bluuebunny/crossref_metadata_2025 huggingface dataset:
Computerized Image Analysis to Differentiate Benign and Malignant Breast Tumors on Magnetic Resonance Diffusion Weighted Image: A Preliminary Study
Authors: Mao Ning , Wang Qinglin , Liu Meijie , Dong Jianjun , Xiao Chuanguang , Sun Ning , Zhang Xuexi , Xie Haizhu , Yin Ping , Hong Nan
Published: October 2018

Purpose

This work aims to determine the feasibility of using a computer-aided diagnosis system to differentiate benign and malignant breast tumors on magnetic resonance diffusion-weighted image (DWI).

Materials and Methods

Institutional review board approval was obtained. This retrospective study included 76 patients who underwent breast magnetic resonance imaging before neoadjuvant chemotherapy from March 10, 2017, to October 12, 2017, with a total of 80 breast tumors including 40 cases of breast cancers and 40 cases of benign breast tumors. The textural features of DWI images were analyzed. The area under the receiver operating characteristic curve was calculated to evaluate the diagnostic efficiency of texture parameters. Multiple linear regression analysis was used to determine the efficiency of texture parameters for distinguishing the 2 types of breast tumors.

Results

Computer vision algorithms were applied to extract 67 imaging features from lesions indicated by a breast radiologist on DWI images. A total of 19 texture feature parameters, such as variance, standard deviation, intensity, and entropy, out of 67 texture parameters were statistically significant in the 2 sets of data (P < 0.05). By comparing the receiver operating characteristic curves, we found that the mean and relative deviations exhibited high diagnostic values in differentiating between benign and malignant tumors. The accuracy of Fisher discriminant analysis for the 2 types of breast tumors was 92.5%.

Conclusions

Breast lesions exhibit certain characteristic features in DWI images that can be captured and quantified with computer-aided diagnosis, which enables good discrimination of benign and malignant breast tumors.
Virtual Monoenergetic Images for Diagnostic Assessment of Hypodense Lesions Within the Liver: Semiautomatic Estimation of Window Settings Using Linear Models
Authors: Große Hokamp Nils , Obmann Verena C. , Kessner Rivka , Gilkeson Robert C. , Gupta Amit , Persigehl Thorsten , Haneder Stefan , Ramaiya Nikhil
Published: October 2018

Objective

The aim of the study was to establish the reference window settings for display of virtual monoenergetic images (VMIs) from spectral detector computed tomography when assessing hypodense liver lesions.

Methods

In patients with cysts (n = 24) or metastases (n = 26), objective (HU, signal-to-noise ratio [SNR]) and subjective (overall image quality, lesion conspicuity and noise) were assessed. Furthermore, 2 readers determined optimal window center/width (C/W) for conventional images (CIs) and VMIs of 40 to 120 keV. Center/width were modeled against HUliv with and without respect to the keV level (models A and B).

Results

Attenuation and SNR were significantly higher in low-keV VMIs and improved overall image quality and lesion conspicuity (P ≤ 0.05). Model B provided valid estimations of C/W, whereas model A was slightly less accurate.

Conclusions

The increase in attenuation and SNR on low-keV VMIs requires adjustment of C/W, and they can be estimated in dependency of HUliv using linear models. Reference values for standard display of VMIs of 40 to 120 keV are reported.
Iron-Containing Abdominal Pathologies: Exploiting Magnetic Susceptibility Artifact on Dual-Echo Gradient-Echo Magnetic Resonance Imaging
Authors: Thomas Aaron J. , Morani Ajaykumar C. , Liu Peter S. , Weadock William J. , Hussain Hero K. , Elsayes Khaled M.
Published: October 2018

A multitude of pathologic entities involve abnormal iron deposition in the abdomen. These lesions demonstrate decreased signal on longer magnetic resonance sequences with longer echo time due to T2* effect. Dual-echo gradient-echo sequences demonstrate increased susceptibility artifact with longer echo sequences. In this article, the spectrum of iron-containing abdominal pathologies is illustrated, with their characteristic distributions. Included is a brief discussion of the physics of magnetic resonance imaging of iron-containing lesions.
How to Incorporate Dual-Energy Computed Tomography Into Your Neuroradiology Practice: Questions and Answers
Authors: Sachs Jeffrey R. , West Thomas G. , Lack Christopher M. , Perry Brad , Zapadka Michael E.
Published: October 2018

Dual-energy computed tomography (DECT) has many current and evolving applications in neuroradiology including material decomposition, improving conspicuity of iodinated contrast enhancement, and artifact reduction. However, there are multiple challenges in incorporating DECT into practice including hardware selection, postprocessing software requirements, technologist and physician training, and numerous workflow issues. This article reviews in a question-and-answer format common issues that arise when incorporating DECT into a busy neuroradiology practice.
Quality and Safety in Health Care, Part XLVIII
Authors: Harolds Jay A.
Published: October 2018

Discussion groups are one of the methods advocated to help prevent burnout and help in recovery from burnout. Balint groups, Schwartz Rounds, narrative medicine and reflection groups, discussion workshops to gain certain skills, and general support groups are examples of these groups. Participation in these groups produces other positive ramifications for health care providers and health care systems including promoting teamwork, collegiality, support networking, decreasing stress, and finding meaning in work.
Increased 131I Accumulation in the Gallbladder and High-grade Serous Ovarian Adenocarcinoma
Authors: Yao Xiaobo , Wang Jiaqiong , Xia Menghua , Xia Junyong , Cheng Yizhuang
Published: October 2018

It is unusual to observe 131I accumulation in the gallbladder and high-grade serous ovarian adenocarcinoma during posttherapeutic 131I scan. We report the case of a 55-year-old woman with papillary thyroid cancer, who received total thyroidectomy and then 3 courses of 131I therapy. The posttherapeutic whole-body scan after the third dose of 131I therapy revealed abnormal 131I uptake in the right upper abdomen, overlapping the liver, and the pelvis. Further SPECT/CT imaging found that they were from an enlarged gallbladder and a large pelvic complex solid and cystic mass, which was pathologically confirmed as bilateral high-grade serous ovarian adenocarcinoma.
Simultaneous 18F-FDG PET/MRI Assists Diagnosis of a Rare Disease, MELAS
Authors: Liu Fang , Ruan Weiwei , Wang Yichun , Lan Xiaoli
Published: October 2018

MELAS (mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes) is a rare congenital mitochondrial DNA mutation disease. Here, we report a 4-year-old girl, who presented with short stature, mental retardation, and recurrent seizures, underwent simultaneous 18F-FDG PET/MRI examination. An interesting contradiction images were found on bilateral frontal, left temporal, occipital, and parietal lobes, which were with high blood flow shown on 3D-ASL perfusion images, but low uptake of 18F-FDG on PET images. The contradiction of high blood flow and low glucose metabolism gave us a clue to make the diagnosis of MELAS. The final diagnosis was MELAS confirmed by genetic testing.
18F-FDG PET/CT of Squamous Cell Carcinoma in a Thyroglossal Duct Cyst
Authors: Moreno Albert J. , Wang Bin
Published: October 2018

Thyroglossal duct cyst is a common congenital cyst in the neck. The incidence of primary carcinoma of the thyroglossal duct is less than 1% in all age groups. We present the case of a 63-year-old man with rapid expansion of a known thyroglossal duct cyst with mixed solid/cystic components. 18F-FDG PET/CT showed a large anterior neck mass with a non–FDG-avid cystic component and a hypermetabolic heterogeneous mass on the right side confirmed by histopathology to be squamous cell carcinoma. Although rare, 18F-FDG PET/CT can assist with evaluating the extent of malignant involvement in thyroglossal duct cyst squamous cell carcinoma.
Distinct Imaging Characteristics of Different Metastases From Primary Prostate Adenocarcinoma and Rectal Carcinoid Tumor on 18F-Fluciclovine and 68Ga-DOTATATE PET/CT
Authors: Bosserman Andrew John , Dai Dong , Lu Yang
Published: October 2018

A 71-year-old man with history of prostate cancer is evaluated for rising prostate-specific antigen. The patient also has a history of rectal well-differentiated neuroendocrine tumor. On 18F-fluciclovine PET/CT, 2 retroperitoneal lymph nodes exhibited intense fluciclovine avidity, whereas one enlarged perirectal lymph node only showed background uptake. On further 68Ga-DOTATATE PET/CT, the perirectal lymph node revealed intense DOTATATE avidity, whereas the 2 retroperitoneal lymph nodes only with similar to background DOTATATE avidity. Biopsy of the perirectal lymph node confirmed metastasis from neuroendocrine tumor. The distinct imaging characteristics of metastases from different primary malignancies correlated with their underlying different pathology.
Large Paraesophageal Schwannoma With Intense Prostate-Specific Membrane Antigen Expression on 68Ga-PSMA-PET/CT Mimicking Lymph Node Metastasis in a Patient With Prostate Cancer
Authors: Ries Martin , Khreish Fadi , Veith Christian , von den Hoff Joachim , Ezziddin Samer
Published: October 2018

Prostate-specific membrane antigen (PSMA)-PET/CT as an emerging modality in molecular imaging will lead to earlier detection and localization of relapse in prostate cancer but will undoubtedly also lead to false-positive findings, as it becomes clear that this new tracer is not as specific as its name would suggest. In this context, we present a case of a large PSMA-expressing schwannoma, a rare nerve sheath tumor mimicking paraesophageal lymph node metastasis in a patient with a history of prostate cancer and biochemical recurrence.
The Use of the Incremental Shuttle Walk Test to Identify Instrumental Activity Daily Living Disability and to Predict Peak Oxygen Consumption in Older Adults
Authors: de Carvalho Bastone Alessandra , de Souza Vasconcelos Karina Simone , Lacerda Ana Cristina Rodrigues , Neves Camila Danielle Cunha , Mendonça Vanessa Amaral , Dias João Marcos Domingues , Dias Rosângela Corrêa
Published: October 2018

Aerobic capacity is essential for physical function. The aims of this study were to identify the peak oxygen consumption (

JOURNAL/tgere/04.03/00013614-201810000-00002/2FSM1/v/2023-10-01T043932Z/r/image-gif

o
2 peak) and the incremental shuttle walk test (ISWT) distance associated with disability and to develop an equation to predict

JOURNAL/tgere/04.03/00013614-201810000-00002/2FSM1/v/2023-10-01T043932Z/r/image-gif

o
2 peak, based on the ISWT distance. Fifteen disabled and 13 nondisabled older adults performed the ISWT using a portable telemetric gas analyzer. The

JOURNAL/tgere/04.03/00013614-201810000-00002/2FSM1/v/2023-10-01T043932Z/r/image-gif

o
2 peak and the distance associated with disability were 15.8 mL/kg/min or less and 230 m or less, respectively. The coefficient of determination from the predictive model was 0.54. The ISWT might be considered to assess aerobic capacity in older adults.
Effects of Acute Transcranial Direct Current Stimulation on Gait Kinematics of Individuals With Parkinson Disease
Authors: da Silva Débora Cristina Lima , Lemos Thiago , de Sá Ferreira Arthur , Horsczaruk Carlos Henrique Ramos , Pedron Carla Andressa , de Carvalho Rodrigues Erika , de Oliveira Laura Alice Santos
Published: October 2018

Background:

One of the most disabling problems in Parkinson disease (PD) is gait impairment. Noninvasive brain stimulation techniques, such as transcranial direct current stimulation (tDCS), have been introduced as a therapeutic alternative for coping with PD motor problems. However, the effects of tDCS on gait performance in PD have not yet been fully established. Therefore, the main objective of this study was to evaluate whether a single session of tDCS modifies gait kinematics in individuals with PD.

Methods:

Twenty-one individuals with PD were included in this randomized, double-blinded, sham-controlled design study. They were randomly allocated in one real (N = 8) or sham (N = 9) tDCS group. Real tDCS comprises a 2-mA anodic current applied over 15 minutes in the supplementary motor area and medial areas of the primary motor cortices through a bipolar electrode montage. Gait kinematics and the Unified Parkinson's Disease Rating Scale Part III (UPDRS-III) were assessed before and immediately after a single stimulation session. Pre- minus poststimulation (Δ) values were computed and compared through a Mann-Whitney test. Data are shown as the median (lower, upper quartile).

Results:

There was a significant group difference with a large effect size for Δ values of gait cadence (P = .014, d = 0.87), indicating its reduction after anodic stimulation in the real (−0.28 [−1.16, 0.01] steps/s) compared with sham tDCS group (0.17 [0.00, 0.40] steps/s). No other significant effect was found.

Conclusion:

The findings of this study suggest that anodic tDCS administered in a single session improves gait cadence in PD individuals.
Teacher Well-Being Attributes Are Positively Associated With Teacher Perceptions of Fuel for Fun Tasting Lessons
Authors: Prescott Melissa Pflugh , Lohse Barbara , Balgopal Meena M. , Smith Stephanie , Addington Renae , Cunningham-Sabo Leslie
Published: October 2018

This cross-sectional study examined the relationships of fourth-grade teachers' (n = 20) body mass index, cooking attitudes and behaviors, and the Satter eating competence inventory (ecSI 2.0) with their attitudes toward Fuel for Fun classroom tasting lessons. Teachers who liked to cook rated student engagement with the lessons and student application of academic skills higher than teachers who do not like cooking (P < .02, P < .01, respectively). Teacher body mass index was inversely associated with their ratings of student engagement (P < .03). Findings support inclusion of teacher nutrition-related attitudes and behaviors in the evaluations of healthful eating interventions of school-aged children.
Developing a Food Exchange List for Traditional Foods Commonly Consumed in Saudi Arabia
Authors: AlFaris Nora Abdullah
Published: October 2018

Food exchange lists are a practical meal-planning tool. This project was conducted to develop a food exchange list for traditional Saudi foods. The most commonly consumed 25 traditional Saudi foods were selected. The homemade foods (n = 15) were prepared and the out-of-home foods (n = 10) were purchased. Food samples were analyzed for their macronutrient content. The food exchange list of 25 traditional Saudi foods has been developed and is ready to be used by dietitians who work with Saudis. The contribution of a Saudi food exchange list as an educational tool raises awareness to prevention strategies needed to control a national diabetes crisis.
Energy velocity and reactive fields
Authors: Schantz Hans G.
Published: October 2018

Conventional definitions of ‘near fields’ set bounds that describe where near fields may be found. These definitions tell us nothing about what near fields are, why they exist or how they work. In 1893, Heaviside derived the electromagnetic energy velocity for plane waves. Subsequent work demonstrated that although energy moves in synchronicity with radiated electromagnetic fields at the speed of light, in reactive fields the energy velocity slows down, converging to zero in the case of static fields. Combining Heaviside's energy velocity relation with the field Lagrangian yields a simple parametrization for the reactivity of electromagnetic fields that provides profound insights to the behaviour of electromagnetic systems. Fields guide energy. As waves interfere, they guide energy along paths that may be substantially different from the trajectories of the waves themselves. The results of this paper not only resolve the long-standing paradox of runaway acceleration from radiation reaction, but also make clear that pilot wave theory is the natural and logical consequence of the need for quantum mechanics correspond to the macroscopic results of the classical electromagnetic theory.

This article is part of the theme issue ‘Celebrating 125 years of Oliver Heaviside's ‘Electromagnetic Theory’’.
From theory to engineering practice: shared telecommunications knowledge between Oliver Heaviside and his brother and GPO engineer Arthur West Heaviside
Authors: Bruton Elizabeth
Published: October 2018

In May 1900, renowned General Post Office (GPO) engineer Arthur West Heaviside gave the Inaugural Address of the Institution of Electrical Engineers Newcastle local section. With a career spanning the pre-Telegraph Act private telegraph networks as well as the subsequent GPO management and licensing of British inland telecommunications, Arthur Heaviside outlined his innovative and experimental work with all three forms of telecommunication in his various GPO engineering roles based in Newcastle. Omitted from the address was the contribution made by Arthur's younger brother, Oliver Heaviside. Throughout Arthur's career at the GPO, the two brothers exchanged frequent correspondence—some of which has survived in the IET Archives—and Arthur regularly consulted his brother about his experimental work and published papers, incorporating his brother's ideas, suggestions and corrections. The two brothers informally collaborated and published separately upon two key areas of experimentation: duplex telegraphy and the ‘bridge system’ of telephony. The separate publication of the brothers' work in telecommunications was notable: senior and influential GPO electrical engineer William Preece strongly resisted the theoretical work of Oliver Heaviside and other so-called Maxwellians. It was not until the ‘Kennelly–Heaviside layer’, independently proposed by Oliver Heaviside and American electrical engineer Arthur Kennelly in 1902, was experimentally demonstrated in the 1920s that the GPO began to formally engage with the work of Oliver Heaviside. This paper will explore the difficult and complex relationship between Preece and the two Heaviside brothers and how these personal relationships reflect the wider reception of Maxwellian ideas and theorists in British electrical engineering as well as the engineering practice of the GPO, a state institution that could be both innovative and resistant to change in equal measure.

This article is part of the theme issue ‘Celebrating 125 years of Oliver Heaviside's ‘Electromagnetic Theory’’.
On Heaviside's contributions to transmission line theory: waves, diffusion and energy flux
Authors: Donaghy-Spargo Christopher
Published: October 2018

This paper surveys some selected contributions of Oliver Heaviside FRS (1850–1925) to classical electromagnetic theory and electrical engineering science. In particular, the paper focuses on his contributions to the development of electrical transmission line theory and his deep insights into the ‘physical’ nature of the phenomena relating to nineteenth century telegraphic problems. Following a brief historical introduction to the life of Heaviside to put his achievements in context, we explore his contributions to the reformulation of Maxwell's equations and the understanding of electromagnetic wave propagation along the external region of transmission lines. This leads naturally to his researches regarding the electromagnetic diffusion process inside the line conductors and his subsequent realization that the circuital parameters, usually assumed constant, are not always so. Finally, taking both these internal and external viewpoints of the conductors, his important work regarding the flow of energy described by his ‘energy current’ concept is presented.

This article is part of the theme issue ‘Celebrating 125 years of Oliver Heaviside's ‘Electromagnetic Theory’’.
Oliver Heaviside and the Heaviside layer
Authors: Griffiths Hugh
Published: October 2018

In an entry in the
Encyclopaedia Britannica
in 1902, Oliver Heaviside had suggested the existence of a reflecting layer in the upper atmosphere to account for long range beyond line-of-sight radio propagation of the type demonstrated by Guglielmo Marconi in 1901, in the first transatlantic radio transmission. In about 1910, William Eccles proposed the name ‘Heaviside Layer’ for this phenomenon, and the name has subsequently been adopted and used quite widely. This paper describes the basis of Marconi's experiments and various interpretations of the results in the context of Heaviside's wider work. It also describes some later experiments to measure the height of the ionosphere.

This article is part of the theme issue ‘Celebrating 125 years of Oliver Heaviside's ‘Electromagnetic Theory’’.
A catalogue of hidden momenta
Authors: Griffiths David J.
Published: October 2018

Electromagnetic fields carry momentum:

. But if the centre of energy of a (localized) system is at rest, its
total
momentum must be zero. The compensating term has come to be called ‘hidden’ momentum:
P
h
 =  − 
P
em
. It is (typically) ordinary
mechanical
momentum, relativistic in nature, and is ‘hidden’ only in the sense that it is not associated with motion of the system as a whole—only with that of its constituent parts. This article develops a catalogue of field momenta and hidden momenta for ideal electric and magnetic dipoles—both the ‘standard’ variety made from electric charges and currents and the ‘anomalous’ variety made from hypothetical magnetic monopoles and their currents—in the presence of electric and magnetic fields (which themselves may be produced by ‘standard’ or ‘anomalous’ sources).

This article is part of the theme issue ‘Celebrating 125 years of Oliver Heaviside's ‘Electromagnetic Theory’’.
Estimating likelihood from simulations in bayesian inference of ecological models with historical contingency
Authors: Dupas Stéphane
Published: October 2018

Ecological patterns result from historical contingency and deterministic processes. Taking apart these processes to extract probabilistic models of ecological dynamics is of major importance for ecological forecasting. Due to the high dimensionality of historical contingency it is usually difficult to sample history from observed patterns. In environmental population genetics, the number of possible genealogies linking genetic data and environemental data through demographic and niche models is almost infinite. In ecosystem dynamics time series, the patterns are determined as much by probabilitic model parameters, as by historical variables contingency. Aproximate bayesian computation allows to use simulations to aproximate this inference process. The rationale is to simulate data, extract summary statistics and retain in the posterior, the parameters values that produced simulations with summary statistic close to observed summary statistics. The major drawbacks of this approach is that summary statistics distance is not exhaustive regarding model likelihood and may biais the results. In the present work, I show that if we can simulate the historical contingency from observed data and probabilistic model in a backward approach, we can to use the simulations to estimate a pseudo likelihood that can be used in bayesian inference. I apply to genealogy sampling in environmental demogenetics and ecosystem dynamics modelling.
Experience-dependent effects of muscimol-induced hippocampal excitation on mnemonic discrimination
Authors: Johnson Sarah A. , Turner Sean M. , Lubke Katelyn N. , Cooper Tara L. , Fertal Kaeli E. , Bizon Jennifer L. , Maurer Andrew P. , Burke Sara N.
Published: October 2018

Memory requires similar episodes with overlapping features to be represented distinctly, a process that is disrupted in many clinical conditions as well as normal aging. Data from humans have linked this ability to activity in hippocampal CA3 and dentate gyrus (DG). While animal models have shown the perirhinal cortex is critical for disambiguating similar stimuli, hippocampal activity has not been causally linked to discrimination abilities. The goal of the current study was to determine how disrupting CA3/DG activity would impact performance on a rodent mnemonic discrimination task. Rats were surgically implanted with bilateral guide cannulae targeting dorsal CA3/DG. In Exp.1, the effect of intra-hippocampal muscimol on target-lure discrimination was assessed within subjects in randomized blocks. Muscimol initially impaired discrimination across all levels of target-lure similarity, but performance improved on subsequent test blocks irrespective of stimulus similarity and infusion condition. To clarify these results, Exp.2 examined whether prior experience with objects influenced the effect of muscimol on target-lure discrimination. Rats that received vehicle infusions in a first test block, followed by muscimol in a second block, did not show discrimination impairments for target-lure pairs of any similarity. In contrast, rats that received muscimol infusions in the first test block were impaired across all levels of target-lure similarity. Sustained effects of muscimol in disrupting behavioral performance after repeated infusions were verified in a spatial alternation task. At the conclusion of behavioral experiments, fluorescence in situ hybridization for the immediate-early genes Arc and Homer1a was used to determine the proportion of neurons active following muscimol infusion. Contrary to expectations, muscimol increased neural activity in DG. An additional experiment was carried out to quantify neural activity in naïve rats that received an intra-hippocampal infusion of vehicle or muscimol. Results confirmed that muscimol led to DG excitation, likely through its actions on interneuron populations in hilar and molecular layers of DG and consequent disinhibition of principal cells. Taken together, our results suggest disruption of coordinated neural activity across the hippocampus impairs mnemonic discrimination when lure stimuli are novel.
Vaccine-induced protection from homologous Tier 2 simian-human immunodeficiency virus challenge in nonhuman primates
Authors: Pauthner Matthias G. , Nkolola Joseph P. , Havenar-Daughton Colin , Murrell Ben , Reiss Samantha M. , Bastidas Raiza , Prévost Jérémie , Nedellec Rebecca , Bredow Benjamin von , Abbink Peter , Cottrell Christopher A. , Kulp Daniel W. , Tokatlian Talar , Nogal Bartek , Bianchi Matteo , Li Hui , Lee Jeong Hyun , Butera Salvatore T. , Evans David T. , Hangartner Lars , Finzi Andrés , Wilson Ian A. , Wyatt Rich T. , Irvine Darrell J. , Schief William R. , Ward Andrew B. , Sanders Rogier W. , Crotty Shane , Shaw George M. , Barouch Dan H. , Burton Dennis R.
Published: October 2018

Passive administration of HIV neutralizing antibodies (nAbs) can protect macaques from hard-to-neutralize (Tier 2) chimeric simian-human immunodeficiency virus (SHIV) challenge. However, conditions for nAb-mediated protection following vaccination have not been established. Here, we selected groups of 6 rhesus macaques with either high or low serum nAb titers from a total of 78 animals immunized with recombinant native-like (SOSIP) Env trimers from the BG505 HIV isolate. Repeat intrarectal challenge with homologous Tier 2 SHIVBG505 led to rapid infection in unimmunized and low-titer animals. In contrast, high-titer animals demonstrated protection that was gradually lost as nAb titers waned over weeks to months. From these results, we determined that an autologous serum ID50 nAb titer of ~1:500 was required to afford over 90% protection from medium-dose SHIV infection. We further identified autologous nAb titers, but not ADCC or T cell activity, as strong correlates of protection. These results provide proof-of-concept that Env protein-based vaccination strategies can protect against hard-to-neutralize SHIV challenge in rhesus macaques by inducing Tier 2 nAbs, provided appropriate neutralizing titers can be reached and maintained.
Genomic epidemiology supports multiple introductions and cryptic transmission of Zika virus in Colombia
Authors: Black Allison , Moncla Louise H. , Laiton-Donato Katherine , Potter Barney , Pardo Lissethe , Rico Angelica , Tovar Catalina , Rojas Diana P. , Longini Ira M. , Halloran M. Elizabeth , Peláez-Carvajal Dioselina , Ramírez Juan D. , Mercado-Reyes Marcela , Bedford Trevor
Published: October 2018

Background

Colombia was the second most affected country during the American Zika virus (ZIKV) epidemic, with over 109,000 reported cases. Despite the scale of the outbreak, limited genomic sequence data were available from Colombia. We sought to sequence additional samples and use genomic epidemiology to describe ZIKV dynamics in Colombia.

Methods

We sequenced ZIKV genomes directly from clinical diagnostic specimens and infected Aedes ae-gypti samples selected to cover the temporal and geographic breadth of the Colombian outbreak. We performed phylogeographic analysis of these genomes, along with other publicly-available ZIKV genomes from the Americas, to estimate the frequency and timing of ZIKV introductions to Colombia.

Results

We attempted PCR amplification on 184 samples; 19 samples amplified sufficiently to perform sequencing. Of these, 8 samples yielded sequences with at least 50% coverage. Our phylogeo-graphic reconstruction indicates two separate introductions of ZIKV to Colombia, one of which was previously unrecognized. We find that ZIKV was first introduced to Colombia in February 2015 (95%CI: Jan 2015 - Apr 2015), corresponding to 5 to 8 months of cryptic ZIKV transmission prior to confirmation in September 2015. Despite the presence of multiple introductions, we find that the majority of Colombian ZIKV diversity descends from a single introduction. We find evidence for movement of ZIKV from Colombia into bordering countries, including Peru, Ecuador, Panama, and Venezuela.

Conclusions

Similarly to genomic epidemiologic studies of ZIKV dynamics in other countries, we find that ZIKV circulated cryptically in Colombia. This more accurate dating of when ZIKV was circulating refines our definition of the population at risk. Additionally, our finding that the majority of ZIKV transmission within Colombia was attributable to transmission between individuals, rather than repeated travel-related importations, indicates that improved detection and control might have succeeded in limiting the scale of the outbreak within Colombia.
Interpretable classification of Alzheimer’s disease pathologies with a convolutional neural network pipeline
Authors: Tang Ziqi , Chuang Kangway V. , DeCarli Charles , Jin Lee-Way , Beckett Laurel , Keiser Michael J. , Dugger Brittany N.
Published: October 2018

Neuropathologists assess vast brain areas to identify diverse and subtly-differentiated morphologies. Standard semi-quantitative scoring approaches, however, are coarse-grained and lack precise neuroanatomic localization. We report a proof-of-concept deep learning pipeline identifying specific neuropathologies—amyloid plaques and cerebral amyloid angiopathy—in immunohistochemically-stained archival slides. Using automated segmentation of stained objects and a cloud-based interface, we annotated >70,000 plaque candidates from 43 whole slide images (WSIs) to train and evaluate convolutional neural networks. Networks achieved strong plaque classification on a 10-WSI hold-out set (0.993 and 0.743 areas under the receiver operating characteristic and precision recall curve, respectively). Prediction confidence maps visualized morphology distributions for WSIs at high resolution. Resulting plaque-burden scores correlated well with established semi-quantitative scores on a 30-WSI blinded hold-out. Finally, saliency mapping demonstrated that networks learned patterns agreeing with accepted pathologic features. This scalable means to augment a neuropathologist’s ability may suggest a route to neuropathologic deep phenotyping.
Wood modification by furfuryl alcohol caused delayed decomposition response inRhodonia (Postia) placenta
Authors: Skrede Inger , Solbakken Monica Hongrø , Hess Jaqueline , Fossdal Carl Gunnar , Hegnar Olav , Alfredsen Gry
Published: October 2018

The aim of this study was to investigate differential expression profiles of the brown rot fungusRhodonia placenta(previouslyPostia placenta) harvested at several time points when grown onPinus radiata(radiata pine) andP. radiatawith three different levels of modification by furfuryl alcohol, an environmentally benign commercial wood protection system. For the first time the entire gene expression pattern of a decay fungus is followed in untreated and modified wood from initial to advanced stages of decay. Results support the current model of a two-step decay mechanism, with an initial oxidative depolymerization followed by hydrolysis of cell-wall polysaccharides. The wood decay process is finished, and the fungus goes into starvation mode after five weeks when grown on unmodifiedP. radiatawood. The pattern of repression of oxidative processes and oxalate synthesis found inP. radiataat later stages of decay is not mirrored for the high furfurylation treatment. The high treatment level provided a more unpredictable expression pattern throughout the entire incubation period. Furfurylation does not seem to directly influence the expression of core plant cell wall hydrolyzing enzymes, as a delayed and prolonged, but similar pattern was observed in theP. radiataand the modified experiments. This indicates that the fungus starts a common decay process in the modified wood, but proceeds at a slower pace as access to the plant cell wall polysaccharides is restricted. This is further supported by the downregulation of hydrolytic enzymes for the high treatment level at the last harvest point (mass loss 14%). Moreover, the mass loss does not increase the last weeks. Collectively, this indicates a potential threshold for lower mass loss for highly modified wood.

IMPORTANCE

Fungi are important decomposers of woody biomass in natural habitats. Investigation of the mechanisms employed by decay fungi in their attempt to degrade wood is important for both the basic scientific understanding of ecology and carbon cycling in nature, and for applied uses of woody materials. For wooden building materials long service life and carbon storage is essential, but decay fungi are responsible for massive losses of wood in service. Thus, optimizing durable wood products for the future are of major importance. In this study we have investigated the fungal genetic response to furfurylated wood, a commercial environmentally benign wood modification approach, that improves service life of wood in outdoor applications. Our results show that there is a delayed wood decay by the fungus as a response to furfurylated wood and new knowledge about the mechanisms behind the delay is provided.
Sexual antagonism drives the displacement of polymorphism across gene regulatory cascades
Authors: Hill Mark , Reuter Max , Stewart Alexander J.
Published: October 2018

Males and females have different reproductive roles and are often subject to contrasting selection pressures. This sexual antagonism can lead, at a given locus, to different alleles being favoured in each sex and, consequently, to genetic variation being maintained in a population. Although the presence of antagonistic polymorphisms has been documented across a range of species, their evolutionary dynamics remain poorly understood. Here we study antagonistic selection on gene expression, which is fundamental to sexual dimorphism, via the evolution of regulatory binding sites. We show that for sites longer than 1 nucleotide, polymorphism is maintained only when intermediate expression levels are deleterious to both sexes. We then show that, in a regulatory cascade, polymorphism tends to become displaced over evolutionary time from the target of antagonistic selection to upstream regulators. Our results have consequences for understanding the evolution of sexual dimorphism, and provide specific empirical predictions for the regulatory architecture of genes under antagonistic selection
Soil microbial communities with greater investment in resource acquisition have lower growth yield
Authors: Malik Ashish A. , Puissant Jeremy , Goodall Tim , Allison Steven D. , Griffiths Robert I.
Published: October 2018

Resource acquisition and growth yield are fundamental traits of microorganisms that have consequences for ecosystem functioning. However, there is a lack of empirical observations linking these traits. Using a landscape-scale survey of temperate near-neutral pH soils, we show tradeoffs in key community-level parameters linked to these traits. Increased investment into extracellular enzymes was associated with reduced growth yield; this reduction was linked more to carbon than nitrogen acquisition enzymes suggesting smaller stoichiometric constraints on community metabolism in examined soils.
Tuning of ventral tenia tecta neurons of the olfactory cortex to distinct scenes of feeding behavior
Authors: Shiotani Kazuki , Manabe Hiroyuki , Tanisumi Yuta , Murata Koshi , Hirokawa Junya , Sakurai Yoshio , Mori Kensaku
Published: October 2018

Ventral tenia tecta (vTT) is a part of the olfactory cortex that receives both olfactory sensory signals from the olfactory bulb and top-down signals from the prefrontal cortex. To address the question whether and how the neuronal activity of the vTT is modulated by prefrontal cognitive processes such as attention, expectation and working memory that occurs during goal-directed behaviors, we recorded individual neuronal responses in the vTT of freely moving awake mice that performed learned odor-guided feeding and drinking behaviors. We found that the firing pattern of individual vTT cells had repeatable behavioral correlates such that the environmental and behavioral scene the mouse encountered during the learned behavior was the major determinant of when individual vTT neurons fired maximally. Furthermore, spiking activity of these scene cells was modulated not only by the present scene but also by the future scene that the mouse predicted. We show that vTT receives afferent input from the olfactory bulb and top-down inputs from the medial prefrontal cortex and piriform cortex.

These results indicate that different groups of vTT cells are activated at different scenes and suggest that processing of olfactory sensory information is handled by different scene cells during distinct scenes of learned feeding and drinking behaviors. In other words, during the feeding and drinking behavior, vTT changes its working mode moment by moment in accord with the scene change by selectively biasing specific scene cells. The scene effect on olfactory sensory processing in the vTT has implications for the neuronal circuit mechanisms of top-down attention and scene-dependent encoding and recall of olfactory memory.
Cryo-EM structures and functional characterization of the lipid scramblase TMEM16F
Authors: Alvadia Carolina , Lim Novandy K. , Mosina Vanessa Clerico , Oostergetel Gert T. , Dutzler Raimund , Paulino Cristina
Published: October 2018

The lipid scramblase TMEM16F initiates blood coagulation by catalyzing the exposure of phosphatidylserine in platelets. The protein is part of a family of membrane proteins, which encompasses calcium-activated channels for ions and lipids. Here, we reveal features of TMEM16F that underlie its function as lipid scramblase and ion channel. The cryo-EM structures of TMEM16F in Ca2+-bound and Ca2+-free states display a striking similarity to the scrambling-incompetent anion channel TMEM16A, yet with distinct differences in the catalytic site and in the conformational changes upon activation. In conjunction with functional data, we demonstrate the relationship between ion conduction and lipid scrambling. Although activated by a common mechanism, which likely resembles an equivalent process defined in the homologue nhTMEM16, both functions appear to be mediated by alternate protein conformations, which are at equilibrium in the ligand-bound state.
Knock-in rat lines with Cre recombinase at the dopamine D1 and adenosine 2a receptor loci
Authors: Pettibone Jeffrey R. , Yu Jai Y. , Derman Rifka C. , Faust Thomas W. , Hughes Elizabeth D. , Filipiak Wanda E. , Saunders Thomas L. , Ferrario Carrie R. , Berke Joshua D.
Published: October 2018

Genetically-modified mice have become standard tools in neuroscience research. Our understanding of the basal ganglia in particular has been greatly assisted by BAC mutants with selective transgene expression in striatal neurons forming the direct or indirect pathways. However, for more sophisticated behavioral tasks and larger intracranial implants, rat models are preferred. Furthermore, BAC lines can show variable expression patterns depending upon genomic insertion site. We therefore used CRISPR/Cas9 to generate two novel knock-in rat lines specifically encoding Cre recombinase immediately after the dopamine D1 receptor (Drd1a) or adenosine 2a receptor (Adora2a) loci. Here we validate these lines usingin situhybridization and viral vector mediated transfection to demonstrate selective, functional Cre expression in the striatal direct and indirect pathways respectively. We used whole-genome sequencing to confirm the lack of off-target effects, and established that both rat lines have normal locomotor activity and learning in simple instrumental and Pavlovian tasks. We expect these new D1-Cre and A2a-Cre rat lines will be widely used to study both normal brain functions and neurological and psychiatric pathophysiology.
Mendelian Randomization analysis reveals a causal influence of circulating sclerostin levels on bone mineral density and fractures
Authors: Zheng Jie , Maerz Winfried , Gergei Ingrid , Kleber Marcus , Drechsler Christiane , Wanner Christoph , Brandenburg Vincent , Reppe Sjur , Gautvik Kaare M , Medina-Gomez Carolina , Shevroja Enisa , Gilly Arthur , Park Young-Chan , Dedoussis George , Zeggini Eleftheria , Lorentzon Mattias , Henning Petra , Lerner Ulf H. , Nilsson Karin , Movérare-Skrtic Sofia , Baird Denis , Elsworth Benjamin , Falk Louise , Groom Alix , Capellini Terence D. , Grundberg Elin , Nethander Maria , Ohlsson Claes , Smith George Davey , Tobias Jonathan H.
Published: October 2018

In bone, sclerostin is mainly osteocyte-derived and plays an important local role in adaptive responses to mechanical loading. Whether circulating levels of sclerostin also play a functional role is currently unclear, which we aimed to examine by two sample Mendelian Randomisation (MR). A genetic instrument for circulating sclerostin, derived from a genome wide association study (GWAS) meta-analysis of serum sclerostin in 10,584 European-descent individuals, was examined in relation to femoral neck bone mineral density (BMD; n= 32,744) in GEFOS, and estimated BMD by heel ultrasound (eBMD; n=426,824), and fracture risk (n=426,795), in UK Biobank. Our GWAS identified two novel serum sclerostin loci, B4GALNT3 (standard deviation (SD)) change in sclerostin per A allele (β=0.20, P=4.6×10−49), and GALNT1 (β=0.11 per G allele, P=4.4×10−11). B4GALNT3 is an N-acetyl-galactosaminyltransferase, adding a terminal LacdiNAc disaccharide to target glycocoproteins, found to be predominantly expressed in kidney, whereas GALNT1 is an enzyme causing mucin-type O-linked glycosylation. Using these two SNPs as genetic instruments, MR revealed an inverse causal relationship between serum sclerostin and femoral neck BMD (β= −0.12, 95%CI= −0.20 to −0.05) and eBMD (β= −0.12, 95%CI= −0.14 to −0.10), and a positive relationship with fracture risk (β= 0.11, 95%CI= 0.01 to 0.21). Colocalization analysis demonstrated common genetic signals within the B4GALNT3 locus for higher sclerostin, lower eBMD, and greater B4GALNT3 expression in arterial tissue (Probability>99%). Our findings suggest that higher sclerostin levels are causally related to lower BMD and greater fracture risk. Hence, strategies for reducing circulating sclerostin, for example by targeting glycosylation enzymes as suggested by our GWAS results, may prove valuable in treating osteoporosis.
Definitive demonstration by synthesis of genome annotation completeness
Authors: Jaschke Paul R. , Dotson Gabrielle A , Hung Kay , Liu Diane , Endy Drew
Published: October 2018

Bacteriophage øX174 was the first DNA genome to be sequenced. The genome is well studied by classical methods and is known to encode 11 essential genes. At least 23 closely-relatedBullavirinaegenome sequences are now available. We identified 315 potential open reading frames (ORFs) within the genome via bioinformatic analysis, and a subset of 82 highly-conserved ORFs that have no known gene products or functions. Using genome scale design and synthesis we made a mutant genome in which all 11 essential genes are simultaneously disrupted, leaving intact only the 82 conserved-but-cryptic ORFs. The resulting genome is not viable, as expected. Cell-free gene expression followed by mass spectrometry revealed only a single peptide expressed from both the cryptic-ORF and wild-type genomes, suggesting a potential new gene. A second synthetic genome in which 71 conserved cryptic ORFs were simultaneously disrupted is viable but with ~50% reduced fitness relative to the wild type. However, rather than finding any new genes, repeated evolutionary adaptation revealed a single point mutation modulating translation of gene H, a known essential gene, that fully suppressed the fitness defect. Taken together, we conclude that the annotation of ORFs for the øX174 genome is formally complete. Sequencing and bioinformatics followed by synthesis-enabled reverse genomics, proteomics, and evolutionary adaptation can definitely establish the sufficiency and completeness of natural genome annotations.
Embedding single-cell experimental conditions to reveal manifold structure of cancer drug perturbation effects
Authors: Chen William S. , Zivanovic Nevena , van Dijk David , Wolf Guy , Bodenmiller Bernd , Krishnaswamy Smita
Published: October 2018

Previously, the effect of a drug on a cell population was measured based on simple metrics such as cell viability. However, as single-cell technologies are becoming more advanced, drug screen experiments can now be conducted with more complex readouts such as gene expression profiles of individual cells. The increasing complexity of measurements from these multi-sample experiments calls for more sophisticated analytical approaches than are currently available. We developed a novel method called PhEMD (Phenotypic Earth Mover’s Distance) and show that it can be used to embed the space of drug perturbations on the basis of the drugs’ effects on cell populations. When testing PhEMD on a newly-generated, 300-sample CyTOF kinase inhibition screen experiment, we find that the state space of the perturbation conditions is surprisingly low-dimensional and that the network of drugs demonstrates manifold structure. We show that because of the fairly simple manifold geometry of the 300 samples, we can accurately capture the full range of drug effects using a dictionary of only 30 experimental conditions. We also show that new drugs can be added to our PhEMD embedding using similarities inferred from other characterizations of drugs using a technique called Nystrom extension. Our findings suggest that large-scale drug screens can be conducted by measuring only a small fraction of the drugs using the most expensive high-throughput single-cell technologies—the effects of other drugs may be inferred by mapping and extending the perturbation space. We additionally show that PhEMD can be useful for analyzing other types of single-cell samples, such as patient tumor biopsies, by mapping the patient state space in a similar way as the drug state space. We demonstrate that PhEMD is scalable, compatible with leading batch effect correction techniques, and generalizable to multiple experimental designs. Altogether, our analyses suggest that PhEMD may facilitate drug discovery efforts and help uncover the network geometry of a collection of single-cell samples.