bluuebunny/crossref_metadata_2025 huggingface dataset:
A 1-Month Physical Therapy–Based Outpatient Program for Adults Awaiting Lung Transplantation: A Retrospective Analysis of Exercise Capacity, Symptoms, and Quality of Life
Authors: Byrd Rebecca , Smith Patrick , Mohamedaly Omar , Snyder Laurie D. , Pastva Amy M.
Published: July 2018

Purpose:

Rehabilitation can improve health outcomes in candidates for lung transplantation. The purpose of this study was to retrospectively evaluate the effect of a 1-month physical therapy (PT)–based outpatient program on exercise capacity, symptoms, quality of life (QOL) and examine predictors of functional outcome changes in adults awaiting lung transplantation.

Methods:

Participants (n = 141) completed a 23-session exercise and educational program over 1 month. Outcomes included 6-minute walk distance (6MWD), San Diego shortness of breath questionnaire (SOBQ), Center for Epidemiological Studies-Depression Scale (CESD), and Ferrans and Powers QOL Index Pulmonary Version III.

Results:

Participants were older (median age 63) with restrictive (59%) or obstructive (24%) disease. Moderate-to-large improvements in 6MWD were observed (69 m, P < .001, d = 0.72), independent of demographics, symptoms, and QOL. Lower initial 6MWD and lower oxygen utilization were associated with greater 6MWD improvements, with largest gains occurring in initial 6MWD <305 m. Small-to-moderate improvements were observed on CESD (P < .001, d = 0.26) and in overall QOL (P < .001, d = 0.27), with a nonsignificant improvement observed on SOBQ (P = .248, d = 0.13).

Conclusions:

Completion of a 1-month PT-based outpatient rehabilitation program was associated with improved exercise capacity, depressive symptoms, and QOL.
Cardiovascular and Pulmonary Research: The Year (2017) in Review
Authors: Ricard Paul E. H. , Cahalin Lawrence P.
Published: July 2018

Practitioners need access to and the ability to openly discuss advancement in practice and concepts as they apply to the practice of cardiovascular and pulmonary physical therapy (PT). Lack of accessibility to research literature, limited personal time, or insufficient knowledge to adequately review the breadth of literature published each year can hinder this process. This article provides an overview of cardiovascular an d pulmonary research published in 2017 that the authors believe is most important and relevant or speaks to the volume or trend of current topics in the clinical practice of cardiovascular and pulmonary PT. Several key sections are used to describe selected articles and are followed by a brief overview of the clinical relevance of this material presented at the 2018 Combined Sections Meeting in New Orleans, Louisiana.
Evaluation of Limb Muscle Strength and Function in People With Chronic Obstructive Pulmonary Disease
Authors: Mathur Sunita , Dechman Gail , Bui Kim-Ly , Camp Pat G. , Saey Didier
Published: July 2018

Purpose:

Muscle weakness is an observable consequence of limb muscle dysfunction in people with chronic obstructive pulmonary disease (COPD). The purpose of this review is to describe clinically applicable methods of muscle strength testing and functional tests that are associated with muscle strength in people with COPD.

Summary of Key Points:

Several tests and devices for evaluating muscle strength have been described in COPD. Isometric quadriceps strength testing, which is associated with clinical outcomes in COPD, can be reliably tested using fixed dynamometers or strain gauges in clinical and laboratory settings. Functional tests that are correlated with muscle strength in COPD include the Stair Climb Power Test, Sit-to-Stand test, and Timed Up and Go test. These tests are easy to conduct in the clinical setting and are relevant to daily activities; however, performance depends on factors such as balance and coordination in addition to leg muscle strength.

Conclusions:

Muscle strength assessment should be considered an integral part of the evaluation of people with COPD. Clinicians and researchers can select from a variety of valid and reliable tests to evaluate muscle strength based on their available resources and goals of the patient.
Correlation Between Functional Ability and Physical Activity in Individuals With Transtibial Amputations: A Cross-Sectional Study
Authors: Pepin Marie-Eve , Devour Alegra , Coolsaet Robin , Galen Sujay
Published: July 2018

Purpose:

The aim of this study was to investigate the association between functional ability and physical activity (PA) in individuals with transtibial amputations.

Methods:

Twenty participants with unilateral transtibial amputation were recruited from outpatient prosthetic fitting clinics. Subjects completed the amputee mobility predictor (AMP), the L-Test, timed up and go (TUG), 2-minute walk test (TMWT), and self-reported activity restrictions questionnaire (Prosthesis Evaluation Questionnaire-Mobility Subscale). The subject's PA was monitored continuously for 7 days using a body-worn PA monitor. Descriptive statistics, comparison of mean values, and analysis of associations were performed with significance set at P < .05.

Results:

Data from 19 subjects were used for analysis. Descriptive analysis indicated that the participants spent on average 19.7 (SD = 0.5) hours per day laying/sitting, 3.5 (SD = 0.4) hours standing, 0.77 (SD = 0.07) hours stepping, and walked an average of 3145 (SD = 378) steps/day. There was a moderate to good correlation between the AMP and the average steps/day (r = 0.535, P = .009) and a fair correlation between the TMWT, the TUG, and steps per day (r = 0.404 and r = −0.442, respectively, P < .05).

Conclusions:

Individuals with transtibial amputations on average recorded 3145 steps/day, placing them in the sedentary category. The number of steps per day had a moderate to good correlation with the AMP and a fair correlation with the TUG and TMWT.
Spatial Distribution of Pancreatic Stones in Chronic Pancreatitis
Authors: Zeng Xiang-Peng , Zhu Xing-Yi , Li Bai-Rong , Pan Chun-Shu , Hao Lu , Pan Jun , Wang Dan , Bi Ya-Wei , Ji Jun-Tao , Xin Lei , Liao Zhuan , Du Ting-Ting , Lin Jin-Huan , Zhang Di , Ye Bo , Zou Wen-Bin , Chen Hui , Xie Ting , Zheng Zhao-Hong , Li Zhao-Shen , Hu Liang-Hao
Published: July 2018

Objectives

The aim of this study was to establish a standard to describe the spatial distribution of pancreatic stones in chronic pancreatitis (CP).

Methods

Two hundred forty-seven CP patients with pancreatic stones from June to December 2012 were enrolled. Two-dimensional images from coronal projection of 3-dimensional computed tomography images of pancreatic stones were gained. The number (n) of all stones and the geometric standard deviation (σ) of distances between the centroid of all stones and the centroids of every stone that represented the spatial distribution nonuniformity were calculated by Stone Reconstruction and Identification Programming System.

Results

The mean value of n and σ were 13.6 and 22.5; n > 13.6 and σ > 22.5 were determined as “multistones” and “nonuniform,” respectively. Compared with alcoholic CP, idiopathic CP was less prone to multistones (odds ratio [OR], 0.310) and more prone to nonuniform (OR, 3.247). Pancreatic pseudocyst (OR, 2.211) in CP course was a risk factor of multistones, whereas diabetes mellitus in first-/second-/third-degree relatives (OR, 0.382) was a protective factor. Age at diagnosis of pancreatic stones (OR, 1.022) was a risk factor of nonuniformity.

Conclusions

Compared with idiopathic CP, alcoholic CP patients were prone to more pancreatic stones that distribute more uniformly.
Adverse Oncologic Impact of New-Onset Diabetes Mellitus on Recurrence in Resected Pancreatic Ductal Adenocarcinoma
Authors: Lee Seungho , Hwang Ho Kyoung , Kang Chang Moo , Lee Woo Jung
Published: July 2018

Objectives

Diabetes mellitus (DM) is prevalent with pancreatic ductal adenocarcinoma (PDAC). Importantly, new-onset DM is characteristic of the disease and could be an early sign of PDAC. The clinical outcome of PDAC with new-onset DM may differ from that in patients without DM or long-standing DM.

Methods

We retrospectively reviewed medical records of PDAC patients who underwent curative resection between 2006 and 2014. New-onset DM was defined as a diagnosis of DM within 24 months before the diagnosis of PDAC. Survival analysis and Cox regression were performed to evaluate oncologic outcomes.

Results

No significant differences in clinical characteristics were found in 3 groups. Overall survival of patients with new-onset DM was worse than non-DM (22 vs 33 months, P = 0.039). New-onset DM was highly associated with early recurrence (hazard ratio, 1.451; 95% confidence interval, 1.054–1.999; P = 0.022). Poor oncologic outcome of new-onset DM was more pronounced in low T stage patients (overall survival in low vs high T stage, 33 vs 18 months; P = 0.129).

Conclusions

Pancreatic ductal adenocarcinoma with new-onset DM has worse oncologic outcomes than non-DM or long-standing DM. These results suggest that new-onset DM represents aggressive tumor biology, especially in the early stage of PDAC.
A Clinical Model for the Early Diagnosis of Acute Pancreatitis in the Emergency Department
Authors: Jin David X. , Lacson Ronilda , Cochon Laila R. , Alper Emily C. , McNabb-Baltar Julia , Banks Peter A. , Khorasani Ramin
Published: July 2018

Objective

This study aimed to develop a diagnostic model that predicts acute pancreatitis (AP) risk before imaging.

Methods

Emergency department patients with serum lipase elevated to 3 times the upper limit of normal or greater were identified retrospectively (September 1, 2013–August 31, 2015). An AP diagnosis was established by expert review of full hospitalization records. Candidate predictors included demographic and clinical characteristics at presentation. Using a derivation set, a multivariable logistic regression model and corresponding point-based scoring system was developed to predict AP. Discrimination accuracy and calibration were assessed in a separate validation set.

Results

In 319 eligible patients, 182 (57%) had AP. The final model (area under curve, 0.92) included 8 predictors: number of prior AP episodes; history of cholelithiasis; no abdominal surgery (prior 2 months); time elapsed from symptom onset; pain localized to epigastrium, of progressively worsening severity, and severity level at presentation; and extent of lipase elevation. At a diagnostic risk threshold of 8 points or higher (≥99%), the model identified AP with a sensitivity of 45%, and a specificity and a positive predictive value of 100%.

Conclusions

In emergency department patients with lipase elevated to 3 times the upper limit of normal or greater, this model helps identify AP risk before imaging. Prospective validation studies are needed to confirm diagnostic accuracy.
Pathologic Evaluation of Surgical Margins in Pancreatic Cancer Specimens Using Color Coding With Tissue Marking Dyes
Authors: Takahashi Daigoro , Kojima Motohiro , Sugimoto Motokazu , Kobayashi Shin , Takahashi Shinichiro , Konishi Masaru , Gotohda Naoto , Nagino Masato
Published: July 2018

Objectives

Processing of pancreatoduodenectomy specimens is not standardized; the clinical impact of pathologic surgical margins remains controversial. We used the color-coding method using tissue-marking dyes to evaluate margin status of resected specimens to assess its association with postoperative recurrence.

Methods

We developed a unified processing approach to assess pancreatoduodenectomy specimens. Five surgical margins of resected pancreatic specimens were marked with 5 colors. Microscopic resection margin distance (RMD) from margin closest to the tumor was evaluated for each surgical margin. Forty patients assessed using nonunified protocols, and 98 patients assessed using unified protocols were included.

Results

The frequency of tumors with RMD of 1 mm or less in posterior margin was significantly lower and that in portal vein/superior mesenteric vein margin was significantly higher in unified protocol group than in nonunified protocol group (P < 0.001). In unified protocol group, tumors with RMD of 1 mm or less correlated with locoregional recurrence (P = 0.025) and recurrence-free survival (P = 0.030). Multivariate analysis revealed that tumor size and lymph node metastasis were independent indicators for disease recurrence.

Conclusions

Resection margin distance of 1 mm or less was a predictor for disease recurrence, particularly for locoregional recurrence. Early detection of small-sized tumors without lymph node metastasis is necessary for improved clinical outcomes in pancreas cancers.
The Impact of the End-of-Life Nurse Education Consortium on Attitudes of Undergraduate Nursing Students Toward Care of Dying Patients
Authors: Lin Jie , Supiano Katherine P. , Madden Connie , McLeskey Nanci
Published: July 2018

This mixed methods study explored the impact of the End-of-Life Nursing Education Consortium (ELNEC)–Undergraduate Curriculum on perceived preparedness of undergraduate nursing students in the care of dying patients and the relationship between personal loss experience and undergraduate nursing students’ attitudes regarding the ELNEC-Undergraduate Curriculum. Of the 36 undergraduate nursing students who completed ELNEC, 24 reported a personal loss of a close family member or friend to death and 12 reported no loss. Findings confirmed the overall positive impact and acceptability of ELNEC, but this effect was observed differently between students with and without previous loss. Students with personal loss were more aware of the challenges of end-of-life care before taking ELNEC and incorporated the content into a greater sense of preparedness. Study recommendations include placing ELNEC within didactic instruction by well-prepared faculty, creating simulation debrief groups composed of both students with and without loss, and faculty attention to the loss experiences of students.
Palliative Care and Stroke
Authors: Molidor Stephanie , Overbaugh Kristen J. , James Deborah , White Carole L.
Published: July 2018

Stroke survivors often experience life-altering functional and cognitive changes and burdensome symptoms. Palliative care could provide additional support to improve outcomes of stroke patients and their families. The purpose of this review was to describe how palliative care is conceptualized and implemented within stroke care.

An integrative review of the literature published between 1990 and 2016 using the terms “palliative care,” “stroke,” or “acute stroke” was conducted. Of the 363 articles identified, 44 were screened, 21 met inclusion criteria, and 2 additional articles were identified through reference list review, resulting in a final sample of 23 articles.

Palliative care was predominantly understood as end-of-life care and was most commonly offered in acute stages when patients were expected to die. Patients, families, and providers reported challenges surrounding decision making, uncertainty regarding transitions to palliative care, and needs related to communication and physical and psychosocial support. The quality of the research was moderate to good but was limited by retrospective designs, reliability of data collection procedures and tools, recall bias, and generalizability.

This review highlights gaps in access to palliative care throughout the illness trajectory and underscores the need for study of models that integrate palliative care into stroke care.
Simulation With Advanced Care Providers in a Nurse Residency Program
Authors: Justus Phyllis D. , Appel Susan J.
Published: July 2018

As many hospitals are implementing residency programs for new graduate nurses, the utilization of high-fidelity simulation has become common. This pilot program compared simulation with participation of only new graduate nurses and new graduates with advanced care providers. Results found a statistically significant increase in knowledge of differing roles and skills in simulations that included both groups. Nursing professional development practitioners will find this helpful in designing residency programs for new graduate nurses.
Promoting Learning Using Case-Based Strategies in Nursing Professional Development
Authors: Pilcher Jobeth
Published: July 2018

Realistic situations can be used to develop a variety of learning activities, including case reports, standard and evolving case studies, and problem-based learning. Most case-based strategies are aimed at promoting learner interaction, problem solving, and collaborative learning. This article provides a description and discussion of how each can be applied. Hints for developing the different types of cases are included, followed by specific examples.
Interprofessional Education
Authors: Hovland Cynthia A. , Whitford Maureen , Niederriter Joan
Published: July 2018

The central research questions of this study sought to understand the experiences of nursing students participating in an interprofessional simulation experience. This study used a nonrandom, purposive sample of 75 nursing students from one Midwestern university. Conventional content analysis was used to analyze the data. Five primary themes emerged from the data: (a) benefits of interprofessional collaboration, (b) communication, (c) “real-life” learning, (d) increased self-confidence, and (e) intraprofessional collaboration. The results of this study reveal the value of participation in interprofessional simulation activities and emphasize the need for continued development and implementation of such activity into nursing education.
Functional Maturation and In Vitro Differentiation of Neonatal Porcine Islet Grafts
Authors: Hassouna Tarek , Seeberger Karen L. , Salama Bassem , Korbutt Gregory S.
Published: July 2018

Background

There is a strong rationale to pursue the use of neonatal porcine islets (NPIs) as an unlimited source of islets for clinical xenotransplantation. Because NPIs are composed of immature insulin producing beta (ß) cells and ductal precursor cells, they provide an ideal model to examine culture conditions to enhance ß cell proliferation and/or ß cell neoformation from ductal cells. In an attempt to optimize the potential of NPIs as a source of ß cell grafts, we used an in vitro differentiation protocol and measured its effect on the functional maturation and differentiation of NPIs.

Methods

Pancreata from 1- to 3-day-old neonatal pigs were digested and cultured in standard Ham's F10 media for 5 days. Each independent preparation was then further cultured in Dulbecco's modified Eagle medium nutrient mixture-F12 differentiation media containing growth factors added in a stepwise fashion, or cultured in control Ham's F10 media. After 20 days in culture, islets were assessed for insulin secretory capacity, cellular composition, gene expression, and metabolic activity after transplantation in immunodeficient mice with diabetes.

Results

Compared with control islets, differentiated islets exhibited a significantly higher proportion of endocrine cells, proliferating cell nuclear antigen double positive ß cells, and an enhanced glucose-stimulated insulin secretory activity. Mice transplanted with differentiated islets had significantly lower blood glucose values at weeks 18 and 20 compared with nondifferentiated controls and were shown to be more glucose tolerant.

Conclusions

Culturing NPIs in a 20-day stepwise differentiation media increases the proportion of endocrine cells and augments both in vitro and in vivo function of the islets.
Is it impossible to acquire absolute pitch in adulthood?
Authors: Wong Yetta Kwailing , Lui Kelvin F. H. , Yip Ken H.M. , Wong Alan C.-N.
Published: July 2018

Absolute pitch (AP) refers to the rare ability to name the pitch of a tone without external reference. It is widely believed that AP is only for the selected few with rare genetic makeup and early musical training during the critical period. Accordingly, acquiring AP in adulthood is impossible. Previous studies have not offered a strong test of the effect of training because of issues like small sample size and insufficient training. In three experiments, adults learned to name pitches in a computerized and personalized protocol for 12 to 40 hours. They improved considerably, with a continuous distribution of learning progress among them. 14% of the participants (6 out of 43) were able to name twelve pitches at accuracy of 90% or above, comparable to that of ‘AP possessors’ as defined in the literature. In general, AP learning showed classic characteristics of perceptual learning, including generalization of learning dependent on the training stimuli, and sustained improvement for at least one to three months. Overall, the finding that AP continues to be learnable in adulthood calls for reconsidering the role of learning in the occurrence of AP. The finding also pushes the field to pinpoint and explain, if any, the differences between the aspects of AP more trainable in adulthood and the aspects of AP that are potentially exclusive for the few exceptional AP possessors.
Evaluation of habitat protection under the European Natura 2000 conservation network – the example for Germany
Authors: Friedrichs Martin , Hermoso Virgilio , Bremerich Vanessa , Langhans Simone D.
Published: July 2018

The world’s largest network of protected areas - Natura 2000 (N2000) - has been implemented to protect Europe’s biodiversity. N2000 is built upon two cornerstones, the Birds Directive, which lists 230 bird species and the Habitats Directive, which lists next to a variety of species 230 habitat types, to be protected. There is evidence of the positive impact of the Directives on the EU’s biodiversity, although the overall improvement reported for species in favourable condition in the last assessment was low. However, most of the assessments are species focused, while habitats have received very little attention. Here we developed a generic workflow, which we exemplified for Germany, to assess the status of habitat coverage within the N2000 network, combining information from publicly available data sources. Applying the workflow allows identifying gaps in habitat protection, followed by the prioritization of potential areas of high protection value, using the conservation planning software Marxan. We found that, in Germany, N2000 covers all target habitats. However common habitats were proportionally underrepresented relative to rare ones, which contrasts with comparable studies for species. Moreover, the German case study suggests that especially highly protected areas (i.e. covered by more than 90% with N2000 sites) build an excellent basis towards a cost-effective and efficient conservation network. Our workflow provides a generic approach to deal with the popular problem of missing habitat distribution data outside of N2000 sites, information which is however crucial for managers to plan conservation action appropriately across Europe. To avoid a biased representation of habitat types within N2000, our results underpin the importance of defining qualitative and quantitative conservation targets which will allow assessing the trajectory of habitat protection in Europe as well as adjusting the network accordingly - a future necessity in the light of climate change.
Physiological Dynamic Compression Regulates Central Energy Metabolism in Primary Human Chondrocytes
Authors: Salinas Daniel , Mumey Brendan M. , June Ronald K.
Published: July 2018

Chondrocytes use the pathways of central metabolism to synthesize molecular building blocks and energy for cartilage homeostasis. An interesting feature of thein vivochondrocyte environment is the cyclical loading generated in various activities (e.g. walking). However, it is unknown if central metabolism is altered by mechanical loading. We hypothesized that physiological dynamic compression alters central metabolism in chondrocytes to promote production of amino acid precursors for matrix synthesis. We measured the expression of central metabolites (e.g. glucose, its derivatives, and relevant co-factors) for primary human osteoarthritic chondrocytes in response to 0-30 minutes of compression. To analyze the data, we used principal components analysis and ANOVA simultaneous components analysis, as well as metabolic ﬂux analysis. Compression induced metabolic responses consistent with our hypothesis. Additionally, these data show that chondrocyte samples from different patient donors exhibit different sensitivity to compression. Most important, we ﬁnd that grade IV osteoarthritic chondrocytes are capable of synthesizing non-essential amino acids and precursors in response to mechanical loading. These results suggest that further advances in metabolic engineering of chondrocyte mechanotransduction may yield novel translational strategies for cartilage repair.
The return to water in ancestralXenopuswas accompanied by a novel mechanism for producing and shaping vocal signals
Authors: Kwong-Brown Ursula , Tobias Martha L. , Elias Damian O. , Hall Ian C. , Elemans Coen P.H. , Kelley Darcy B.
Published: July 2018

Species-specific vocal signals allow listeners to locate potential mates. During the tetrapod transition from water to land, lungs replaced gills, allowing expiration to drive sound production. Several groups,e.g. cetaceans and some frogs, then returned to water. Here we explore how air-driven sound production changed upon re-entry and how essential acoustic information on species identity was preserved in the secondarily aquatic frogXenopus. We filmed movements of cartilage and muscles during evoked sound production in isolated larynges. Our results refute the current theory forXenopusvocalization, cavitation, and instead favor sound production by mechanical excitation of laryngeal resonance modes following rapid separation of laryngeal arytenoid discs. The resulting frequency resonance modes (dyads) are intrinsic to the larynx rather than due to neuromuscular control. We show that dyads are a distinctive acoustic signature across species. While dyad component frequencies overlap across species, their ratio is shared within eachXenopusclade and thus provide information on species identity, potentially facilitating both conspecific localization and ancient species divergence.
Triggering mechanisms for motor actions: A mini meta-analysis and experimental data
Authors: Leow Li-Ann , Uchida Aya , Egberts Jamie-Lee , Riek Stephan , Lipp Ottmar V. , Tresilian James , Marinovic Welber
Published: July 2018

Motor actions can be released much sooner than normal when the go-signal is of very high intensity (> 100dBa). Although statistical evidence from individual studies has been mixed, it has been assumed that sternocleidomastoid (SCM) muscle activity could be used to distinguish between two neural circuits involved in movement triggering. We summarized meta-analytically the available evidence for this hypothesis, comparing the difference in premotor reaction time (RT) of actions where SCM activity was elicited (SCM+ trials) by loud acoustic stimuli against trials in which it was absent (SCM- trials). We found ten studies, all reporting comparisons between SCM+ and SCM- trials. Our mini meta-analysis showed that premotor RTs are faster in SCM+ than in SCM- trials. We also present experimental data showing the effects of foreperiod predictability can induce differences in RT that would be of similar size to those attributed to the activation of different neurophysiological pathways to trigger prepared actions. We discuss plausible physiological mechanisms that would explain differences in premotor RTs between SCM+ and SCM-trials.
IDEA: a web server for Interactive Differential Expression Analysis with R Packages
Authors: Zhao Qi , Xie Yubin , Nie Peng , Diao Rucheng , Sun Lichen , Zuo Zhixiang , Ren Jian
Published: July 2018

Differential expression (DE) analysis is a fundamental task in the downstream analysis of the next-generation sequencing (NGS) data. Up to now, a number of R packages have been developed for detecting differentially expressed genes. Although R language has an interaction-oriented programming design, for many biology researchers, a lack of basic programming skills has greatly hindered the application of these R packages. To address this issue, we developed the Interactive Differential Expression Analyzer (IDEA), a Shiny-based web application integrating the differential expression analysis related R packages into a graphical user interface (GUI), allowing users to run the analysis without writing any new code. A wide variety of charts and tables are generated to facilitate the interpretation of the results. In addition, IDEA also provides a combined analysis framework which helps to reconcile any discrepancy from different computational methods. As a public data analysis server, IDAE is implemented in HTML, CSS and JavaScript, and is freely available at http://idea.renlab.org.
Gut Microbial succession during conventionalization of germfree chicken
Authors: Thomas Milton , Wongkuna Supapit , Ghimire Sudeep , Doerner Kinchel C. , Singery Aaron , Nelson Eric , Woyengo Tofuko , Chankhamhaengdecha Surang , Janvilisri Tavan , Scaria Joy
Published: July 2018

A gnotobiotic chicken model was developed to study the succession of intestinal microflora from hatching to 18 days of age. Intestinal samples were collected from a local population of feral chickens and administered orally to germ-free 3 day old chicks. Animals were enthanized on 0, 9 and 18 days of age and intestinal samples were collected and subjected to genomic analysis. The five most prevalent phyla were Bacteroidetes (45.73±3.35%), Firmicutes (36.47±2.60%), Proteobacteria (8.28±0.91%), Actinobacteria (5.09±0.52%), and Spriochetes (2.10±0.38%). Principle coordinate analysis indicated the 0, 9 day and 18 day variables clustered together and the microbial communities changed temporally. The Morista-Horn index values ranged from 0.72 to 1, indicating the communities at 0, 9 or 18 days were more similar than dissimilar. The predicted functional profiles of the microbiomes of 0, 9 and 18 days were also similar. These results indicate the gnotobiotic chicks stably maintain the phylogentic diversity and predicted metabolic functionality of the inoculum community.

Importance

The domestic chicken is the cornerstone of animal agriculture worldwide with a flock population exceeding 40 billion birds/year. It serves as the economically valuable source of protein globally. Microbiome of poultry has important effects on chicken growth, feed conversion, immune status and pathogen resistance. The significance of our research is in developing a gnotobiotic chicken model to study chicken gut microbiota function. Our experimental model shows that young germfree chicks are able to colonize diverse set of gut bacteria. Therefore, besides using this model to study mechanisms of gut microbiota interactions in the chicken gut, our model could be also used for applied aspects such as determining the safety and efficacy of new probiotic strains derived from chicken gut microbiota.
A new computational method for membrane compressibility: Bilayer mechanical thickness revisited
Authors: Doktorova M. , LeVine M.V. , Khelashvili G. , Weinstein H.
Published: July 2018

Because lipid bilayers can bend and stretch in ways similar to thin elastic sheets, physical models of bilayer deformation have utilized mechanical constants such as the moduli for bending rigidity (κC) and area compressibility (KA). However, the use of these models to quantify the energetics of membrane deformation associated with protein-membrane interactions and the membrane response to stress is often hampered by the shortage of experimental data suitable for the estimation of the mechanical constants of various lipid mixtures. While computational tools such as Molecular Dynamics (MD) simulations can provide alternative means to estimateKAvalues, current approaches suffer significant technical limitations. Here, we present a novel computational framework that allows for a direct estimation ofKAvalues for individual bilayer leaflets. The theory is based on the concept of elasticity and derivesKAfrom real-space analysis of local thickness fluctuations sampled in MD simulations. We explore and validate the model on a large set of single and multicomponent bilayers of different lipid composition and sizes, simulated at different temperatures. The calculated bilayer compressibility moduli agree with values estimated previously from experiments and those obtained from a standard computational method based on a series of constrained tension simulations. We further validate our framework in a comparison with an existing polymer brush model (PBM) and confirm the PBM’s predicted linear relationship with proportionality coefficient of 24 using elastic parameters calculated from the simulation trajectories. The robustness of the results that emerge from the new method allows us to revisit the origins of the bilayer mechanical (compressible) thickness and in particular, its dependence on acyl chain unsaturation and the presence of cholesterol.
Impact of Different Acoustic Components on EEG-based Auditory Attention Decoding in Noisy and Reverberant Conditions
Authors: Aroudi Ali , Mirkovic Bojana , De Vos Maarten , Doclo Simon
Published: July 2018

Recently, a least-squares-based method has been proposed to decode auditory attention from single-trial EEG recordings for an acoustic scenario with two competing speakers. This method aims at reconstructing the attended speech envelope from the EEG recordings using a trained spatio-temporal filter. While the performance of this method has been mainly studied for noiseless and anechoic acoustic conditions, it is important to fully understand its performance in realistic noisy and reverberant acoustic conditions. In this paper, we investigate auditory attention decoding (AAD) using EEG recordings for different acoustic conditions (anechoic, reverberant, noisy, and reverberant-noisy). In particular, we investigate the impact of different acoustic conditions for AAD filter training and for decoding. In addition, we investigate the influence on the decoding performance of the different acoustic components (i.e. reverberation, background noise and interfering speaker) in the reference signals used for decoding and the training signals used for computing the filters. First, we found that for all considered acoustic conditions it is possible to decode auditory attention with a decoding performance larger than 90%, even when the acoustic conditions for AAD filter training and for decoding are different. Second, when using reference signals affected by reverberation and/or background noise, a comparable decoding performance as when using clean reference signals can be obtained. In contrast, when using reference signals affected by the interfering speaker, the decoding performance significantly decreases. Third, the experimental results indicate that it is even feasible to use training signals affected by reverberation, background noise and/or the interfering speaker for computing the filters.
Cancer cell exosomes can initiate malignant cell transformation
Authors: Stefanius Karoliina , Servage Kelly A. , de Souza Santos Marcela , Toombs Jason , Gray Hillery Fields , Chimalapati Suneeta , Kim Min S. , Brekken Rolf A. , Orth Kim
Published: July 2018

Cancer evolves through a multistep process that occurs by the temporal accumulation of genetic mutations mediated by intracellular and extracellular cues. We observe that exosomes isolated from pancreatic cancer cells, but not normal pancreatic cells, can initiate the first step of malignant cell transformation. Injection of exosome-initiated transformed cells into mice results in aggressive tumor growth. Using proteomic profiling and DNA sequencing of exosome-treated and transformed cells, we show that cancer cell exosomes act as a classic initiator by causing random genetic changes in recipient cells. Our studies provide new insight into a function of cancer cell exosomes and how they might specifically contribute to orchestrated local cell transformation.

One Sentence Summary

Exosomes function as aninitiatorof tumor formation.
Allatostatin C/AstC-R2 is a Novel Pathway to Modulate Circadian Activity Pattern in Drosophila
Authors: Díaz Madelen M. , Schlichting Matthias , Abruzzi Katharine C. , Rosbash Michael
Published: July 2018

Six neuropeptides are expressed within the Drosophila brain circadian network. Our previous mRNA profiling suggested that AllatostatinC is a seventh neuropeptide and specifically expressed in dorsal clock neurons (DN1s). Our results here show that AstC is indeed expressed in DN1s, where it oscillates. AstC is also expressed in two less well-characterized circadian neuronal clusters, the DN3s and lateral posterior neurons (LPNs). Behavioral experiments indicate that clock neuron-derived AstC is required to mediate evening locomotor activity under short (winter-like) photoperiods. The AstC-Receptor 2 (AstC-R2) is expressed in LNds, the clock neurons that drive evening locomotor activity, and AstC-R2 is required in these neurons to modulate the same short photoperiod evening phenotype. Ex vivo calcium imaging indicates that AstC directly inhibits a single LNd neuron. The results suggest that a novel AstC/AstC-R2 signaling pathway, from dorsal circadian neurons to an LNd, regulates the behavioral response to changing photoperiod in Drosophila.
The hyperstability and composition ofGiardia’s ventral disc highlights the remarkable versatility of microtubule organelles
Authors: Nosala C. , Hagen K.D. , Chase T.M. , Jones K. , Loudermilk R. , Nguyen K. , Dawson S.C.
Published: July 2018

Giardiais a common protistan parasite that causes diarrheal disease worldwide. Motile trophozoites colonize the small intestine, attaching to the villi with the ventral disc, a unique and complex microtubule (MT) organelle. Attachment to the host epithelium allowsGiardiato resist peristalsis during infection of the host gastrointestinal tract. Despite our emerging view of the complexity of ventral disc architecture, we are still in the very preliminary stages of understanding how specific structural elements contribute to disc stability or generate forces for attachment. The ventral disc is a large, dome-shaped, spiral MT array decorated with microribbon-crossbridge protein complexes (MR-CB) that extend upward into the cytoplasm. To find additional disc-associated proteins (DAPs), we used a modified method for disc biochemical fractionation in high salt followed by shotgun proteomic analyses and validation by GFP-tagging. Using this method in conjunction with an ongoing subcellular localization screen, we identified 54 new DAPs. Of the 87 DAPs confirmed to date, 54 localize only to the disc, and the remainder localize to additional structures including the flagella, basal bodies, or median body. Almost one third of the known DAPs lack any homology to proteins in other eukaryotes and another one third simply contain ankyrin repeat domains. Many DAPs localize to specific structural regions of the disc, including the ventral groove region and disc margin. Lastly, we show that spiral singlet MT array comprising the disc is hyperstable and lacks dynamic instability, and we attribute these unique properties to the presence of both novel DAPs as well conserved MAPs and MIPs that are known to stabilize ciliary doublet and triplet MTs.
Distinct profiles of temporal and frontoparietal cortex in representing actions across vision and language
Authors: Wurm Moritz F. , Caramazza Alfonso
Published: July 2018

Both temporal and frontoparietal brain areas are associated with the representation of knowledge about the world, in particular about actions. However, what these brain regions represent and precisely how they differ remains unknown. Here, we reveal fundamentally distinct functional profiles of lateral temporal and frontoparietal cortex: Using fMRI-based MVPA we found that frontoparietal areas encode representations of observed actions and corresponding written sentences in an overlapping way, but these representations did not generalize across stimulus type. By contrast, only left lateral posterior temporal cortex (LPTC) encoded action representations that generalize across observed action scenes and sentences. The representational organization of stimulus-general action information in LPTC could be predicted from models that describe basic agent-patient relations (object- and person-directedness) and the general semantic similarity between actions. The match between action videos and sentences in LPTC and its representational profile indicate that this region encodes general, conceptual aspects of actions whereas frontoparietal representations appear to be tied to specific stimulus types.
Differential expression of PKCα and -β in the zebrafish retina
Authors: Haug Marion F. , Berger Manuela , Gesemann Matthias , Neuhauss Stephan C. F.
Published: July 2018

The retina is a complex neural circuit in which visual information is transmitted and processed from light perceiving photoreceptors to projecting retinal ganglion cells. Much of the computational power of the retina rests on signal integrating interneurons, such as bipolar cells in the outer retina. While mammals possess about 10 different bipolar cell types, zebrafish (Danio rerio) has at least six ON-type, seven OFF-type, and four mixed-input bipolar cells. Commercially available antibodies against bovine and human conventional protein kinase C (PKC) α and -β are frequently used as markers for retinal ON-bipolar cells in different species, despite the fact that it is not known which bipolar cell subtype(s) they actually label.

Moreover, the expression pattern of the five prkc genes (coding for PKC proteins) has not been systematically determined. While prkcg is not expressed in retinal tissue, the other four prkc (prkcaa, prkcab, prkcba, prkcbb) transcripts were found in different parts of the inner nuclear layer and some as well in the retinal ganglion cell layer.

Immunohistochemical analysis in adult zebrafish retina using PKCα and PKCβ antibodies showed an overlapping immunolabeling of ON-bipolar cells that are most likely of the BON s6L or RRod type and of the BON s6 type. However, comparison of transcript expression with immunolabling, implies that these antibodies are not specific for one single zebrafish conventional PKC, but rather detect a combination of PKC -α and -β variants.
Phase transitions in evolutionary dynamics
Authors: Cuesta Fernando Alcalde , Sequeiros Pablo González , Rojo Álvaro Lozano
Published: July 2018

The evolutionary dynamics of a finite population where resident individuals are replaced by mutant ones depends on its spatial structure. The population adopts the form of an undirected graph where the place occupied by each individual is represented by a node and it is bidirectionally linked to the places that can be occupied by its clonal offspring. There are undirected graph structures that act as amplifiers of selection increasing the probability that the offspring of an advantageous mutant spreads through the graph reaching any node. But there also are undirected graph structures acting as suppressors of selection where, on the contrary, the fixation probability of an advantageous mutant is less than that of the same individual placed in a homogeneous population. Here, we show that some undirected graphs exhibit phase transitions between both evolutionary regimes when the mutant fitness varies. Firstly, as was already observed for small order random graphs, we show that most graphs of order 10 or less are amplifiers of selection or suppressors that become amplifiers from a unique transition phase. Secondly, we give examples of amplifiers of order 7 that become suppressors from some critical value. For graphs of order 6 and 7, we apply computer aided techniques to exactly determine their fixation probabilities and then their evolutionary regimes, as well as the exact critical values for which each graph changes its regime. A similar technique is used to explore a general method to suppress selection in bigger orders, namely from 8 to 15, up to some critical fitness value. The analysis of all graphs from order 8 to order 10 reveals a complex and rich evolutionary dynamics, which have not been examined in detail until now, and poses some new challenges in computing fixation probabilities and times of evolutionary graphs.
Human CD4+CD103+ cutaneous resident memory T cells are found in the circulation of healthy subjects
Authors: Klicznik M. M. , Morawski P. A. , Höllbacher B. , Varkhande S. R. , Motley S. , Kuri-Cervantes L. , Goodwin E. , Rosenblum M. D. , Long S. A. , Brachtl G. , Duhen T. , Betts M.R. , Campbell D. J. , Gratz I. K.
Published: July 2018

Tissue-resident memory T cells (TRM) persist locally in non-lymphoid tissues where they provide front-line defense against recurring insults. TRM at barrier surfaces express the markers CD103 and/or CD69 which function to retain them in epithelial tissues. In humans, neither the long-term migratory behavior of TRM nor their ability to re-enter the circulation and potentially migrate to distant tissue sites have been investigated. Using tissue explant cultures, we found that CD4+CD69+CD103+ TRM in human skin can downregulate CD69 and exit the tissue.

Additionally, we identified a skin-tropic CD4+CD69−CD103+ population in human lymph and blood that is transcriptionally, functionally and clonally related to the CD4+CD69+CD103+ TRM population in the skin. Using a skin xenograft model, we confirmed that a fraction of the human cutaneous CD4+CD103+ TRM population can re-enter circulation, and migrate to secondary human skin sites where they re-assume a TRM phenotype. Thus, our data challenge current concepts regarding the strict tissue compartmentalization of CD4+ T cell memory in humans.

One Sentence Summary

Human CD4+CD103+ cutaneous resident memory T cells are found in the circulation of healthy subjects, and these cells can seed distant skin sites.
Multiple infection of cells changes the dynamics of basic viral evolutionary processes
Authors: Wodarz Dominik , Levy David N. , Komarova Natalia L.
Published: July 2018

The infection of cells by multiple copies of a given virus can impact virus evolution in a variety of ways, for example through recombination and reassortment, or through intra-cellular interactions among the viruses in a cell, such as complementation or interference. Surprisingly, multiple infection of cells can also influence some of the most basic evolutionary processes, which has not been studied so far. Here, we use computational models to explore how infection multiplicity affects the fixation probability of mutants, the rate of mutant generation, and the timing of mutant invasion. This is investigated for neutral, disadvantageous, and advantageous mutants. Among the results, we note surprising growth dynamics for neutral and disadvantageous mutants: Starting from a single mutant-infected cell, an initial growth phase is observed which is more characteristic of an advantageous mutant and is not observed in the absence of multiple infection. Therefore, in the short term, multiple infection increases the chances that neutral or dis-advantageous mutants are present. Following this initial growth phase, however, the mutant dynamics enter a second phase that is driven by neutral drift or negative selection, respectively, which determines the long-term fixation probability of the mutant. Contrary to the short-term dynamics, the probability of mutant fixation, and thus existence, is lower in the presence compared to the absence of multiple infection, and declines with infection multiplicity. Hence, while infection multiplicity promotes mutant existence in the short term, it makes it less likely in the longer term. Understanding of these dynamics is essential for the investigation of more complex viral evolutionary processes, for which the dynamics described here for the basis. We demonstrate relevance to the interpretation of experiments in the context of published data on phage φ6 evolution at low and high multiplicities.