bluuebunny/crossref_metadata_2025 huggingface dataset:
Neural preservation underlies speech improvement from auditory deprivation in young cochlear implant recipients
Authors: Feng Gangyi , Ingvalson Erin M. , Grieco-Calub Tina M. , Roberts Megan Y. , Ryan Maura E. , Birmingham Patrick , Burrowes Delilah , Young Nancy M. , Wong Patrick C. M.
Published: January 2018

Significance

The ability to accurately predict speech improvement for young children who use cochlear implants (CIs) would be a first step in the development of a personalized therapy to enhance language development. Despite decades of outcome research, no useful clinical prediction tool exists. An accurate predictive model that relies on routinely obtained presurgical neuroanatomic data has the potential to transform clinical practice while enhancing our understanding of neural organization resulting from auditory deprivation. Using presurgical MRI neuroanatomical data and multivariate pattern analysis techniques, we found that neural systems that were unaffected by auditory deprivation best predicted young CI candidates’ postsurgical speech-perception outcomes. Our study provides an example of how research in cognitive neuroscience can inform basic science and lead to clinical application.
Streamlined circular proximity ligation assay provides high stringency and compatibility with low-affinity antibodies
Authors: Jalili Roxana , Horecka Joe , Swartz James R. , Davis Ronald W. , Persson Henrik H. J.
Published: January 2018

Significance

Quantitative detection of protein biomarkers over a wide concentration range from minute amounts of blood is essential for clinical diagnostics. Proximity ligation assay combines antibody–oligo conjugates, enzymatic ligation, and PCR amplification into a sensitive method for quantitative protein detection from small volumes. This report describes a streamlined and more stringent assay format that takes advantage of DNA circle formation to remove unwanted DNA molecules. Kinetic analysis of antibody–antigen interactions shows that variation in assay performance between various biomarkers is an effect of antibody quality. We show that this assay format enables compatibility with low-affinity reagents, a major limitation for most protein quantitation methods, while improving sensitivity and reproducibility.
Global spectral clustering in dynamic networks
Authors: Liu Fuchen , Choi David , Xie Lu , Roeder Kathryn
Published: January 2018

Significance

Statistical theory has mostly focused on static networks observed as a single snapshot in time. In reality, networks are generally dynamic, and it is of substantial interest to discover the clusters within each network to visualize and model their connectivities. We propose the persistent communities by eigenvector smoothing algorithm for detecting time-varying community structure and apply it to a recent dataset in which gene expression is measured during a broad range of developmental periods in rhesus monkey brains. The analysis suggests the existence of change points as well as periods of persistent community structure; these are not well estimated by standard methods due to the small sample size of any one developmental period or region of the brain.
Cell-type-specific role for nucleus accumbens neuroligin-2 in depression and stress susceptibility
Authors: Heshmati Mitra , Aleyasin Hossein , Menard Caroline , Christoffel Daniel J. , Flanigan Meghan E. , Pfau Madeline L. , Hodes Georgia E. , Lepack Ashley E. , Bicks Lucy K. , Takahashi Aki , Chandra Ramesh , Turecki Gustavo , Lobo Mary Kay , Maze Ian , Golden Sam A. , Russo Scott J.
Published: January 2018

Significance

Although mutations in the neuroligin-3 and neuroligin-4 genes are implicated in autism syndromes, very little is known about the contribution of neuroligin-2 to neuropsychiatric disease states. We report a decrease in neuroligin-2 gene expression in the postmortem nucleus accumbens (NAc) of depressed patients. Reverse translation of this finding in chronic social defeat stress, an animal model of depression that enables investigation of both susceptibility and resiliency mechanisms, uncovers an important functional role for NAc neuroligin-2 in stress susceptibility. We detail a cell-type-specific role for NAc neuroligin-2 in modulating social avoidance behavior and dominance behaviors important for resiliency. Together, these findings describe a role for NAc neuroligin-2 in depression and chronic stress behaviors.
Standards‐based reform to senior‐secondary curriculum and metacognition in the literacy domain
Authors: Fenwick Lisl
Published: January 2018

This study analyses the intended and enacted curricula that are produced when metacognition is included as an element within standards‐based reforms for schooling. Reformers of the senior‐secondary curriculum for South Australia (SA) and the Northern Territory (NT) hoped to improve the academic outcomes of all students, and especially those from low‐SES and Indigenous backgrounds, by creating a curriculum that required year‐10 students to reflect on their capacities. Reflection on learning in the literacy domain was a particular emphasis during the reforms. A constructionist epistemology and case‐study methodology informed the approach taken in the study. Data collection and analysis involved accessing and analysing the intended curriculum, as well as the curriculum planning documentation designed by four teachers in one NT high school. The results indicate that learning opportunities to reflect on literacy capacities will not be created when the intended curriculum provides teachers, who are not literacy specialists, with little guidance about practices associated with metacognition and literacy.
Development of intestinal M cells and follicle-associated epithelium is regulated by TRAF6-mediated NF-κB signaling
Authors: Kanaya Takashi , Sakakibara Sayuri , Jinnohara Toshi , Hachisuka Masami , Tachibana Naoko , Hidano Shinya , Kobayashi Takashi , Kimura Shunsuke , Iwanaga Toshihiko , Nakagawa Tomoo , Katsuno Tatsuro , Kato Naoya , Akiyama Taishin , Sato Toshiro , Williams Ifor R. , Ohno Hiroshi
Published: January 2018

M cells are located in the follicle-associated epithelium (FAE) that covers Peyer’s patches (PPs) and are responsible for the uptake of intestinal antigens. The differentiation of M cells is initiated by receptor activator of NF-κB. However, the intracellular pathways involved in M cell differentiation are still elusive. In this study, we demonstrate that the NF-κB pathway activated by RANK is essential for M cell differentiation using in vitro organoid culture. Overexpression of NF-κB transcription factors enhances the expression of M cell–associated molecules but is not sufficient to complete M cell differentiation. Furthermore, we evaluated the requirement for tumor necrosis factor receptor–associated factor 6 (TRAF6). Conditional deletion of TRAF6 in the intestinal epithelium causes a complete loss of M cells in PPs, resulting in impaired antigen uptake into PPs. In addition, the expression of FAE-associated genes is almost silenced in TRAF6-deficient mice. This study thus demonstrates the crucial role of TRAF6-mediated NF-κB signaling in the development of M cells and FAE.
Design and validation of a microfluidic device for blood–brain barrier monitoring and transport studies
Authors: Ugolini Giovanni Stefano , Occhetta Paola , Saccani Alessandra , Re Francesca , Krol Silke , Rasponi Marco , Redaelli Alberto
Published: January 2018

In vitro blood–brain barrier models are highly relevant for drug screening and drug development studies, due to the challenging task of understanding the transport mechanism of drug molecules through the blood–brain barrier towards the brain tissue. In this respect, microfluidics holds potential for providing microsystems that require low amounts of cells and reagent and can be potentially multiplexed for increasing the ease and throughput of the drug screening process. We here describe the design, development and validation of a microfluidic device for endothelial blood–brain barrier cell transport studies. The device comprises of two microstructured layers (top culture chamber and bottom collection chamber) sandwiching a porous membrane for the cell culture. Microstructured layers include two pairs of physical electrodes, embedded into the device layers by geometrically defined guiding channels with computationally optimized positions. These electrodes allow the use of commercial electrical measurement systems for monitoring trans-endothelial electrical resistance (TEER). We employed the designed device for performing preliminary assessment of endothelial barrier formation with murine brain endothelial cells (Br-bEnd5). Results demonstrate that cellular junctional complexes effectively form in the cultures (expression of VE-Cadherin and ZO-1) and that the TEER monitoring systems effectively detects an increase of resistance of the cultured cell layers indicative of tight junction formation. Finally, we validate the use of the described microsystem for drug transport studies demonstrating that Br-bEnd5 cells significantly hinder the transport of molecules (40 kDa and 4 kDa dextran) from the top culture chamber to the bottom collection chamber.
A novel recession rate physics methodology for space applications at CIRA by means of CIRCE radioactive beam tracers
Authors: De Cesare M , Di Leva A , Del Vecchio A , Gialanella L
Published: January 2018

Thermal protection systems (TPSs) of spacecrafts, either for single use or reusable, experience wear by ablation and erosion, due to the high heat fluxes during a re-entry phase in the atmosphere. The determination of the wear rate is a crucial point, which is presently mainly possible in aerospace on-ground measurements by means of invasive diagnostics. The purpose of this paper is to present novel contactless, online, high-sensitivity and non-intrusive diagnostics for wear measurements based on radioactive tracers. We propose the technique for future on-ground experiments that might later be developed to perform in-flight TPSs monitoring, thus significantly increasing the safety of the aerospace vehicles. The basic ideas of the method, its sensitivity investigated by GEANT4 simulations, and the future experimental validation are outlined.
Inferring and analyzing module-specific lncRNA–mRNA causal regulatory networks in human cancer
Authors: Zhang Junpeng , Le Thuc Duy , Liu Lin , Li Jiuyong
Published: January 2018

It is known that noncoding RNAs (ncRNAs) cover ∼98% of the transcriptome, but do not encode proteins. Among ncRNAs, long noncoding RNAs (lncRNAs) are a large and diverse class of RNA molecules, and are thought to be a gold mine of potential oncogenes, anti-oncogenes and new biomarkers. Although only a minority of lncRNAs is functionally characterized, it is clear that they are important regulators to modulate gene expression and involve in many biological functions. To reveal the functions and regulatory mechanisms of lncRNAs, it is vital to understand how lncRNAs regulate their target genes for implementing specific biological functions. In this article, we review the computational methods for inferring lncRNA–mRNA interactions and the third-party databases of storing lncRNA–mRNA regulatory relationships. We have found that the existing methods are based on statistical correlations between the gene expression levels of lncRNAs and mRNAs, and may not reveal gene regulatory relationships which are causal relationships. Moreover, these methods do not consider the modularity of lncRNA–mRNA regulatory networks, and thus, the networks identified are not module-specific. To address the above two issues, we propose a novel method, MSLCRN, to infer and analyze module-specific lncRNA–mRNA causal regulatory networks. We have applied it into glioblastoma multiforme, lung squamous cell carcinoma, ovarian cancer and prostate cancer, respectively. The experimental results show that MSLCRN, as an expression-based method, could be a useful complementary method to study lncRNA regulations.
Haystack: systematic analysis of the variation of epigenetic states and cell-type specific regulatory elements
Authors: Pinello Luca , Farouni Rick , Yuan Guo-Cheng
Published: January 2018

Motivation

With the increasing amount of genomic and epigenomic data in the public domain, a pressing challenge is to integrate these data to investigate the role of epigenetic mechanisms in regulating gene expression and maintenance of cell-identity. To this end, we have implemented a computational pipeline to systematically study epigenetic variability and uncover regulatory DNA sequences.

Results

Haystack is a bioinformatics pipeline to identify hotspots of epigenetic variability across different cell-types, cell-type specific cis-regulatory elements, and associated transcription factors. Haystack is generally applicable to any epigenetic mark and provides an important tool to investigate the mechanisms underlying epigenetic switches during development. This software is accompanied by a set of precomputed tracks, which may be used as a valuable resource for functional annotation of the human genome.

Availability and implementation

The Haystack pipeline is implemented as an open-source, multiplatform, Python package called haystack_bio freely available at https://github.com/pinellolab/haystack_bio.

Supplementary information

Supplementary data are available at Bioinformatics online.
Predicting plant biomass accumulation from image-derived parameters
Authors: Chen Dijun , Shi Rongli , Pape Jean-Michel , Neumann Kerstin , Arend Daniel , Graner Andreas , Chen Ming , Klukas Christian
Published: January 2018

Background

Image-based high-throughput phenotyping technologies have been rapidly developed in plant science recently, and they provide a great potential to gain more valuable information than traditionally destructive methods. Predicting plant biomass is regarded as a key purpose for plant breeders and ecologists. However, it is a great challenge to find a predictive biomass model across experiments.

Results

In the present study, we constructed 4 predictive models to examine the quantitative relationship between image-based features and plant biomass accumulation. Our methodology has been applied to 3 consecutive barley (Hordeum vulgare) experiments with control and stress treatments. The results proved that plant biomass can be accurately predicted from image-based parameters using a random forest model. The high prediction accuracy based on this model will contribute to relieving the phenotyping bottleneck in biomass measurement in breeding applications. The prediction performance is still relatively high across experiments under similar conditions. The relative contribution of individual features for predicting biomass was further quantified, revealing new insights into the phenotypic determinants of the plant biomass outcome. Furthermore, methods could also be used to determine the most important image-based features related to plant biomass accumulation, which would be promising for subsequent genetic mapping to uncover the genetic basis of biomass.

Conclusions

We have developed quantitative models to accurately predict plant biomass accumulation from image data. We anticipate that the analysis results will be useful to advance our views of the phenotypic determinants of plant biomass outcome, and the statistical methods can be broadly used for other plant species.
Variable Rates of Simple Satellite Gains across the Drosophila Phylogeny
Authors: Wei Kevin H -C , Lower Sarah E , Caldas Ian V , Sless Trevor J S , Barbash Daniel A , Clark Andrew G
Published: January 2018

Simple satellites are tandemly repeating short DNA motifs that can span megabases in eukaryotic genomes. Because they can cause genomic instability through nonallelic homologous exchange, they are primarily found in the repressive heterochromatin near centromeres and telomeres where recombination is minimal, and on the Y chromosome, where they accumulate as the chromosome degenerates. Interestingly, the types and abundances of simple satellites often vary dramatically between closely related species, suggesting that they turn over rapidly. However, limited sampling has prevented detailed understanding of their evolutionary dynamics. Here, we characterize simple satellites from whole-genome sequences generated from males and females of nine Drosophila species, spanning 40 Ma of evolution. We show that PCR-free library preparation and postsequencing GC-correction better capture satellite quantities than conventional methods. We find that over half of the 207 simple satellites identified are species-specific, consistent with previous descriptions of their rapid evolution. Based on a maximum parsimony framework, we determined that most interspecific differences are due to lineage-specific gains. Simple satellites gained within a species are typically a single mutation away from abundant existing satellites, suggesting that they likely emerge from existing satellites, especially in the genomes of satellite-rich species. Interestingly, unlike most of the other lineages which experience various degrees of gains, the lineage leading up to the satellite-poor D. pseudoobscura and D. persimilis appears to be recalcitrant to gains, providing a counterpoint to the notion that simple satellites are universally rapidly evolving.
Smoking Status and Survival Among a National Cohort of Lung and Colorectal Cancer Patients
Authors: Japuntich Sandra J , Kumar Pallavi , Pendergast Jane F , Juarez Caballero Grelda Yazmin , Malin Jennifer L , Wallace Robert B , Chrischilles Elizabeth A , Keating Nancy L , Park Elyse R
Published: January 2018

Introduction

The purpose of this study was to explore the association of smoking status and clinically relevant duration of smoking cessation with long-term survival after lung cancer (LC) or colorectal cancer (CRC) diagnosis. We compared survival of patients with LC and CRC who were never-smokers, long-term, medium-term, and short-term quitters, and current smokers around diagnosis.

Methods

We studied 5575 patients in Cancer Care Outcomes Research and Surveillance (CanCORS), a national, prospective observational cohort study, who provided smoking status information approximately 5 months after LC or CRC diagnosis. Smoking status was categorized as: never-smoker, quit >5 years prior to diagnosis, quit between 1–5 years prior to diagnosis, quit less than 1 year before diagnosis, and current smoker. We examined the relationship between smoking status around diagnosis with mortality using Cox regression models.

Results

Among participants with LC, never-smokers had lower mortality risk compared with current smokers (HR 0.71, 95% CI 0.57 to 0.89). Among participants with CRC, never-smokers had a lower mortality risk as compared to current smokers (HR 0.79, 95% CI 0.64 to 0.99).

Conclusions

Among both LC and CRC patients, current smokers at diagnosis have higher mortality than never-smokers. This effect should be further studied in the context of tumor biology. However, smoking cessation around the time of diagnosis did not affect survival in this sample.

Implications

The results from our analysis of patients in the CanCORS consortium, a large, geographically diverse cohort, show that both LC and CRC patients who were actively smoking at diagnosis have worse survival as compared to never-smokers. While current smoking is detrimental to survival, cessation upon diagnosis may not mitigate this risk.
Caregiver-Provided Physical Therapy Home Programs for Children with Motor Delay: A Scoping Review
Authors: Gorgon Edward James R
Published: January 2018

Background

Caregiver-provided physical therapy home programs (PTHP) play an important role in enhancing motor outcomes in pediatric patient populations.

Purpose

This scoping review systematically mapped clinical trials of caregiver–provided PTHP that were aimed at enhancing motor outcomes in children who have or who are at risk for motor delay, with the purpose of (1) describing trial characteristics; (2) assessing methodologic quality; and (3) examining the reporting of caregiver-related components.

Data Sources

Physiotherapy Evidence Database (PEDro), Cochrane CENTRAL, PubMed, Scopus, ScienceDirect, ProQuest Central, CINAHL, LILACS, and OTseeker were searched up to July 31, 2017.

Study Selection

Two reviewers independently assessed study eligibility. Randomized or quasi-randomized controlled trials on PTHP administered by parents, other family members, friends, or informal caregivers to children who had or who were at risk for motor delay were included.

Data Extraction

Two reviewers independently appraised trial quality on the PEDro scale and extracted data.

Data Synthesis

Twenty-four articles representing 17 individual trials were identified. Populations and interventions investigated were heterogeneous. Most of the trials had important research design limitations and methodological issues that could limit usefulness in ascertaining the effectiveness of caregiver-provided PTHP. Few (4 of 17) trials indicated involvement of caregivers in the PTHP planning, assessed how the caregivers learned from the training or instructions provided, or carried out both.

Limitations

Included studies were heterogeneous, and unpublished data were excluded.

Conclusions

Although caregiver-provided PTHP are important in addressing motor outcomes in this population, there is a lack of evidence at the level of clinical trials to guide practice. More research is urgently needed to determine the effectiveness of care-giver-provided PTHP. Future studies should address the many important issues identified in this scoping review to improve the usefulness of the trial results.
The Relationship Between Socioeconomic Status (SES) and NCLEX-RN: Comparing SES Indicators in Mediated Logistic Regression
Authors: Meyers Timothy W. , Karpinski Aryn C.
Published: January 2018

The main purpose of this study was to examine the relationship between socioeconomic status (SES), ACT test scores, and the National Council Licensure Examination–Registered Nurse (NCLEX-RN) through a mediated logistic regression model. ACT is often considered one of the strongest predictors of success on the NCLEX-RN. Data from nursing students (N = 1,176) at a large, Midwestern university were analyzed. The goal was to determine if the predictive power of ACT on the NCLEX-RN stems from the influence of SES on ACT. A significant indirect effect through the causal chain of Pell Grant eligibility (i.e., SES)→ACT→NCLEX-RN was found.
Menopausal Hormone Therapy and Long-Term All-Cause and Cause-Specific Mortality: The Women’s Health Initiative Randomized Trials
Authors: Manson JoAnn E. , Aragaki Aaron K. , Rossouw Jacques E. , Anderson Garnet L. , Prentice Ross L. , LaCroix Andrea Z. , Chlebowski Rowan T. , Howard Barbara V. , Thomson Cynthia A. , Margolis Karen L. , Lewis Cora E. , Stefanick Marcia L. , Jackson Rebecca D. , Johnson Karen C. , Martin Lisa W. , Shumaker Sally A. , Espeland Mark A. , Wactawski-Wende Jean
Published: January 2018

(Abstracted from JAMA 2017;318(10):927–938)

This study was a further investigation of the data accumulated in the hormone trials of the Women's Health Initiative (WHI). While the general results derived from the WHI hormone trials have been reported previously, this study focused on the long-term follow-up of the all-cause mortality rates.
Update on metal-induced occupational lung disease
Authors: Wyman Anne E. , Hines Stella E.
Published: January 2018

Purpose of review

Occupational and environmental exposures to metals can result in multiple pulmonary conditions. This article will review recent epidemiologic and mechanistic studies that have enhanced our understanding of the association between particular lung diseases and exposure to specific metals.

Recent findings

Recent studies have broadened our understanding of the mechanisms of lung diseases such as CBD in established industries and drawn attention to conditions that may arise from exposure to metals such as indium in developing technologies. New diagnostic techniques such as elemental tissue analysis may help establish a diagnosis of metal-induced occupational lung disease. Electronic cigarette devices, environmental pollutants, and the growing use of nanoparticle-sized metals pose additional risks to workers and consumers.

Recognizing the risks of pulmonary disease in workers exposed to metals and performing a thorough occupational history and diagnostic work-up in patients with unexplained respiratory findings is necessary to promote understanding and prevention of metal-induced lung disease.
Associations Between Nurse-Guided Variables and Plasma Oxytocin Trajectories in Premature Infants During Initial Hospitalization
Authors: Weber Ashley , Harrison Tondi M. , Sinnott Loraine , Shoben Abigail , Steward Deborah
Published: January 2018

Background:

Oxytocin (OT) is a social hormone that may help researchers understand how nurse-guided interventions during initial infant hospitalization, such as supporting human milk expression, promoting comforting touch, and reducing exposure to stressors, affect preterm brain development.

Purpose:

To determine whether factors related to human milk, touch, or stressor exposure are related to plasma OT trajectories in premature infants.

Methods:

Plasma from 33 premature infants, born gestational ages 25 to

JOURNAL/ancr/04.03/00149525-201802000-00014/14FSM1/v/2023-07-21T043926Z/r/image-gif

weeks, was collected at 14 days of life and then weekly until 34 weeks' corrected gestational age (CGA). Variables related to feeding volumes of human milk and formula; touch, as indexed by skin-to-skin contact (SSC) and swaddled holding; and clinical stressors were extracted from the electronic medical record. Linear mixed-models tested associations between nurse-guided variables and plasma OT trajectories.

Results:

In the final model, same-day SSC was positively related not only to plasma OT levels at 27 weeks' CGA (β= .938, P = .002) but also to a decline in plasma OT levels over time (β=−.177, P = .001). Volume of enteral feeds (mL/kg/d), its interaction with CGA, and number of stressful procedures were not statistically significant (β= .011, P = .077; β=−.002, P = .066; and β= .007, P = .062, respectively).

Implications for Practice:

Nurse-guided interventions are associated with infant plasma OT levels, suggesting nurses may impact the neurobiology of the developing premature infant.

Implications for Research:

Replication with larger sample sizes and randomized controlled trial designs is needed to test effects of specific nursing interventions on infant OT.
Gadolinium-Based Contrast Agent During Pelvic MRI: Contribution to Patient Management in Rectal Cancer
Authors: Corines Marina J. , Nougaret Stephanie , Weiser Martin R. , Khan Monika , Gollub Marc J.
Published: January 2018

BACKGROUND:

Few publications exist regarding gadolinium-enhanced sequences in rectal MRI. None have evaluated its potential impact on patient management.

OBJECTIVE:

This study aimed to assess whether gadolinium-enhanced sequences, including dynamic contrast enhancement, change radiologic interpretation and clinical management of rectal cancer.

DESIGN:

This is a retrospective analysis of 100 rectal MRIs (50 baseline and 50 postneoadjuvant treatment), both without and with gadolinium-enhanced sequences. Treatment plans were rendered based on each radiologic interpretation for each case by a single experienced surgeon. Differences in radiologic interpretation and management were statistically analyzed.

SETTINGS:

The study was conducted at the Memorial Sloan Kettering Cancer Center.

PATIENTS:

Patients undergoing rectal MRI between 2011 and 2015 for baseline tumor staging and/or postneoadjuvant restaging were included.

MAIN OUTCOME MEASURES:

Primary outcome measures were changes in radiologic tumor stage, tumor margins, and surgical planning with the use of gadolinium at baseline and postneoadjuvant time points.

RESULTS:

At baseline, tumor downstaging occurred in 8 (16%) of 50 and upstaging in 4 (8%) of 50 with gadolinium. Postneoadjuvant treatment, upstaging occurred in 1 (2%) of 50 from T2 to T3a. At baseline, mean distances from tumor to anorectal ring, anal verge, and mesorectal fascia were not statistically different with gadolinium. However, in 7 patients, differences could have resulted in treatment changes, accounted for by changes in relationships to anterior peritoneal reflection (n = 4), anorectal ring (n = 2), or anal verge (n = 1). Postneoadjuvant treatment, distances to anorectal ring and anal verge (in centimeters) were statistically smaller with gadolinium (p = 0.0017 and p = 0.0151) but could not have resulted in clinically significant treatment changes.

LIMITATIONS:

This study was limited by its retrospective design.

CONCLUSIONS:

The use of gadolinium at baseline MRI could have altered treatment in 24% of patients because of differences in tumor stage or position. Postneoadjuvant treatment, gadolinium resulted in statistically smaller distances to sphincters, which could influence surgical decision for sphincter-preserving rectal resection. See Video Abstract at http://links.lww.com/DCR/A444.
Lémann Index at Diagnosis Predicts the Risk of Early Surgery in Crohn’s Disease
Authors: Liu Wei , Zhou Wei , Xiang Jianjian , Cao Qian , Zhu Jinzhou , Qi Weilin , Chen Pengpeng , Xie Qingwen
Published: January 2018

BACKGROUND:

Identifying patients with Crohn’s disease with rapid disease progress or high risk of early surgery is crucial to clinical decision making.

OBJECTIVE:

The aim was to evaluate the correlation between the Lémann index at diagnosis and abdominal surgery in the first year after Crohn’s disease diagnosis and to find the risk factors for early surgery.

DESIGN:

This was a retrospective cohort study.

SETTINGS:

The study was conducted at a single tertiary hospital.

PATIENTS:

Patients diagnosed with Crohn’s disease between 2013 and 2015 in our center were included.

MAIN OUTCOME MEASURES:

The outcome of interest was the need for an abdominal surgery within 1 year after the Lémann index evaluation at diagnosis.

RESULTS:

Of 212 eligible patients, 48 patients underwent abdominal surgery during follow-up. Lémann index was much higher in the surgery group (5.3 vs 2.6; p < 0.001). On tertiles of the Lémann index, the frequency of surgery grew (2.8%, 9.9%, and 55.7%; p < 0.001) as the Lémann index increased. The receiver operating characteristic curve was constructed taking into account the Lémann index for selecting patients with a high risk of surgery. Specificity, sensitivity, and area under receiver operating characteristic curve were 84.8%, 81.3%, and 0.89 of the Lémann Index at a cutoff level of 3.7. Patients with Lémann index ≥3.7 carried a higher risk of abdominal surgery (OR = 18.6; p < 0.001). Stricturing and penetrating disease were predictors for abdominal surgery, whereas antitumor necrosis factor treatment was associated with a significant reduction of surgical requirements.

LIMITATIONS:

This study was limited by its retrospective design. The ability of the Lémann index to predict the long-term risk of surgery was unknown.

CONCLUSIONS:

Lémann index at diagnosis is a reliable index to predict the risk of abdominal surgery in the first year after diagnosis of Crohn’s disease. Patients with a high Lémann index might need closer follow-up or aggressive medical therapy. See Video Abstract at http://links.lww.com/DCR/A518.
Comparison of Western and Asian Guidelines Concerning the Management of Colon Cancer
Authors: Pellino Gianluca , Warren Oliver , Mills Sarah , Rasheed Shahnawaz , Tekkis Paris P. , Kontovounisios Christos
Published: January 2018

BACKGROUND:

Guidelines are important to standardize treatments and optimize outcomes. Several societies have published authoritative guidelines for patients with colon cancer, and a certain degree of variation can be predicted.

OBJECTIVE:

This study aims to compare Western and Asian guidelines for the management of colon cancer.

DATA SOURCES:

A literature review was performed following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines for studies published between 2010 and 2017 by the online resources from the official Web sites of the societies/panels. Sources included guidelines by European Society of Medical Oncology, the Japanese Society for Cancer of the Colon and Rectum, and the National Comprehensive Cancer Network.

STUDY SELECTION:

Only full-text studies and the latest guidelines dealing with colon cancer were included. Studies and guidelines were separately assessed by 2 authors, who independently identified discrepancies and areas for further research. These were discussed and agreed with by all the authors.

MAIN OUTCOME MEASURES:

The recommendations of the guidelines of each society were compared, seeking discrepancies and potential areas for improvement.

RESULTS:

Endoscopic techniques for the management of early colon cancer are discussed in detail in the Asian guidelines. Asian guidelines advocate extended (D3) lymphadenectomy on a routine basis in T3/T4 and in selected T2 patients, whereas such an approach is still under investigation in Western countries. Only US guidelines describe neoadjuvant chemotherapy and radiotherapy. All the guidelines recommend adjuvant treatment in selected stage II patients, but agreement exists that this is performed without solid evidence, because better outcomes are hypothesized based on studies including stage III or stage II/III patients. The role of cytoreductive surgery with intra-abdominal chemotherapy is dubious, and European guidelines only recommend it in the setting of trials. Asian guidelines endorse an aggressive surgical approach to peritoneal disease. Only US guidelines include a patient advocate in the drafting panel.

LIMITATIONS:

Bias may have arisen from country-specific socioeconomic and cultural issues, and from the latest available updates.

CONCLUSIONS:

Surgical approaches to colon cancer differ significantly among Western and Asian guidelines, reflecting different concepts of treatment. The role of adjuvant treatment in node-negative disease and quality-of-life assessment need further research.
Adverse reactions to ophthalmic medicines
Authors: Badyal K.K. , Badyal I.S.
Published: January 2018

Drugs used topically in the eye can cause systemic adverse effects that can range from mild to fatal. Ocular drugs can cause adverse effects by draining through the nasolacrimal duct and being absorbed into the blood stream, or by precipitating in the eye, or by causing an increase in intraocular pressure.
Acne Basics
Authors: Masterson Katrina Nice
Published: January 2018

Acne is a chronic condition affecting the pilosebaceous unit. Presenting almost daily in the typical dermatology practice, the condition poses numerous treatment challenges due to the complex interaction of its clinical presentation and unique patient needs. The following discussion will provide basic pathophysiology and describe the clinical presentation of acne vulgaris and many of its variants. Several of the standard treatment options will be described. Uncommon variants, acute forms, and more complex treatment regimens will not be discussed here.
Clinical Use of Isotretinoin
Authors: Jellerichs Bradley
Published: January 2018

Isotretinoin is an oral medication with clinical indications for several variants of acne. This medication is teratogenic and is associated with several adverse effects. It should be prescribed with appropriate caution in select patients. Recent evidence suggests a lack of correlation between isotretinoin use and diseases such as inflammatory bowel disease or depression. This article discusses the clinical use of oral isotretinoin by the dermatology nurse practitioner with a focus on management of adverse effects.
The ever-expanding saga of the proprotein convertases and their roles in body homeostasis: emphasis on novel proprotein convertase subtilisin kexin number 9 functions and regulation
Authors: Seidah Nabil G. , Chrétien Michel , Mbikay Majambu
Published: January 2018

Purpose of review

The nine members of the proprotein convertase family play major physiological roles during development and in the adult, and their dysregulation leads to various diseases. The primary objective of this article is to review recent findings on the clinical importance of some of these convertases concentrating mostly on PCSK9, the ninth member of the convertase family. This includes the transcriptional and translational regulation of PCSK9, its ability to enhance the degradation of LDL receptor (LDLR), and the implication of PCSK9 in inflammation and sepsis.

Recent findings

PCSK9 levels are upregulated by E2F1 and reduced by specific miRNAs and by Annexin A2 that bind the 3’ end of its mRNA. The implication of the LDLR in the clearance of pathogenic bacterial debris in mice and human puts in perspective a new role for PCSK9 in the regulation of sepsis. The specific implication of the LDLR in the clearance of Lp(a) is now confirmed by multiple studies of PCSK9 inhibition in human cohorts.

Emerging data suggest that PCSK9 can be regulated at the transcriptional and translational levels by specific factors and miRNAs. The identification of a novel pocket in the catalytic domain of PCSK9 represents a harbinger for a new class of small inhibitor drugs. The implication of the LDLR in reducing the effects of bacterially induced sepsis has been supported by both human and mouse data. Outcome studies confirmed the clinical importance of reducing PCSK9 levels. The present review puts in perspective new developments in the PCSK9 biology and its regulation of the LDLR.

Video abstract

http://links.lww.com/COL/A17
New antibiotics for ventilator-associated pneumonia
Authors: Bassetti Matteo , Vena Antionio , Castaldo Nadia , Righi Elda , Peghin Maddalena
Published: January 2018

Purpose of review

Ventilator-associated pneumonia (VAP) caused by multidrug-resistant (MDR) bacteria represents a global emerging problem. Delayed prescription of an adequate treatment for VAP has been associated with higher morbidity and mortality. New molecules have been developed to face the need of compounds that are active against resistant Gram-positive and Gram-negative pathogens. The aim of this review is to summarize the current scenario of new therapeutic options for the treatment of VAP.

Recent findings

A number of new antibiotics with activity against MDR have been recently approved for the treatment of VAP, and other agents are under investigation. In this review, the authors summarize the current therapeutic options for the treatment of VAP that showed promising implications for clinical practice, including new compounds belonging to old antibiotic classes (e.g., ceftolozane/tazobactam, ceftazidime/avibactam meropenem/vaborbactam, imipenem/relebactam, tedizolid, cefiderocol, eravacycline, and plazomicin) and novel chemical classes, such as murepavadin. Nebulized antibiotics that are currently in development for the treatment of pneumonia in mechanically ventilated patients are also presented.

Newly approved and investigational drugs for the treatment of VAP are expected to offer many advantages for the management of patients with respiratory infections caused by MDR. Promising characteristics of new compounds include high activity against both methicillin-resistant Staphylococcus aureus and MDR Gram-negative bacteria and a favorable safety profile.
Frequency and Severity of Acute Allergic-Like Reactions to Intravenously Administered Gadolinium-Based Contrast Media in Children
Authors: Forbes-Amrhein Monica M. , Dillman Jonathan R. , Trout Andrew T. , Koch Bernadette L. , Dickerson Julie M. , Giordano Richard M. , Towbin Alexander J.
Published: January 2018

Objectives

The purpose of this study is to determine the frequency and severity of acute allergic-like reactions to gadolinium-based contrast media (GBCM) in children before, during, and after the transition from gadopentetate dimeglumine to gadoterate meglumine as our primary clinical GBCM.

Materials and Methods

Institutional review board approval was obtained for this Health Insurance Portability and Accountability Act–compliant retrospective investigation. Allergic-like reactions to GBCM in pediatric patients were retrospectively assessed from January 2009 to January 2017, which included a departmental change of GBCM from gadopentetate dimeglumine to gadoterate meglumine. Allergic-like reactions were identified from departmental and hospital databases. The number of doses of GBCM was obtained from billing data. Allergic-like reaction frequencies for each GBCM were calculated and compared using the chi-squared test.

Results

A total of 32,365 administrations of GBCM occurred during the study period (327 for gadofosveset trisodium; 672 for gadoxetate disodium; 12,012 for gadoterate meglumine; and 19,354 for gadopentetate dimeglumine). Allergic-like reactions occurred after 21 (0.06%) administrations. Reaction frequencies were not significantly different among the GBCM (0.3% gadofosveset trisodium; 0% gadoxetate disodium, 0.06% gadoterate meglumine, 0.08% gadopentetate dimeglumine; P > 0.05). Ten (47.6%) reactions were mild, 10 (47.6%) were moderate, and 1 (4.8%) was severe. The overall reaction frequency peaked during the 6-month transition period from gadopentetate dimeglumine to gadoterate meglumine (0.20%), compared with 0.07% pretransition (P = 0.048) and 0.04% posttransition (P = 0.0095).

Conclusion

Allergic-like reactions to GBCM in children are rare. Gadoterate meglumine has a reaction frequency that does not significantly differ from other GBCMs. During the transition from gadopentetate dimeglumine to gadoterate meglumine, an increase in the frequency of reported allergic-like reactions was observed, likely reflective of the Weber effect.
Serum Admission 25-Hydroxyvitamin D Levels and Outcomes in Initially Non-Septic Critically Ill Patients
Authors: Vassiliou Alice G. , Jahaj Edison , Mastora Zafeiria , Stagaki Eleni , Orfanos Stylianos E. , Kotanidou Anastasia
Published: January 2018

Introduction:

To examine whether very low levels of 25-hydroxyvitamin D {25(OH)D} upon admission to the intensive care unit (ICU) are associated with worse outcomes.

Methods:

Retrospective observational cohort study of critically ill patients treated in a multidisciplinary ICU. Two hundred twenty seven initially non-septic, critically ill patients, in whom 25-hydroxyvitamin D was measured at ICU admission. An additional group of 192 healthy subjects was also used. Patients were categorized according to their vitamin D levels at admission; the two patient groups were those with severely low 25-hydroxyvitamin D levels (<7 ng/mL, N = 101) and those with vitamin D levels ≥7 ng/mL, N = 126.

Results:

ICU admission 25-hydroxyvitamin D levels of critically ill patients were much lower than those of healthy subjects (P < 0.0001). The median time to sepsis for the two patient groups did not differ, nor did the length of ICU stay (days). Both groups exhibited similar hospital mortality rates. However, among the fraction of patients who eventually became septic (N = 145), the odds ratio (OR) for developing respiratory infections in patients with admission vitamin levels < 7 ng/mL compared with patients with admission vitamin D levels ≥7 ng/mL was 5.25 {95% confidence interval (CI) 1.5–18.32, P = 0.009}.

Conclusions:

Initially non-septic critically ill patients appear to have very low ICU admission 25-hydroxyvitamin D levels. Among critically ill patients, severely low vitamin D levels (<7 ng/mL) at ICU admission do not predict sepsis development, increased risk of in-hospital mortality, or longer stay in the ICU. However, these severely low admission vitamin D levels in patients who will eventually develop sepsis are associated with development of respiratory tract infections.
Somatic growth and telomere dynamics in vertebrates: relationships, mechanisms and consequences
Authors: Monaghan Pat , Ozanne Susan E.
Published: January 2018

Much telomere loss takes place during the period of most rapid growth when cell proliferation and potentially energy expenditure are high. Fast growth is linked to reduced longevity. Therefore, the effects of somatic cell proliferation on telomere loss and cell senescence might play a significant role in driving the growth-lifespan trade-off. While different species will have evolved a growth strategy that maximizes lifetime fitness, environmental conditions encountered during periods of growth will influence individual optima. In this review, we first discuss the routes by which altered cellular conditions could influence telomere loss in vertebrates, with a focus on oxidative stress in both
in vitro
and
in vivo
studies. We discuss the relationship between body growth and telomere length, and evaluate the empirical evidence that this relationship is generally negative. We further discuss the potentially conflicting hypotheses that arise when other factors are taken into account, and the further work that needs to be undertaken to disentangle confounding variables.

This article is part of the theme issue ‘Understanding diversity in telomere dynamics’.
Ignavigranum ruoffiae, a rare pathogen that caused a skin abscess
Authors: De Paulis Adriana N. , Bertona Eugenia , Gutiérrez Miguel A. , Ramírez María S. , Vay Carlos A. , Predari Silvia C.
Published: January 2018

Introduction.
Ignavigranum ruoffiae is an extremely rare cause of human infections.

Case presentation. An 83-year-old male with a painless, ten-day-old, erythematous skin abscess on his left flank, which had showed a purulent discharge for 48 h, was admitted to the Emergency service. He was treated with cephalexin, disinfection with Codex water and spray of rifampicin. Five days later, surgical drainage of the abscess was proposed due to the torpid evolution of the patient. Samples were taken for culture, and antibiotic treatment with trimethoprim-sulfamethoxazole was established. The patient returned after 10 days showing healing of the abscess. Microbiological studies showed a few Gram-positive cocci present as single cells and short chains that grew after 72 h of incubation at 35 °C with CO2 on 5 % sheep blood agar. Colonies presented a strong sauerkraut odour. Initial biochemical test results were negative for catalase, aesculin and bile-aesculin, and positive for pyrrolidonyl arylamidase, leucine aminopeptidase and growth in 6.5 % NaCl broth, which prompted the preliminary identification of Facklamia species or I. ruoffiae. The positive result for arginine deamination and negative result for hippurate hydrolysis, failure to produce acid from mannitol, sucrose, sorbitol or trehalose, plus the distinctive sauerkraut odour identified the organism as I. ruoffiae. The phenotypic identification was confirmed by 16S rRNA gene sequence analysis. The strain seemed to be susceptible to the antimicrobials tested but had decreased susceptibility to carbapenems.

Conclusion. This case provides more insights into the phenotypic characteristics and antimicrobial resistance profile of I. ruoffiae.
Identifying long indels in exome sequencing data of patients with intellectual disability
Authors: Pajusalu Sander , Pfundt Rolph , Vissers Lisenka E.L.M. , Kwint Michael P. , Reimand Tiia , Õunap Katrin , Veltman Joris A. , Hehir-Kwa Jayne Y.
Published: January 2018

Exome sequencing is a powerful tool for detecting both single and multiple nucleotide variation genome wide. However long indels, in the size range 20 – 200bp, remain difficult to accurately detect. By assessing a set of common exonic long indels, we estimate the sensitivity of long indel detection in exome sequencing data to be 92%. To clarify the role of pathogenic long indels in patients with intellectual disability (ID), we analysed exome sequencing data from 820 patients using two variant callers, Pindel and Platypus. We identified three indels explaining the patients’ clinical phenotype by disrupting the UBE3A, PGAP3 and MECP2 genes. Comparison of different tools demonstrated the importance of both correct genotyping and annotation variants. In conclusion, specialized long indel detection can improve diagnostic yield in ID patients.