bluuebunny/crossref_metadata_2025 huggingface dataset:
Protein secondary structure prediction improved by recurrent neural networks integrated with two-dimensional convolutional neural networks
Authors: Guo Yanbu , Wang Bingyi , Li Weihua , Yang Bei
Published: August 2018

Protein secondary structure prediction (PSSP) is an important research field in bioinformatics. The representation of protein sequence features could be treated as a matrix, which includes the amino-acid residue (time-step) dimension and the feature vector dimension. Common approaches to predict secondary structures only focus on the amino-acid residue dimension. However, the feature vector dimension may also contain useful information for PSSP. To integrate the information on both dimensions of the matrix, we propose a hybrid deep learning framework, two-dimensional convolutional bidirectional recurrent neural network (2C-BRNN), for improving the accuracy of 8-class secondary structure prediction. The proposed hybrid framework is to extract the discriminative local interactions between amino-acid residues by two-dimensional convolutional neural networks (2DCNNs), and then further capture long-range interactions between amino-acid residues by bidirectional gated recurrent units (BGRUs) or bidirectional long short-term memory (BLSTM). Specifically, our proposed 2C-BRNNs framework consists of four models: 2DConv-BGRUs, 2DCNN-BGRUs, 2DConv-BLSTM and 2DCNN-BLSTM. Among these four models, the 2DConv- models only contain two-dimensional (2D) convolution operations. Moreover, the 2DCNN- models contain 2D convolutional and pooling operations. Experiments are conducted on four public datasets. The experimental results show that our proposed 2DConv-BLSTM model performs significantly better than the benchmark models. Furthermore, the experiments also demonstrate that the proposed models can extract more meaningful features from the matrix of proteins, and the feature vector dimension is also useful for PSSP. The codes and datasets of our proposed methods are available at https://github.com/guoyanb/JBCB2018/ .
The Contemporary Evolution of Fitness
Authors: Hendry Andrew P. , Schoen Daniel J. , Wolak Matthew E. , Reid Jane M.
Published: August 2018

The rate of evolution of population mean fitness informs how selection acting in contemporary populations can counteract environmental change and genetic degradation (mutation, gene flow, drift, recombination). This rate influences population increases (e.g., range expansion), population stability (e.g., cryptic eco-evolutionary dynamics), and population recovery (i.e., evolutionary rescue). We review approaches for estimating such rates, especially in wild populations. We then review empirical estimates derived from two approaches: mutation accumulation (MA) and additive genetic variance in fitness (IAw). MA studies inform how selection counters genetic degradation arising from deleterious mutations, typically generating estimates of <1% per generation. IAw studies provide an integrated prediction of proportional change per generation, nearly always generating estimates of <20% and, more typically, <10%. Overall, considerable, but not unlimited, evolutionary potential exists in populations facing detrimental environmental or genetic change. However, further studies with diverse methods and species are required for more robust and general insights.
Insights into Pathogenic Interactions Among Environment, Host, and Tumor at the Crossroads of Molecular Pathology and Epidemiology
Authors: Ogino Shuji , Nowak Jonathan A. , Hamada Tsuyoshi , Milner Danny A. , Nishihara Reiko
Published: August 2018

Evidence indicates that diet, nutrition, lifestyle, the environment, the microbiome, and other exogenous factors have pathogenic roles and also influence the genome, epigenome, transcriptome, proteome, and metabolome of tumor and nonneoplastic cells, including immune cells. With the need for big-data research, pathology must transform to integrate data science fields, including epidemiology, biostatistics, and bioinformatics. The research framework of molecular pathological epidemiology (MPE) demonstrates the strengths of such an interdisciplinary integration, having been used to study breast, lung, prostate, and colorectal cancers. The MPE research paradigm not only can provide novel insights into interactions among environment, tumor, and host but also opens new research frontiers. New developments—such as computational digital pathology, systems biology, artificial intelligence, and in vivo pathology technologies—will further transform pathology and MPE. Although it is necessary to address the rarity of transdisciplinary education and training programs, MPE provides an exemplary model of integrative scientific approaches and contributes to advancements in precision medicine, therapy, and prevention.
Moving from the Trial to the Real World: Improving Medication Adherence Using Insights of Implementation Science
Authors: Zullig Leah L. , Deschodt Mieke , Liska Jan , Bosworth Hayden B. , De Geest Sabina
Published: August 2018

Medication nonadherence is a serious public health concern. Although there are promising interventions that improve medication adherence, most interventions are developed and tested in tightly controlled research environments that are dissimilar from the real-world settings where the majority of patients receive health care. Implementation science methods have the potential to facilitate and accelerate the translation shift from the trial world to the real world. We demonstrate their potential by reviewing published, high-quality medication adherence studies that could potentially be translated into clinical practice yet lack essential implementation science building blocks. We further illustrate this point by describing an adherence study that demonstrates how implementation science creates a junction between research and real-world settings. This article is a call to action for researchers, clinicians, policy makers, pharmaceutical companies, and others involved in the delivery of care to adopt the implementation science paradigm in the scale-up of adherence (research) programs.
Error-related Persistence of Motor Activity in Resting-state Networks
Authors: Bernardi Nicolò F. , Van Vugt Floris T. , Valle-Mena Ricardo Ruy , Vahdat Shahabeddin , Ostry David J.
Published: August 2018

The relationship between neural activation during movement training and the plastic changes that survive beyond movement execution is not well understood. Here we ask whether the changes in resting-state functional connectivity observed following motor learning overlap with the brain networks that track movement error during training. Human participants learned to trace an arched trajectory using a computer mouse in an MRI scanner. Motor performance was quantified on each trial as the maximum distance from the prescribed arc. During learning, two brain networks were observed, one showing increased activations for larger movement error, comprising the cerebellum, parietal, visual, somatosensory, and cortical motor areas, and the other being more activated for movements with lower error, comprising the ventral putamen and the OFC. After learning, changes in brain connectivity at rest were found predominantly in areas that had shown increased activation for larger error during task, specifically the cerebellum and its connections with motor, visual, and somatosensory cortex. The findings indicate that, although both errors and accurate movements are important during the active stage of motor learning, the changes in brain activity observed at rest primarily reflect networks that process errors. This suggests that error-related networks are represented in the initial stages of motor memory formation.
The Emergence of Hyper-Consumerism in UAE Society: A Socio-Cultural Perspective
Authors: Kazim Aqil
Published: August 2018

This study examines how consumers in the United Arab Emirates (UAE) are actively employing consumer goods and services to express and forge their own unique socio-cultural identities. It seeks to address such significant issues by exploring the ways through which diverse consumers construct and present their socio-economic status. The study demonstrates how consumer practices, especially those related to luxurious commodities and affluence, function as producers of socio-cultural discourses. Methodologically, this study relies on fieldwork research that was conducted by the researcher over a period of several years (2011-2018) in the different emirates of the UAE. Qualitative methods were employed in particular. Different consumption sites—mainly mega shopping malls—were visited regularly, and various consumers belonging to different socio-economic segments of the society were interviewed. Both structured and unstructured types of interviews were conducted to collect ethnographic data. The study results show the transformation of UAE society consumption patterns from traditional consumption to hyper-consumption. During the 1960s, the UAE shifted overall into a consumer society. In fact, the results show the expansion both of the hyper-consumer, mega malls, the traditional souqs, and online internet shopping within this new hyper-consumer culture. The study also shows how the lifestyle in UAE has changed in the last few decades, as people’s shopping behaviors have shifted from the traditional marketplace to include the newer mega shopping malls and brand stores. In addition, the study shows how consumers construct and present their socio-economic status according to their class, gender, and ethnicity through their own shopping experiences.
Eight new species of Polystichum (subg. Haplopolystichum; Dryopteridaceae) from limestone caves in Guangdong and Yunnan, China, with reference to species diversity in the karst terrains at high elevations in subtropical areas
Authors: HAN MENG-QI , LIU YAN , ZHANG LI-BING
Published: August 2018

Eight new fern species of Polystichum subg. Haplopolystichum (Dryopteridaceae) are described and illustrated from Guangdong and Yunnan provinces, southern and southwestern China, respectively. These eight species include P. deltatum, P. gejiuense, P. malipoense, P. oblongipinnarum, P. pingbianense, P. rectum, and P. superum from Yunnan, and P. hanmengqii from Guangdong. Four of the eight species are described from high elevations (around 2000 m) demonstrating that the limestone areas at high elevations in subtropical areas are species-rich and deserve special conservation attention. All eight species are so far known only from single caves; they are all classified as Critically Endangered (CR) following IUCN Red List criteria.
A revision of Kerivoula hardwickii and occurrence of K. furva (Chiroptera: Vespertilionidae) in China
Authors: YU WEN-HUA , LI FENG , CSORBA GABOR , XU ZHONG-XIAN , WANG XIAO-YUN , GUO WEI-JIAN , LI YU-CHUN , WU YI
Published: August 2018

Although increased survey efforts using improved capture methods (particularly harp traps) have greatly expanded the quantity of Kerivoula specimens available in China, the understanding of the genus has been long constrained. After the recently published revision of the hardwickii-complex with the description of K. furva and re-evaluation of occurrence of K. titania in Taiwan, the critical overview of the previous data of Chinese Kerivoula (with the exception of K. picta, a strikingly colored and unmistakable species) is imperative. To clarify the taxonomy and distribution of the hardwickii-complex in China, 40 additional specimens collected from South China were studied through detailed morphological comparisons, multivariate statistical methods and phylogenetic inference. Our results evidently classified these specimens as K. furva instead of K. titania or K. hardwickii sensu stricto and together with the critical review of literature data indicate that all previous Chinese records of the two latter species were based on either misidentifications or outdated taxonomy. K. furva have so far been recorded in the Chinese provinces of Chongqing, Fujian, Guangdong, Guangxi, Hainan, Hunan, Jiangxi, Yunnan and Taiwan, but more field surveys are needed to confirm whether it could be found in other nearby provinces.
Escalonius, a new subgenus of Calochromus Guérin-Méneville, 1833 identified by the molecular phylogeny of Calochromini (Coleoptera: Lycidae)
Authors: MOTYKA MICHAL , BOCAK LADISLAV
Published: August 2018

Calochromini is a net-winged beetle lineage with seven genera and world-wide distribution. The recently collected morphologically divergent Calochromus amabilis Lea, 1899 was sequenced to recover its relationships and a three-marker DNA dataset was assembled from 27 Calochromini from GenBank and new data for C. amabilis. The phylogenetic analysis recovered C. amabilis nested deep within Calochromus s. l. in a sister-position to Calochromus s. str. C. amabilis represents an early diversified and morphologically distinct species, for which the subgenus Escalonius subgen. nov. is erected. In contrast with its phylogenetic relationships, Escalonius subgen. nov. differs from other morphologically uniform Calochromus subgenera. Calochromus (Escalonius) amabilis has a small body, serrate antennae, the pronotum with concave lateral margins, and the long phallus surpassing the apices of parameres. The results demonstrate the unlinked morphological and molecular evolution of Calochromini.         The key to world genera and subgenera is presented and all diagnostic characters are illustrated.
A new Drepanosticta species from Seram, Moluccas (Odonata: Platystictidae)
Authors: TOL JAN VAN , BEDJANIČ MATJAŽ
Published: August 2018

Drepanosticta seramensis sp. nov. (holotype ♂: Indonesia, Moluccas, Seram Island, 36 km SW of Wahai, S 2.9768, E 129.2269; 2-xii-1996; deposited in RMNH, Leiden), is described as new to science. It is closely related to D. moluccana Lieftinck, 1938 from Buru and D. amboinensis van Tol, 2007 from Ambon.
A Southern Hemisphere Horizontal Sounding System: A Preliminary Study 1
Authors: Giles K. C. , Angell J. K.
Published: August 2018

As part of a feasibility study for a Southern Hemisphere horizontal sounding system, for five mid-season months daily 500-mb geostrophic trajectories of 14 days' duration were constructed from four possible constant-level balloon launch sites in the Southern Hemisphere. In the main belt of westerlies such a balloon release rate would yield upper-air data at approximately 1000 n mi intervals at any given time, and would yield data at approximately 750 n mi intervals if “off-time” reports could be utilized. A seven-station radio-direction-finding network, including one station in Antarctica, appears capable of providing constant-level balloon positioning with at least a 60 per cent chance of obtaining a “fix” based upon three or more bearings south of latitude 40S and at least a 70 per cent chance of obtaining “fix” based upon two or more bearings south of 25S.
marine air invasion of the Pacific Coast a problem analysis
Authors: Schroeder Mark J. , Fosberg Michael A. , Cramer Owen P. , O'Dell Clyde A.
Published: August 2018

This paper reviews the literature on the main aspects of marine air invasion on the Pacific coast. In particular, it considers the sea breeze, Pacific coast monsoon, and airflow over coastal mountains. The major problems associated with marine air invasion are: 1) the relationship of microscale convection, waves, and banded convection- waves to the sea-breeze energetics and sea-breeze front, 2) the interaction of energy forming and dissipating processes from the general circulation down to the micrometeorological scale, 3) the climatology and dynamics of the monsoon, and 4) the mechanism of the lee waves observed in the lee of the heated coastal mountains. Lee waves often form in a statically unstable atmosphere.
what do we not know about the sea-surface wind stress1
Authors: Kraus E. B.
Published: August 2018

A simple sampling experiment gives a several octave range of values for the zonal surface stress obtainable from synoptic maps over the North Atlantic. Uncertainty about the value of the drag coefficient account for about half the variance. The different methods that have been used to specify this quantity are reviewed and an attempt is made to state explicitly the assumptions involved in each case.
lidar observations of atmospheric motion in forest valleys1
Authors: Collis Ronald T. H.
Published: August 2018

In connection with studies of aerial insecticide spraying techniques being carried out by the U. S. Forest Service, Stanford Research Institute personnel have been making lidar observations of smoke and spray material discharged by aircraft flying over forest terrain. The motion of the smoke and suspended spray droplet clouds can be tracked by lidar even when they are not visible to the eye. This makes it possible to study the motion and diffusion of parcels of air caused by micrometeorological factors, such as the insolation of valley slopes. While of primary interest in connection with aerial spraying operations, this research provides new quantitative information regarding atmospheric motion in forest valleys.

The ruby and neodymium lidar instrumentation used is described and the methods of observation explained. Representative results are presented and discussed.
lidar for routine meteorological observations
Authors: Collis R. T. H.
Published: August 2018

Lidar, using pulsed lasers as energy sources, applies the radar principle at wavelengths in and near the visual spectrum to probe the atmosphere. It can detect particulate matter of much smaller dimensions and sparser concentration than is possible with meteorological radar. Lidar may be used to measure cloud base heights although difficulties arise with diffuse clouds, especially in foggy conditions. Inhomogeneities in turbidity that occur at the heights of temperature inversions in the relatively clear atmosphere are also revealed by lidar. Examples of work in progress that show promise of providing a measurement of visibility are presented.

It is concluded that lidar can already contribute usefully in routine meteorological service, but that its full potential in ceilometry and visibility measurement awaits further developments. For routine unattended use, high pulse-rate low peak-power lidars are advocated on grounds of safety.
Quality Improvement Initiatives to Reduce Mortality: An Opportunity to Engage Palliative Care and Improve Advance Care Planning
Authors: Flieger Signe Peterson , Spatz Erica , Cherlin Emily J. , Curry Leslie A.
Published: August 2018

Background:

Despite substantial efforts to integrate palliative care and improve advance care planning, both are underutilized. Quality improvement initiatives focused on reducing mortality may offer an opportunity for facilitating engagement with palliative care and advance care planning.

Objective:

In the context of an initiative to reduce acute myocardial infarction (AMI) mortality, we examined challenges and opportunities for engaging palliative care and improving advance care planning.

Methods:

We performed a secondary analysis of qualitative data collected through the Leadership Saves Lives initiative between 2014 and 2016. Data included in-depth interviews with hospital executives, clinicians, administrators, and quality improvement staff (n = 28) from 5 hospitals participating in the Mayo Clinic Care Network. Focused analysis examined emergent themes related to end-of-life experiences, including palliative care and advance care planning.

Results:

Participants described challenges related to palliative care and advance care planning in the AMI context, including intervention decisions during an acute event, delivering care aligned with patient and family preferences, and the culture around palliative care and hospice. Participants proposed strategies for addressing such challenges in the context of improving AMI quality outcomes.

Conclusions:

Clinicians who participated in an initiative to reduce AMI mortality highlighted the challenges associated with decision-making regarding interventions, systems for documenting patient goals of care, and broader engagement with palliative care. Quality improvement initiatives focused on mortality may offer a meaningful and feasible opportunity for engaging palliative care. Primary palliative care training is needed to improve discussions about patient and family goals of care near the end of life.
The Role of Direct Oral Anticoagulants in Patients With Coronary Artery Disease
Authors: Turgeon Ricky D. , Ackman Margaret L. , Babadagli Hazal E. , Basaraba Jade E. , Chen June W. , Omar Mohamed , Zhou Jian Song
Published: August 2018

Despite contemporary management, patients with coronary artery disease (CAD) remain at high risk for thrombotic events. Several randomized controlled trials have evaluated the use of direct oral anticoagulants (DOACs) in patients with CAD, including in the setting of acute coronary syndrome (ACS) and stable CAD, and in patients with concomitant atrial fibrillation. Trials of apixaban and dabigatran in patients with ACS demonstrate no benefit with an increased risk of bleeding. Conversely, rivaroxaban at a reduced dose of 2.5 mg twice daily reduced thrombotic events and all-cause mortality when added to dual antiplatelet therapy in patients with ACS. Similarly, the addition of low-dose rivaroxaban to acetylsalicylic acid reduced the risk of thrombotic events in patients with stable CAD. However, the addition of a DOAC to antiplatelet therapy increased the risk of major bleeding. In patients with atrial fibrillation undergoing percutaneous coronary intervention, dual-pathway or low-dose triple therapy regimens including dabigatran or rivaroxaban reduced bleeding risk compared to traditional warfarin-based triple therapy, although it remains unclear whether these regimens preserve antithrombotic efficacy. DOAC–based antithrombotic regimens prove useful in patients with CAD in various settings; however, careful selection of patients and regimens per trial protocols are critical to achieving net benefit.
Clinical profile of children experiencing in-hospital clinical deterioration requiring transfer to a higher level of care
Authors: Jensen Claus Sixtus , Kirkegaard Hans , Aagaard Hanne , Olesen Hanne Vebert
Published: August 2018

Few studies have described the various reasons for unplanned transfer to a higher level of care due to clinical deterioration and the clinical profile of those paediatric patients. However, an understanding of the nature of illness is important to patient safety. This study aimed to describe the frequency and clinical characteristics of children who experience unplanned transfer to a higher level of care due to clinical deterioration. A retrospective, descriptive registry study design was used. Of the 92 paediatric patients included, 69% ( n = 64) was male. The median age was 2.1 years (interquartile range 0.4–6.9) with 33% being infants under 1 year. The highest number (61.3%) of transfers occurred between 8 and 16 hours. In the 24 hours leading up to a transfer due to clinical deterioration, 15 patients had no vital parameters documented, and 77 patients had least one vital parameter measured. Physiological abnormalities were present in 19 (37.7%) of the 77 patients where vital parameters were documented. This study provides essential baseline data to inform further research to improve care and treatment for critically ill children in paediatric wards. This study’s findings suggest reporting of vital parameters is incomplete and infrequent.
Attitudes, Motivators, and Barriers to Emergency Preparedness Using the 2016 Styles Survey
Authors: Kruger Judy , Chen Brenda , Heitfeld Suzanne , Witbart Lauren , Bruce Crystal , Pitts Dana L.
Published: August 2018

This study assessed adults’ perceptions toward preparedness to better inform emergency planning efforts for households and communities. The 2016 Styles, an Internet panel survey, was used to assess emergency preparedness competencies. Descriptive analyses were performed to describe the sociodemographic factors by preparedness status. Multivariable logistic regressions were used to examine the association between perceived preparedness and characteristics associated with preparedness attitudes, motivators, and barriers. Approximately 40% of adults surveyed reported that they were prepared for emergencies. The main motivator for those prepared was awareness of local disasters (38.9%), and a leading barrier was confusion about how to plan for the unknown (23.7%). Those prepared were more likely to have the right supplies (adjusted odds ratio [AOR] = 1.25, 95% confidence interval [CI] = [1.05, 1.50]), discuss emergency plans (AOR = 1.21, 95% CI = [1.02-1.42]), and act before an emergency occurred (AOR = 1.35, 95% CI = [1.15, 1.59]), compared with adults who did not report being prepared. Results from this research indicate that identifying motivation to prepare for emergencies can contribute to public health disaster planning. Preparation is a critical step that allows the community and its citizens to be more equipped to function during and after a disaster.
Sexual health and health‐related quality of life among women with pulmonary arterial hypertension
Authors: Banerjee Debasree , Vargas Sara E. , Guthrie Kate M. , Wickham Brittany M. , Allahua Melissa , Whittenhall Mary E. , Palmisciano Amy J. , Ventetuolo Corey E.
Published: August 2018

Pulmonary arterial hypertension (PAH) is characterized by progressive limitations in physical activity and health‐related quality of life (HRQoL). HRQoL deficits may extend beyond the traditional domains of physical activity, psychological health, and emotional wellbeing to sexual health and function. Sexual HRQoL has not been studied in PAH, nor has the impact of PAH therapies themselves on sexual health and intimacy. In this initial investigation, we sought to explore HRQoL among women diagnosed with PAH and to determine if PAH treatment type (intravenous or subcutaneous prostanoids versus oral medications) was associated with levels of self‐reported HRQoL assessed by validated measures for PAH‐specific, general, and sexual HRQoL. We administered the emPHasis‐10, Short Form (SF)‐36, Female Sexual Dysfunction Scale‐Revised (FSDS‐R), and the Arizona Sexual Experience Scale (ASEX) to 35 women with self‐reported World Health Organization Group 1 PAH at the 2016 Pulmonary Hypertension Association International Conference and Scientific Sessions. HRQoL instruments demonstrated excellent internal reliability. Women with PAH had high levels of sexual distress captured with the FSDS‐R scale. The FSDS‐R (but not ASEX) was significantly correlated to emPHasis‐10 (r = 0.64, p < 0.01) and most SF‐36 domains (r = − 0.36 to − 0.64, p < 0.05). Participants treated with intravenous or subcutaneous prostanoids had higher (worse) FSDS‐R scores than those on oral therapies while ASEX, emPHasis‐10, and SF‐36 scores were similar across treatment types. Sexual HRQoL may impact overall quality of life in PAH and specific assessment of sexual health and functioning within intimate relationships may detect deficits in wellbeing not addressed by established HRQoL metrics. Further study to address all aspects of HRQoL in PAH is required.
Right ventricular afterload predicts long‐term transition from parenteral to oral treprostinil in pulmonary arterial hypertension
Authors: Maestas Travis , Hansen Lillian M. , Vanderpool Rebecca R. , Desai Ankit A. , Airhart Sophia , Knapp Shannon M. , Cohen Adam , Feldman Jeremy , Rischard Franz P.
Published: August 2018

Despite the increasing trends, reports on long‐term follow‐up are limited on transitioning from parenteral to oral treprostinil therapy in patients with pulmonary arterial hypertension (PAH). We investigated both the effectiveness of parenteral to oral treprostinil transition and the characteristics associated with transition failure over a duration of two years. The study included 37 Group I functional class I and II patients with PAH on combination therapy. Patients were excluded if cardiac index ≤2.2 L/min/m2, right atrial pressure ≥11 mmHg, or 6‐min walk distance ≤250 m. Patients were categorized as successful (STransition) or unsuccessful (UTransition) transition based on clinical stability, or a parenteral comparator (CParenteral) if they remained on parenteral therapy (no transition). All patients underwent two right heart catheterizations, one at enrollment and a second post transition. Of 24 total transition patients, 46% were classified as UTransition. UTransition occurred on average 577 days post transition. Both UTransition and STransition had similar hemodynamics at diagnosis and treprostinil dose before and after transition. Before transition, the pulmonary vascular resistance (PVR) was significantly higher in the UTransition (6.7 ± 2 WU) vs. STransition group (3.5 ± 1.5 WU). At follow‐up catheterization, the UTransition group demonstrated further increases in PVR, greater than the CParenteral group, without recovery despite “rescue” therapy in the UTransition group. A pre‐transition PVR of 4.16 WU discriminated the UTransition from the STransition group. While a subset of PAH patients on combination therapy may be safely transitioned from parenteral to oral treprostinil, caution should be exercised in patients with elevated baseline PVR to avoid irreversible destabilization.
Impact of Baseline Steroids on Efficacy of Programmed Cell Death-1 and Programmed Death-Ligand 1 Blockade in Patients With Non–Small-Cell Lung Cancer
Authors: Arbour Kathryn C. , Mezquita Laura , Long Niamh , Rizvi Hira , Auclin Edouard , Ni Andy , Martínez-Bernal Gala , Ferrara Roberto , Lai W. Victoria , Hendriks Lizza E.L. , Sabari Joshua K. , Caramella Caroline , Plodkowski Andrew J. , Halpenny Darragh , Chaft Jamie E. , Planchard David , Riely Gregory J. , Besse Benjamin , Hellmann Matthew D.
Published: August 2018

Purpose

Treatment with programmed cell death-1 or programmed death ligand 1 (PD-(L)1) inhibitors is now standard therapy for patients with lung cancer. The immunosuppressive effect of corticosteroids may reduce efficacy of PD-(L)1 blockade. On-treatment corticosteroids for treatment of immune-related adverse events do not seem to affect efficacy, but the potential impact of baseline corticosteroids at the time of treatment initiation is unknown. Clinical trials typically excluded patients who received baseline corticosteroids, which led us to use real-world data to examine the effect of corticosteroids at treatment initiation.

Methods

We identified patients who were PD-(L)1–naïve with advanced non–small-cell lung cancer from two institutions—Memorial Sloan Kettering Cancer Center and Gustave Roussy Cancer Center—who were treated with single-agent PD-(L)1 blockade. Clinical and pharmacy records were reviewed to identify corticosteroid use at the time of beginning anti–PD-(L)1 therapy. We performed multivariable analyses using Cox proportional hazards regression model and logistic regression.

Results

Ninety (14%) of 640 patients treated with single-agent PD-(L)1 blockade received corticosteroids of ≥ 10 mg of prednisone equivalent daily at the start of the PD-(L)1 blockade. Common indications for corticosteroids were dyspnea (33%), fatigue (21%), and brain metastases (19%). In both independent cohorts, Memorial Sloan Kettering Cancer Center (n = 455) and Gustave Roussy Cancer Center (n = 185), baseline corticosteroids were associated with decreased overall response rate, progression-free survival, and overall survival with PD-(L)1 blockade. In a multivariable analysis of the pooled population, adjusting for smoking history, performance status, and history of brain metastases, baseline corticosteroids remained significantly associated with decreased progression-free survival (hazard ratio, 1.3; P = .03), and overall survival (hazard ratio, 1.7; P < .001).

Conclusion

Baseline corticosteroid use of ≥ 10 mg of prednisone equivalent was associated with poorer outcome in patients with non–small-cell lung cancer who were treated with PD-(L)1 blockade. Prudent use of corticosteroids at the time of initiating PD-(L)1 blockade is recommended.
ANGUSTIFOLIA contributes to the regulation of three-dimensional morphogenesis in the liverwort Marchantia polymorpha
Authors: Furuya Tomoyuki , Hattori Koro , Kimori Yoshitaka , Ishida Sakiko , Nishihama Ryuichi , Kohchi Takayuki , Tsukaya Hirokazu
Published: August 2018

Arabidopsis thaliana mutants deficient in ANGUSTIFOLIA (AN) exhibit several phenotypes at the sporophyte stage, such as narrow and thicker leaves, trichomes with two branches, and twisted fruits. It is thought that these phenotypes are caused by abnormal arrangement of cortical microtubules (MTs). AN homologs are present in the genomes of diverse land plants, including the basal land plant Marchantia polymorpha, and their molecular functions have been shown to be evolutionarily conserved in terms of the ability to complement the A. thaliana an-1 mutation. However, the roles of ANs in bryophytes, the life cycle of which includes a dominant haploid gametophyte generation, remain unknown. Here, we have examined the roles of AN homologs in the model bryophyte M. polymorpha (MpAN). Mpan knockout mutants showed abnormal twisted thalli and suppressed thallus growth along the growth axis. Under weak blue light conditions, elongated thallus growth was observed in wild-type plants, whereas it was suppressed in the mutants. Moreover, disordered cortical MT orientations were observed. Our findings suggest that MpAN contributes to three-dimensional morphogenesis by regulating cortical MT arrangement in the gametophytes of bryophytes.
ROCK-nmMyoII, Notch and Neurog3 gene-dosage link epithelial morphogenesis with cell fate in the pancreatic endocrine-progenitor niche
Authors: Bankaitis Eric D. , Bechard Matthew E. , Gu Guoqiang , Magnuson Mark A. , Wright Christopher V. E.
Published: August 2018

During mouse pancreas organogenesis, endocrine cells are born from progenitors residing in an epithelial plexus niche. After a period in a lineage-primed Neurog3LO state, progenitors become endocrine committed via upregulation of Neurog3. We find that the Neurog3LO to Neurog3HI transition is associated with distinct stages of an epithelial egression process: narrowing the apical surface of the cell, basalward cell movement and eventual cell-rear detachment from the apical lumen surface to allow clustering as nascent islets under the basement membrane. Apical narrowing, basalward movement and Neurog3 transcriptional upregulation still occur without Neurog3 protein, suggesting that morphogenetic cues deployed within the plexus initiate endocrine commitment upstream or independently of Neurog3. Neurog3 is required for cell-rear detachment and complete endocrine-cell birth. The ROCK-nmMyoII pathway coordinates epithelial-cell morphogenesis and the progression through Neurog3-expressing states. NmMyoII is necessary for apical narrowing, basalward cell displacement and Neurog3 upregulation, but all three are limited by ROCK activity. We propose that ROCK-nmMyoII activity, Neurog3 gene-dose and Notch signaling integrate endocrine fate allocation with epithelial plexus growth and morphogenesis, representing a feedback control circuit that coordinates morphogenesis with lineage diversification in the endocrine-birth niche.
Foot-propelled swimming kinematics and turning strategies in common loons
Authors: Clifton Glenna T. , Biewener Andrew A
Published: August 2018

Loons (Gaviiformes) are arguably one of the most successful groups of swimming birds. As specialist foot-propelled swimmers, loons are capable of diving up to 70 meters, remaining underwater for several minutes, and capturing fish. Despite the swimming prowess of loons, their undomesticated nature has prevented prior quantitative analysis. Our study used high-speed underwater cameras to film healthy common loons (Gavia immer) at the Tufts Wildlife Clinic in order to analyze their swimming and turning strategies. Loons swim by synchronously paddling their feet laterally at an average of 1.8 Hz. Combining flexion-extension of the ankle with rotation at the knee, loon swimming resembles grebe swimming and likely generates lift forces for propulsion. Loons modulate swimming speed by altering power stroke duration and use head-bobbing to enhance underwater vision. We observed that loons execute tight but slow turns compared to other aquatic swimmers, potentially associated with hunting by flushing fish from refuges at short range. To execute turns, loons use several strategies. Loons increase the force produced on the outside of the turn by increasing the speed of the outboard foot, which also begins its power stroke before the inboard foot. During turns, loons bank their body away from the turn and alter the motion of the feet to maintain the turn. Our findings demonstrate that foot-propelled swimming has evolved convergently in loon and grebes, but divergently from cormorants. The swimming and turning strategies used by loons that allow them to capture fish could inspire robotic designs or novel paddling techniques.
Oxidative cost of interspecific hybridization: a case study of twoTriturusspecies and their hybrids
Authors: Prokić Marko D. , Despotović Svetlana G. , Vučić Tijana Z. , Petrović Tamara G. , Gavrić Jelena P. , Gavrilović Branka R. , Radovanović Tijana B. , Saičić Zorica S.
Published: August 2018

Oxidative stress has most recently been suggested as one of possible mechanisms responsible for reduced fitness of hybrids. To explore possible oxidative cost of hybridization, we examined antioxidant defense system parameters (superoxide dismutase, catalase, glutathione peroxidase, glutathione s-transferase, glutathione reductase, glutathione, SH groups), their interconnectedness (index of integration), and levels of oxidative damage (concentrations of lipid peroxides-TBARS) in lab-reared newt species, Triturus macedonicus and T. ivanbureschi, and their hybrid. Our results showed that parental species differed in antioxidant defense system parameters, but not in the levels of integration of the whole system and oxidative damage. Individuals of T. ivanbureschi had higher activities of superoxide dismutase, glutathione s-transferase and concentrations of glutathione. Hybrid individuals of crested newts displayed higher levels of the antioxidant defense system (higher superoxide dismutase, catalase, glutathione peroxidase activities and concentrations of SH groups), and a lower overall correlation of antioxidant system (lower index of integration) in comparison to both parental species, suggesting that they may possess a less efficient antioxidant defense system and a higher investment in maintaining oxidative balance. The higher investment in the antioxidant system could divert limited resources away from other functions and affect further hybrid fitness. The presented findings contribute to a better understanding of the antioxidant defense system of crested newts and their interspecies differences, and support the hypothesis that oxidative stress is one of the costs of interspecific hybridization.
Individual differences in heart rate reveal a broad range of autonomic phenotypes in a free-living seabird population
Authors: Müller Martina S. , Vyssotski Alexei L. , Yamamoto Maki , Yoda Ken
Published: August 2018

Animals in the same population consistently differ in their physiology and behaviour, but the underlying mechanisms remain poorly understood. As the autonomic nervous system regulates wide-ranging physiological functions, many of these phenotypic differences may be generated by autonomic activity. We investigated for the first time in a free-living animal population (the long-lived seabird Streaked Shearwater, Calonectris leucomelas), whether individuals consistently differ in autonomic activity, over time and across contexts. We repeatedly recorded electrocardiograms from individual shearwaters, and from heart rate and heart rate variability quantified sympathetic activity, which drives the ‘fight-or-flight’ response, and parasympathetic activity, which promotes ‘rest-and-digest’ processes. We found a broad range of autonomic phenotypes that persisted even across years: heart rate consistently differed among individuals during stress and non-stress and these differences were driven by parasympathetic activity, thus identifying the parasympathetic ‘rest-and-digest’ system as a central mechanism that can drive broad phenotypic variation in natural animal populations.
Evidence for spatial vision in Chiton tuberculatus, a chiton with eyespots
Authors: Kingston Alexandra C. N. , Chappell Daniel R. , Speiser Daniel I.
Published: August 2018

To better understand relationships between the structures and functions of the distributed visual systems of chitons, we are comparing how morphological differences between the light-sensing structures of these animals relate to their visually-guided behaviors. All chitons have sensory organs – termed aesthetes – embedded within their protective shell plates. In some species, the aesthetes are interspersed with small, image-forming eyes. In other species, the aesthetes are paired with pigmented eyespots. Previously, we compared the visually-influenced behaviors of chitons with aesthetes to those of chitons with both aesthetes and eyes. Here, we characterize the visually-influenced behaviors of chitons with aesthetes and eyespots. We find that chitons with eyespots engage in behaviors consistent with spatial vision, but appear to use spatial vision for different tasks than chitons with eyes. Unlike chitons with eyes, Chiton tuberculatus and C. marmoratus fail to distinguish between sudden appearances of overhead objects and equivalent, uniform changes in light levels. We also find that C. tuberculatus orients to static objects with angular sizes as small as 10°. Thus, C. tuberculatus demonstrates spatial resolution that is at least as fine as that demonstrated by chitons with eyes. The eyespots of Chiton are smaller and more numerous than the eyes found in other chitons and they are separated by angles of<0.5°, suggesting that the light-influenced behaviors of Chiton may be more accurately predicted by the network properties of their distributed visual system than by the structural properties of their individual light-detecting organs.
Glyphosate impairs learning in mosquito larvae (Aedes aegypti) at field-realistic doses
Authors: Baglan Hugo , Lazzari Claudio R. , Guerrieri Fernando J.
Published: August 2018

Glyphosate is the most widely used herbicide in the world. In the last years, the number of studies revealing deleterious effects of glyphosate on non-target species has been increasing. We studied the impact of glyphosate at field-realistic doses on learning in mosquito larvae (Aedes aegypti). Larvae of A. aegypti live in small water bodies and perform a stereotyped escape response when a moving object projects its shadow on the water surface. Repeated presentations of an innocuous visual stimulus induce a decrease in response due to habituation, a non-associative form of learning. In this study, different groups of larvae were reared in water containing different concentrations of glyphosate that can be found in the field (50 µg/l, 100 µg/l, 210 µg/l and 2 mg/l). Larvae reared in a glyphosate solution of 2 mg/l could complete their development. However, glyphosate impaired habituation. The higher the dose, the stronger the deleterious effects on learning abilities. This protocol opens new avenues to further studies aiming at understanding how glyphosate affects non-target organisms as insects. Habituation in mosquito larvae could serve as a parameter for testing the impact of pollutants in water bodies.
Influence of flow on locomotion, feeding behaviour and spatial distribution of a suspension-feeding sea cucumber
Authors: Sun Jiamin , Hamel Jean-François , Mercier Annie
Published: August 2018

While movement in response to environmental conditions represents a fundamental link between animal behaviour and population ecology, it is rarely investigated in suspension feeders because they are generally perceived as sessile. Here, the interplay between water flow and fine locomotor and feeding behaviours was experimentally investigated for the first time in a free-moving suspension-feeding sea cucumber (Echinodermata: Holothuroidea) using time-lapse videography in a mesocosm setting. Individuals moved away from static conditions in the weakest flow treatment and fled the strongest flows >40 cm s−1 in the more dynamic treatments. The tentacles of individuals located in areas with flows of ≥40 cm s−1 was aligned with the direction of the current, whereas in flows <40 cm s−1, they were typically perpendicular to the direction of flow. Tentacle deployment and insertion rates (TIRs, i.e. feeding rate) increased with flow, from 0.95 min−1 at 10 cm s−1 to 1.13 min−1 at 40 cm s−1. Three modes of locomotion were detected. Forward crawling was most frequent at flows ≤40 cm s−1, passive rolling dominated at flows >40 cm s−1, and active rolling occurred randomly at flows between 0-120 cm s−1. Overall, the flow regime favoured by Cucumaria frondosa was determined to be between 21-40 cm s−1, under which an optimal balance between efficient food capture and energy expenditure for attachment to the bottom was presumably found. These findings provide insight into the distribution and population dynamics of suspension-feeding holothuroids, and may also assist the fisheries management and aquaculture development of commercial species.
Impaired Recent, but Preserved Remote, Autobiographical Memory in Pediatric Brain Tumor Patients
Authors: Sekeres Melanie J. , Riggs Lily , Decker Alexandra , de Medeiros Cynthia B. , Bacopulos Agnes , Skocic Jovanka , Szulc-Lerch Kamila , Bouffet Eric , Levine Brian , Grady Cheryl L. , Mabbott Donald J. , Josselyn Sheena A. , Frankland Paul W.
Published: August 2018

Medulloblastomas, the most common malignant brain tumor in children, are typically treated with radiotherapy. Refinement of this treatment has greatly improved survival rates in this patient population. However, radiotherapy also profoundly affects the developing brain and is associated with reduced hippocampal volume and blunted hippocampal neurogenesis. Such hippocampal (as well as extrahippocampal) abnormalities likely contribute to cognitive impairments in this population. While several aspects of memory have been examined in this population, the impact of radiotherapy on autobiographical memory has not previously been evaluated. Here we evaluated autobiographical memory in male and female patients who received radiotherapy for posterior fossa tumors (PFTs), including medulloblastoma, during childhood. Using the Children's Autobiographical Interview, we retrospectively assessed episodic and nonepisodic details for events that either preceded (i.e., remote) or followed (i.e., recent) treatment. For post-treatment events, PFT patients reported fewer episodic details compared with control subjects. For pretreatment events, PFT patients reported equivalent episodic details compared with control subjects. In a range of conditions associated with reduced hippocampal volume (including medial temporal lobe amnesia, mild cognitive impairment, Alzheimer's disease, temporal lobe epilepsy, transient epileptic amnesia, frontal temporal dementia, traumatic brain injury, encephalitis, and aging), loss of episodic details (even in remote memories) accompanies hippocampal volume loss. It is therefore surprising that pretreatment episodic memories in PFT patients with reduced hippocampal volume are retained. We discuss these findings in light of the anterograde and retrograde impact on memory of experimentally suppressing hippocampal neurogenesis in rodents.

SIGNIFICANCE STATEMENTPediatric medulloblastoma survivors develop cognitive dysfunction following cranial radiotherapy treatment. We report that radiotherapy treatment impairs the ability to form new autobiographical memories, but spares preoperatively acquired autobiographical memories. Reductions in hippocampal volume and cortical volume in regions of the recollection network appear to contribute to this pattern of preserved preoperative, but impaired postoperative, memory. These findings have significant implications for understanding disrupted mnemonic processing in the medial temporal lobe memory system and in the broader recollection network, which are inadvertently affected by standard treatment methods for medulloblastoma tumors in children.