bluuebunny/crossref_metadata_2025 huggingface dataset:
Achieving Social Bowel Continence in Children With Hypermotility After Repair of Anorectal Malformations and Hirschsprung
Authors: Kreiss Jennifer , Holder Monica , Kern Patricia , Kneis Kristina
Published: September 2018

Children presenting to the Pediatric Colorectal Bowel Management clinic with soiling after surgical repair of anorectal malformations or Hirschsprung can be categorized into two groups: Most are constipated and managed with laxatives and/or enemas, whereas the second subset has frequent loose stools. This second group, children with multiple loose stools, presents a unique challenge for the achievement of social bowel continence. We present three case studies illustrating various clinical presentations of incontinence with loose stools, along with dietary and pharmacologic management strategies and a treatment algorithm. Children who soil with loose stools can achieve social continence using a combination approach using toileting supports, diet manipulation, fiber supplementation, medications, and small-volume enemas.
Escalator Injuries in the Pediatric Population
Authors: Cirilli Andrea , Schera Laura
Published: September 2018

Introduction

There has been an increase in the number of children with escalator-related foot injuries. Lim et al. (2010) reviewed the charts of 17 children who sustained escalator foot injuries within a 2-year time span, 13 of them were wearing rubber clogs. Nine of these 13 children sustained severe foot injuries, and one child had an unsalvageable traumatic amputation. The injuries included a traumatic amputation of the great toe and others with fractures, lacerations, and cuts. This abstract and poster is a case study of an escalator injury.

Methods:

This is a case study of a 7-year-old, Spanish-speaking boy who sustained a right foot traumatic amputation after getting it caught in a moving escalator. He presented to a Level I pediatric trauma center in an urban setting where he was brought emergently to the operating room and admitted under the trauma service. This case study reviews the hospital course including surgical procedures, postoperative care, complications, and outcomes.

Result

Escalator-related traumatic amputations result in severe tissue-mangling injuries that require multiple trips to the operating room and interdisciplinary collaboration. Educating parents and caregivers on escalator safety can help prevent injures and hospitalizations.

Conclusion

The U.S. Consumer Product Safety Commission has published a general interest in safety brochure on escalator injuries; however, it has not reconsidered mandatory standards (accessed on November 11, 2016). By enforcing safety behaviors within the community, there is a potential decrease in the incidence of injuries and, subsequently, hospitalizations.
Home Is Where the HeartWare Is: Preparing Pediatric Patients and Caregivers for Discharge to Home and Integration Into the Community
Authors: DiFusco Leigh Ann , Patton Ashley M. , White Rachel M. , Bober Carley M. , Miller Kelley D.
Published: September 2018

The Cardiac Center at The Children’s Hospital of Philadelphia has cared for patients with implanted ventricular assist device (VAD) technology since 1998. Historically, patients requiring VAD support were managed exclusively in the Cardiac Intensive Care Unit with the first medically stable transition to the Cardiac Care Unit (step-down) taking place in 2001. Patient management was confined to the inpatient setting, as the primary device used at the time was paracorporeal and not suitable for home use. Continuous-flow devices, such as the HeartWare HVAD, have gained popularity because of miniaturized size and lower profiles of side effects and adverse events, making them more suitable for home use. This article describes a single-center experience with transitioning the VAD-supported pediatric patient to the outpatient setting, highlighting outcomes, strategies, and lessons learned in order to support VAD patients and their caregivers in the hospital and community setting.
Mitochondrial disease genetics update: recent insights into the molecular diagnosis and expanding phenotype of primary mitochondrial disease
Authors: McCormick Elizabeth M. , Zolkipli-Cunningham Zarazuela , Falk Marni J.
Published: September 2018

Purpose of review

Primary mitochondrial disease (PMD) is a genetically and phenotypically diverse group of inherited energy deficiency disorders caused by impaired mitochondrial oxidative phosphorylation (OXPHOS) capacity. Mutations in more than 350 genes in both mitochondrial and nuclear genomes are now recognized to cause primary mitochondrial disease following every inheritance pattern. Next-generation sequencing technologies have dramatically accelerated mitochondrial disease gene discovery and diagnostic yield. Here, we provide an up-to-date review of recently identified, novel mitochondrial disease genes and/or pathogenic variants that directly impair mitochondrial structure, dynamics, and/or function.

Recent findings

A review of PubMed publications was performed from the past 12 months that identified 16 new PMD genes and/or pathogenic variants, and recognition of expanded phenotypes for a wide variety of mitochondrial disease genes.

Broad-based exome sequencing has become the standard first-line diagnostic approach for PMD. This has facilitated more rapid and accurate disease identification, and greatly expanded understanding of the wide spectrum of potential clinical phenotypes. A comprehensive dual-genome sequencing approach to PMD diagnosis continues to improve diagnostic yield, advance understanding of mitochondrial physiology, and provide strong potential to develop precision therapeutics targeted to diverse aspects of mitochondrial disease pathophysiology.
Challenges and opportunities for effective delivery of clinical genetic services in the U.S. healthcare system
Authors: Flannery David B.
Published: September 2018

Purpose of review

Demand for clinical genetics and genomics services is increasing. As discussed in this study, the clinical genetics and genomics workforce is small. How to meet the demand with a limited workforce requires innovation.

Recent findings

Background data regarding the current state of clinical genetic services including volume of services and make-up of the clinical genetics workforce are presented. The study then identifies opportunities to increase access to clinical genetic service providers using new models of service and discusses examples of solutions which have been implemented in some practice settings. Creative uses of technology to increase providers’ efficiency are highlighted.

Clinical genetics service providers need to rise to the occasion and lead the transformation of clinical genetic service delivery. Many of the examples of solutions described in the study can be implemented by other providers now. Additionally, the described solutions may serve to inspire genetic providers to create their own new solutions, which should then be shared with the provider community.
Role of Radiological Imaging in the Diagnosis and Characterization of Pancreatic Cystic Lesions
Authors: Mohamed Eyas , Jackson Richard , Halloran Christopher M. , Ghaneh Paula
Published: September 2018

The evidence on the ability of radiological tests to predict a specific diagnosis and also their aptitude in identifying pathological markers indicative of malignancy in cystic lesions of the pancreas remains inconclusive. We conducted a systematic review on MEDLINE for the use of computed tomography (CT), magnetic resonance imaging, and positron emission tomography/CT (PET/CT) in the diagnosis and characterization of these cysts. The accuracy of CT scan for reaching a specific diagnosis was 39% to 61.4%, whereas its accuracy for differentiating benign from malignant lesions was 61.9% to 80%. Magnetic resonance imaging showed a better accuracy in identifying a specific diagnosis of 50% to 86%, whereas its accuracy in differentiating benign from malignant lesions was 55.6% to 87%. The use of magnetic resonance imaging was superior to CT scan in identifying septations, mural nodules, and ductal communication. The sensitivity of PET/CT in diagnosing malignancy was 85.7% to 100% with a reported accuracy of 88% to 95%. The evidence gathered from this review suggests that the adequacy of CT imaging in full characterization of pancreatic cysts is suboptimal, and therefore a low threshold for supplementary imaging is advised. The use of PET/CT should be considered in high-risk patients with equivocal findings.
Vitamin D Intake and Status of Children With Sickle Cell Disease in Montreal, Canada
Authors: Grégoire-Pelchat Pascale , Alos Nathalie , Ribault Virginie , Pastore Yves , Robitaille Nancy , Mailhot Geneviève
Published: September 2018

Sickle cell disease (SCD) and vitamin D deficiency share manifestations such as bone complications and bony pains. Canadian SCD children are characterized by compromised sun exposure all year long and potential dietary deficiency, which combined to SCD-causing high nutritional demands, may lead to impaired vitamin D status. The objectives of this study were to document vitamin D status and intake and assess the relationship between vitamin D status and SCD-related outcomes in Canadian children with SCD followed in a tertiary pediatric center. Our study population included 119 children (47% males, median age [interquartile range]: 11.1 [9.2-14.8]) mainly of Haitian and Sub-Saharan African origin who had at least one measure of serum 25-hydroxyvitamin D (25OHD) performed between June 2015 and February 2017. Predominant genotypes were homozygous hemoglobin S (60%) and sickle hemoglobin-C (32%). Vitamin D deficiency (25OHD<30 nmol/L) and insufficiency (30 to 49 nmol/L) were present in 31% and 37% of children, respectively. Vitamin D-sufficient children (25OHD>50 nmol/L) had higher hemoglobin levels, lower leukocyte, reticulocyte, and neutrophil counts, compared with vitamin D-deficient and insufficient children. Vitamin D intake was low and modestly correlated to serum 25OHD levels. Acute SCD complications in the preceding 2 years were not associated with vitamin D status in these children.
Concurrent Detection of Bacterial Pathogens in Hospital Roommates
Authors: Cohen Bevin , Spirito Christopher M. , Liu Jianfang , Cato Kenrick D. , Larson Elaine
Published: September 2018

Background

Some nurse-driven interventions have successfully reduced rates of healthcare-associated infections, though incidence remains unacceptably high. Bacterial contamination in patient rooms may be a source of exposure for patients and thus a target for future interventions; however, few studies have investigated the role of the patient room on organism acquisition.

Objectives

The purpose of this study was to determine the incidence of concurrent detection of bacterial pathogens among patients sharing a hospital room.

Methods

We performed a retrospective network analysis using electronic administrative and clinical data collected from all patients admitted in 2006 through 2012 to four New York City hospitals, totaling 2,065 beds within 183 inpatient units. A computerized algorithm identified concurrent organism detection among roommates, defined as two patients who shared a room on at least 1 day and had a first positive culture for the same organism within 3 days following cohabitation.

Results

In total, 741,271 patient admissions were included. The algorithm identified 373 concurrent detection events: 158 (42%) in which the patients’ first positive cultures were drawn after they were no longer sharing a room but within 3 days of cohabitation, 144 (39%) in which the patients’ first positive cultures were drawn while they were still sharing a room but on different days, and 71 (19%) in which the patients’ first positive cultures were drawn while they were sharing a room on the same day.

Discussion

Methods to improve environmental decontamination should be included as part of a comprehensive approach to infection prevention in hospitals. Nurses have an important role to play in the planning and implementation of interventions to reduce bioburden in the patient environment.
Cutaneous Lymphoproliferative Disorders: What’s New in the Revised 4th Edition of the World Health Organization (WHO) Classification of Lymphoid Neoplasms
Authors: Sundram Uma
Published: September 2018

Cutaneous lymphoproliferative disorders remain a challenging aspect of dermatopathology, in part due to the rarity of the entities and extreme variability in clinical outcomes. Although many of the entities remain unchanged, the approach to some of them has changed in the new 2016 classification scheme of the World Health Organization. Chief among these are Epstein-Barr virus–associated lymphoproliferative disorders such as Epstein-Barr virus–associated mucocutaneous ulcer and hydroa vacciniforme-like lymphoproliferative disorder, primary cutaneous CD8+ aggressive epidermotropic cytotoxic T-cell lymphoma, primary cutaneous acral CD8+ T-cell lymphoma, primary cutaneous CD4+ small/medium T-cell lymphoproliferative disorder, and breast implant–associated anaplastic large cell lymphoma. In addition, translocations and gene rearrangements such as those involving the 6p25.3 locus have started to inform diagnosis and classification of anaplastic large cell lymphoma and lymphomatoid papulosis. In this review, we will examine what is new in the diagnostic toolbox of cutaneous lymphoproliferative disorders.
Safety of Tranexamic Acid During Pediatric Trauma: A Nationwide Database Study*
Authors: Maeda Takuma , Michihata Nobuaki , Sasabuchi Yusuke , Matsui Hiroki , Ohnishi Yoshihiko , Miyata Shigeki , Yasunaga Hideo
Published: September 2018

Objectives:

The present study aimed to examine the association between tranexamic acid use and adverse effects (seizures, thromboembolism, and renal dysfunction) in a pediatric trauma population using a national inpatient database in Japan. We also assessed the association between tranexamic acid use and in-hospital mortality.

Design:

A nationwide, retrospective cohort study using propensity score analyses.

Setting:

Japanese Diagnosis Procedure Combination inpatient database.

Patients:

Pediatric patients less than or equal to 12 years old admitted in hospital with the diagnosis of trauma between July 2010 and March 2014 (n = 61,779).

Interventions:

None.

Measurements and Main Results:

Propensity score matching created 1,914 pairs of patients with and without tranexamic acid administration. Propensity-matched analysis showed that the proportion of seizures was significantly higher in the tranexamic acid group than in the nontranexamic acid group (7/1,914, 0.37% vs 0/1,914, 0%; difference, 0.37%; 95% CI, 0.10–0.64; p = 0.008). However, none of the other outcomes were significantly different between the groups.

Conclusions:

Tranexamic acid use is associated with a significantly increased risk of seizures. However, no difference exists among any other outcomes between the tranexamic acid and nontranexamic acid groups.
Radioaerosol Imaging Predicts the Utility of Aerosolized Antifungal Therapy in Allergic Bronchopulmonary Aspergillosis
Authors: Rodriguez Karen , Siegel Alan
Published: September 2018

A 10-year-old girl with a history of complicated cystic fibrosis was hospitalized for pulmonary exacerbation with allergic bronchopulmonary aspergillosis and severe right upper lobe bronchiectasis diagnosed with chest radiograph and CT. She was started on itraconazole during the hospitalization in attempt to decrease her systemic steroid dose, but she had ongoing coughing and wheezing. The possibility was raised that the right upper lobe bronchiectasis may be a nidus for ongoing aspergillosis. Radioaerosol imaging was performed to determine whether the aerosolized antifungals would reach the area of bronchiectasis.
The Influence of Donor to Recipient Size Matching on Kidney Transplant Outcomes
Authors: Arshad Adam , Hodson James , Chappelow Imogen , Nath Jay , Sharif Adnan
Published: September 2018

Background

Nephron endowment in renal transplantation is infrequently considered, but may have important implications for post kidney transplantation outcomes. In this population-cohort study, we analyzed the deceased-donor kidney transplant outcomes stratified by donor-to-recipient size ratios.

Methods

Data for all deceased-donor adult kidney transplantation recipients between 2003 and 2015 were extracted from the UK Transplant Registry. We used weight as a surrogate marker for kidney size and defined the following mismatch categories (donor weight/recipient weight × 100): less than 75% (small donor kidney), 75% to 125% (weight matched kidney), and greater than 125% (large donor kidney). Univariable and multivariable analyses were undertaken to assess the relationship between this marker and patient outcomes.

Results

Outcomes for 11 720 transplants were analyzed with weight mismatch stratified as follows; small donor kidney (n = 1608, 13.7%), weight matched kidney (n = 7247, 61.8%) and large donor kidney (n = 2865, 24.4%). On multivariable analysis, no significant differences were detected in overall (P = 0.876) or death-censored (P = 0.173) graft survival, or in rates of delayed graft function (P = 0.396) between these 3 groups. However, 12-month creatinine levels were found to decline progressively across the groups (P < 0.001), with adjusted averages of 144.2 μmol/L for recipients of small donor kidneys, 134.7 μmol/L in weight matched kidneys, and 124.9 μmol/L in recipients of large donor kidneys. In addition, patient survival was found to be significantly shorter in recipients of larger kidneys than those with weight matched kidneys (hazard ratio, 1.21; 95% confidence interval, 1.05-1.40; P = 0.009), which is inconsistent with the existing literature.

Conclusions

Our data demonstrate that 12-month creatinine is influenced by donor-to-recipient difference in body weight, but that no such difference is observed for either delayed graft function or death-censored graft survival. However, we observed increased mortality in recipients receiving larger kidneys; an observation which conflicts with the existing literature and warrants further investigation.
Australia and New Zealand Islets and Pancreas Transplant Registry Annual Report 2018—Pancreas Waiting List, Recipients, and Donors
Authors: Webster Angela C. , Hedley James , Robertson Paul , Mulley William R. , Pilmore Helen L. , Pleass Henry , Kelly Patrick J.
Published: September 2018

Background

This is a synopsis of the registry report from the Australia and New Zealand islet and pancreas transplant registry. The full report is available at http://anziptr.org/reports/.

Methods

We report data for all solid organ pancreas transplant activity from inception in 1984 to end 2017. Islet-cell transplantation activity is reported elsewhere. Data analysis was performed using Stata software version 14 (StataCorp, College Station, TX).

Results

From 1984 to 2017 a total of 809 solid organ pancreas transplants have been performed in Australia and New Zealand, in 790 individuals. In 2017, 52 people received a pancreas transplant. By center, this was; Auckland (4), Monash (17), and Westmead (31). In 2017, 51 transplants were simultaneous pancreas kidney, whereas 1 was pancreas after kidney, and none were pancreas transplant alone.

Conclusions

The number of pancreas transplants performed in Australia and New Zealand was slightly lower in 2017 but continues to increase over time.
Epidemic dynamics, interactions and predictability of enteroviruses associated with hand, foot and mouth disease in Japan
Authors: Takahashi Saki , Metcalf C. Jessica E. , Arima Yuzo , Fujimoto Tsuguto , Shimizu Hiroyuki , Rogier van Doorn H. , Le Van Tan , Chan Yoke-Fun , Farrar Jeremy J. , Oishi Kazunori , Grenfell Bryan T.
Published: September 2018

Outbreaks of hand, foot and mouth disease have been documented in Japan since 1963. This disease is primarily caused by the two closely related serotypes of Enterovirus A71 (EV-A71) and Coxsackievirus A16 (CV-A16). Here, we analyse Japanese virologic and syndromic surveillance time-series data from 1982 to 2015. As in some other countries in the Asia Pacific region, EV-A71 in Japan has a 3 year cyclical component, whereas CV-A16 is predominantly annual. We observe empirical signatures of an inhibitory interaction between the serotypes; virologic lines of evidence suggest they may indeed interact immunologically. We fit the time series to mechanistic epidemiological models: as a first-order effect, we find the data consistent with single-serotype susceptible–infected–recovered dynamics. We then extend the modelling to incorporate an inhibitory interaction between serotypes. Our results suggest the existence of a transient cross-protection and possible asymmetry in its strength such that CV-A16 serves as a stronger forcing on EV-A71. Allowing for asymmetry yields accurate out-of-sample predictions and the directionality of this effect is consistent with the virologic literature. Confirmation of these hypothesized interactions would have important implications for understanding enterovirus epidemiology and informing vaccine development. Our results highlight the general implication that even subtle interactions could have qualitative impacts on epidemic dynamics and predictability.
Antibiotic-driven escape of host in a parasite-induced Red Queen dynamics
Authors: Anzia Elizabeth L. , Rabajante Jomar F.
Published: September 2018

Winnerless coevolution of hosts and parasites could exhibit Red Queen dynamics, which is characterized by parasite-driven cyclic switching of expressed host phenotypes. We hypothesize that the application of antibiotics to suppress the reproduction of parasites can provide an opportunity for the hosts to escape such winnerless coevolution. Here, we formulate a minimal mathematical model of host–parasite interaction involving multiple host phenotypes that are targeted by adapting parasites. Our model predicts the levels of antibiotic effectiveness that can steer the parasite-driven cyclic switching of host phenotypes (oscillations) to a stable equilibrium of host survival. Our simulations show that uninterrupted application of antibiotic with high-level effectiveness (greater than 85%) is needed to escape the Red Queen dynamics. Interrupted and low level of antibiotic effectiveness are indeed useless to stop host–parasite coevolution. This study can be a guide in designing good practices and protocols to minimize the risk of further progression of parasitic infections.
Arsenic removal from aqueous solutions by diethylenetriamine-functionalized resin: isotherm, kinetics, selectivity and mechanism
Authors: Zhang Juncai , Chen Youning , Zhao Wei , Li Yuhong
Published: September 2018

The surface-initiated atom transfer radical polymerization method was used to graft glycidyl methacrylate (GMA) on chloromethylated cross-linked styrene-divinylbenzene resin, and then the novel diethylenetriamine-functionalized resin was prepared through the amination reaction between amino group of diethylenetriamine and epoxy group in GMA. The adsorption properties were evaluated with As(V). The adsorption of As(V) was mainly regarded as the electrostatic interaction between the adsorbent and the adsorbate by analysing the relationship between adsorption capacity with the solution pH, adsorption isotherm and adsorption kinetics. The maximum sorption capacity of As(V) was 5.25 mmol g
−1
. The adsorption isotherms of As(V) were best described by the Langmuir model, and its adsorption kinetics followed the pseudo-second-order kinetic equation. The adsorption of As(V) ions was hardly affected by common coexisting ions such as Na(I), K(I), Ca(II) and Mg(II), whereas it was slightly decreased when Fe(II) and Zn(II) coexisted in the solution, which illustrates the selective adsorption of As(V) from wastewater. Ten adsorption–desorption cycles demonstrated that the resin possessed high recycling efficiency and stability and was suitable for efficient removal of metal ions from aqueous solution.
Long-tailed macaques (
Macaca fascicularis
) can use simple heuristics but fail at drawing statistical inferences from populations to samples
Authors: Placì Sarah , Eckert Johanna , Rakoczy Hannes , Fischer Julia
Published: September 2018

Human infants, apes and capuchin monkeys engage in intuitive statistics: they generate predictions from populations of objects to samples based on proportional information. This suggests that statistical reasoning might depend on some core knowledge that humans share with other primate species. To aid the reconstruction of the evolution of this capacity, we investigated whether intuitive statistical reasoning is also present in a species of Old World monkey. In a series of four experiments, 11 long-tailed macaques were offered different pairs of populations containing varying proportions of preferred versus neutral food items. One population always contained a higher proportion of preferred items than the other. An experimenter simultaneously drew one item out of each population, hid them in her fists and presented them to the monkeys to choose. Although some individuals performed well across most experiments, our results imply that long-tailed macaques as a group did not make statistical inferences from populations of food items to samples but rather relied on heuristics. These findings suggest that there may have been convergent evolution of this ability in New World monkeys and apes (including humans).
Analysis of Biological Record Data: Improvements of the Occupancy–Detection Models
Authors: Li Shiyu
Published: September 2018

Many indicators are used to monitor the progress of the target which aims to stop the biodiversity loss by 2020. However, the occupancy-detection model which is currently applied to calculate the indicator is biased. Hence, more robust models are required to track the trend of the species precisely. This research first reviews the previous works on improving this occupancy-detection model by changing the prior distributions of one of the quantities and of the models considered previously, a model based on a random walk is found to be the most appropriate although it has some potential deficiencies. Then this research provides some potential improvements of the random walk model by changing the way of modelling the prior distributions of each quantity and changing the model structure. Then the hoverflies datasets are used in this research to analyse the performance of the models. These models are compared by the running times of fitting the models and the plots of the trend of the species of all models. As a result, the categorical list length model is considered to be the most precise model among all models with a reasonable running time. Then, we fit this model with a large dataset, however, it takes a long running time to get the result. Finally, some potential improvements are suggested which may be useful for further research.
Detection ofWolbachiain Field-Collected Mosquito Vector,Aedes aegypti
Authors: Carvajal Thaddeus M. , Hashimoto Kazuki , Harnandika Reza Kurniawan , Amalin Divina M , Watanabe Kozo
Published: September 2018

It was the impression from past literature thatWolbachiais not naturally found inAe. aegypti. However, there are have been reports that recently reveals the presence of this endosymbiont in this mosquito vector. With this, our study presents additional support ofWolbachiainfection inAe. aegyptiby screening field-collected adult mosquitoes usingWolbachiaspecific 16S rDNA and its surface protein (wsp) makers under optimized PCR conditions. From a total of 672Ae. aegpytiadult mosquito samples collected in Metropolitan Manila, Philippines, 113 (16.8%) and 89 (13.2%) individual mosquito samples were determined to beWolbachiainfected using thewspand 16S rDNA markers, respectively. TheAe. aegpyti wspsample sequences were similar or identical to five knownWolbachiastrains belonging to supergroups A or B while majority of 16S rDNA sample sequences were similar to strains belonging to supergroup B. Overall, 80 (11.90%) individual mosquito samples revealed to show positive amplifications in both markers and 69.0% showed congruence in supergroup identification (supergroup B). Our findings illustrate that the infection status ofWolbachiainAe. aegyptimay appear common than previously recognized.
Fine-grained mapping of cortical somatotopies in chronic Complex Regional Pain Syndrome
Authors: Mancini Flavia , Wang Audrey P , Schira Mark M. , Isherwood Zoey J. , McAuley James H. , Iannetti Giandomenico D , Sereno Martin I. , Moseley G. Lorimer , Rae Caroline D.
Published: September 2018

It has long been thought that severe chronic pain conditions, such as Complex Regional Pain Syndrome (CRPS), are not only associated with, but even maintained by a reorganisation of the somatotopic representation of the affected limb in primary somatosensory cortex (S1). This notion has driven treatments that aim to restore S1 representations, such as sensory discrimination training and mirror therapy. However, this notion is based on both indirect and incomplete evidence obtained with imaging methods with low spatial resolution. Here, we used functional MRI to characterize the S1 representation of the affected and unaffected hand in patients with unilateral CRPS. At the group level, the cortical area, location, and geometry of the S1 representation of the CRPS hand were largely comparable to those of the healthy hand and controls. However, the area of the map of the affected hand was modulated by disease duration (the smaller the map, the more chronic the CRPS), but not by pain intensity, pain sensitivity and severity of the physical disability. Thus, if any map reorganization occurs, it does not appear to be directly related to our pain measures. These findings compel us to reconsider the cortical mechanisms underlying CRPS and the rationale for interventions that aim to “restore” somatotopic representations to treat pain.

Significance statement

This study shows that the spatial map of the fingers in S1 is largely preserved in chronic CRPS. Shrinkage of the area of the affected hand map can occur in the most chronic stages of disease. Map shrinkage is related to CRPS duration rather than diagnosis, and is unrelated to how much pain patients experience or to the severity of the physical disability. These findings challenge the rationale for using sensory interventions to treat pain by restoring somatotopic representations in CRPS patients.
Late-life mortality plateaus through error, not evolution
Authors: Newman Saul Justin
Published: September 2018

This study highlights how the mortality plateau in Barbi et al. [1] can be generated by low frequency, randomly distributed age misreporting errors. Furthermore, sensitivity of the late-life mortality plateau in Barbi et al. [1] to the particular age range selected for regression is illustrated. Collectively, the simulation of age misreporting errors in late-life human mortality data and a less specific model choice than that of Barbi et al. [1] highlight a clear alternative hypothesis to the cessation of ageing.
The novel lncRNA lnc-NR2F1 is pro-neurogenic and mutated in human neurodevelopmental disorders
Authors: Ang Cheen Euong , Ma Qing , Wapinski Orly L. , Fan Shenghua , Flynn Ryan A. , Coe Bradley , Onoguchi Masahiro , Olmos Victor H. , Do Brian T. , Dukes-Rimsky Lynn , Xu Jin , Lee Qian Yi , Tanabe Koji , Wang Liangjiang , Elling Ulrich , Penninger Josef , Qu Kun , Eichler Evan E. , Srivastava Anand , Wernig Marius , Chang Howard Y.
Published: September 2018

Long noncoding RNAs (lncRNAs) have been shown to act as important cell biological regulators including cell fate decisions but are often ignored in human genetics. Combining differential lncRNA expression during neuronal lineage induction with copy number variation morbidity maps of a cohort of children with autism spectrum disorder/intellectual disability versus healthy controls revealed focal genomic mutations affecting several lncRNA candidate loci. Here we find that a t(5:12) chromosomal translocation in a family manifesting neurodevelopmental symptoms disrupts specifically lnc-NR2F1. We further show that lnc-NR2F1 is an evolutionarily conserved lncRNA functionally enhances induced neuronal cell maturation and directly occupies and regulates transcription of neuronal genes including autism-associated genes. Thus, integrating human genetics and functional testing in neuronal lineage induction is a promising approach for discovering candidate lncRNAs involved in neurodevelopmental diseases.
Identifying Representative Network Motifs for Inferring Higher-order Structure of Biological Networks
Authors: Tao Wang , Wang Yadong , Peng Jiajie , Jin Chen
Published: September 2018

Network motifs are recurring significant patterns of inter-connections, which are recognized as fundamental units to study the higher-order organizations of networks. However, the principle of selecting representative network motifs for local motif based clustering remains largely unexplored. We present a scalable algorithm called FSM for network motif discovery. FSM accelerates the motif discovery process by effectively reducing the number of times to do subgraph isomorphism labeling. Multiple heuristic optimizations for subgraph enumeration and subgraph classification are also adopted in FSM to further improve its performance. Experimental results show that FSM is more efficient than the compared models on computational efficiency and memory usage. Furthermore, our experiments indicate that large and frequent network motifs may be more appropriate to be selected as the representative network motifs for discovering higher-order organizational structures in biological networks than small or low-frequency network motifs.
Genome-wide association studies in Samoans give insight into the genetic architecture of fasting serum lipid levels
Authors: Carlson Jenna C. , Weeks Daniel E. , Hawley Nicola L. , Sun Guangyun , Cheng Hong , Naseri Take , Reupena Muagututi‘a Sefuiva , Deka Ranjan , McGarvey Stephen T. , Minster Ryan L.
Published: September 2018

The current understanding of the genetic architecture of lipids has largely come from genome-wide association studies. To date, few studies have examined the genetic architecture of lipids in Polynesians, and none have in Samoans, whose unique population history, including many population bottlenecks, may provide insight into the biological foundations of variation in lipid levels. Here we performed a genome-wide association study of four fasting serum lipid levels: total cholesterol (TC), high-density lipoprotein (HDL), low-density lipoprotein (LDL), and triglycerides (TG) in a sample of 2,849 Samoans, with validation genotyping for associations in a replication cohort comprising 1,798 Samoans and American Samoans. We identified multiple genome-wide significant associations (P < 5 × 10−8) previously seen in other populations – APOA1 with TG, CETP with HDL, and APOE with TC and LDL – and several suggestive associations (P < 1 × 10−5), including an association of variants downstream of MGAT1 and RAB21 with HDL. However, we observed different association signals for variants near APOE than what has been previously reported in non-Polynesian populations. The association with several known lipid loci combined with the newly-identified associations with variants near MGAT1 and RAB21 suggest that while some of the genetic architecture of lipids is shared between Samoans and other populations, part of the genetic architecture may be Polynesian-specific.
No cell is an island: circulating T cell:monocyte complexes are markers of immune perturbations
Authors: Burel Julie G. , Pomaznoy Mikhail , Lindestam Arlehamn Cecilia S. , Weiskopf Daniela , da Silva Antunes Ricardo , Jung Yunmin , Babor Mariana , Schulten Veronique , Seumois Grégory , Greenbaum Jason A. , Premawansa Sunil , Premawansa Gayani , Wijewickrama Ananda , Vidanagama Dhammika , Gunasena Bandu , Tippalagama Rashmi , deSilva Aruna D. , Gilman Robert H. , Saito Mayuko , Taplitz Randy , Ley Klaus , Vijayanand Pandurangan , Sette Alessandro , Peters Bjoern
Published: September 2018

Our results highlight for the first time that a significant proportion of cell doublets in flow cytometry, previously believed to be the result of technical artefacts and thus ignored in data acquisition and analysis, are the result of true biological interaction between immune cells. In particular, we show that cell:cell doublets pairing a T cell and a monocyte can be directly isolated from human blood, and high resolution microscopy shows polarized distribution of LFA1/ICAM1 in many doublets, suggesting in vivo formation. Intriguingly, T cell:monocyte complex frequency and phenotype fluctuate with the onset of immune perturbations such as infection or immunization, reflecting expected polarization of immune responses. Overall these data suggest that cell doublets reflecting T cell-monocyte in vivo immune interactions can be detected in human blood and that the common approach in flow cytometry to avoid studying cell:cell complexes should be revisited.
Transcriptomic analyses reveal groups of co-expressed, syntenic lncRNAs in four species of the genus Caenorhabditis
Authors: Pegueroles Cinta , Iraola-Guzmán Susana , Chorostecki Uciel P. , Ksiezopolska Ewa , Saus Ester , Gabaldón Toni
Published: September 2018

Long non-coding RNAs (lncRNAs) are a heterogeneous class of genes that do not code for proteins. Since lncRNAs (or a fraction thereof) are expected to be functional, many efforts have been dedicated to catalog lncRNAs in numerous organisms, but our knowledge of lncRNAs in non vertebrate species remains very limited. Here, we annotated lncRNAs using transcriptomic data from the same larval stage of four Caenorhabditis species. The number of annotated lncRNAs in self-fertile nematodes was lower than in out-crossing species. We used a combination of approaches to identify putatively homologous lncRNAs: synteny, sequence conservation, and structural conservation. We classified a total of 1,532 out of 7,635 genes from the four species into families of lncRNAs with conserved synteny and expression at the larval stage, suggesting that a large fraction of the predicted lncRNAs may be species specific. Despite both sequence and local secondary structure seem to be poorly conserved, sequences within families frequently shared BLASTn hits and short sequence motifs, which were more likely to be unpaired in the predicted structures. We provide the first multi-species catalog of lncRNAs in nematodes and identify groups of lncRNAs with conserved synteny and expression, that share exposed motifs.
Chromatin-loop extrusion and chromatin unknotting
Authors: Racko Dusan , Benedetti Fabrizio , Goundaroulis Dimos , Stasiak Andrzej
Published: September 2018

It has been a puzzle how decondensed interphase chromosomes remain essentially unknotted. The natural expectation is that in the presence of type II DNA topoisomerases that permit passages of double-stranded DNA regions through each other, all chromosomes should reach the state of topological equilibrium. The topological equilibrium in highly crowded interphase chromosomes forming chromosome territories would result in formation of highly knotted chromatin fibres. However, Chromosome Conformation Capture (3C) methods revealed that the decay of contacts with the genomic distance in interphase chromosomes is practically the same as in the crumpled globule state that is formed when long polymers condense without formation of any knots. To remove knots from highly crowded chromatin, one would need an active process that should not only provide the energy to move the system from the state of topological equilibrium but also guide topoisomerase-mediated passages in such a way that knots would be efficiently unknotted instead of making the knots even more complex. We show here that the process of chromatin-loop extrusion is ideally suited to actively unknot chromatin fibres in interphase chromosomes.

SIGNIFICANCE STATEMENT

Similar to earphone cables crammed into a pocket, long and crowded chromatin fibres that form chromosomes in living cells have the natural tendency to get knotted. This is exacerbated by the action of DNA topoisomerases that transiently cut some chromatin fibres and let other to pass through. Yet, the knotting frequency of chromatin fibres is very low and it has been a puzzle how this is achieved. Recently a novel active mechanism known as chromatin loop extrusion has been proposed to be involved in shaping chromosomes by forming sequential arrays of ca 1 Mb large chromatin loops. Using numerical simulations, we show here that chromatin loop extrusion is ideally suited to remove knots from chromatin fibres.
A Low-Cost Biological Agglutination Assay for Medical Diagnostic Applications
Authors: Kylilis Nicolas , Riangrungroj Pinpunya , Lai Hung-En , Salema Valencio , Fernández Luis Ángel , Stan Guy-Bart V , Freemont Paul S , Polizzi Karen M
Published: September 2018

Affordable, easy-to-use diagnostic tests that can be readily deployed for point-of-care (POC) testing are key in addressing challenges in the diagnosis of medical conditions and for improving global health in general. Ideally, POC diagnostic tests should be highly selective for the biomarker, user-friendly, have a flexible design architecture and a low cost of production. Here we developed a novel agglutination assay based on wholeE. colicells surface-displaying nanobodies which bind selectively to a target protein analyte. As a proof-of-concept, we show the feasibility of this design as a new diagnostic platform by the detection of a model analyte at nanomolar concentrations. Moreover, we show that the design architecture is flexible by building assays optimized to detect a range of model analyte concentrations supported using straight-forward design rules and a mathematical model. Finally, we re-engineerE. colicells for the detection of a medically relevant biomarker by the display of two different antibodies against the human fibrinogen and demonstrate a detection limit as low as 10 pM in diluted human plasma. Overall, we demonstrate that our agglutination technology fulfills the requirement of POC testing by combining low-cost nanobody production, customizable detection range and low detection limits. This technology has the potential to produce affordable diagnostics for both field-testing in the developing world, emergency or disaster relief sites as well as routine medical testing and personalized medicine.
Accounting for individual-specific variation in habitat-selection studies: Efficient estimation of mixed-effects models using Bayesian or frequentist computation
Authors: Muff Stefanie , Signer Johannes , Fieberg John
Published: September 2018

1. Popular frameworks for studying habitat selection include resource-selection functions (RSFs) and step-selection functions (SSFs) estimated using logistic and conditional logistic regression, respectively. Both frameworks compare environmental covariates associated with locations animals visit with environmental covariates at a set of locations assumed available to the animal. Conceptually, random coefficients could be used to accommodate inter-individual heterogeneity with either approach, but straightforward and efficient one-step procedures for fitting SSFs with random coefficients are currently lacking.

2. We take advantage of the fact that the conditional logistic regression model (i. e., the SSF) is likelihood-equivalent to a Poisson model with stratum-specific intercepts. By interpreting the intercepts as a random effect with a large (fixed) variance, inference becomes feasible with standard Bayesian techniques, but also with frequentist methods that allow one to fix the variance of a random effect. We compare this approach to other commonly applied alternatives, including random intercept-only models, and to a two-step algorithm for fitting mixed-effects models.

3. We also reinforce the need to weight available points when fitting RSFs, since models fit using “infinitely weighted logistic regression” have been shown to be equivalent to an inhomogeneous Poisson process (IPP). We generalize this result to “infinitely weighted Poisson regression”, which converges to the same underlying IPP distribution.

4. Using data from Eurasian otters (Lutra lutra) and mountain goats (Oreamnos americanus), we illustrate that our models lead to valid and feasible inference. In addition, we conduct a simulation study to demonstrate the importance of including random slopes when estimating individual- and population-level habitat-selection parameters.

5. By providing coded examples using integrated nested Laplace approximations (INLA) and Template Model Builder (TMB) for Bayesian and frequentist analysis via the R packagesR-INLAandglmmTMB, we hope to make efficient estimation of RSFs and SSFs with random effects accessible to anyone in the field. SSFs with individual-specific coefficients are particularly attractive since they can provide insights into movement and habitat-selection processes at fine-spatial and temporal scales, but these models had previously been very challenging to fit.
Molecular safeguarding of CRISPR gene drive experiments
Authors: Champer Jackson , Chung Joan , Lee Yoo Lim , Liu Chen , Yang Emily , Wen Zhaoxin , Clark Andrew G. , Messer Philipp W.
Published: September 2018

CRISPR-based gene drives have sparked both enthusiasm and deep concerns due to their potential for genetically altering entire species. This raises the question about our ability to prevent the unintended spread of such drives from the laboratory into a natural population. Here, we experimentally demonstrate the suitability of synthetic target sites and split drives as flexible safeguarding strategies for gene drive experiments.
FGF1 PromotesXenopus laevisLens Regeneration
Authors: Moore Lisa , Perry Kimberly J. , Sun Cindy , Henry Jonathan J.
Published: September 2018

Background

The frogXenopus laevishas notable regenerative capabilities, including that of the lens. The neural retina provides the factors that trigger lens regeneration from the cornea, but the identity of these factors is largely unknown. In contrast to the cornea, fibroblast growth factors FGF1, 8, and 9 are highly expressed within the retina, and are potential candidates for those factors. The purpose of this study is to determine whether specific FGF proteins can induce lens formation, and if perturbation of FGFR signaling inhibits lens regeneration.

Methods

A novel cornea epithelial culture method was developed to investigate the sufficiency of FGFs in lens regeneration. Additionally, transgenic larvae expressing dominant negative FGFR1 were used to investigate the necessity of FGFR signaling in lens regeneration.

Results

Treatment of cultured corneas with FGF1 induced lens regeneration in a dose-dependent manner, whereas treatment with FGF2, FGF8, or FGF9 did not result in significant lens regeneration. Inhibition of FGFR signaling decreased the lens regeneration rate forin vitroeye cultures.

Conclusion

The culture techniques developed here, and elsewhere, have provided reliable methods for examining the necessity of various factors that may be involved in lens regeneration. Based on the results demonstrated in this study, we found that FGF1 signaling and FGFR activation are key factors for lens regeneration inXenopus.