bluuebunny/crossref_metadata_2025 huggingface dataset:
Balanced feedforward inhibition and dominant recurrent inhibition in olfactory cortex
Authors: Large Adam M. , Vogler Nathan W. , Mielo Samantha , Oswald Anne-Marie M.
Published: February 2016

Significance

Understanding the interplay between excitation and inhibition in feedforward and recurrent circuits is essential for elucidating the mechanisms of cortical function. However, disentangling the relative contributions of feedforward or recurrent inhibition to cortical responses has been difficult. This study capitalizes on the unique laminar architecture of the piriform cortex to investigate feedforward and recurrent circuits in isolation. We find that feedforward inhibition and excitation are balanced, whereas recurrent inhibition dominates intracortical excitation. Furthermore, we find that feedforward and recurrent circuits differentially recruit the three classes of cortical excitatory neurons, functionally segregating their roles in the cortical representation of olfactory information. This study provides insight to circuit mechanisms that regulate subthreshold and suprathreshold processing of afferent input to the cortex.
Activation of RNase L is dependent on OAS3 expression during infection with diverse human viruses
Authors: Li Yize , Banerjee Shuvojit , Wang Yuyan , Goldstein Stephen A. , Dong Beihua , Gaughan Christina , Silverman Robert H. , Weiss Susan R.
Published: February 2016

Significance

RNase L, an antiviral enzyme activated during infection, degrades viral and cellular RNAs, inhibits protein synthesis, and restricts the replication and spread of diverse viruses. RNase L activation depends on 2′,5′-oligoadenylates synthesized by different oligoadenylate synthetases (OASs), i.e., OAS1, OAS2, and OAS3. OASs are induced by interferon and are activated by viral dsRNA. It has been unclear which of these OAS proteins is necessary and/or sufficient to activate RNase L during viral infections. We show that OAS3, but not OAS1 or OAS2, is required to activate RNase L and to restrict the replication of four different human viruses. These findings suggest that OAS3 may provide a target for antiviral therapies and that OAS1 and OAS2 may have alternative roles.
Mesoscale texture of cement hydrates
Authors: Ioannidou Katerina , Krakowiak Konrad J. , Bauchy Mathieu , Hoover Christian G. , Masoero Enrico , Yip Sidney , Ulm Franz-Josef , Levitz Pierre , Pellenq Roland J.-M. , Del Gado Emanuela
Published: February 2016

Significance

Calcium–silicate–hydrate (C–S–H) nanoscale gels are the main binding agent in cement and concrete, crucial for the strength and the long-term evolution of the material. Even more than the molecular structure, the C–S–H mesoscale amorphous texture over hundreds of nanometers plays a crucial role for material properties. We use a statistical physics framework for aggregating nanoparticles and numerical simulations to obtain a first, to our knowledge, quantitative model for such a complex material. The extensive comparison with experiments ranging from small-angle neutron scattering, SEM, adsorption/desorption of N
2
, and water to nanoindentation provides new fundamental insights into the microscopic origin of the properties measured.
Proteomic comparison defines novel markers to characterize heterogeneous populations of extracellular vesicle subtypes
Authors: Kowal Joanna , Arras Guillaume , Colombo Marina , Jouve Mabel , Morath Jakob Paul , Primdal-Bengtson Bjarke , Dingli Florent , Loew Damarys , Tkach Mercedes , Théry Clotilde
Published: February 2016

Significance

The last decade has seen a rapid expansion of interest in extracellular vesicles (EVs), proposed to mediate cell–cell communication in patho/physiological conditions. Although heterogeneity of EVs has become obvious, as highlighted recently by the International Society for Extracellular Vesicles, the field is lacking specific tools to distinguish EVs of different intracellular origins, and thus probably different functions. Here, thanks to a comprehensive comparison of different types of EVs isolated from a single cell type, we define proteins generically present in EVs, small EV-specific and -excluded ones, and a few specific of endosome-derived exosomes or nonexosomal small EVs. This work will allow proper evaluation of the molecular mechanisms of biogenesis and secretion and the respective functions of subtypes of EVs.
Inbreeding drives maize centromere evolution
Authors: Schneider Kevin L. , Xie Zidian , Wolfgruber Thomas K. , Presting Gernot G.
Published: February 2016

Significance

The diversity of centromere-specific DNA repeats in different species (centromere paradox) and the seemingly parallel rapid evolution of the cenH3 histone protein have previously been interpreted to be related to evolutionary pressures acting on both molecules based on their interaction (centromere drive hypothesis). Here we describe the detailed mechanism and chronology of centromere repeat replacement, and identify inbreeding as a major driver of centromeric DNA replacement that ultimately gives rise to new tandem centromere repeats at genetically indistinguishable loci. These insights explain both the frequently observed disturbance of established centromeres in crop plants following their domestication and the rapid appearance of novel centromere repeat sequences in genetically isolated individuals in nature during speciation.
Engineering super mycovirus donor strains of chestnut blight fungus by systematic disruption of multilocus
vic
genes
Authors: Zhang Dong-Xiu , Nuss Donald L.
Published: February 2016

Significance

Allorecognition, termed “vegetative incompatibility” (
vic
), in filamentous fungi limits the efficacy of virulence-attenuating mycoviruses for biological control (hypovirulence). Because mycoviruses lead exclusive intracellular lifestyles, horizontal transmission relies on cytoplasmic exchange during hyphal fusion (anastomosis). Fusion between
vic-
incompatible strains results in localized cell death restricting mycovirus transmission. We report the systematic disruption of multilocus
vic
genes and excision of exogenic genes to generate strains of the chestnut blight fungus able to transmit hypovirulence to strains with genotypic differences at any or all of the defined
vic
loci. The results demonstrate the feasibility of modulating fungal allorecognition to promote transmission of virulence-attenuating mycoviruses for enhanced biocontrol potential.
Topological constraints and modular structure in the folding and functional motions of GlpG, an intramembrane protease
Authors: Schafer Nicholas P. , Truong Ha H. , Otzen Daniel E. , Lindorff-Larsen Kresten , Wolynes Peter G.
Published: February 2016

Significance

Membrane proteins perform diverse functions in the cell while being embedded in lipid bilayers, but the presence of the anisotropic, nonpolar membrane environment has slowed progress in understanding how these proteins fold and function. Herein, we study GlpG, an intramembrane protease, using computationally efficient models to fill in structural details that are currently invisible to experimental techniques and inaccessible to atomistic simulations. We find that GlpG’s modular functional architecture leaves an imprint throughout its folding and functional landscape, leading to multiple possible folding pathways and the population of near-native states with functional significance. We propose a mechanism by which destabilizing mutations can accelerate folding in detergent micelles, a previously puzzling experimental observation.
Microstructure and tensile behaviour of pure titanium produced after high-energy shot peening
Authors: Dai S. , Zhu Y. , Huang Z.
Published: February 2016

In this study, the microstructure and tensile behaviour of pure titanium processed by means of high-energy shot peening have been studied. The results show that a nanocrystalline surface layer is prepared on the surface of pure titanium. During severe deformation, the dislocations, twins and slip bands with single orientation are formed first, then the intersections of twins and slip bands are observed, and then the subgrains appear near or in the slip bands and finally the randomly oriented nano-grains are formed due to the further breakdown. After high-energy shot peening, the ultimate tensile strength and the yield strength increase by 27 and 40%, while the elongation decreases by 64% after treatment, due to the increasing dislocation density, micro-strain and the grain refinement.
The evolution of collectivity in nuclei and the proton–neutron interaction
Authors: Casten R F , Cakirli R B
Published: February 2016

We survey the evolution of nuclear structure with N and Z, focusing on collective behavior and its relation to the underlying single particle configurations, and their interactions. We exploit a number of complementary observables, from multiple perspectives, and interpret the observed behavior in terms of simple models. The paper includes a discussion of key observables, how to evaluate theories, and some of the dangers of statistical tests. We conclude with a discussion of schemes to predict the properties of unknown nuclei, founded on the importance of valence proton–neutron interactions, and correlate empirical values for these interactions with the onset of collectivity and deformation.
Harnessing next-generation informatics for personalizing medicine: a report
from AMIA’s 2014 Health Policy Invitational Meeting
Authors: Wiley Laura K , Tarczy-Hornoch Peter , Denny Joshua C , Freimuth Robert R , Overby Casey L , Shah Nigam , Martin Ross D , Sarkar Indra Neil
Published: February 2016

The American Medical Informatics Association convened the 2014 Health Policy Invitational Meeting to develop recommendations for updates to current policies and to establish an informatics research agenda for personalizing medicine. In particular, the meeting focused on discussing informatics challenges related to personalizing care through the integration of genomic or other high-volume biomolecular data with data from clinical systems to make health care more efficient and effective. This report summarizes the findings ( n  = 6) and recommendations ( n  = 15) from the policy meeting, which were clustered into 3 broad areas: (1) policies governing data access for research and personalization of care; (2) policy and research needs for evolving data interpretation and knowledge representation; and (3) policy and research needs to ensure data integrity and preservation. The meeting outcome underscored the need to address a number of important policy and technical considerations in order to realize the potential of personalized or precision medicine in actual clinical contexts.
Modeling information flows in clinical decision support: key insights for enhancing system effectiveness
Authors: Medlock Stephanie , Wyatt Jeremy C , Patel Vimla L , Shortliffe Edward H , Abu-Hanna Ameen
Published: February 2016

A fundamental challenge in the field of clinical decision support is to determine what characteristics of systems make them effective in supporting particular types of clinical decisions. However, we lack such a theory of decision support itself and a model to describe clinical decisions and the systems to support them. This article outlines such a framework. We present a two-stream model of information flow within clinical decision-support systems (CDSSs): reasoning about the patient (the clinical stream), and reasoning about the user (the cognitive-behavioral stream). We propose that CDSS “effectiveness” be measured not only in terms of a system’s impact on clinical care, but also in terms of how (and by whom) the system is used, its effect on work processes, and whether it facilitates appropriate decisions by clinicians and patients. Future research into which factors improve the effectiveness of decision support should not regard CDSSs as a single entity, but should instead differentiate systems based on their attributes, users, and the decision being supported.
Extracting information from the text of electronic medical records to improve case detection: a systematic review
Authors: Ford Elizabeth , Carroll John A , Smith Helen E , Scott Donia , Cassell Jackie A
Published: February 2016

Background Electronic medical records (EMRs) are revolutionizing health-related research. One key issue for study quality is the accurate identification of patients with the condition of interest. Information in EMRs can be entered as structured codes or unstructured free text. The majority of research studies have used only coded parts of EMRs for case-detection, which may bias findings, miss cases, and reduce study quality. This review examines whether incorporating information from text into case-detection algorithms can improve research quality.

Methods A systematic search returned 9659 papers, 67 of which reported on the extraction of information from free text of EMRs with the stated purpose of detecting cases of a named clinical condition. Methods for extracting information from text and the technical accuracy of case-detection algorithms were reviewed.

Results Studies mainly used US hospital-based EMRs, and extracted information from text for 41 conditions using keyword searches, rule-based algorithms, and machine learning methods. There was no clear difference in case-detection algorithm accuracy between rule-based and machine learning methods of extraction. Inclusion of information from text resulted in a significant improvement in algorithm sensitivity and area under the receiver operating characteristic in comparison to codes alone (median sensitivity 78% (codes + text) vs 62% (codes), P  = .03; median area under the receiver operating characteristic 95% (codes + text) vs 88% (codes), P  = .025).

Conclusions Text in EMRs is accessible, especially with open source information extraction algorithms, and significantly improves case detection when combined with codes. More harmonization of reporting within EMR studies is needed, particularly standardized reporting of algorithm accuracy metrics like positive predictive value (precision) and sensitivity (recall).
Data interchange using i2b2
Authors: Klann Jeffrey G , Abend Aaron , Raghavan Vijay A , Mandl Kenneth D , Murphy Shawn N
Published: February 2016

Objective Reinventing data extraction from electronic health records (EHRs) to meet new analytical needs is slow and expensive. However, each new data research network that wishes to support its own analytics tends to develop its own data model. Joining these different networks without new data extraction, transform, and load (ETL) processes can reduce the time and expense needed to participate. The Informatics for Integrating Biology and the Bedside (i2b2) project supports data network interoperability through an ontology-driven approach. We use i2b2 as a hub, to rapidly reconfigure data to meet new analytical requirements without new ETL programming.

Materials and Methods Our 12-site National Patient-Centered Clinical Research Network (PCORnet) Clinical Data Research Network (CDRN) uses i2b2 to query data. We developed a process to generate a PCORnet Common Data Model (CDM) physical database directly from existing i2b2 systems, thereby supporting PCORnet analytic queries without new ETL programming. This involved: a formalized process for representing i2b2 information models (the specification of data types and formats); an information model that represents CDM Version 1.0; and a program that generates CDM tables, driven by this information model. This approach is generalizable to any logical information model.

Results Eight PCORnet CDRN sites have implemented this approach and generated a CDM database without a new ETL process from the EHR. This enables federated querying within the CDRN and compatibility with the national PCORnet Distributed Research Network.

Discussion We have established a way to adapt i2b2 to new information models without requiring changes to the underlying data. Eight Scalable Collaborative Infrastructure for a Learning Health System sites vetted this methodology, resulting in a network that, at present, supports research on 10 million patients’ data.

Conclusion New analytical requirements can be quickly and cost-effectively supported by i2b2 without creating new data extraction processes from the EHR.
Integrating patient voices into health information for self-care and patient-clinician partnerships: Veterans Affairs design recommendations for patient-generated data applications
Authors: Woods Susan S , Evans Neil C , Frisbee Kathleen L
Published: February 2016

Electronic health record content is created by clinicians and is driven largely by intermittent and brief encounters with patients. Collecting data directly from patients in the form of patient-generated data (PGD) provides an unprecedented opportunity to capture personal, contextual patient information that can supplement clinical data and enhance patients’ self-care. The US Department of Veterans Affairs (VA) is striving to implement the enterprise-wide capability to collect and use PGD in order to partner with patients in their care, improve the patient healthcare experience, and promote shared decision making. Through knowledge gained from Veterans’ and healthcare teams’ perspectives, VA created a taxonomy and an evolving framework on which to design and develop applications that capture and help physicians utilize PGD. Ten recommendations for effectively collecting and integrating PGD into patient care are discussed, addressing health system culture, data value, architecture, policy, data standards, clinical workflow, data visualization, and analytics and population reach.
Properties of galaxies around AGNs with the most massive supermassive black holes revealed by clustering analysis
Authors: Shirasaki Yuji , Komiya Yutaka , Ohishi Masatoshi , Mizumoto Yoshihiko
Published: February 2016

We present results of the clustering analysis between active galactic nuclei (AGNs) and galaxies at redshift 0.1–1.0, which was performed to investigate the properties of galaxies associated with the AGNs and reveal the nature of the fueling mechanism of supermassive black holes (SMBHs). We used 8059 AGNs/quasi-stellar objects (QSOs) for which virial masses of individual SMBHs were measured, and divided them into four mass groups.Cross-correlation analysis was performed to reconfirm our previous result that cross-correlation length increases with SMBH mass MBH; we obtained consistent results. A linear bias of AGN for each mass group was measured as 1.47 for MBH = 107.5–108.2 M⊙ and 3.08 for MBH = 109–1010 M⊙. The averaged color and luminosity distributions of galaxies around the AGNs/QSOs were also derived for each mass group. The galaxy color Dopt-IR was estimated from a spectral energy distribution (SED) constructed from a catalog derived by merging the Sloan Digital Sky Survey (SDSS) and the UKIRT Infrared Deep Sky Survey (UKIDSS) catalogs. The distributions of color and luminosity were derived by a subtraction method, which does not require redshift information of galaxies. The main results of this work are as follows. (1) A linear bias increases by a factor of two from the lower-mass group to the highest-mass group. (2) The environment around AGNs with the most massive SMBHs (MBH > 109 M⊙) is dominated by red sequence galaxies. (3) Marginal indication of decline in luminosity function at dimmer side of MIR > −19.5 is found for galaxies around AGNs with MBH = 108.2–109 M⊙ and nearest redshift group (z = 0.1–0.3). These results indicate that AGNs with the most massive SMBHs reside in haloes where a large fraction of galaxies have been transited to the red sequence. The accretion of hot halo gas as well as recycled gas from evolving stars can be one of the plausible mechanisms to fuel the SMBHs above ∼ 109 M⊙.
Return of Voice for Ventilated Tracheostomy Patients in ICU: A Randomized Controlled Trial of Early-Targeted Intervention*
Authors: Freeman-Sanderson Amy L. , Togher Leanne , Elkins Mark R. , Phipps Paul R.
Published: February 2016

Objectives:

A cuffed tracheostomy tube facilitates prolonged mechanical ventilation and weaning but usually leads to prolonged voicelessness, which can be one of the most negative experiences of hospitalization. No randomized trials have examined the effects of targeted early communication intervention for the restoration of voice in ventilated tracheostomy patients in the ICU.

Design:

A prospective randomized clinical trial.

Setting:

The trial was conducted in the ICU of an urban tertiary level hospital.

Patients:

Thirty adult participants enrolled, with 15 randomly allocated to the intervention and control groups.

Interventions:

The early intervention group received early cuff deflation and insertion of an in-line speaking valve during mechanical ventilation. The control group received standard cuff deflation and a speaking valve during self-ventilation. A speech-language pathologist provided all treatments.

Measurements and Main Results:

The primary outcome measure was time from tracheostomy insertion to phonation. Early intervention significantly hastened return to phonation (median difference = 11 d; hazard ratio = 3.66; 95% CI, 1.54–8.68) with no significant effect on duration of tracheostomy cannulation (hazard ratio = 1.40; 95% CI, 0.65–3.03), duration of mechanical ventilation in days from tracheostomy insertion (hazard ratio = 1.19; 95% CI, 0.58–2.51), length of stay in ICU (hazard ratio = 1.16; 95% CI, 0.54–2.52), or time to return to oral intake (hazard ratio = 2.35; 95% CI, 0.79–6.98). Adverse events were low and equal in both groups. There was no significant change in measures of quality of life.

Conclusions:

Focused early intervention for communication during mechanical ventilation allows the restoration of phonation significantly sooner than standard treatment, with no increase in complications in a small patient cohort. Although these results are favorable, further research is needed to determine whether the effects on any of the secondary outcomes are statistically significant and clinically important.
Bacterial Bioburden Decrease in Orthokeratology Lens Storage Cases After Forewarning: Assessment by the DNA Dot Hybridization Assay
Authors: Fang Po-Chiung , Lo Jung , Chang Tsung C. , Chien Chun-Chih , Hsiao Chang-Chun , Tseng Shin-Ling , Lai Yu-Hsuan , Kuo Ming-Tse
Published: February 2016

Background:

The aim of this study was to measure the changes in the bacterial bioburden in orthokeratology (OK) lens storage cases using the DNA dot hybridization assay (DHA) after forewarning patients about their bacterial contamination severity.

Methods:

Thirty-one OK lens wearers were prospectively enrolled in this study. Dot hybridization assay was used for serial measurements of bacterial bioburden in OK storage cases after lenses had been soaked for approximately 6 hr. After the first assessment, the lens wearers were informed of the extent of case contamination and the possible risk of microbial keratitis (MK), and best practices for lens care and lens case hygiene were reviewed and reinforced. A second assessment by the same DHA method was performed after approximately 6 months.

Results:

Two universal bacterial probes confirmed a significant decrease in bacterial bioburden at the second assessment (P<0.01 and P<0.001). Genus-specific probes showed significant reductions in Acinetobacter and Klebsiella (P=0.02 and P=0.01), but not in Pseudomonas (P=0.42).

Conclusions:

Making OK lens wearers aware of the bacterial bioburden in their lens cases resulted in improved quality of case care and reduced bioburden. Our results suggest that a strategy of bioburden assessment with forewarning could be a useful method to decrease the incidence of OK-related MK.
Biomarkers p16, Human Papillomavirus and p53 Predict Recurrence and Survival in Early Stage Squamous Cell Carcinoma of the Vulva
Authors: Hay Casey M. , Lachance Jason A. , Lucas F.L. , Smith Kahsi A. , Jones Michael A.
Published: February 2016

Objective

Vulvar squamous cell carcinoma (VSCC) develops through 2 distinct molecular pathways, one involving high-risk human papillomavirus (HPV) infection and the other through early p53 suppressor gene mutation. We sought to evaluate the influence of p53 mutation, HPV status, and p16 expression on local recurrence and disease-specific mortality in early stage VSCC.

Materials and Methods

We performed a retrospective chart review of all patients with stage I VSCC at the Maine Medical Center from 1998 to 2007 (n = 92). Tumor size, depth of invasion, lymphatic/vascular space invasion, and growth pattern were recorded. Paraffin-embedded tissue blocks were stained by immunohistochemistry for p16 and p53; high-risk HPV was detected by polymerase chain reaction assay. Margin distance was determined by a gynecologic pathologist. Survival analyses were conducted to examine predictors of VSCC recurrence and disease-specific mortality.

Results

Age, depth of invasion, lymphatic/vascular space invasion, growth pattern, and margin status were not significant predictors of recurrence or disease-specific mortality. Tumor size of greater than 4.0 cm indicated a 4-fold increase in disease-specific mortality but did not significantly increase recurrence. p16-Positive patients were less likely to recur and had no VSCC-related deaths. Human papillomavirus–positive patients were less likely to recur and had no VSCC-related deaths. p53-positive patients were 3 times more likely to recur and nearly 7 times more likely to die from vulvar cancer.

Conclusions

Our findings suggest that HPV and the surrogate biomarker p16 indicate a less aggressive type of vulvar cancer. p53 positivity was associated with poor prognosis and significantly increased both recurrence and disease-specific mortality.
p16 Staining of Cervical Biopsies May Decrease the Frequency of Unnecessary Loop Electrosurgical Excision Procedures
Authors: de Sam Lazaro Shireen , Newbill Colin P. , Berlin Michelle , Morgan Terry K.
Published: February 2016

Objective

Loop electrosurgical excision procedures (LEEPs) are negative for high-grade cervical intraepithelial neoplasia (CIN 2+) after a hematoxylin and eosin–based CIN 2+ colposcopic biopsy diagnosis in 14% to 24% of cases. This may be due to diagnostic errors or biopsy-related regression of the dysplasia. Because p16 immunohistochemical staining of cervical biopsies improves diagnostic accuracy, we hypothesized that p16-based cervical biopsy diagnoses may reduce the frequency of negative LEEPs.

Materials and Methods

We performed a retrospective cross-sectional study of all cervical LEEPs completed at our institution from 2002 to 2012. We recorded patient age, sexual history, smoking history, pathologic diagnoses (including whether the diagnosis was p16 based), the number of days from biopsy to follow-up LEEP, and clinical follow-up. This yielded 593 study subjects meeting inclusion criteria of CIN 2+ colposcopic diagnoses with follow-up LEEP and 2 years of clinical follow-up. Colposcopic biopsies and follow-up LEEPs were reviewed and p16 immunostaining was performed on all samples to provide criterion standard results. Data were analyzed by χ2 and regression modeling.

Results

Our practice employed p16 to aid cervical biopsy diagnoses by 2006. The frequency of negative LEEPs before 2006 was 12 (10%) of 126. The frequency dropped during the p16 era (2006–2012) to 23 (5%) of 467. Overall, we observed an inverse relationship between the frequency of p16 employment and the frequency of negative LEEP outcomes (R2 = 0.71; p < .001), independent of potential covariates.

Conclusions

Our data suggest that more accurate p16-based diagnoses may reduce the frequency of unnecessary LEEPs.
Solitary Pouch Ulcer
Authors: Pricolo Victor E.
Published: February 2016

Solitary rectal ulcer syndrome is a well-known clinical entity, likely secondary to a defecatory dysfunction. In patients who have undergone restorative proctocolectomy with ileoanal reservoir, it is conceivable that a similar pathophysiology may lead to “solitary pouch ulcer,” but such a syndrome has not been reported to date. This article reports 2 such cases and clinical success with lasting symptomatic relief through local therapy and behavior modification rather than anti-inflammatory.
Additional Protein Fortification Is Necessary in Extremely Low‐Birth‐Weight Infants Fed Human Milk
Authors: Picaud Jean‐Charles , Houeto Nellie , Buffin Rachel , Loys Claire‐Marie , Godbert Isabelle , Haÿs Stephane
Published: February 2016

In the present study, approximately one in three (49/152, 32.2%) extremely low‐birth‐weight infants were demonstrated to require additional protein intake to supplement the standard fortification to achieve satisfactory weight gain. This additional protein fortification also resulted in a rapid increase in length‐for‐age (P < 0.001) and head circumference‐for‐age (P = 0.02) z scores.
Neurodevelopment of Preterm Infants at 24 Months After Neonatal Supplementation of a Prebiotic Mix
Authors: van den Berg Jolice P. , Westerbeek Elisabeth A.M. , Bröring‐Starre Tinka , Garssen Johan , van Elburg Ruurd M.
Published: February 2016

Objectives:

Fetal brain maturation is disrupted by preterm birth. Inflammation during the neonatal period may further harm neurodevelopmental outcomes. The present study aimed to determine the effect of short‐chain galacto‐oligosaccharides/long‐chain fructo‐oligosaccharides/pectin‐derived acidic oligosaccharides (scGOS/lcFOS/pAOS) on neurodevelopmental outcomes measured by Bayley Scales of Infant and Toddler Development in preterm infants at 24 months.

Methods:

In this randomized controlled trial, scGOS/lcFOS/pAOS or placebo was supplemented between days 3 and 30 of life. Serum samples at day 1, 7, and 14 were analyzed for cytokine levels. Stool samples at day 1, 7, 14, and 30 were measured for bacterial count and bifidobacteria percentage. At 24 months corrected age infants were followed up by a blinded pediatric psychologist for the Bayley Scales of Infant and Toddler Development II or III.

Results:

Seventy‐seven of one hundred one (76%) eligible infants participated in the follow‐up study. Neurodevelopmental outcomes were not different in the scGOS/lcFOS/pAOS and placebo group. Infections during the neonatal period, lower percentages of bifidobacteria at day 7 (F = 3.8, P = 0.05) and day 14 (F = 5.0, P = 0.02) and higher levels of Interleukine (IL)‐1β (F = 4.0, P = 0.04) and IL‐8 (F = 8.0, P = 0.01) at day 7 are associated with lower mental developmental index. Lower psychomotor outcomes are associated with IL‐2 (F = 4.0, P = 0.05), IL‐4 (F = 6.0, P = 0.02) at birth, and interferon gamma at day 7 (F = 4.4, P = 0.04).

Conclusions:

scGOS/lcFOS/pAOS showed no significant improvement of neurodevelopmental outcomes at 24 months in preterm infants. Infections, lower bifidobacteria counts, and higher serum cytokine levels during the neonatal period were associated with lower neurodevelopmental outcomes at 24 months of age indicating the relevance of microbiome and immune responses in neurodevelopmental processes.
Antroduodenal Manometry Is Abnormal in Children Presenting With Orthostatic Intolerance and Gastrointestinal Symptoms
Authors: Moak Jeffrey P. , Fabian Robin R. , Clarke Lindsay C. , Hanumanthaiah Sridhar , Desbiens John , Darbari Anil
Published: February 2016

Objectives:

Gastrointestinal (GI) symptoms of nausea, vomiting, and abdominal pain are common in patients with orthostatic intolerance (OI), including neurally mediated hypotension (NMH) and postural orthostatic tachycardia syndrome (POTS). Autonomic dysregulation is considered the underlying pathophysiology behind the cardiovascular symptoms of POTS. Because the autonomic nervous system also regulates GI motility, we hypothesized that patients with POTS and GI symptoms will have evidence of autonomic dysmotility of the upper GI tract.

Methods:

Thirty‐five subjects with OI and GI symptoms were studied. All the subjects had a 24‐hour antroduodenal manometry (ADM) study, in conjunction with pharmacologic challenge and autonomic and tilt table testing (TTT).

Results:

The mean subject age was 16.2 ± 2.8 years (range 10–23.8 years), and male to female ratio was 10:25. TTT was abnormal in all the 35 subjects, whereas Valsalva testing was abnormal (+40 mmHG) in 21 of 34 (62%) subjects, and corrected QT interval was ≥0.44 seconds in 19 of 35 (54%) subjects. During TTT, GI symptoms were reproduced in 31 of 35 (89%) studies. ADM was found to be abnormal at baseline, before the TTT in 5 of 35 (14%) subjects, whereas it became abnormal in 23 of 34 (68%) subjects during TTT. In addition, the expected response to the pharmacologic challenge was limited. Overall, ADM was abnormal in 26 of 35 (74%) patients either at baseline or during TTT in these subjects with OI.

Conclusions:

ADM is frequently abnormal in children with OI and GI symptoms. Upper GI motility studies should be a part of the comprehensive evaluation in this population.
Potential mechanism of IL-22 on microbial agents and cutaneous wound healing
Authors: Ziaei Hezarjaribi Hajar , Hafezi Nasim , Ghaffarifar Fatemeh
Published: February 2016

Interleukin (IL)-22 structurally belongs to the IL-10 family of cytokines, which is expressed by Th22 cells, in addition to natural killer cells, lymphoid tissue inducer cells, lymphoid tissue inducer-like cells, and some other cells. Recently, the role of IL-22 in creating the protection and natural defense mechanism for controlling the bacterial infections, viral hemostasis, and the tissue recovery has been proved. IL-22 plays a protective role in wound healing of tissues such as skin. IL-22 acts by heterodimeric receptors consisting of IL-22R1 and IL-10R2. Human skin has the highest IL-22R1 expression among other tissues. The effect of IL-22 on skin tissue is related to the level of this cytokine and in a limited range has extraordinary wound healing effect, and out of this range, IL-22 may also have contradictory results. IL-22 provokes expression of molecules such as keratin 6, which provokes hyperplasia of reconstituted human epidermis. In addition, keratinocyte migration is increased by IL-22 stimulation.
The effect of upper limb casting on gait pattern
Authors: Dreyfuss Daniel , Elbaz Avi , Mor Amit , Segal Ganit , Calif Edward
Published: February 2016

Casting of the arm may interfere with normal walking patterns because of additional load of the cast or prevention of arm swing. This study aimed to determine the effect of applying various casts on temporospatial walking parameters, including gait velocity and cadence, step length, and single limb support. A computerized gait system was used to assess these variables for 23 healthy individuals in four walking modes: normal walking, with a cast above the elbow and a sling, and with a cast below the elbow, with and without a sling. Thirteen participants had their dominant hand casted and 10 had their nondominant hand casted. On average, casted participants took significantly smaller steps with the leg on the casted side and spent less time supported on the casted side. The least changes were noted with the arm in a cast below the elbow and no sling, and the greatest changes were noted with the arm in a cast above the elbow and in a sling. This difference was heightened when the dominant hand was casted and lessened when the nondominant hand was casted. No differences were found in walking velocity or cadence between the walking modes. Casting of the upper limb has significant effects on gait, which should be taken into consideration, especially in individuals with previous gait abnormalities.
Pediatric Spontaneous Pneumomediastinum
Authors: Gasser Celine Rey-Bellet , Pellaton Rachel , Rochat Cosette Pharisa
Published: February 2016

Introduction

Described since 1939 in the adult population, spontaneous pneumomediastinum is less known in children. Because of its symptoms and a generally benign evolution, it is probably an underestimated diagnosis. However, it has to be considered in the differential diagnosis of acute thoracic pain.

Methods

The incidence being low, we conducted a narrative literature review to identify the circumstances leading to a spontaneous pneumomediastinum, the most relevant signs and symptoms, investigations, as well as treatment recommendations.

Results

Of 216 patients, 66.2% are boys, and mean ages range from 6.9 to 14 years. The most frequent comorbidity in children is asthma (22.2%), and the most common trigger factors are bronchospasm (49%), cough (45.6%), various respiratory tract infections, vomiting (10.3%), and foreign body aspiration (8.3%). It remains idiopathic in 33.3%. Relevant signs are chest pain (54.6%), neck pain and/or sore throat (53.3%), and dyspnea (41.2%). The most relevant sign is palpation of subcutaneous emphysema (66.4%). The classically described Hamman crunch is only present in 11.6%. Chest x-ray provides the right diagnosis in 99.5% of the patients. Pneumothorax is associated in 11.6%. Most patients are hospitalized (88.3%); treatment is based on oxygen therapy, painkillers, and rest. In some series, there can be up to 25.8% of patients requiring intensive care and 5.5% requiring drainage of associated pneumothorax. Survival rate is 92.5%, and long-term follow-up shows normal x-rays after 4 days and no recurrence.

Conclusions

Spontaneous pneumomediastinum is uncommon in children but must be considered in pediatric patients with acute chest and/or neck pain. History taking, physical examination, and standard chest x-ray are most often diagnostic, and there is rarely a need for other investigation.

Hospitalization is not always indispensable; ambulatory management can be considered. Outcome is good, and follow-up can be clinical, therefore avoiding further x-rays.
Brief Report: A High Rate of β7+ Gut-Homing Lymphocytes in HIV-Infected Immunological Nonresponders is Associated With Poor CD4 T-Cell Recovery During Suppressive HAART
Authors: Girard Alexandre , Vergnon-Miszczycha Delphine , Depincé-Berger Anne-Emmanuelle , Roblin Xavier , Lutch Frederic , Lambert Claude , Rochereau Nicolas , Bourlet Thomas , Genin Christian , Paul Stéphane
Published: February 2016

Objective:

Correlation between GALT homing markers on lymphocytes and the low blood CD4 T-cell reconstitution in immunological nonresponders (INRs) has been studied.

Design:

Thirty-one INRs, 19 immunological responders (IRs), and 12 noninfected controls were enrolled in this study. INRs were defined by an undetectable plasma viral load RNA less than 40 copies per milliliter and CD4+ T-cell count <500 cells per cubic milliliter in at least 3 years.

Methods:

A complete peripheral and mucosal lymphocyte immunophenotyping was performed on these patients with a focus on the CCR9, CCR6, and α4β7 gut-homing markers.

Results:

A highly significant upregulation of α4β7 on INRs peripheral lymphocytes compared with that of IRs has been observed. This upregulation impacts different lymphocyte subsets namely CD4+, CD8+, and B lymphocytes. The frequency of β7+ Th17 and Treg cells are increased compared with IRs and healthy controls. The frequency of β7+ CD8+ T cells in the blood is negatively correlated with integrated proviral DNA in rectal lymphoid cells in contrast to β7+ CD4+ T cells associated with HIV integration.

Conclusions:

Alteration of lymphocyte homing abilities would have deleterious effects on GALT reconstitution and could participate to HIV reservoir constitution. These results emphasize the great interest to consider α4β7-targeted therapy in INR patients to block homing of lymphocytes and/or to directly impair gp120-α4β7 interactions.
Prediction Model For Extensive Ductal Carcinoma In Situ Around Early-Stage Invasive Breast Cancer
Authors: Knuttel Floortje M. , van der Velden Bas H.M. , Loo Claudette E. , Elias Sjoerd G. , Wesseling Jelle , van den Bosch Maurice A.A.J. , Gilhuijs Kenneth G.A.
Published: February 2016

Objectives

Ductal carcinoma in situ (DCIS) is a risk factor for incomplete resection of breast cancer. Especially, extensive DCIS (E-DCIS) or extensive intraductal component often results in positive resection margins. Detecting DCIS around breast cancer before treatment may therefore alter surgery. The purpose of this study was to develop a prediction model for E-DCIS around early-stage invasive breast cancer, using clinicohistopathological and dynamic contrast-enhanced magnetic resonance imaging (MRI) features.

Materials and Methods

Dynamic contrast-enhanced MRI and local excision were performed in 322 patients with 326 ductal carcinomas. Tumors were segmented from dynamic contrast-enhanced MRI, followed by 3-dimensional extension of the margins with 10 mm. Amount of fibroglandular tissue (FGT) and enhancement features in these extended margins were automatically extracted from the MRI scans. Clinicohistopathological features were also obtained. Principal component analysis and multivariable logistic regression were used to develop a prediction model for E-DCIS. Discrimination and calibration were assessed, and bootstrapping was applied for internal validation.

Results

Extensive DCIS occurred in 48 (14.7%) of 326 tumors. Incomplete resection occurred in 56.3% of these E-DCIS–positive versus 9.0% of E-DCIS–negative tumors (P < 0.001). Five components with eigenvalue exceeding 1 were identified; 2 were significantly associated with E-DCIS. The first, positively associated, component expressed early and overall enhancement in the 10-mm tissue margin surrounding the MRI-visible tumor. The second, positively associated, component expressed human epidermal growth factor receptor 2 and amount of FGT around the MRI-visible tumor. The area under the curve value was 0.79 (0.76 after bootstrapping).

Conclusions

Human epidermal growth factor receptor 2 status, early and overall enhancement in the 10-mm margin around the MRI-visible tumor, and amount of FGT in the 10 mm around the MRI-visible tumor were associated with E-DCIS.
Misidentification Delusions
Authors: Perini Giulia , Carlini Alessandro , Pomati Simone , Alberoni Margherita , Mariani Claudio , Nemni Raffaello , Farina Elisabetta
Published: February 2016

Misidentification delusions (MDs) are considered relatively rare psychopathologic phenomena that may occur within the context of psychiatric or neurological conditions. The purpose of this study was to assess the prevalence of MD in different types of dementia, correlate the presence of MD with demographic and clinical variables, and validate a specific questionnaire. We examined 146 subjects with Alzheimer disease, 21 with Lewy body dementia, 6 with frontotemporal dementia, and 13 with vascular dementia (subcortical type), who were consecutively enrolled in the study from 2 Memory Clinics. Patients had a mean age of 78.7±6.4 years and an Mini-Mental State Examination average score of 16.9±6.1. The Neuropsychiatric Inventory delusion subscale and a new Misidentification Delusion Questionnaire aimed at specific assessment of 11 delusional misidentification syndromes were administrated to the caregivers. On the basis of the Neuropsychiatric Inventory, MDs were present in 33.3% of the subjects, whereas according to the Misidentification Delusion Questionnaire they were present in 36.0% of the subjects. Specifically, 34.2% of Alzheimer disease, 52.4% of Lewy body dementia, and 46.1% of vascular dementia patients experienced at least 1 MD. None of the patients with frontotemporal dementia developed MD. The most frequent MD was house misidentification, followed by splitting of people and reduplicative paramnesia. Our self-administered questionnaire proved to be an accurate and specific tool for the detection of MD.
What did Erwin mean? The physics of information from the materials genomics of aperiodic crystals and water to molecular information catalysts and life
Authors: Varn D. P. , Crutchfield J. P.
Published: February 2016

Erwin Schrödinger famously and presciently ascribed the vehicle transmitting the hereditary information underlying life to an ‘aperiodic crystal’. We compare and contrast this, only later discovered to be stored in the linear biomolecule DNA, with the information-bearing, layered quasi-one-dimensional materials investigated by the emerging field ofchaotic crystallography. Despite differences in functionality, the same information measures capture structure and novelty in both, suggesting an intimate coherence between the information character of biotic and abiotic matter—a broadly applicable physics of information. We review layered solids and consider three examples of how information- and computation-theoretic techniques are being applied to understand their structure. In particular, (i) we review recent efforts to apply new kinds of information measures to quantify disordered crystals; (ii) we discuss the structure of ice I in information-theoretic terms; and (iii) we recount recent investigations into the structure of tris(bicyclo[2.1.1]hexeno)benzene, showing how an information-theoretic analysis yields additional insight into its structure. We then illustrate a new Second Law of Thermodynamics that describes information processing in active low-dimensional materials, reviewing Maxwell's Demon and a new class of molecular devices that act as information catalysts. Lastly, we conclude by speculating on how these ideas from informational materials science may impact biology.
Self-referring DNA and protein: a remark on physical and geometrical aspects
Authors: Tlusty Tsvi
Published: February 2016

All known life forms are based upon a hierarchy of interwoven feedback loops, operating over a cascade of space, time and energy scales. Among the most basic loops are those connecting DNA and proteins. For example, in genetic networks, DNA genes are expressed as proteins, which may bind near the same genes and thereby control their own expression. In this molecular type of self-reference, information is mapped from the DNA sequence to the protein and back to DNA. There is a variety of dynamic DNA–protein self-reference loops, and the purpose of this remark is to discuss certain geometrical and physical aspects related to the back and forth mapping between DNA and proteins. The mappings are examined as dimensional reductions and expansions between high- and low-dimensional manifolds in molecular spaces. The discussion raises basic questions regarding the nature of DNA and proteins as self-referring matter, which are examined in a simple toy model.
The problems of biological information
Authors: Ball Philip
Published: February 2016

The discovery of genetic encoding in the DNA molecule, and its mode of translation into protein structures, secured the modern view of biology as an information science. But it remains unclear what kind of information science it is. The all-too-ready analogy with computer programs stored on spools of magnetic tape has been hard to relinquish, even while the complexity of information storage and flow in the cell has become ever more apparent. To understand how life is sustained and evolves through encoding and processing of information, new ideas are now required, within which genetic encoding in DNA seems likely to provide only one part of a much broader and more profound puzzle. In particular, it seems likely that the emerging picture will need to take a more subtle view of causation, context and meaning in the orchestrated, hierarchical processes that make life possible.