compared with the annotated sesquiterpene synthases. This analysis indicated regions of terpene synthase sequence space which so far are unexplored experimentally. Finally, we present a case describing mutational studies on residues altering product specificity, for which we analyzed conservation in our database. This demonstrates an application of our database in choosing likely-functional residues for mutagenesis studies aimed at understanding or changing sesquiterpene synthase product specificity.
A Modified Hodgkin-Huxley model to Show the Effect of Motor Cortex Stimulation on the Trigeminal Neuralgia Network
Authors: Khodashenas Mohammadreza , Baghdadi Golnaz , Towhidkhah Farzad
Published: November 2018

Background

Trigeminal neuralgia (TN) is a severe neuropathic pain, which has an electric shock like characteristic. There are some common treatments for this pain such as medicine, microvascular decompression or radio frequency. In this regard, transcranial direct current stimulation (tDCS) is another therapeutic method to reduce the pain, which has been recently attracting the therapists’ attention. The positive effect of tDCS on TN was shown in many previous studies. However, the mechanism of tDCS effect has remained unclear

Objective

This study aims to model the neuronal behavior of the main known regions of the brain participating in TN pathways to study the effect of transcranial direct current stimulation

Method

The proposed model consists of several blocks (block diagram): 1) trigeminal nerve, 2) trigeminal ganglion, 3) PAG (Periaqueductal gray in the brainstem), 4) thalamus, 5) motor cortex (M1) and 6) somatosensory cortex (S1). Each of these components represented by a modified Hodgkin-Huxley (HH) model (a mathematical model). The modification of the HH model was done based on some neurological facts of pain sodium channels. The input of the model is any stimuli to ‘trigeminal nerve,’ which cause the pain, and the output is the activity of the somatosensory cortex. An external current, which is considered as electrical current, was applied to the motor cortex block of the model

Result

The results showed that by decreasing the conductivity of the slow sodium channels (pain channels) and applying tDCS over the M1, the activity of the somatosensory cortex would be reduced. This reduction can cause pain relief

Conclusion

The proposed model provided some possible suggestions about the relationship between the effects of tDCS and associated components in TN, and also the relationship between the pain measurement index, somatosensory cortex activity, and the strength of tDCS.
Single-cell RNA sequencing reveals a dynamic stromal niche within the evolving tumour microenvironment
Authors: Davidson Sarah , Efremova Mirjana , Riedel Angela , Mahata Bidesh , Pramanik Jhuma , Huuhtanen Jani , Kar Gozde , Vento-Tormo Roser , Hagai Tzachi , Chen Xi , Haniffa Muzlifah A. , Shields Jacqueline D. , Teichmann Sarah A.
Published: November 2018

Non-cancerous stromal cells represent a highly diverse compartment of the tumour, yet their role across tumour evolution remains unclear. We employed single-cell RNA sequencing to determine stromal adaptations in murine melanoma at different points of tumour development. Naive lymphocytes recruited from lymph nodes underwent activation and clonal expansion within the tumour, prior to PD1 and Lag3 expression, while tumour-associated myeloid cells promoted the formation of a suppressive niche through cytokine secretion and inhibitory T cell interactions. We identified three temporally distinct cancer-associated fibroblast (CAF) populations displaying unique signatures, and verified these in human datasets. In early tumours, immune CXCL12/CSF1 and complement-expressing CAFs supported recruitment of macrophages, whereas contractile CAFs became more prevalent in later tumours. This study highlights the complex interplay and increasing diversity among cells that co-evolve with the tumour, indicating that from early stages of development, stromal cells acquire the capacity to modulate the immune landscape towards suppression.
Behavioral evolution drives hindbrain diversification among Lake Malawi cichlid fish
Authors: York Ryan A. , Byrne Allie , Abdhilleh Kawther , Patil Chinar , Streelman J. Todd , Finger Thomas E. , Fernald Russell D.
Published: November 2018

The evolutionary diversification of animal behavior is often associated with changes in the structure and function of nervous systems. Such evolutionary changes arise either through alterations of individual neural components (“mosaically”) or through scaling of the whole brain (“conceitedly”). Here we show that the evolution of a specific courtship behavior in Malawi cichlid fish, the construction of mating nests known as bowers, is associated with rapid, extensive, and specific diversification of orosensory, gustatory centers in the hindbrain. We find that hindbrain volume varies significantly between species that build pit (depression) compared to castle (mound) type bowers and that hindbrain features evolve rapidly and independently of phylogeny among castle-building species. Using immediate early gene expression, we confirmed a functional role for hindbrain structures during bower building. Comparisons of bower building species in neighboring Lake Tanganyika show patterns of neural diversification parallel to those in Lake Malawi. Our results suggest that mosaic brain evolution via alterations to individual brain structures is more extensive and predictable than previously appreciated.
Variability in the Analgesic Response to Ibuprofen Following Third-Molar Extraction is Associated with Differences in Activation of the Cyclooxygenase Pathway
Authors: Theken Katherine N. , Hersh Elliot V. , Lahens Nicholas F. , Lee Hyo Min , Granquist Eric J. , Giannakopoulos Helen , Levin Lawrence M. , Secreto-Dankanich Stacey A. , Grant Gregory R. , Detre John A. , FitzGerald Garret A. , Grosser Tilo , Farrar John T.
Published: November 2018

The analgesic efficacy of non-steroidal anti-inflammatory drugs (NSAIDs) has long been recognized to be limited by substantial interindividual variability in pain relief, but the underlying mechanisms are not well understood. We performed pain phenotyping, functional neuroimaging, pharmacokinetic/pharmacodynamic assessments, inflammation biomarkers, and gene expression profiling in healthy subjects who underwent surgical extraction of bony impacted third molars, in order to characterize factors associated with heterogeneity in response to ibuprofen.

Subjects were treated with rapid-acting ibuprofen (400 mg; N=19) or placebo (N=10) in a randomized, double-blind design. Compared to placebo, ibuprofen-treated subjects exhibited greater reduction in pain scores, alterations in regional cerebral blood flow in brain regions associated with pain processing, and inhibition of ex vivo cyclooxygenase activity and urinary prostaglandin metabolite excretion as indices of biochemical drug action (p<0.05). As expected, ibuprofen-treated subjects could be stratified into partial responders (N=9, required rescue medication within the dosing interval) and complete responders (N=10, no rescue medication). This was also reflected by differences in pain scores (p<0.01) as early as 30 minutes following drug administration (p<0.05). Variability in analgesic efficacy was not associated with demographic or clinical characteristics, ibuprofen pharmacokinetics, metabolizing enzyme genotype, or the degree of cyclooxygenase inhibition by ibuprofen. However, complete responders had higher concentrations of inflammatory biomarkers in urine and serum, than partial responders. Specifically, a stable urinary prostaglandin E2metabolite, serum TNFα and IL-8 were higher in patients who did not require rescue medication compared those who did (p < 0.05). RNAseq gene expression analysis in PBMCs collected after surgery and ibuprofen administration showed enrichment of inflammation related pathways among genes differentially expressed (q < 0.2) between complete and partial responders

These findings suggest that patients who receive substantial pain relief from ibuprofen have a more pronounced activation of the prostanoid biosynthetic pathway and regulation of the inflammatory pain phenotype differs from those patients who are insufficiently treated with ibuprofen alone and may require an opioid or other therapeutic intervention.
Germline deletion reveals a non-essential role of the atypical MAPK6/ERK3
Authors: Ronkina N. , Schuster-Gossler K. , Hansmann F. , Kunze-Schumacher H. , Sandrock I. , Yakovleva T. , Lafera J. , Baumgärtner W. , Krueger A. , Prinz I. , Gossler A. , Kotlyarov A. , Gaestel M.
Published: November 2018

MAPK6/ERK3 is an atypical member of the MAPKs. An essential role has been suggested by the perinatal lethal phenotype of ERK3 knockout mice carrying a lacZ insertion in exon 2 due to pulmonary disfunction and by defects in function, activation and positive selection of T cells. To study the role of ERK3in vivo, we generated mice carrying a conditionalErk3allele with exon3 flanked by LoxP sites. Loss of ERK3 protein was validated after deletion of Erk3 in the female germ line using zona pellucida 3 (Zp3)-creand a clear reduction of the protein kinase MK5 is detected, providing first evidence for the existence of the ERK3/MK5 signaling complexin vivo.In contrast to the previously reported Erk3 knockout phenotype, these mice are viable and fertile, do not display pulmonary hypoplasia, acute respiratory failure, abnormal T cell development, reduction of thymocyte numbers or altered T cells selection. Hence, ERK3 is dispensable for pulmonary and T-cell functions. The perinatal lethality, lung and T-cell defects of the previous ERK3 knockout mice are likely due to ERK3-unrelated effects of the inserted lacZ-neomycin-resistance-cassette. The knockout mouse of the closely related atypical MAPK ERK4/MAPK4 is also normal suggesting redundant functions of both protein kinases.
Embracing the dropouts in single-cell RNA-seq data
Authors: Qiu Peng
Published: November 2018

One primary reason that makes the analysis of single-cell RNA-seq data challenging is dropouts, where the data only captures a small fraction of the transcriptome of each cell. Many computational algorithms developed for single-cell RNA-seq adopted gene selection and dimension reduction strategies to address the dropouts. Here, an opposite view is explored. Instead of treating dropouts as a problem to be fixed, we embrace it as a useful signal for defining cell types. We present an iterative co-occurrence clustering algorithm that works with binarized single-cell RNA-seq count data. Surprisingly, although all the quantitative information is removed after the data is binarized, co-occurrence clustering of the binarized data is able to effectively identify cell populations, as well as cell-type specific pathways. We demonstrate that the binary dropout patterns of the data provides not only overlapping but also complementary information compared to the quantitative gene expression counts in single-cell RNA-seq data.
Single-nuclei RNA-seq on human retinal tissue provides improved transcriptome profiling
Authors: Liang Qingnan , Dharmat Rachayata , Owen Leah , Shakoor Akbar , Li Yumei , Kim Sangbae , Vitale Albert , Kim Ivana , Morgan Denise , Wu Nathaniel , DeAngelis Margaret , Chen Rui
Published: November 2018

Gene expression profiling is an effective way to provide insights into cell function. However, for heterogeneous tissues, bulk RNA-Seq can only provide the average gene expression profile for all cells from the tissue, making the interpretation of the sequencing result challenging. Single-cell RNA-seq, on the other hand, generates transcriptomic profiles of individual cell and cell types, making it a powerful method to decode the heterogeneity in complex tissues.

The retina is a heterogeneous tissue composed of multiple cell types with distinct functions. Here we report the first single-nuclei RNA-seq transcriptomic study on human neural retinal tissue to identify transcriptome profile for individual cell types. Six retina samples from three healthy donors were profiled and RNA-seq data with high quality was obtained for 4730 single nuclei. All seven major cell types were observed from the dataset and signature genes for each cell type were identified by differential gene express analysis. The gene expression of the macular and peripheral retina was compared at the cell type level, showing significant improvement from previous bulk RNA-seq studies. Furthermore, our dataset showed improved power in prioritizing genes associated with human retinal diseases compared to both mouse single-cell RNA-seq and human bulk RNA-seq results. In conclusion, we demonstrated that feasibility of obtaining single cell transcriptome from human frozen tissues to provide additional insights that is missed by either the human bulk RNA-seq or the animal models.