bluuebunny/crossref_metadata_2025 huggingface dataset:
First-Attempt Success, Longevity, and Complication Rates of Ultrasound-Guided Peripheral Intravenous Catheters in Children
Authors: Vinograd Alexandra M. , Zorc Joseph J. , Dean Anthony J. , Abbadessa Mary Kate F. , Chen Aaron E.
Published: February 2017

Objective

The aim of this study was to examine the success rates, longevity, and complications of ultrasound-guided peripheral intravenous lines (USgPIVs) placed in a pediatric emergency department.

Methods

The study analyzed 300 USgPIV attempts in an urban tertiary-care pediatric emergency department. Data regarding USgPIV placement were collected from a 1-page form completed by the clinician placing the USgPIV. The time and reason for USgPIV removal were extracted from the medical record for patients with USgPIVs admitted to the hospital. A Kaplan-Meier survival analysis was performed.

Results

This study demonstrated a success rate of 68% and 87% for the first and second attempts with USgPIV. Fifty-five percent of patients had 1 or more prior traditional intravenous access attempt. Most USgPIVs placed on patients admitted to the hospital were removed because they were no longer needed (101/160). We calculated a Kaplan-Meier median survival of 143 hours (6 days; interquartile range, 68–246 hours). The failure rate at 48 hours was 25%.

Conclusion

Ultrasound-guided intravenous access is a feasible alternative to traditional peripheral intravenous access in the pediatric emergency setting. We observed a high first-stick success rate even in patients who had failed traditional peripheral intravenous access attempts, few complications, and a long intravenous survival time.
The Elusive Diagnosis of Adolescent Systemic Lupus Erythematosus
Authors: Mancini Michelino
Published: February 2017

Systemic lupus erythematosus (SLE) is an autoimmune disease affecting multiple systems, and its various symptoms are often mistaken for other diseases. This case report describes a 15-year-old girl who presented to the emergency department with complaints of diffuse abdominal pain, facial swelling, joint pain, low-grade fever, and rash. An initial autoimmune process was suspected, and, with prompt referral, a diagnosis of SLE was confirmed. This case report and discussion review the difficulty of diagnosing SLE and the importance of maintaining autoimmune diseases, such as SLE, on an emergency physician's differential.
Risk Factors for Recurrent Intussusception After Fluoroscopy-Guided Air Enema
Authors: Kim Jung Heon , Lee Jong Seung , Ryu Jeong Min , Lim Kyoung Soo , Kim Won Young
Published: February 2017

Objectives

The aim of this study was to identify risk factors for recurrent intussusception after a successful reduction by fluoroscopy-guided air enema, the time required for recurrence, and the association between delayed reduction and the recurrence.

Methods

Medical records of 479 consecutive children with intussusception who underwent fluoroscopy-guided air enema between January 2004 and September 2014 were reviewed. Recurrent intussusception was defined as a recurrence within 48 hours of a reduction. Symptom-to-door time was defined as the time from symptom onset to emergency department arrival. Door-to-reduction time was defined as the time from emergency department arrival to reduction. Time-to-recurrence was defined as the time required for recurrence from the first ultrasound diagnosis.

Results

Of the 360 eligible children, 32 had recurrent intussusceptions (8.9%). Multivariable logistic regression showed that age 2 years or older is an independent predictor of recurrent intussusception (odds ratio, 2.39; 95% confidence interval, 1.13–5.02; P = 0.02). Median time to recurrence was 25 hours (18.0–36.0 hours). Although symptom-to-door and door-to-reduction times tended to be longer in the recurrence group, these differences were not significant (12.5 vs 7.0 hours, P = 0.18; 154.0 vs 143.0 minutes, P = 0.67, respectively).

Conclusions

Our data suggest that provision for early recurrence and extended observation may be beneficial for children 2 years or older. Delayed reduction was not associated with recurrent intussusception, but further studies with larger sample sizes are needed to explain this issue.
L1CAM and HER2 Expression in Early Endometrioid Uterine Cancer
Authors: Abdel Azim Samira , Sprung Susanne , Mutz-Dehbalaie Irene , Fessler Siegfried , Zeimet Alain G. , Marth Christian
Published: February 2017

Recently L1CAM was shown to be a promising biomarker for early-stage endometrial carcinoma (EC). As L1CAM expression was found to be related to serous ECs and areas of serous differentiation in endometrioid carcinomas, there is evidence that L1CAM-positive cancers more likely resemble type II carcinomas. Furthermore, expression of growth factor receptor HER2 has been found to be closely associated with serous ECs. We conducted a retrospective study on 142 patients in FIGO stages I and II with endometrioid EC and analyzed L1CAM and HER2 expression by double-staining immunohistochemistry. The association between these 2 transmembrane molecules and their impact on patient outcome was analyzed. Both L1CAM and HER2 showed a significant association with recurrent disease (P<0.001 and P=0.007, respectively). We found 39 (27%) L1CAM-positive cases and 17 (12%) HER2-positive cases. About 6.3% of cases were positive for both biomarkers. Survival of L1CAM-positive patients showed a significant difference between HER2-positive and HER2-negative patients (P=0.019) regarding disease-free survival. The most unfavorable disease-free survival and overall survival was found for patients with L1CAM and HER2 double-positive tumors (P<0.001). Double immunostaining revealed a mutually exclusive staining pattern for L1CAM and HER2 expression on the level of tumor cells. In early endometrioid uterine carcinoma, an additional expression of HER2 to L1CAM seems to further worsen disease-free survival and overall survival. In terms of “personalized medicine,” detection of these molecules in endometrioid ECs may open new avenues for targeted therapies with the newly available anti-HER2 drugs and/or with the upcoming humanized anti-L1CAM antibodies.
Association of Li-Fraumeni Syndrome With Small Cell Carcinoma of the Ovary, Hypercalcemic Type and Concurrent Pleomorphic Liposarcoma of the Cervix
Authors: Tandon Bevan , Hagemann Ian S. , Maluf Horacio M. , Pfeifer John D. , Al-Kateb Hussam
Published: February 2017

Small cell carcinoma of the ovary, hypercalcemic type (SCCOHT), is a rare, highly lethal malignancy predominantly affecting young adult females. We report a patient with widely metastatic SCCOHT and concurrent uterine cervical pleomorphic liposarcoma. Clinical targeted next-generation sequencing was performed on both neoplasms and demonstrated hemizygous stop-gain TP53 mutations (p.R196*), and wild-type SMARCA4 in both tumors. Microarray analyses of both tumors revealed similar but not identical widespread loss of heterozygosity over most chromosomes associated with loss of chromosomal copy number in the SCCOHT and pleomorphic liposarcoma tumors, amplification of FGFR1 in both tumors, and amplification of MYC in the SCCOHT. Immunohistochemistry demonstrated that SMARCA4 and SMARCB1 were retained in both tumors, and that SMARCA2 expression was retained but TP53 expression was lost in the SCCOHT. Germline testing using Sanger sequencing showed heterozygous TP53 mutation, confirming the diagnosis of Li-Fraumeni syndrome. These findings are novel and for the first time associate SCCOHT with Li-Fraumeni syndrome.
Misinterpretation of Frozen Section in Endometrial Cancer Cases: Does It Have Any Effect on Disease-free and Overall Survival?
Authors: Şenol Taylan , Polat Mesut , Özkaya Enis , Karateke Ateş
Published: February 2017

The aim of this study was to assess whether misinterpretation of frozen sections in endometrial cancer cases is associated with survival and determine the factors leading to mismatch. One hundred fifty endometrial cancer cases treated in Zeynep Kamil Maternity and Children’s Health Training and Research Hospital between January 2010 and December 2014 were included in the study. Frozen sections and final histopathologic reports were screened from a prospectively collected database and analyzed on whether mismatch between the initial and the final reports has any impact on disease-free survival. There were 31 patients with mismatched frozen sections with the final report, whereas in 119 patients, frozen sections and final reports were consistent. The recurrence-free survival time was similar between groups (51 vs. 49, P=0.813). Overall survivals were also similar between groups (55 vs. 52, P=0.880). Frozen section misinterpretation does not affect disease-free and overall survival in endometrial cancer cases.
Systematic Review and Meta-analysis of Interventions for Depression and Anxiety in Persons With Rheumatoid Arthritis
Authors: Fiest Kirsten M. , Hitchon Carol A. , Bernstein Charles N. , Peschken Christine A. , Walker John R. , Graff Lesley A. , Zarychanski Ryan , Abou-Setta Ahmed , Patten Scott B. , Sareen Jitender , Bolton James , Marrie Ruth Ann
Published: February 2017

Background

Psychiatric comorbidities, such as depression and anxiety, are very common in persons with rheumatoid arthritis (RA) and can lead to adverse outcomes. By appropriately treating these comorbidities, disease-specific outcomes and quality of life may be improved.

Objective

The aim of this study was to systematically review the literature from controlled trials of treatments for depression and anxiety in persons with RA.

Methods

We searched multiple online databases from inception until March 25, 2015, without restrictions on language, date, or location of publication. We included controlled trials conducted in persons with RA and depression or anxiety. Two independent reviewers extracted information including trial and participant characteristics. The standardized mean differences (SMDs) of depression or anxiety scores at postassessment were pooled between treatment and comparison groups, stratified by active versus inactive comparators.

Results

From 1291 unique abstracts, we included 8 RA trials of depression interventions (6 pharmacological, 1 psychological, 1 both). Pharmacological interventions for depression with inactive comparators (n = 3 trials, 143 participants) did not reduce depressive symptoms (SMD, −0.21; 95% confidence interval [CI], −1.27 to 0.85), although interventions with active comparators (n = 3 trials, 190 participants) did improve depressive symptoms (SMD, −0.79; 95% CI, −1.34 to −0.25). The single psychological trial of depression treatment in RA did not improve depressive symptoms (SMD, −0.44; 95% CI, −0.96 to 0.08). Seven of the trials had an unclear risk of bias.

Conclusions

Few trials examining interventions for depression or anxiety in adults with RA exist, and the level of evidence is low to moderate because of the risk of bias and small number of trials.
Hyperpolarized Helium-3 Diffusion-weighted Magnetic Resonance Imaging Detects Abnormalities of Lung Structure in Children With Bronchopulmonary Dysplasia
Authors: Flors Lucia , Mugler John P. , Paget-Brown Alix , Froh Deborah K. , de Lange Eduard E. , Patrie James T. , Altes Talissa A.
Published: February 2017

Purpose:

The aim of the study was to determine whether hyperpolarized 3He diffusion-weighted magnetic resonance imaging detects abnormalities in the lungs in children with bronchopulmonary dysplasia (BPD) as compared with age-matched normal children.

Materials and Methods:

All experiments were compliant with Health Insurance Portability and Accountability Act (HIPAA) and performed with Food and Drug Administration approval under an IND application. The protocol was approved by our Institutional Review Board, and written informed consent was obtained. Hyperpolarized 3He diffusion-weighted magnetic resonance imaging was performed in 16 subjects with a history of preterm birth complicated by BPD (age range, 6.8 to 13.5 y; mean, 9.0 y) and in 29 healthy term-birth subjects (age range, 4.5-14.7 y; mean, 9.2 y) using a gradient-echo sequence with bipolar diffusion gradients and with measurements at 2 b values (0 and 1.6 s/cm2). Age-related comparison of the whole-lung mean apparent diffusion coefficient (ADC), 90th percentile ADC, and percentage of whole-lung volume with ADC>0.2 cm2/s between the 2 groups was examined using ordinary least-squares multiple regression.

Results:

The mean ADC was significantly greater in subjects with BPD (0.187 vs. 0.152 cm2/s, P<0.001). The 90th percentile ADC and mean percentage lung volume with ADC>0.2 cm2/s were also higher in the BPD group (0.258 vs. 0.215 cm2/s, 30.3% vs. 11.9%, P<0.001 for both). The body surface area–adjusted ventilated lung volume was similar in the 2 groups (1.93 vs. 1.91 L, P=0.90).

Conclusions:

Children with BPD had higher ADCs and the same lung volumes when compared with age-matched healthy subjects, suggesting that children with BPD have enlarged alveoli that are reduced in number.
Additional Magnetic Resonance Imaging–Detected Suspicious Lesions in Known Patients With Breast Cancer
Authors: Koh Jieun , Kim Eun-Kyung , Kim Min Jung , Yoon Jung Hyun , Moon Hee Jung
Published: February 2017

Purpose

The aim of the study was to compare the performances of second-look digital breast tomosynthesis (DBT) and ultrasonography (US) for additional magnetic resonance imaging (MRI)–detected suspicious lesions in patients referred for breast cancer.

Methods

Fifty-five patients (52.5 [9.3] years) with breast cancers newly diagnosed at a referring hospital underwent MRI and afterward DBT and US in our institution. The frequency for detecting additional MRI-detected suspicious lesions on DBT and US and performances of DBT and US were compared.

Results

Of 37 additional MRI-detected suspicious lesions, 27 were detected on DBT and/or US; 2 were detected on both DBT and US, 1 was detected only on DBT, and 24 were detected only on US. Ultrasonography detected more additional suspicious lesions than DBT (P < 0.0001). Twelve (44.4%) of the 27 lesions were malignant. The sensitivity and negative predictive value of US (100.0% and 100.0%) were significantly higher than those of DBT (16.7% and 83.6%, P < 0.001 and P = 0.001). The specificity of DBT was significantly higher (98.1%) than that of US (78.9%, P = 0.002). Positive predictive values of DBT and US were not significantly different (66.7% vs 52.2%, P = 0.598). The area under the receiver operating characteristic curve of US was significantly higher (0.894) than that of DBT (0.574, P < 0.001).

Conclusions

Second-look US showed higher performances than DBT for detecting and characterizing suspicious lesions additionally detected on MRI in patients referred for breast cancer.
The Effect of the Amniotic Fluid Index on the Accuracy of Ultrasonographic-Estimated Fetal Weight
Authors: Karahanoglu Ertugrul , Altinboga Orhan , Akpinar Funda , Gultekin Ismail Burak , Ozdemirci Safak , Akyol Aysegul , Yalvac Serdar
Published: February 2017

Background

Fetal weight estimation is one of the most important aspects of antenatal care. The effects of amniotic fluid volume on the accuracy of estimated fetal weight (EFW) depend on the amount of fluid, in particular whether it is polyhydramnios or oligohydramnios. Previous studies have reported conflicting results of the effects of amniotic fluid volume on EFW accuracy.

Aim

The aim of the study was to evaluate the effects of isolated oligohydramnios cases and polyhydramnios on the accuracy of EFW.

Materials and Methods

A retrospective study was conducted at a tertiary center. The study groups consisted of 1069 term isolated oligohydramnios cases, 182 term isolated polyhydramnios cases, and 392 term-matched cases with a normal volume of amniotic fluid. Estimated fetal weight error was determined and expressed in terms of systematic error, calculated from mean percentage error and random error.

Results

The systematic error did not differ significantly between polyhydramnios and oligohydramnios cases (−3.60 [8.94%] vs −2.73 [9.7%]). The random error was 8.94% in polyhydramnios cases and 9.7% in oligohydramnios cases. The overestimation rate was 63.6% in polyhydramnios cases and 66.3% in oligohydramnios cases.

Conclusions

There were no significant differences in the accuracy of EFW between oligohydramnios and polyhydramnios. However, there was a tendency for overestimation in both types of cases.
Activation of the hypothalamic feeding centre upon visual prey detection
Authors: Muto Akira , Lal Pradeep , Ailani Deepak , Abe Gembu , Itoh Mari , Kawakami Koichi
Published: February 2017

The visual system plays a major role in food/prey recognition in diurnal animals, and food intake is regulated by the hypothalamus. However, whether and how visual information about prey is conveyed to the hypothalamic feeding centre is largely unknown. Here we perform real-time imaging of neuronal activity in freely behaving or constrained zebrafish larvae and demonstrate that prey or prey-like visual stimuli activate the hypothalamic feeding centre. Furthermore, we identify prey detector neurons in the pretectal area that project to the hypothalamic feeding centre. Ablation of the pretectum completely abolishes prey capture behaviour and neurotoxin expression in the hypothalamic area also reduces feeding. Taken together, these results suggest that the pretecto-hypothalamic pathway plays a crucial role in conveying visual information to the feeding centre. Thus, this pathway possibly converts visual food detection into feeding motivation in zebrafish.
Mass spectrometrists should search for all peptides, but assess only the ones they care about
Authors: Sticker Adriaan , Martens Lennart , Clement Lieven
Published: February 2017

In shotgun proteomics identified mass spectra that are deemed irrelevant to the scientific hypothesis are often discarded. Noble (2015)1therefore urged researchers to remove irrelevant peptides from the database prior to searching to improve statistical power. We here however, argue that both the classical as well as Noble’s revised method produce suboptimal peptide identifications and have problems in controlling the false discovery rate (FDR). Instead, we show that searching for all expected peptides, and removing irrelevant peptides prior to FDR calculation results in more reliable identifications at controlled FDR level than the classical strategy that discards irrelevant peptides post FDR calculation, or than Noble’s strategy that discards irrelevant peptides prior to searching.
Learning place cells, grid cells and invariances: A unifying model
Authors: Weber Simon N. , Sprekeler Henning
Published: February 2017

Neurons in the hippocampus and adjacent brain areas show a large diversity in their tuning to location and head direction. The underlying circuit mechanisms are not fully resolved. In particular, it is unclear why certain cell types are selective to one spatial variable, but invariant to another. For example, a place cell is highly selective to location, but typically invariant to head direction. Here, we propose that all observed spatial tuning patterns – in both their selectivity and their invariance – are a consequence of the same mechanism: Excitatory and inhibitory synaptic plasticity that is driven by the spatial tuning statistics of synaptic inputs. Using simulations and a mathematical analysis, we show that combined excitatory and inhibitory plasticity can lead to localized, grid-like or invariant activity. Combinations of different input statistics along different spatial dimensions reproduce all major spatial tuning patterns observed in rodents. The model is robust to changes in parameters, develops patterns on behavioral time scales and makes distinctive experimental predictions. Our results suggest that the interaction of excitatory and inhibitory plasticity is a general principle for the formation of neural representations.
Parsing propagule pressure: Number, not size, of introductions drives colonization success in a novel environment
Authors: Koontz Michael J , Oldfather Meagan F , Melbourne Brett A , Hufbauer Ruth A
Published: February 2017

Predicting whether individuals will colonize a novel habitat is of fundamental ecological interest and is crucial to both conservation efforts and invasive species management. A consistently supported predictor of colonization success is the number of individuals introduced, also called propagule pressure. Propagule pressure increases with the number of introductions and the number of individuals per introduction (the size of the introduction), but it is unresolved which process is a stronger driver of colonization success. Furthermore their relative importance may depend upon the environment, with multiple introductions potentially enhancing colonization of fluctuating environments. To evaluate the relative importance of the number and size of introductions and its dependence upon environmental variability, we paired demographic simulations with a microcosm experiment. UsingTriboliumflour beetles as a model system, we introduced a fixed number of individuals into replicated novel habitats of stable or fluctuating quality, varying the number of introductions through time and size of each introduction. We evaluated establishment probability and the size of extant populations after 7 generations. In the simulations and microcosms, we found that establishment probability increased with more, smaller introductions, but was not affected by biologically realistic fluctuations in environmental quality. Population size was not significantly affected by environmental variability in the simulations, but populations in the microcosms grew larger in a stable environment, especially with more introduction events. In general, the microcosm experiment yielded higher establishment probability and larger populations than the demographic simulations. We suggest that genetic mechanisms likely underlie these differences and thus deserve more attention in efforts to parse propagule pressure. Our results highlight the importance of preventing further introductions of undesirable species to invaded sites, and suggest conservation efforts should focus on increasing the number of introductions or re-introductions of desirable species rather than increasing the size of those introduction events.
Individual differences in responsivity to social rewards: Insights from two eye-tracking tasks
Authors: Chakrabarti Bhismadev , Haffey Anthony , Canzano Loredana , P. Taylor Christopher , McSorley Eugene
Published: February 2017

Humans generally prefer social over nonsocial stimuli from an early age. Reduced preference for social rewards has been observed in individuals with autism spectrum conditions (ASC). This preference has typically been noted in separate tasks that measure orienting toward and engaging with social stimuli. In this experiment, we used two eye-tracking tasks to index both of these aspects of social preference in in 77 typical adults. We used two measures, global effect and preferential looking time. The global effect task measures saccadic deviation toward a social stimulus (related to ‘orienting’), while the preferential looking task records gaze duration bias toward social stimuli (relating to ‘engaging’). Social rewards were found to elicit greater saccadic deviation and greater gaze duration bias, suggesting that they have both greater salience and higher value compared to nonsocial rewards. Trait empathy was positively correlated with the measure of relative value of social rewards, but not with their salience. This study thus elucidates the relationship of empathy with social reward processing.
Reproducibility2020: Progress and Priorities
Authors: Freedman Leonard P. , Venugopalan Gautham , Wisman Rosann
Published: February 2017

The preclinical research process is a cycle of idea generation, experimentation, and reporting of results. The biomedical research community relies on the reproducibility of published discoveries to create new lines of research and to translate research findings into therapeutic applications. Since 2012, when scientists from Amgen reported that they were able to reproduce only 6 of 53 “landmark” preclinical studies, the biomedical research community began discussing the scale of the reproducibility problem and developing initiatives to address critical challenges. GBSI released the “Case for Standards” in 2013, one of the first comprehensive reports to address the rising concern of irreproducible biomedical research. Further attention was drawn to issues that limit scientific self-correction including reporting and publication bias, underpowered studies, lack of open access to methods and data, and lack of clearly defined standards and guidelines in areas such as reagent validation. To evaluate the progress made towards reproducibility since 2013, GBSI identified and examined initiatives designed to advance quality and reproducibility. Through this process, we identified key roles for funders, journals, researchers and other stakeholders and recommended actions for future progress. This paper describes our findings and conclusions.
The Stochastic Early Reaction, Inhibition, and Late Action (SERIA) Model for Antisaccades
Authors: Aponte Eduardo A. , Schoebi Dario , Stephan Klaas E. , Heinzle Jakob
Published: February 2017

The antisaccade task is a classic paradigm used to study the voluntary control of eye movements. It requires participants to suppress a reactive eye movement to a visual target and to concurrently initiate a saccade in the opposite direction. Although several models have been proposed to explain error rates and reaction times in this task, no formal model comparison has yet been performed. Here, we describe a Bayesian modeling approach to the antisaccade task that allows us to formally compare different models on the basis of their evidence. First, we provide a formal likelihood function of actions (pro- and antisaccades) and reaction times based on previously published models. Second, we introduce theStochastic Early Reaction, Inhibition, and late Action model(SERIA), a novel model postulating two different mechanisms that interact in the antisaccade task: an early GO/NO-GO race decision process and a late GO/GO decision process. Third, we apply these models to a data set from an experiment with three mixed blocks of pro- and antisaccade trials. Bayesian model comparison demonstrates that the SERIA model explains the data better than competing models that do not incorporate a late decision process. Moreover, we show that the race decision processes postulated by the SERIA model are, to a large extent, insensitive to the cue presented on a single trial. Finally, we use parameter estimates to demonstrate that changes in reaction time and error rate due to the probability of a trial type (prosaccade or antisaccade) are best explained by faster or slower inhibition and the probability of generating late voluntary prosaccades.

Author summary

One widely replicated finding in schizophrenia research is that patients tend to make more errors in the antisaccade task, a psychometric paradigm in which participants are required to look in the opposite direction of a visual cue. This deficit has been suggested to be an endophenotype of schizophrenia, as first order relatives of patients tend to show similar but milder deficits. Currently, most models applied to experimental findings in this task are limited to fit average reaction times and error rates. Here, we propose a novel statistical model that fits experimental data from the antisaccade task, beyond summary statistics. The model is inspired by the hypothesis that antisaccades are the result of several competing decision processes that interact nonlinearly with each other. In applying this model to a relatively large experimental data set, we show that mean reaction times and error rates do not fully reflect the complexity of the processes that are likely to underlie experimental findings. In the future, our model could help to understand the nature of the deficits observed in schizophrenia by providing a statistical tool to study their biological underpinnings.
Holographic deep learning for rapid optical screening of anthrax spores
Authors: Jo YoungJu , Park Sangjin , Jung JaeHwang , Yoon Jonghee , Joo Hosung , Kim Min-hyeok , Kang Suk-Jo , Choi Myung Chul , Lee Sang Yup , Park YongKeun
Published: February 2017

Establishing early warning systems for anthrax attacks is crucial in biodefense. Here we present an optical method for rapid screening ofBacillus anthracisspores through the synergistic application of holographic microscopy and deep learning. A deep convolutional neural network is designed to classify holographic images of unlabeled living cells. After training, the network outperforms previous techniques in all accuracy measures, achieving single-spore sensitivity and sub-genus specificity. The unique ‘representation learning’ capability of deep learning enables direct training fromraw imagesinstead of manually extracted features. The method automatically recognizes key biological traits encoded in the images and exploits them as fingerprints. This remarkable learning ability makes the proposed method readily applicable to classifying various single cells in addition toB. anthracis, as demonstrated for the diagnosis ofListeria monocytogenes, without any modification. We believe that our strategy will make holographic microscopy more accessible to medical doctors and biomedical scientists for easy, rapid, and accurate diagnosis of pathogens, and facilitate exciting new applications.
Whole exome sequencing reveals a mutation inARMC9as a cause of mental retardation, ptosis and polydactyly
Authors: Kar Anjana , Phadke Shubha R , Bhowmik Aneek Das , Dalal Ashwin
Published: February 2017

Intellectual disability (ID) refers to deficits in mental abilities, social behaviour and motor skills to perform activities of daily living as compared to peers. Numerous genetic and environmental factors may be responsible for ID. We report on identification of a novel gene for syndromic ID, using homozygosity mapping followed by exome sequencing in a family with mental retardation, ptosis and polydactyly. The analysis revealed a synonymous mutation c.879G>A which leads to a splicing defect inARMC9gene. The variant is present in conserved region of ARM domain of ARMC9 protein which is predicted to form a platform for protein interaction. This domain is likely to be altered in patients due to splicing defect caused by this synonymous mutation. Our study was helpful in elucidation of molecular basis of mental retardation, ptosis and polydactyly phenotype and addition ofARMC9to group of genes leading to syndromic ID.
A Fluorescent Split Aptamer for Visualizing RNA-RNA AssemblyIn Vivo
Authors: Alam Khalid K. , Tawiah Kwaku D. , Lichte Matthew F. , Porciani David , Burke Donald H.
Published: February 2017

RNA-RNA assembly governs key biological processes and is a powerful tool for engineering synthetic genetic circuits. Characterizing RNA assembly in living cells often involves monitoring fluorescent reporter proteins, which are at best indirect measures of underlying RNA-RNA hybridization events and are subject to additional temporal and load constraints associated with translation and activation of reporter proteins. In contrast, RNA aptamers that sequester small molecule dyes and activate their fluorescence are increasingly utilized in genetically-encoded strategies to report on RNA-level events. Split-aptamer systems have been rationally designed to generate signal upon hybridization of two or more discrete RNA transcripts, but none directly function when expressedin vivo. We reasoned that the improved physiological properties of the Broccoli aptamer enable construction of a split-aptamer system that could function in living cells. Here we present the Split-Broccoli system, in which self-assembly is nucleated by a thermostable, three-way junction RNA architecture and fluorescence activation requires both strands. Functional assembly of the system approximately follows second order kineticsin vitroand improves when cotranscribed, rather than when assembled from purified components. Split-Broccoli fluorescence is digitalin vivoand retains functional modularity when fused to RNAs that regulate circuit function through RNA-RNA hybridization, as demonstrated with an RNA Toehold switch. Split-Broccoli represents the first functional split-aptamer system to operatein vivo. It offers a genetically-encoded and nondestructive platform to monitor and exploit RNA-RNA hybridization, whether as an all-RNA, stand-alone AND gate or as a tool for monitoring assembly of RNA-RNA hybrids.
Linking soil biology and chemistry using bacterial isolate exometabolite profiles
Authors: Swenson Tami L. , Karaoz Ulas , Swenson Joel M. , Bowen Benjamin P. , Northen Trent
Published: February 2017

Sequencing provides a window into microbial community structure and metabolic potential; however, linking these data to exogenous metabolites that microorganisms process and produce (the exometabolome) remains challenging. Previously, we observed strong exometabolite niche partitioning among bacterial isolates from biological soil crust (biocrust). Here we examine native biocrust to determine if these patterns are reproduced in the environment. Overall, most soil metabolites displayed the expected relationship (positive or negative correlation) with four dominant bacteria following a wetting event and across biocrust developmental stages. For metabolites that were previously found to be consumed by an isolate, 78% were negatively correlated with the abundance ofin situisolate phylotypes whereas for released metabolites, 73% were positively correlated. Our results demonstrate that metabolite profiling, sequencing and exometabolomics can be successfully integrated to functionally link metagenomes and microbial community structure with environmental chemistry.
Genome sequencing reveals Zika virus diversity and spread in the Americas
Authors: H.C. Metsky , C.B. Matranga , S. Wohl , S.F. Schaffner , C.A. Freije , S.M. Winnicki , K. West , J. Qu , M.L. Baniecki , A. Gladden-Young , A.E. Lin , C.H. Tomkins-Tinch , S.H. Ye , D.J. Park , C.Y. Luo , K.G. Barnes , R.R. Shah , B. Chak , G. Barbosa-Lima , E. Delatorre , Y.R. Vieira , L.M. Paul , A.L. Tan , C.M. Barcellona , M.C. Porcelli , C. Vasquez , A.C. Cannons , M.R. Cone , K.N. Hogan , E.W. Kopp , J.J. Anzinger , K.F. Garcia , L.A. Parham , R.M. Gélvez Ramírez , M.C. Miranda Montoya , D.P. Rojas , C.M. Brown , S. Hennigan , B. Sabina , S. Scotland , K. Gangavarapu , N.D. Grubaugh , G. Oliveira , R. Robles-Sikisaka , A. Rambaut , L. Gehrke , S. Smole , M.E. Halloran , L.A. Villar Centeno , S. Mattar , I. Lorenzana , J. Cerbino-Neto , C. Valim , W. Degrave , P.T. Bozza , A. Gnirke , K.G. Andersen , S. Isern , S.F. Michael , F.A. Bozza , T.M.L. Souza , I. Bosch , N.L. Yozwiak , B.L. MacInnis , P.C. Sabeti
Published: February 2017

Despite great attention given to the recent Zika virus (ZIKV) epidemic in the Americas, much remains unknown about its epidemiology and evolution, in part due to a lack of genomic data. We applied multiple sequencing approaches to generate 110 ZIKV genomes from clinical and mosquito samples from 10 countries and territories, greatly expanding the observed viral genetic diversity from this outbreak. We analyzed the timing and patterns of introductions into distinct geographic regions; our phylogenetic evidence suggests rapid expansion of the outbreak in Brazil and multiple introductions of outbreak strains into Puerto Rico, Honduras, Colombia, other Caribbean islands, and the continental US. We find that ZIKV circulated undetected in multiple regions for many months before the first locally transmitted cases were confirmed, highlighting the importance of viral surveillance. We identify mutations with possible functional implications for ZIKV biology and pathogenesis, as well as those potentially relevant to the effectiveness of diagnostic tests.
Commentary on Sanborn and Chater: Posterior Modes are Attractor Basins
Authors: Alday Phillip , Schlesewsky Matthias , Bornkessel-Schlesewsky Ina
Published: February 2017

Sanborn and Chater propose an interesting theory of cognitive and brain function based on Bayesian sampling instead of asymptotic Bayesian inference. Their proposal unifies many current observations and models and, in spite of focusing primarily on cognitive phenomena, their work provides a springboard for unifying several proposed theories of brain function. It has the potential to serve as a bridge between three influential overarching current theories of cognitive and brain function: Bayesian models, Friston's theory of cortical responses based on the free-energy principle, and attractor-basin dynamics. Specifically, their proposal suggests a high-level perspective on Friston's theory, which in turn proposes a sampling procedure including appropriate handling of autocorrelation as well as a plausible neurobiological implementation. In turn, these two theories together link into attractor-basin dynamics at the level of networks (via Friston) as well at the level of behavior (via the relationship between the modes of prior and posterior distributions, as discussed by Sanborn and Chater). We will argue here that, by linking Sanborn and Chater's approach to neurobiological models based on the free-energy principle on the one hand and attractor-basin dynamics on the other, the scope of their proposal can be broadened considerably. Moreover, a unified perspective along these lines provides an elegant solution to several of Sanborn and Chater's Outstanding Questions relating to the neural implementation of sampling.
Patterns of shared signatures of recent positive selection across human populations
Authors: Johnson Kelsey Elizabeth , Voight Benjamin F.
Published: February 2017

Scans for positive selection in human populations have identified hundreds of sites across the genome with evidence of recent adaptation. These signatures often overlap across populations, but the question of how often these overlaps represent a single ancestral event remains unresolved. If a single positive selection event spread across many populations, the same sweeping haplotype should appear in each population and the selective pressure could be common across diverse populations and environments. Identifying such shared selective events would be of fundamental interest, pointing to genomic loci and human traits important in recent history across the globe. Additionally, genomic annotations that recently became available could help attach these signatures to a potential gene and molecular phenotype that may have been selected across multiple populations. We performed a scan for positive selection using the integrated haplotype score on 20 populations, and compared sweeping haplotypes using the haplotype-clustering capability of fastPHASE to create a catalog of shared and unshared overlapping selective sweeps in these populations. Using additional genomic annotations, we connect these multi-population sweep overlaps with potential biological mechanisms at several loci, including potential new sites of adaptive introgression, the glycophorin locus associated with malarial resistance, and the alcohol dehydrogenase cluster associated with alcohol dependency.
Significance estimation for large scale untargeted metabolomics annotations
Authors: Scheubert Kerstin , Hufsky Franziska , Petras Daniel , Wang Mingxun , Nothias Louis-Félix , Dührkop Kai , Bandeira Nuno , Dorrestein Pieter C , Bocker Sebastian
Published: February 2017

The annotation of small molecules in untargeted mass spectrometry relies on the matching of fragment spectra to reference library spectra. While various spectrum-spectrum match scores exist, the field lacks statistical methods for estimating the false discovery rates (FDR) of these annotations. We present empirical Bayes and target-decoy based methods to estimate the false discovery rate. Relying on estimations of false discovery rates, we explore the effect of different spectrum-spectrum match criteria on the number and the nature of the molecules annotated. We show that the spectral matching settings needs to be adjusted for each project. By adjusting the scoring parameters and thresholds, the number of annotations rose, on average, by +139% (ranging from −92% up to +5705%) when compared to a default parameter set available at GNPS. The FDR estimation methods presented will enable a user to define the scoring criteria for large scale analysis of untargeted small molecule data that has been essential in the advancement of large scale proteomics, transcriptomics, and genomics science.
From Sequence to Function: Coevolving Amino Acids Encode Structural and Functional Domains
Authors: Granata Daniele , Ponzoni Luca , Micheletti Cristian , Carnevale Vincenzo
Published: February 2017

Amino acids interactions within protein families are so optimized that the sole analysis of evolutionary co-mutations can identify pairs of contacting residues. It is also known that evolution conserves functional dynamics, i.e., the concerted motion or displacement of large protein regions or domains. Is it, therefore, possible to use a pure sequence-based analysis to identify these dynamical domains? To address this question, we introduce here a general co-evolutionary coupling analysis strategy and apply it to a curated sequence database of hundreds of protein families. For most families, the sequence-based method partitions amino acids into few clusters. When viewed in the context of the native structure, these clusters have the signature characteristics of viable protein domains: they are spatially separated but individually compact. They have a direct functional bearings too, as shown for various reference cases. We conclude that even large-scale structural and functionally-related properties can be recovered from inference methods applied to evolutionary-related sequences. The method introduced here is available as a software package and web server (http://spectrus.sissa.it/spectrus-evo_webserver).
A novel mitochondrial enriched antioxidant protects neurons against acute oxidative stress
Authors: Drummond Nicola J. , Davies Nick O. , Lovett Janet E. , Miller Mark R. , Cook Graeme , Becker Thomas , Becker Catherina G. , McPhail Donald B. , Kunath Tilo
Published: February 2017

Excessive reactive oxygen species (ROS) can damage proteins, lipids, and DNA, which result in cell damage and death. The outcomes can be acute, as seen in stroke, or more chronic as observed in age-related diseases such as Parkinson’s disease. Here we investigate the antioxidant ability of a novel synthetic flavonoid, Proxison (7-decyl-3-hydroxy-2-(3,4,5-trihydroxyphenyl)-4-chromenone), using a range ofin vitroandin vivoapproaches. We show that, while it has radical scavenging ability on par with other flavonoids in a cell-free system, Proxison is orders of magnitude more potent than natural flavonoids at protecting neural cells against oxidative stress and is capable of rescuing damaged cells. The unique combination of a lipophilic hydrocarbon tail with a modified polyphenolic head group promotes efficient cellular uptake and mitochondrial localisation of Proxison. Importantly,in vivoadministration of Proxison demonstrated effective and well tolerated neuroprotection against oxidative stress in a zebrafish model of dopaminergic neuronal loss.
HistMapR: Rapid digitization of historical land-use maps in R
Authors: Auffret Alistair G. , Kimberley Adam , Plue Jan , Skånes Helle , Jakobsson Simon , Waldén Emelie , Wennbom Marika , Wood Heather , Bullock James M. , Cousins Sara A. O. , Gartz Mira , Hooftman Danny A. P. , Tränk Louise
Published: February 2017

1.Habitat destruction and degradation represent serious threats to biodiversity, and quantification of land-use change over time is important for understanding the consequences of these changes to organisms and ecosystem service provision.

2.Comparing land use between maps from different time periods allows estimation of the magnitude of habitat change in an area. However, digitizing historical maps manually is time-consuming and analyses of change are usually carried out at small spatial extents or at low resolutions.

3.We developed a method to semi-automatically digitize historical land-use maps using the R environment. We created a number of functions that use the existingrasterpackage to classify land use according to a map’s colours, as defined by the RGB channels of the raster image. The method was tested on three different types of historical land-use map and results were compared to manual digitisations.

4.Our method is fast, and agreement with manually-digitised maps of around 80-92% meets common targets for image classification. We hope that the ability to quickly classify large areas of historical land-use will promote the inclusion of land-use change into analyses of biodiversity, species distributions and ecosystem services.
Using remote camera traps to assess mammal and bird assemblages across a complex environmental landscape
Authors: Cloyed Carl S. , Cappelli Laura R. , Tilson David A. , Crawford John A. , Dell Anthony I.
Published: February 2017

Animals must navigate a complex mosaic of habitat types, both natural and artificial. As artificial habitats (e.g., agricultural fields) become increasingly abundant in many landscapes, species will be affected differently, depending on their habitat preferences. We investigated the diversity, richness, abundance, and biomass of mammals and birds with remote camera traps that optimized the capture of both large and small animals. Camera traps allowed us to capture natural rates of mammals and birds, which is difficult to obtain using human observers who can affect the behavior of animals and are limited in their spatio-temporal scope and ability to assess nocturnal communities. Our camera trap arrays were established along two transects in a local conservation reserve; one transect ran from an agricultural field to an upland forest and another from a wetland to an upland forest. Over the 6-week study our cameras recorded 2,245 images, within which we observed 483 individuals comprising 16 species of mammals and birds. Our data showed that species composition and abundances were only marginally different between the two transects, with species common to both transects not exhibiting any statistical difference in abundances. Coyotes and armadillos were unique to the riparian transect, and many more bird species were present along the riparian transect than the agricultural transect. Diversity, richness, and total community biomass did not differ significantly between the two transects nor along each transect but there were non-significant trends in predicted directions. Our results revealed that fewer species use the forest immediately adjacent to the agricultural field, but more species use the wetland and the forest immediately adjacent to the wetland. Our results corroborate other studies revealing that certain species are more common in forested areas but also that some species thought to prefer forested areas may actually be more habitat generalists than previously thought.