bluuebunny/crossref_metadata_2025 huggingface dataset:
Intralymphatic Spread is a Rare Finding Associated With Poor Prognosis in Diffuse Large B-Cell Lymphoma With Extranodal Involvements
Authors: Cheng Chieh-Lung , Su Yung-Cheng , Chao Tsu-Yi , Lin Chung-Wu , Chou Sheng-Chieh , Yao Ming , Kuo Sung-Hsin , Yu Shan-Chi
Published: March 2018

Intralymphatic spread is common in solid cancers, but has been rarely studied in lymphomas. Review of 635 extranodal specimens from 475 diffuse large B-cell lymphoma (DLBCL) patients revealed intralymphatic spread in 10 surgical resection specimens from 10 patients including 9 de novo DLBCLs and 1 Richter transformation. The prevalence in de novo DLBCL with extranodal involvements was 1.65%. The most common involved site of intralymphatic spread was the gastrointestinal tract, followed by the female genital tract and breasts. Lymphatic vessels, lined by D2-40-positive endothelial cells, were expanded by lymphoma cells, reminiscent of intravascular lymphoma or tumor emboli. None of the involved lymphatic vessels were located in the mucosa. Patients with intralymphatic spread had a trend of lower overall response rate and a trend of higher progressive disease than those without intralymphatic spread. Compared with patients without intralymphatic spread, those patients with intralymphatic spread had a shorter median overall survival (14.3 vs. 96.2 mo; P=0.004) and a shorter median progression-free survival (11.2 vs. 64.2 mo; P=0.01), respectively. Multivariate analyses showed that intralymphatic spread was an independent poor prognostic factor for overall survival (hazard ratio, 3.029; 95% confidence interval, 1.315-6.978; P=0.009), irrespective of the National Comprehensive Cancer Network-International Prognostic Index, B symptoms, and serum albumin levels. Among patients who underwent surgical resection, intralymphatic spread was still an independent prognostic factor. In conclusion, our study demonstrated extranodal intralymphatic spread in DLBCL. Inspiringly, this rare morphologic finding may serve as a new negative prognostic indicator in DLBCL with extranodal involvements.
Differentiated Vulvar Intraepithelial Neoplasia-like and Lichen Sclerosus-like Lesions in HPV-associated Squamous Cell Carcinomas of the Vulva
Authors: Rakislova Natalia , Alemany Laia , Clavero Omar , del Pino Marta , Saco Adela , Quirós Beatriz , Lloveras Belen , Alejo Maria , Halec Gordana , Quint Wim , de Sanjosé Silvia , Ordi Jaume
Published: March 2018

Most human papillomavirus (HPV)-associated vulvar squamous cell carcinomas (VSCCs) originate from high-grade squamous intraepithelial lesions, also named usual type vulvar intraepithelial neoplasia. However, growing evidence suggests that morphologic studies have limitations in predicting HPV status in vulvar lesions. We aimed to evaluate adjacent intraepithelial lesions in a series of DNA HPV-positive VSCCs, focusing on unusual histologic patterns mimicking differentiated vulvar intraepithelial neoplasia (dVIN) or lichen sclerosus (LS). We identified 326 DNA HPV-positive VSCC with at least 1 cm of skin adjacent to the invasive tumor and analyzed HPV typing, HPV E6*I mRNA, and p16 immunohistochemistry in all cases. A careful histologic evaluation was conducted. A conclusive association with HPV was based on a positive p16 or HPV E6*I mRNA result or both in addition to the HPV DNA, whereas cases negative for both markers were classified as nonconclusively associated with HPV. One hundred twenty-one tumors (37.1%) had normal adjacent skin, 191 (58.6%) had only high-grade squamous intraepithelial lesions, also named usual type vulvar intraepithelial neoplasia, and unusual intraepithelial lesions were identified in 14 (4.3%) tumors. Seven cases showed dVIN-like features, 5 showed adjacent LS-like lesion, and in 2 cases dVIN-like and LS-like lesions were identified simultaneously. Six of them were conclusively associated with HPV (3 dVIN-like, 2 LS-like, 1 with combined dVIN/LS-like features). All 6 tumors were associated with HPV16 and were positive for both p16 and HPV mRNA, and p16 was also positive in the dVIN-like and LS-like lesions. In summary, a small subset of VSCCs conclusively associated with HPV may arise on intraepithelial lesions, mimicking precursors of HPV-independent VSCC.
Pulmonary Function Diagnosis Based on Respiratory Changes in Lung Density With Dynamic Flat-Panel Detector Imaging
Authors: Tanaka Rie , Tani Tohru , Nitta Norihisa , Tabata Takahisa , Matsutani Noritsugu , Muraoka Shintaro , Yoneyama Tsutomu , Sanada Shigeru
Published: March 2018

Objectives

The aims of this study were to address the relationship between respiratory changes in image density of the lungs and tidal volume, to compare the changes between affected and unaffected lobes, and to apply this new technique to the diagnosis of atelectasis.

Materials and Methods

Our animal care committee approved this prospective animal study. Sequential chest radiographs of 4 pigs were obtained under respiratory control with a ventilator using a dynamic flat-panel detector system. Porcine models of atelectasis were developed, and the correlation between the tidal volume and changes in pixel values measured in the lungs were analyzed. The mean difference in respiratory changes in pixel values between both lungs was tested using paired t tests. To facilitate visual evaluation, respiratory changes in pixel values were visualized in the form of a color display, that is, as changes in color scale.

Results

Average pixel values in the lung regions changed according to forced respiration. High linearity was observed between changes in pixel values and tidal volume in the normal models (r = 0.99). Areas of atelectasis displayed significantly reduced changes in pixel values (P < 0.05). Of all atelectasis models with air trapping and air inflow restriction, 92.7% (19/20) were visualized as color-defective or color-marked areas on functional images, respectively.

Conclusion

Dynamic chest radiography allows for the relative evaluation of tidal volume, the detection of ventilation defects in the lobe unit, and a differential diagnosis between air trapping and air inflow restriction, based on respiratory changes in image density of the lungs, even without the use of contrast media.
A Guide for Cortical Electrical Stimulation Mapping
Authors: So Elson L. , Alwaki Abdulrahman
Published: March 2018

Electrical stimulation mapping (ESM) of the brain remains a major procedure for guiding epilepsy and tumor surgeries. This article collates available experiences and data in ESM to develop a guide for conducting the procedure. There are many factors that influence the yield of ESM. The stimulation parameters offered in this article need to be adjusted within safe limits to address the factors. Each ESM procedure should be tailored to the patient's age and baseline mental or psychological capacity. Stimulation-induced seizures and EEG afterdischarges disrupt ESM procedure and render the interpretation of the results difficult. There are specific measures that can lessen the risk of seizures and afterdischarges during ESM. Electrical stimulation mapping procedure requires several tasks on the part of those conducting the procedure, such as operating the stimulator and the EEG recording equipment, administering behavioral or language tests and observing both patient and EEG responses to the stimulation. A team of experienced staff is necessary for individual assumption of each task. Knowledge of the spatial relationship between electrode contacts and underlying normal or abnormal brain structures is essential for interpreting ESM results. When testing for motor or sensory response, be aware of the distinction between responses at the primary motor area and responses at the supplementary sensorimotor area. The anatomy of supplementary sensorimotor area is more variable and functional than it is fixed and structural, although its general confines and somatotopic organization are known. In addition, negative motor responses to stimulation must be recognized to avoid misinterpretation of ESM results, especially in language mapping.
Electrical Stimulation Mapping of the Brain: Basic Principles and Emerging Alternatives
Authors: Ritaccio Anthony L. , Brunner Peter , Schalk Gerwin
Published: March 2018

The application of electrical stimulation mapping (ESM) of the brain for clinical use is approximating a century. Despite this long-standing history, the value of ESM for guiding surgical resections and sparing eloquent cortex is documented largely by small retrospective studies, and ESM protocols are largely inherited and lack standardization. Although models are imperfect and mechanisms are complex, the probabilistic causality of ESM has guaranteed its perpetuation into the 21st century. At present, electrical stimulation of cortical tissue is being revisited for network connectivity. In addition, noninvasive and passive mapping techniques are rapidly evolving to complement and potentially replace ESM in specific clinical situations. Lesional and epilepsy neurosurgery cases now offer different opportunities for multimodal functional assessments.
Electrical Stimulation Mapping With Stereo-EEG Electrodes
Authors: Britton Jeffrey W.
Published: March 2018

The practice of stereo-EEG (SEEG) is expanding. Electrical stimulation mapping remains an important part of the surgical evaluation process in SEEG, as it is in subdural electrocorticography cases. Because the technique and electrodes used in SEEG and electrocorticography are distinct, the clinician needs to be aware of the important differences between these techniques when performing electrical stimulation mapping. In this review, the advantages, disadvantages, and potential safety concerns related to electrical stimulation mapping in SEEG are discussed. A case is presented illustrating the utility of SEEG cortical stimulation and safety concerns that need to be considered when performing these evaluations.
Cortical Electrical Stimulation Mapping: Special Considerations in Children
Authors: Jayakar Prasanna
Published: March 2018

Cortical electrical stimulation mapping is often required to accurately delineate eloquent function before resective surgery for tumors or epilepsy. Although the technique is well established in adults, mapping poses special challenges in children that are addressed in this article. The concept of what constitutes a critical cortex is more difficult to assess, given the implications of plasticity and impact of deficits. Developmental factors affect the underlying neurophysiologic bases of responses to electrical stimulation, and evolving maturation requires adaptation of methodology. Furthermore, malformative substrates are the commonest substrate and often lead to aberrant representations of eloquent function.
Differences in the Transcranial Motor Evoked Potentials Between Proximal and Distal Lower Extremity Muscles
Authors: Parikh Pooja , Cheongsiatmoy Justin , Shilian Parastou , Gonzalez Andres A.
Published: March 2018

Purpose:

Transcranial motor evoked potentials (TcMEPs) are the preferred modality to monitor the integrity of motor pathways during surgery. Recently, it has also been used as a method to help with detection of nerve roots injuries. Adequate baseline muscle responses are vital to detect nerve injury. We have observed that TcMEP responses are not homogeneous across multiple myotomes, but this has not been studied systematically. Our objective is to determine whether there are any relative differences in amplitude or morphology of TcMEPs across various lower extremity muscles.

Methods:

Clinical and neurophysiological monitoring data from patients who had lumbar spine surgery were obtained retrospectively. Transcranial motor evoked potential responses were evaluated for each limb in the quadriceps, tibialis anterior, and intrinsic foot muscles. We compared TcMEP responses between these muscle groups using paired t-test statistical analysis. Each limb was analyzed separately. Only limbs without deficit in the interested muscle groups were included for analysis.

Results:

A total of 40 patients and 69 limbs were included for analysis. The mean TcMEP amplitude difference between the tibialis anterior and quadriceps muscles was 458 µV (P < 0.0001), and between intrinsic feet and quadriceps muscles was 541 µV (P < 0.0001). Proximal muscles also demonstrated a significantly smaller number of TcMEP phases than their distal counterparts.

Conclusions:

Transcranial motor evoked potential amplitudes are significantly smaller in proximal lower extremity muscles compared with distal lower extremity muscles. The observed difference might be due to cortical representation or higher subcutaneous tissue in thigh muscles.
Predictors of Pressure Injuries in a Critical Care Unit in Lebanon
Authors: El-Marsi Jihad , Zein-El-Dine Salah , Zein Bana , Doumit Rita , Kurdahi Badr Lina
Published: March 2018

PURPOSE:

The purpose of this study was to identify factors associated with pressure injury in a medical-surgical intensive care unit (MSICU).

DESIGN:

Retrospective review of medical records.

SUBJECTS AND SETTING:

We reviewed the medical records of 145 patients who developed a new pressure injury in the MSICU of a 420-bed university medical center in Lebanon.

METHODS:

Medical records of all patients cared for in the MSICU from December 2014 to June 2017 were reviewed by a research assistant using a standardized form. We extracted potential risk factors for pressure injury including sex, age, weight upon admission, weight at discharge, length of MSICU stay, episodes of hypotension, administration of inotropes/vasopressors, admitting diagnosis, comorbid conditions, and cumulative scores on the Braden Scale for Pressure Sore Risk. The outcome variable was development of any new pressure injury during their stay in our intensive care unit.

RESULTS:

Forty-nine patents (33.7%) developed a new pressure injury. Bivariate analysis found statistically significant associations between pressure injury occurrences and administration of vasopressors (odds ratio [OR] = 0.42; 95% confidence interval = 0.29-0.87; P = .02), the administration of dopamine (OR = 0.20; 95% confidence interval = 0.04-0.94; P = .04), and hospital-acquired pressure injury. Among the continuous variables, analysis revealed significant relationships between weight at discharge (t = 2.31, P = .02), MSICU length of stay (t = 5.30; P = .000), cumulative Braden Scale score (t = 3.06; P = .002), hypotension (t =−2.74; P = .007), and development a new pressure injury. Multivariate analysis indicated that length of stay (β= −.110; P = .002), administration of vasopressors (β=−.266; P = .029), and total hours of hypotension (β=−.53; P = .041) were significant predictors of pressure injury.

CONCLUSIONS:

Vasopressor use, hypotension, and length of stay were associated with an increased likelihood of pressure injury in adults managed in an MSICU. None of these factors is specifically evaluated during completion of the Braden Scale for Pressure Sore Risk. Based on these findings we recommend development of a pressure injury scale specific to critically ill adults.
Relationships Among Use of Complementary and Alternative Interventions, Urinary Incontinence, Quality of Life, and Self-esteem in Women With Urinary Incontinence
Authors: Öz Özge , Altay Birsen
Published: March 2018

PURPOSE:

The purpose of this study was to examine associations among sociodemographic characteristics, urinary incontinence (UI) characteristics, UI-specific quality of life and self-esteem, and use of complementary and alternative medicine (CAM) interventions for UI.

DESIGN:

Correlational-descriptive research.

SUBJECTS AND SETTING:

This sample comprised 394 female patients 18 years or older cared for in the urology and gynecology outpatient clinics of a university hospital in Samsun, Turkey.

METHODS:

Participants completed an investigator-developed questionnaire that included 2 validated instruments, King's Health Questionnaire (KHQ) and the Rosenberg Self-esteem Scale. Descriptive statistics were used for demographic data and use of CAM interventions. Variables associated with CAM use were assessed using χ2 analysis. The differences between using CAM and scales points of the KHQ and the Rosenberg Self-esteem Scale were assessed using the t test, and the relationship between the KHQ and the Rosenberg Self-esteem Scale was assessed using correlation analysis.

RESULTS:

Thirty-three percent (n = 130) of women indicated using CAM interventions to manage their UI. The most common CAM intervention, reported by 52.6% of respondents, was prayer. Women with lower UI-specific quality of life and self-esteem scores were more likely to report using CAM interventions (P < .05). Women with lower education level used CAM more frequently than others (P < .05). Analysis revealed weak but statistically significant positive correlations for role limitations, physical limitations, social limitations, emotions, sleep/energy level and the symptom severity (P < .001), and personal relationships (P < .01) subdimensions of the KHQ.

CONCLUSIONS:

One-third of women indicated using CAM methods to manage their UI; the most commonly used intervention was prayer. Women using CAM reported both higher self-esteem and condition-specific health-related quality of life than women who did not use these interventions.
A canonical form of the equation of motion of linear dynamical systems
Authors: Kawano Daniel T. , Salsa Rubens Goncalves , Ma Fai , Morzfeld Matthias
Published: March 2018

The equation of motion of a discrete linear system has the form of a second-order ordinary differential equation with three real and square coefficient matrices. It is shown that, for almost all linear systems, such an equation can always be converted by an invertible transformation into a canonical form specified by two diagonal coefficient matrices associated with the generalized acceleration and displacement. This canonical form of the equation of motion is unique up to an equivalence class for non-defective systems. As an important by-product, a damped linear system that possesses three symmetric and positive definite coefficients can always be recast as an undamped and decoupled system.
How new concepts become universal scientific approaches: insights from citation network analysis of agent-based complex systems science
Authors: Vincenot Christian E.
Published: March 2018

Progress in understanding and managing complex systems comprised of decision-making agents, such as cells, organisms, ecosystems or societies, is—like many scientific endeavours—limited by disciplinary boundaries. These boundaries, however, are moving and can actively be made porous or even disappear. To study this process, I advanced an original bibliometric approach based on network analysis to track and understand the development of the model-based science of agent-based complex systems (ACS). I analysed research citations between the two communities devoted to ACS research, namely agent-based (ABM) and individual-based modelling (IBM). Both terms refer to the same approach, yet the former is preferred in engineering and social sciences, while the latter prevails in natural sciences. This situation provided a unique case study for grasping how a new concept evolves distinctly across scientific domains and how to foster convergence into a universal scientific approach. The present analysis based on novel hetero-citation metrics revealed the historical development of ABM and IBM, confirmed their past disjointedness, and detected their progressive merger. The separation between these synonymous disciplines had silently opposed the free flow of knowledge among ACS practitioners and thereby hindered the transfer of methodological advances and the emergence of general systems theories. A surprisingly small number of key publications sparked the ongoing fusion between ABM and IBM research. Beside reviews raising awareness of broad-spectrum issues, generic protocols for model formulation and boundary-transcending inference strategies were critical means of science integration. Accessible broad-spectrum software similarly contributed to this change. From the modelling viewpoint, the discovery of the unification of ABM and IBM demonstrates that a wide variety of systems substantiate the premise of ACS research that microscale behaviours of agents and system-level dynamics are inseparably bound.
Characterizing the phylogenetic specialism–generalism spectrum of mammal parasites
Authors: Park A. W. , Farrell M. J. , Schmidt J. P. , Huang S. , Dallas T. A. , Pappalardo P. , Drake J. M. , Stephens P. R. , Poulin R. , Nunn C. L. , Davies T. J.
Published: March 2018

The distribution of parasites across mammalian hosts is complex and represents a differential ability or opportunity to infect different host species. Here, we take a macroecological approach to investigate factors influencing why some parasites show a tendency to infect species widely distributed in the host phylogeny (phylogenetic generalism) while others infect only closely related hosts. Using a database on over 1400 parasite species that have been documented to infect up to 69 terrestrial mammal host species, we characterize the phylogenetic generalism of parasites using standard effect sizes for three metrics: mean pairwise phylogenetic distance (PD), maximum PD and phylogenetic aggregation. We identify a trend towards phylogenetic specialism, though statistically host relatedness is most often equivalent to that expected from a random sample of host species. Bacteria and arthropod parasites are typically the most generalist, viruses and helminths exhibit intermediate generalism, and protozoa are on average the most specialist. While viruses and helminths have similar mean pairwise PD on average, the viruses exhibit higher variation as a group. Close-contact transmission is the transmission mode most associated with specialism. Most parasites exhibiting phylogenetic aggregation (associating with discrete groups of species dispersed across the host phylogeny) are helminths and viruses.
A critical role for miR-142 in alveolar epithelial lineage formation
Authors: Shrestha Amit , Carraro Gianni , Nottet Nicolas , Vazquez-Armendariz Ana Ivonne , Herold Susanne , Cordero Julio , Singh Indra Bahadur , Wilhelm Jochen , Barreto Guillermo , Chao Cho-Ming , Agha Elie El , Mari Bernard , Zhang Jin San , Bellusci Saverio
Published: March 2018

The development of a functional lung, capable of gas exchange, requires proper alveologenesis. Mechanisms regulating AT1 and AT2 cell maturation are poorly defined. We report the activation of the glucocorticoid pathway in an in vitro alveolar epithelial lineage differentiation assay led to increased AT2 marker Sftpc and decreased miR-142 expression. Using a constitutive KO mouse model, we further demonstrate a relative increase of AT2 and a decrease in AT1 cell number with a global decrease of AT2 gene profile signature in miR-142 KO AT2 cells. Over-expression of miR-142 in alveolar progenitor cells in vivo led to an opposite effect. Examination of the KO lungs at E18.5, revealed enhanced expression miR-142 targets like Apc, Ep300 and Kras associated with increased Ctnnb1 and p-Erk signaling. Pharmacological inhibition of Ep300-Ctnnb1 in vitro prevented an increase in Sftpc expression triggered by loss of miR-142. These results together suggest glucocorticoid-miR-142-p300 signaling axis controls pneumocyte maturation.
FastSpar: Rapid and scalable correlation estimation for compositional data
Authors: Watts Stephen C. , Ritchie Scott C. , Inouye Michael , Holt Kathryn E.
Published: March 2018

A common goal of microbiome studies is the elucidation of community composition and member interactions using counts of taxonomic units extracted from sequence data. Inference of interaction networks from sparse and compositional data requires specialised statistical approaches. A popular solution is SparCC, however its performance limits the calculation of interaction networks for very high-dimensional datasets. Here we introduce FastSpar, an efficient and parallelisable implementation of the SparCC algorithm which rapidly infers correlation networks and calculatesp-values using an unbiased estimator. We further demonstrate that FastSpar reduces network inference wall time by 2-3 orders of magnitude compared to SparCC. FastSpar source code, precompiled binaries, and platform packages are freely available on GitHub: github.com/scwatts/FastSpar
Nonnegligible role of warming-induced soil drying in regulating warming effect on soil respiration
Authors: Du Enzai
Published: March 2018

Based on results of a 26-year soil warming experiment (soil temperature being elevated by 5 °C) in a Harvard hardwood forest, Melillo et al. demonstrated a four-phase pattern of long-term warming effect on soil respiration, while the mechanisms were not fully elucidated because they neglected the indirect effect due to warming-induced soil drying. By showing a significant correlation between precipitation anomaly and inter-annual variation of warming effect on soil respiration, we suggest a nonnegligible role of warming-induced soil drying in regulating the long-term warming effect on soil respiration. Our analysis recommends further efforts to consider both the direct and indirect (i.e., warming-induced soil drying) warming effects to gain more in-depth understanding of the long-term soil C dynamics.
Perivascular signals alter global gene expression profile of glioblastoma and response to temozolomide in a gelatin hydrogel
Authors: Ngo Mai T. , Harley Brendan A.C.
Published: March 2018

Glioblastoma (GBM) is the most common primary malignant brain tumor, with patients exhibiting poor survival (median survival time: 15 months). Difficulties in treating GBM include not only the inability to resect the diffusively-invading tumor cells but also therapeutic resistance. The perivascular niche (PVN) within the GBM tumor microenvironment contributes significantly to tumor cell invasion, cancer stem cell maintenance, and has been shown to protect tumor cells from radiation and chemotherapy. In this study, we examine how the inclusion of non-tumor cells in culture with tumor cells within a hydrogel impacts the overall gene expression profile of anin vitroartificial perivascular niche (PVN) comprised of endothelial and stromal cells directly cultured with GBM tumor cells within a methacrylamide-functionalized gelatin hydrogel. Using RNA-seq, we demonstrate that genes related to angiogenesis and remodeling are upregulated in the PVN model compared to hydrogels containing only tumor or perivascular niche cells, while downregulated genes are related to cell cycle and DNA damage repair. Signaling pathways and genes commonly implicated in GBM malignancy, such asMGMT, EGFR, PI3K-Akt signaling, and Ras/MAPK signaling are also upregulated in the PVN model. We describe the kinetics of gene expression within the PVN hydrogels over a course of 14 days, observing the patterns associated with tumor cell-mediated endothelial network co-option and regression. We finally examine the effect of temozolomide, a frontline chemotherapy used clinically against GBM, on the PVN culture. Notably, the PVN model is less responsive to TMZ compared to hydrogels containing only tumor cells. Overall, these results demonstrate that inclusion of cellular and matrix-associated elements of the PVN within anin vitromodel of GBM allows for the development of gene expression patterns and therapeutic response relevant to GBM.
Humidity as a non-pharmaceutical intervention for influenza A
Authors: Reiman Jennifer M. , Das Biswadeep , Sindberg Gregory M. , Urban Mark D. , Hammerlund Madeleine E.M. , Lee Han B. , Spring Katie M. , Lyman-Gingerich Jamie , Generous Alex R. , Koep Tyler H. , Ewing Kevin , Lilja Phil , Enders Felicity T. , Ekker Stephen C. , Huskins W. Charles , Fadel Hind J. , Pierret Chris
Published: March 2018

Influenza is a global problem infecting 5-10 % of adults and 20-30 % of children annually. Non-pharmaceutical interventions (NPIs) are attractive approaches to complement vaccination in the prevention and reduction of influenza. Strong cyclical reduction of absolute humidity has been associated with influenza outbreaks in temperate climates. This study tested the hypothesis that raising absolute humidity above seasonal lows would impact influenza virus survival and transmission in a key source of influenza distribution, a community school. Air samples and objects handled by students (e.g. blocks and markers) were collected from preschool classrooms. All samples were processed and PCR used to determine the presence of influenza and its amount. Additionally samples were tested for their ability to infect cells in cultures. Deliberate classroom humidification (with commercial steam humidifiers) resulted in a significant reduction of the total number of influenza positive samples (air and fomite), viral copy number, and efficiency of viral infectivity. This is the first prospective study suggesting that exogenous humidification could serve as a scalable NPI for influenza or other viral outbreaks.

Author summary

Human influenza infections have a substantial impact on society (including lost productivity and medical costs). Children, 3-4 years of age are the main introducers and spreaders of influenza within a household and community. There is evidence from laboratory and epidemiological studies that suggests that low humidity in winter (in temperate climates) may increase the ability of influenza virus to survive and spread between individuals. We wanted to know if added in humidity (through steam humidifiers) could reduce the amount of influenza present and its spread within preschool classrooms (students aged 3-4 years)? Additionally, we looked at the infectivity of the influenza isolated and if there were differences in the number of students with influenza-like illnesses during our study. We show that humidification can reduce the amount of influenza present within samples from preschool classrooms and that there were fewer infectious samples compared to non-humidified rooms. There were small numbers of students ill with influenza like illnesses during our study so additional studies will need to look further at humidification as a way to reduce influenza infection and transmission.
Pleiotropic effects drive correlation between body mass index and cortical myelination
Authors: Ronan Lisa , Medic Nenad , Fletcher Paul C
Published: March 2018

Background

Epidemiological studies have reported significant associations between obesity and neurocognitive decline. Understanding these associations will require deeper analyses of how body mass index (BMI) and brain structure are related. Here we explore the extent to which shared genetic factors (pleiotropy) govern the association between BMI and cortical myelination.

Methods

Statistical models of bivariate heritability were applied to structural MR image data from a cohort of monozyogotic and dizygotic twins. Estimates of phenotypic and genetic correlation between BMI and cortical myelination were derived. A co-twin control design based on monozygotic twins was used to test the hypothesis of a causal relationship between BMI and myelination. The variation in the genetic correlation across the cortex was compared with the average statistical enrichment of genes associated with obesity derived from data from the Allen brain atlas.

Results

Statistically significant phenotypic and genetic correlation between BMI and cortical myelination was observed across the cortex. Taking the heritability of each trait into account, approximately 80% of the phenotypic correlation between the traits was accounted for by shared genetic factors.

Intra-pair differences between traits in monozygotic twins failed to support a causal relationship. Moreover, variation in genetic correlation across the cortex was significantly associated with the statistical enrichment of genes related to obesity.

Conclusions

These results support the hypothesis that pleiotropic effects drive the association between BMI and cortical myelination. This observation may help to explain the co-occurrence of obesity in neurocognitive decline and mental health disorders characterized by changes in myelination and oligodendrocyte function.
Quantifying cell densities and biovolumes of phytoplankton communities and functional groups using scanning flow cytometry, machine learning and unsupervised clustering
Authors: Thomas Mridul K. , Fontana Simone , Reyes Marta , Pomati Francesco
Published: March 2018

Scanning flow cytometry (SFCM) is characterized by the measurement of time-resolved pulses of fluorescence and scattering, enabling the high-throughput quantification of phytoplankton morphology and pigmentation. Quantifying variation at the single cell and colony level improves our ability to understand dynamics in natural communities. Automated high-frequency monitoring of these communities is presently limited by the absence of repeatable, rapid protocols to analyse SFCM datasets, where images of individual particles are not available. Here we demonstrate a repeatable, semi-automated method to (1) rapidly clean SFCM data from a phytoplankton community by removing signals that do not belong to live phytoplankton cells, (2) classify individual cells into trait clusters that correspond to functional groups, and (3) quantify the biovolumes of individual cells, the total biovolume of the whole community and the total biovolumes of the major functional groups. Our method involves the development of training datasets using lab cultures, the use of an unsupervised clustering algorithm to identify trait clusters, and machine learning tools (random forests) to (1) evaluate variable importance, (2) classify data points, and (3) estimate biovolumes of individual cells. We provide example datasets and R code for our analytical approach that can be adapted for analysis of datasets from other flow cytometers or scanning flow cytometers.
Olfactory Projection Neurons From the Moth Antennal Lobe Lateral Cluster exhibit Diverse Morphological and Neurophysiological Characteristics
Authors: Lee Seong-Gyu , Celestino Christine Fogarty , Stagg Jeffrey , Kleineidam Christoph , Vickers Neil J.
Published: March 2018

Olfactory projection neurons convey information from the insect antennal lobe (AL) to higher centers in the brain. Many studies on moths have reported excitatory projection neurons with cell bodies in the medial cell cluster (mcPNs) that predominantly send an axon from the AL to calyces of the mushroom body (CA) via the medial antennal lobe tract (mALT) and then to the lateral horn (LH) of the protocerebrum. These neurons tend to have dendritic arbors restricted to a single glomerulus (i.e. they are uniglomerular). In this study, we report on the physiological and morphological properties of a group of pheromone-responsive olfactory projection neurons with cell bodies in the moth AL lateral cell cluster (lcPNs) of two heliothine moth species. While mcPNs typically exhibit a narrow odor tuning range related to the restriction of their dendritic arbors within a single glomerulus, lcPNs exhibited an array of morphological and physiological configurations. Pheromone-responsive lcPNs varied in their associations with glomeruli (uniglomerular and multiglomerular), dendritic arborization structure and connections to higher brain centers with projections primarily through the lateral antennal lobe tract and to a lesser extent the mediolateral antennal lobe tract to a variety of protocerebral targets including ventrolateral and superior neuropils as well as LH. Physiological characterization of lcPNs also revealed a diversity of response profiles including those either enhanced by or reliant upon presentation of a pheromone blend. These responses manifested themselves as higher maximum firing rates and/or improved temporal resolution of pulsatile stimuli. lcPNs therefore participate in conveying a variety of olfactory information relating to qualitative and temporal facets of the pheromone stimulus to a more expansive number of protocerebral targets than their mcPN counterparts. The role of lcPNs in the overall scheme of olfactory processing is discussed.
A Cross-Platform Comparison of Student’s Perceptions of the Learning Environment in an Introductory Microbiology Course
Authors: Ramirez Melissa V. , Lee Virginia S. , Hamm Lindsay , Taveirne Michael E. , Lee Alice M.
Published: March 2018

Students’ positive perceptions of the learning environment increase retention and persistence in STEM disciplines. This study presents results from a Learning Environment Questionnaire administered at the beginning and end of the semester in a redesigned general/introductory microbiology course offered in traditional lecture, flipped and online sections. Split-sample t-tests and chi-squared tests were used for cross-section and within section analyses, respectively. The findings support the study hypothesis that student perceptions of the learning environment will vary as a function of platform. This work demonstrates the additional effect of the time in the semester when students complete the questionnaire and this effect on students’ perceptions over the course of the semester relative to their initial perceptions. The results of this study offer insight on student perceptions of the learning environment as universities embrace online education in introductory and gateway courses as a response to rising student enrollments and diminishing resources.
The Induction of Larval Resource Preference in Heterogeneous Habitats
Authors: Kumar Vrinda Ravi , Issar Swastika , Agashe Deepa
Published: March 2018

Animals often have to evaluate and choose between multiple food sources in their habitat, and these potentially complex decisions can have a large impact on their fitness. Among other factors, previous experience with an alternative resource can significantly increase subsequent preference for the resource ("induction of preference"). Such induction of resource preference is particularly relevant in spatially or temporally heterogeneous habitats. Although most mobile species – especially generalists – probably frequently encounter habitat heterogeneity, the impact of preference induction on individual behaviour and fitness in heterogeneous habitats is poorly understood. We analysed larval preference induction in wheat-adapted generalist red flour beetles (Tribolium castaneum) under three types of habitat heterogeneity. We first analysed the induction of larval preference for novel resources (other cereal flours) under temporal heterogeneity, exposing larvae to new resources during development. We found that larvae preferred a new resource if they experienced it recently, but that the magnitude of induction varied across resources. Interestingly, we also observed specific induction for a homogenous mix of wheat and a novel resource, with larvae preferring the mix over either pure resource. To analyse induction under spatial heterogeneity, we placed beetle eggs in one of two alternative resource patches and tested the preference of emerged larvae. Unexpectedly, hatching into a novel resource did not always induce preference. Finally, we found that induction of preference for new resources could be maladaptive for larval development. Together, our work demonstrates that experience-based plasticity of larval resource choice may strongly impact larval preference and fitness in heterogeneous habitats.
Muramyl endopeptidase Spr contributes to intrinsic vancomycin resistance inSalmonella entericaserovar Typhimurium
Authors: Vestö Kim , Huseby Douglas L , Iina Snygg , Wang Helen , Hughes Diarmaid , Rhen Mikael
Published: March 2018

The impermeability barrier provided by the outer membrane of enteric bacteria, a feature lacking in Gram-positive bacteria, plays a major role in maintaining resistance to numerous antimicrobial compounds and antibiotics. Here we demonstrate that mutational inactivation ofspr, coding for a muramyl endopeptidase, significantly sensitizesSalmonella entericaserovar Typhimurium to vancomycin without any accompanying apparent growth defect or outer membrane destabilization. A similar phenotype was not achieved by deleting themepA, pbpG, nlpC, yebAoryhdOgenes coding for functional homologues to Spr. Thesprmutant revealed increased autolytic behavior in response to not only vancomycin, but also to penicillin G, an antibiotic for which the mutant displayed a wild-type MIC. A screen for suppressor mutations of thesprmutant phenotype revealed that deletion oftsp(prc), encoding a periplasmic carboxypeptidase involved in processing Spr and PBP3, restored intrinsic resistance to vancomycin and reversed the autolytic phenotype of ansprmutant. Our data suggest that Spr contributes to intrinsic antibiotic resistance in S. Typhimurium without directly affecting the outer membrane permeability barrier. Furthermore, our data suggests that compounds that target specific cell wall endopeptidases might have the potential to expand the activity spectrum of traditional Gram-positive antibiotics.
Metabolic and signalling network map integration: application to cross-talk studies and omics data analysis in cancer
Authors: Sompairac Nicolas , Modamio Jennifer , Barillot Emmanuel , Fleming Ronan M. T. , Zinovyev Andrei , Kuperstein Inna
Published: March 2018

Background

The interplay between metabolic processes and signalling pathways remains poorly understood. Global, detailed and comprehensive reconstructions of human metabolism and signalling pathways exist in the form of molecular maps, but they have never been integrated together. We aim at filling in this gap by creating an integrated resource of both signalling and metabolic pathways allowing a visual exploration of multi-level omics data and study of cross-regulatory circuits between these processes in health and in disease.

Results

We combined two comprehensive manually curated network maps. Atlas of Cancer Signalling Network (ACSN), containing mechanisms frequently implicated in cancer; and ReconMap 2.0, a comprehensive reconstruction of human metabolic network. We linked ACSN and ReconMap 2.0 maps via common players and represented the two maps as interconnected layers using the NaviCell platform for maps exploration. In addition, proteins catalysing metabolic reactions in ReconMap 2.0 were not previously visually represented on the map canvas. This precluded visualisation of omics data in the context of ReconMap 2.0. We suggested a solution for displaying protein nodes on the ReconMap 2.0 map in the vicinity of the corresponding reaction or process nodes. This permits multi-omics data visualisation in the context of both map layers. Exploration and shuttling between the two map layers is possible using Google Maps-like features of NaviCell. The integrated ACSN-ReconMap 2.0 resource is accessible online and allows data visualisation through various modes such as markers, heat maps, bar-plots, glyphs and map staining. The integrated resource was applied for comparison of immunoreactive and proliferative ovarian cancer subtypes using transcriptomic, copy number and mutation multi-omics data. A certain number of metabolic and signalling processes specifically deregulated in each of the ovarian cancer sub-types were identified.

Conclusions

As knowledge evolves and new omics data becomes more heterogeneous, gathering together existing domains of biology under common platforms is essential. We believe that an integrated ACSN-ReconMap 2.0 resource will help in understanding various disease mechanisms and discovery of new interactions at the intersection of cell signalling and metabolism. In addition, the successful integration of metabolic and signalling networks allows broader systems biology approach application for data interpretation and retrieval of intervention points to tackle simultaneously the key players coordinating signalling and metabolism in human diseases.
LIPEA: Lipid Pathway Enrichment Analysis
Authors: Acevedo Aldo , Durán Claudio , Ciucci Sara , Gerl Mathias , Cannistraci Carlo Vittorio
Published: March 2018

Motivation

Analyzing associations among multiple omic variables to infer mechanisms that meaningfully link them is a crucial step in systems biology. Gene Set Enrichment Analysis (GSEA) was conceived to pursue this aim in computational genomics, unveiling significant pathways associated to certain gene signatures under investigation. Lipidomics is a rapidly growing omic field, and absolute quantification of lipid abundance by shotgun mass spectrometry is generating high-throughput datasets that depict lipid metabolism in a plethora of conditions and organisms. In addition, high-throughput lipidomics represents a new important ally to develop personalized medicine approaches, investigate the causes and predict effective biomarkers in metabolic diseases, and not only.

Results

Here, we present Lipid Pathway Enrichment Analysis (LIPEA), a web-tool for over-representation analysis of lipid signatures and detection of the biological pathways in which they are enriched. LIPEA is a new valid resource for biologists and physicians to mine pathways significantly associated to a set of lipids, helping them to discover whether common and collective mechanisms are hidden behind those lipids. LIPEA was extensively tested and we provide two examples where our system gave successfully results related with Major Depression Disease (MDD) and insulin re-sistance.

Availability

The tool is available as web platform at https://lipea.biotec.tu-dresden.de.
Predicting improved protein conformations with a temporal deep recurrent neural network
Authors: Pfeiffenberger Erik , Bates Paul A.
Published: March 2018

Accurate protein structure prediction from amino acid sequence is still an unsolved problem. The most reliable methods centre on template based modelling. However, the accuracy of these models entirely depends on the availability of experimentally resolved homologous template structures. In order to generate more accurate models, extensive physics based molecular dynamics (MD) refinement simulations are performed to sample many different conformations to find improved conformational states. In this study, we propose a deep recurrent network model, called DeepTrajectory, that is able to identify these improved conformational states, with high precision, from a variety of different MD based sampling protocols. The proposed model learns the temporal patterns of features computed from the MD trajectory data in order to classify whether each recorded simulation snapshot is an improved conformational state, decreased conformational state or a none perceivable change in state with respect to the starting conformation. The model is trained and tested on 904 trajectories from 42 different protein systems with a cumulative number of more than 1.7 million snapshots. We show that our model outperforms other state of the art machine-learning algorithms that do not consider temporal dependencies. To our knowledge, DeepTrajectory is the first implementation of a time-dependent deep-learning protocol that is re-trainable and able to adapt to any new MD based sampling procedure, thereby demonstrating how a neural network can be used to learn the latter part of the protein folding funnel.