bluuebunny/crossref_metadata_2025 huggingface dataset:
The Use of Recombinant Antithrombin III in Pediatric and Neonatal ECMO Patients
Authors: Todd Tzanetos Deanna R. , Myers John , Wells Terri , Stewart Dan , Fanning Jeffrey J. , Sullivan Janice E.
Published: November 2016

A retrospective review of 77 pediatric and neonatal extracorporeal membranous oxygenation (ECMO) patients who received recombinant antithrombin III (ATIII) for ATIII activity greater than 80% was conducted. Anticoagulation management was per institutional protocol. An ATIII activity greater than 80% was targeted. Diagnosis, reason for ECMO cannulation, blood product usage, heparin dosing, ATIII activity and doses, thrombotic and bleeding complications, hours on ECMO, and mortality were recorded. We calculated patient-level summary statistics and assessed differences between groups using χ2 tests (categorical variables) and Wilcoxon rank sum tests (continuous variables). Hierarchical generalized linear models were developed to model bleeding and thrombotic complications. The majority (n = 75) received venoarterial ECMO and had cardiac diagnoses (n = 62). Antithrombin III activity was below 80% for an average of 5.2 hours per patient. Antithrombin III activity less than 80% was not associated with thrombotic complications (odds ratio [OR] = 1.02, 95% confidence interval [CI] = 0.97–1.06, p = 0.86). Antithrombin III activity greater than 80% was not associated with bleeding complications (OR = 1.06, 95% CI = 1.01–1.11, p = 0.44). Duration of ECMO was an independent predictor of thrombotic complications (OR = 1.08, 95% CI = 1.02–1.11, p = 0.02). There were no independent predictors of bleeding complications. Antithrombin III activity correlated with anti Xa activity (r = 0.367, p < 0.001) but not with other measures of anticoagulation or with heparin dose (r = 0.16, p = 0.165). ATIII activity was not associated with bleeding, thrombosis, or heparin dose. Antithrombin III activity was associated with anti Xa activity but not with traditional measures of anticoagulation. Antithrombin III replacement for an activity less than 80% did not increase bleeding.
Influence of IABP-Induced Abdominal Occlusions on Aortic Hemodynamics: A Patient-Specific Computational Evaluation
Authors: Caruso Maria Vittoria , Renzulli Attilio , Fragomeni Gionata
Published: November 2016

Intraaortic balloon pump (IABP) is used as temporary mechanical assistance in case of cardiovascular diseases, even if different hemodynamic problems and, thus, clinical complications may happen, such as the decrease of visceral perfusion. A computational fluid dynamic (CFD) study was carried out to investigate the effects of different IABP-induced abdominal occlusions on patient-specific aortic flow. Two possible sizes (25 and 34 cm3) and two locations (2 and 3 cm) of the balloon were compared, modeling four abdominal occlusions and numerically reproducing IAB inflation/deflation behavior. The results highlighted that the perfusion in renal, mesenteric, and iliac arteries decreases when the abdominal occlusion increases with balloon inflation. The study illustrates also how the balloon size affects the flow in aorta vessels in both locations, and that the positioning is of little relevance for the 34 cm3balloon, whereas it influences the aortic flow very much in case of 25 cm3IAB. This analysis demonstrates how the IAB-induced occlusion may vary the abdominal circulation; therefore, the correct size and positioning are emphasized for patient’s outcome.
Pediatric Artificial Lung: A Low-Resistance Pumpless Artificial Lung Alleviates an Acute Lamb Model of Increased Right Ventricle Afterload
Authors: Alghanem Fares , Bryner Benjamin S. , Jahangir Emilia M. , Fernando Uditha P. , Trahanas John M. , Hoffman Hayley R. , Bartlett Robert H. , Rojas-Peña Alvaro , Hirschl Ronald B.
Published: November 2016

Lung disease in children often results in pulmonary hypertension and right heart failure. The availability of a pediatric artificial lung (PAL) would open new approaches to the management of these conditions by bridging to recovery in acute disease or transplantation in chronic disease. This study investigates the efficacy of a novel PAL in alleviating an animal model of pulmonary hypertension and increased right ventricle afterload. Five juvenile lambs (20–30 kg) underwent PAL implantation in a pulmonary artery to left atrium configuration. Induction of disease involved temporary, reversible occlusion of the right main pulmonary artery. Hemodynamics, pulmonary vascular input impedance, and right ventricle efficiency were measured under 1) baseline, 2) disease, and 3) disease + PAL conditions. The disease model altered hemodynamics variables in a manner consistent with pulmonary hypertension. Subsequent PAL attachment improved pulmonary artery pressure (p = 0.018), cardiac output (p = 0.050), pulmonary vascular input impedance (Z.0 p = 0.028; Z.1 p = 0.058), and right ventricle efficiency (p = 0.001). The PAL averaged resistance of 2.3 ± 0.8 mm Hg/L/min and blood flow of 1.3 ± 0.6 L/min. This novel low-resistance PAL can alleviate pulmonary hypertension in an acute animal model and demonstrates potential for use as a bridge to lung recovery or transplantation in pediatric patients with significant pulmonary hypertension refractory to medical therapies.
Fatty acid metabolism in macrophages: a target in cardio-metabolic diseases
Authors: Ménégaut Louise , Thomas Charles , Lagrost Laurent , Masson David
Published: November 2016

Purpose of review

Recent studies have highlighted that macrophages dynamically and autonomously handle all the facets of fatty acid (FA) metabolism including FA oxidation and FA synthesis as well as the synthesis of monounsaturated FAs and long chain n-3 and n-6 polyunsaturated FAs.

Recent findings

Macrophage M2 polarization is associated with an increase of FA oxidation. However, whether increased FA oxidation simply correlates with or is required for M2 polarization needs to be further evaluated. Macrophage M1 polarization is associated with the activation of FA synthesis, which directly contributes to the inflammatory response and affects cholesterol homeostasis and neutral lipid accumulation. Finally, recent evidences suggest that macrophages are able to autonomously produce signaling monounsaturated FAs, such as palmitoleic acid (C16 : 1 n-7), and long chain n-3 and n-6 polyunsaturated FAs, such as arachidonic acid, eicosapentaenoic acid, and docosahexaenoic acid. This pathway is regulated by liver X receptors and has significant consequences on inflammation and on the FA composition of atheroma plaques.

These studies shed new light on the tight relationship between FA metabolism, macrophage polarization, and M1/M2 macrophage functions. These processes may have major consequences for atherosclerosis pathogenesis as well as other metabolic disorders.
Apolipoprotein L1 and apolipoprotein A-IV and their association with kidney function
Authors: Kronenberg Florian
Published: November 2016

Purpose of review

Chronic kidney disease (CKD) is a common disease with an estimated prevalence of 10–12%. There are pronounced differences between ethnicities with a 3-fold to 4-fold higher lifetime risk for end-stage kidney disease in African Americans compared to European Americans. The purpose of this review was to discuss recent findings on two apolipoproteins (apolipoprotein L1 and A-IV) in the context of kidney disease and kidney function.

Recent findings

The observation that certain apolipoprotein L1 risk genotypes that are only present in African Americans might explain a major fraction of the ethnic differences for nondiabetic CKD has set the stage for this otherwise under-researched apolipoprotein. These risk genotypes on the one hand protect African Americans against African sleeping sickness but cause on the other hand several types of nondiabetic CKD. We are currently beginning to understand the mechanisms how apolipoprotein L1 is involved in the modification of lysosomal and cytoplasmic membranes. The second protein, apolipoprotein A-IV (apoA-IV), turned out to be an early marker of kidney impairment not only in patients with primary CKD but also in individuals from the general population. Genetic studies provided strong support of a causal effect of kidney function on apoA-IV concentrations.

These two apolipoproteins have very distinct properties. Apolipoprotein L1 is causally involved in the development of nondiabetic CKD in African Americans. In contrast, apoA-IV is an early marker for kidney impairment.
Burden and Distress in Caregivers of Patients With Panic Disorder and Agoraphobia
Authors: Borgo Evandro Luis Pampani , Ramos-Cerqueira Ana Teresa de Abreu , Torres Albina Rodrigues
Published: November 2016

We estimated the prevalence, severity, and correlates of burden and distress in caregivers of patients with panic disorder and agoraphobia. The instruments used in this cross-sectional study with 40 caregivers and 40 outpatients were Carer Burden Interview (CBI), Family Burden Interview Schedule (FBIS-BR), Self-Reporting Questionnaire (SRQ), Panic and Agoraphobia Scale (PAS), and Mini-international Neuropsychiatric Interview. Bivariate analyses were followed by regression analyses. The patients' mean PAS score was 29.6, and the mean scores in the caregivers' burden scales were 27 (CBI) and 1.64 (FBIS-BR). Distress (or common mental disorder [CMD]) occurred in 37.5% and was associated with higher burden. In the multivariate analysis, the SRQ score was predicted by female sex and worse self-evaluation of health, the CBI score by CMD and public service, the FBIS-BR score by CMD and not living with the patient, the FBIS-objective score by CMD and being employed, the FBIS-subjective score by CMD, and the level of worry by the severity of patients' avoidance and panic attacks.
Public and Private Partnership Research Opportunities
Authors: Korczak Renee , Marquart Len
Published: November 2016

Public and private partnerships (PPPs) are a joint venture between the government, industry, and other public and private sectors. Public and private partnerships are typically formed to leverage expertise from different sectors to identify problems and work collaboratively to come to a common solution. This chapter discusses why PPPs are needed to solve the complex problem of getting healthier, grain- based foods into the food supply. We introduce and describe 3 different research initiatives that require a PPP. Our vision for PPPs is to work to increase the availability of grain-based foods that are practical, healthier, affordable, and desirable with the intention of making the healthy choice the easy and natural choice for citizens.
Citizen Science
Authors: Rowe Sylvia , Alexander Nick
Published: November 2016

With the apparent success in recent years of citizen science (CS) projects in a variety of fields, the authors note the virtual absence of nutrition science in the current CS arena and explore the possibility of creating nutrition and other food-related CS projects. They argue that communicating such ventures might have beneficial effects on public understanding of nutrition/food science and on protecting the public from the misinformation too often promulgated in cyberspace. The article briefly summarizes the CS landscape and offers some modest suggestions for nutrition/food science projects that might lend themselves to a CS strategy. Finally, the authors discuss some of the communication challenges that might be encountered as nutrition science communicators enter this CS arena.
“I Don’t Feel Like Myself”
Authors: Firnhaber Gina C. , Kolasa Kathryn M.
Published: November 2016

Attention to the role diet and nutrition play in frailty may help older adults better perform basic activities of daily living, have a better quality of life, and delay disability. While there are no well-accepted guidelines for the prevention and treatment of frailty, providing patients with strategies for improving their diets may help them prevent, delay, reduce, or reverse prefrailty and frailty. In this article, we present the case of an older adult who might benefit from frailty assessment and dietary counseling.
Prolonged Second Stage: What Is the Optimal Length?
Authors: Gimovsky Alexis C. , Berghella Vincenzo
Published: November 2016

Importance

Prolonged second stage of labor is a clinical dilemma in which controversy exists on whether extending labor in nulliparous women with epidural anesthesia decreases the incidence of cesarean delivery without increasing maternal or neonatal risks.

Objective

This narrative review was conducted to assess the current literature on management of and risks associated with a prolonged second stage in nulliparous women with epidurals.

Evidence Acquisition

A review of the current literature was performed to evaluate the incidence of cesarean delivery and the maternal and neonatal outcomes.

Results

A total of 11.5% of nulliparous women with epidurals have a prolonged second stage; 80.2% of these women deliver vaginally. There is 1 randomized controlled trial on prolonged second stage in nulliparous women with epidurals. In this study, extending the second stage beyond current guidelines decreased the incidence of cesarean delivery by 55% and did not increase maternal or neonatal risks. Most patients (75.6%) with a prolonged second stage delivered by 5 hours and had a vaginal delivery (80.5%). Women with a fetus in occiput anterior position or who presented in spontaneous labor had decreased risk of cesarean delivery (by 83% and 89%, respectively). Maternal risks include postpartum hemorrhage, chorioamnionitis, and third- and fourth-degree lacerations. Neonatal risks may have a small absolute increase.

Conclusions and Relevance

The change of a vaginal delivery is high (over 80%) beyond 3 hours in the second stage. Maternal and neonatal risks need to be further explored by larger, better-designed retrospective reviews or trials.

Target Audience

Obstetricians and gynecologists, family physicians

Learning Objectives

After completing this activity, the learner should be better able to estimate the incidence of prolonged second stage of labor in nulliparas with epidurals as seen in retrospective studies, counsel women about their chances of vaginal delivery with a prolonged second stage, and assess the potential maternal and neonatal risks of prolonged second stage.
Reanalysis of Human Blastocysts With Different Molecular Genetic Screening Platforms Reveals Significant Discordance in Ploidy Status
Authors: Tortoriello Drew V. , Dayal Molina , Beyhan Zeki , Yakut Tahsin , Keskintepe Levent
Published: November 2016

(Abstracted from J Assist Reprod Genet 2016; doi: 10.1007/s10815-016-0766-5)

It is estimated that at least 1 aneuploid cell is present in more than 50% of all embryos. These aneuploidies are seen rarely, if ever, in later-stage fetuses.
Liver Subcapsular Hematoma
Authors: Oualha Dorra , Aissaoui Abir , Belhaj Meriam , Mesrati Mohamed Amin , Moussa Adnene , Salem Nidhal Haj , Zakhama Abdelfateh , Chadly Ali
Published: November 2016

The spontaneous subcapsular hematoma of the liver is very rare. There are only a few reported cases in the literature.

Most reported cases of liver hematoma often occur during pregnancy as part of the hemolysis, elevated liver enzymes, and low platelet count syndrome. The other causes may be due to amylosis, rupture of hepatocellular carcinoma, adenoma, focal nodular hyperplasia, hemorrhagic cyst, or hemopathy. Idiopathic spontaneous subscapular hematoma is a rare and often fatal condition.

We report a case of a 43-year-old woman having Steinert disease who died because of a fatal spontaneous liver hemorrhage occurring without any traumatism. We did not find any apparent cause that could explain this hemorrhage even after a histological study of the liver.
Differences in Health Care Needs, Health Care Utilization, and Health Care Outcomes Among Children With Special Health Care Needs in Ohio: A Comparative Analysis Between Medicaid and Private Insurance
Authors: Sarkar Madhurima , Earley Elizabeth R. , Asti Lindsey , Chisolm Deena J.
Published: November 2016

Objective:

This study explores comparative differentials in health care needs, health care utilization, and health status between Medicaid and private/employer-sponsored insurance (ESI) among a statewide population of children with special health care needs (CSHCN) in Ohio.

Methods:

We used data from the 2012 Ohio Medicaid Assessment Survey to examine CSHCN's health care needs, utilization, status, and health outcomes by insurance type. Adjusted multivariable logistic regression models were used to explore associations between public and private health insurance, as well as the utilization and health outcome variables.

Results:

Bivariate analyses indicate that the Medicaid population had higher care coordination needs (odds ratio [OR] = 1.6; 95% confidence interval [CI], 1.1-2.2) as well as need for mental/educational health care services (OR = 1.5; 95% CI; 1.1-2.0). They also reported higher unmet dental care needs (OR = 2.2; 95% CI, 1.2-4.0), higher emergency department (ED) utilization (OR = 2.3; 95% CI, 1.7-3.2), and worse overall health (OR = 0.6; 95% CI, 0.4-0.7), oral health (OR = 0.4; 95% CI, 0.3-0.5), and vision health (OR = 0.4; 95% CI, 0.2-0.6). After controlling for demographic variables, CSHCN with Medicaid insurance coverage were more likely to need mental health and education services (adjusted odds ratio [AOR] = 1.8; 95% CI; 1.2-2.6), had significantly more ED visits (AOR = 2.3; 95% CI, 1.5-3.5), and were less likely to have excellent overall health (AOR = 0.64; 95% CI, 0.4-0.9), oral health (AOR = 0.43; 95% CI, 0.3-0.7), and vision health (AOR = 0.38; 95% CI, 0.2-0.6) than those with private insurance/ESI.

Conclusion:

The CSHCN population is a highly vulnerable population. While Ohio's Medicaid provides greater coverage to CSHCN, disparities continue to exist within access and services that Medicaid provides versus the ones provided by private insurance/ESI.
Metal Artifact Reduction on Chest Computed Tomography Examinations: Comparison of the Iterative Metallic Artefact Reduction Algorithm and the Monoenergetic Approach
Authors: Pagniez Julien , Legrand Louise , Khung Suonita , Faivre Jean-Baptiste , Duhamel Alain , Krauss Andreas , Remy Jacques , Remy-Jardin Martine
Published: November 2016

Objective

The aim of the study was to compare iterative metallic artefact reduction (iMAR) and monochromatic imaging on metal artifact reduction.

Materials and Methods

Follow-up of 29 occluded pulmonary arteriovenous malformations was obtained with dual-energy computed tomography with reconstruction of averaged images using filtered back projection (group 1), iMAR (group 2), and creation of high-energy monoenergetic images (group 3). Two types of coils had been used: (a) nickel only (group A, n = 18) and (b) nickel and platinum (group B, n = 11).

Results

Compared with group 1, groups 2 and 3 images showed significant reduction in artifact severity. Compared with group 3, group 2 images showed less artifacts on subjective (artifact severity score: P = 0.0118; score of visibility of surrounding structures: P = 0.0056) and objective (artifact attenuation: P < 0.0001) analyses. In group A, there was no significant difference in artifact severity between groups 2 and 3 images (P > 0.05). In group B, metal artifacts were only significantly reduced in group 2 images.

Conclusions

Iterative metallic artefact reduction reduces metal artifacts more efficiently than monoenergetic imaging.
Aortic Volumetry at Contrast-Enhanced Magnetic Resonance Angiography
Authors: Trinh Brian , Dubin Iram , Rahman Ozair , Ferreira Botelho Marcos P. , Naro Nicholas , Carr James C. , Collins Jeremy D. , Barker Alex J.
Published: November 2016

Objectives

Bicuspid aortic valve patients can develop thoracic aortic aneurysms and therefore require serial imaging to monitor aortic growth. This study investigates the reliability of contrast-enhanced magnetic resonance angiography (CEMRA) volumetry compared with 2-dimensional diameter measurements to identify thoracic aortic aneurysm growth.

Materials and Methods

A retrospective, institutional review board–approved, and Health Insurance Portability and Accountability Act–compliant study was conducted on 20 bicuspid aortic valve patients (45 ± 8.9 years, 20% women) who underwent serial CEMRA with a minimum imaging follow-up of 11 months. Magnetic resonance imaging was performed at 1.5 T with electrocardiogram-gated, time-resolved CEMRA. Independent observers measured the diameter at the sinuses of Valsalva (SOVs) and mid ascending aorta (MAA) as well as ascending aorta volume between the aortic valve annulus and innominate branch. Intraobserver/interobserver coefficient of variation (COV) and intraclass correlation coefficient (ICC) were computed to assess reliability. Growth rates were calculated and assessed by Student t test (P < 0.05, significant). The diameter of maximal growth (DMG), defined as the diameter at SOV or MAA with the faster growth rate, was recorded.

Results

The mean time of follow-up was 2.6 ± 0.82 years. The intraobserver COV was 0.01 for SOV, 0.02 for MAA, and 0.02 for volume (interobserver COV: 0.02, 0.03, 0.04, respectively). The ICC was 0.83 for SOV, 0.86 for MAA, 0.90 for DMG, and 0.95 for volume. Average aortic measurements at baseline and (follow-up) were 42 ± 3 mm (42 ± 3 mm, P = 0.11) at SOV, 46 ± 4 mm (47 ± 4 mm, P < 0.05) at MAA, and 130 ± 23 mL (144 ± 24 mL, P < 0.05). Average size changes were 0.2 ± 0.6 mm/y (1% ± 2%) at SOV, 0.5 ± 0.8 mm/y (1% ± 2%) at MAA, 0.7 ± 0.7 mm/y (2% ± 2%) at DMG, and 6 ± 3 mL/y (4% ± 3%) with volumetry.

Conclusions

Three-dimensional CEMRA volumetry exhibited a larger effect when examining percentage growth, a better ICC, and a marginally lower COV. Volumetry may be more sensitive to growth and possibly less affected by error than diameter measurements.
Structured Reporting of Rectal Magnetic Resonance Imaging in Suspected Primary Rectal Cancer
Authors: Nörenberg Dominik , Sommer Wieland H. , Thasler Wolfgang , D'Haese Jan , Rentsch Markus , Kolben Thomas , Schreyer Andreas , Rist Carsten , Reiser Maximilian , Armbruster Marco
Published: November 2016

Objectives

The aim of this study was to evaluate the effect of structured reports (SRs) in comparison to nonstructured, free-text (FT) rectal magnetic resonance imaging (MRI) reports in patients with histologically proven rectal cancer and potential effects of both types of reporting on referring surgeons' satisfaction, interdisciplinary communication, and further clinical decision making.

Materials and Methods

The institutional review board approved this retrospective study with waiver of informed consent. Forty-nine patients with histologically proven rectal cancer were included in this study. All patients underwent rectal MRI for local rectal cancer staging before surgery. Free-text reports and SRs for local MR staging of rectal cancer were generated for all subjects by radiologists. Two experienced abdominal surgeons evaluated a questionnaire that included 9 questions regarding satisfaction with content, presence of reported key features, effort for information extraction, and report quality.

Results

Structured reports achieved significantly higher satisfaction rates with report content and clarity, and included significantly more of the 13 predefined key features compared with FT reports (SRs: mean ± SD, 12.2 ± 4.6 [range, 9–13] versus FT reports: mean ± SD, 9.2 ± 10.8 [range, 5–13]) (P < 0.001). Definite further clinical decision making (surgery vs neoadjuvant radiochemotherapy) was possible in 96% of SRs and only in 60% of FT reports (P < 0.001). In case of surgery, the reported information was considered to be sufficient for surgical planning in 94% of SRs versus only 38% in FT reports (P < 0.001). Structured report received a significantly higher overall report quality rated on a Likert scale from 1 to 6 (1, insufficient; 6, excellent) with a mean of 5.8 ± 0.42 (range, 5–6) in comparison to FT reports with 3.6 ± 1.19 (range, 1–5) (P < 0.001).

Conclusions

Structured reporting of rectal MRI in patients with rectal cancer facilitates surgical planning and leads to a higher satisfaction level of referring surgeons in comparison to FT reports. Abdominal surgeons were more confident about report correctness and further clinical decision making on the basis of SRs.
Comparison of Total Lung Capacity Determined by Plethysmography With Computed Tomographic Segmentation Using CALIPER
Authors: Matsumoto Andrew J. , Bartholmai Brian J. , Wylam Mark E.
Published: November 2016

Purpose:

Traditionally, determination of total lung capacity (TLC) by plethysmography (TLCpleth) has been important in the diagnosis of lung diseases. Alternatively, data acquired from computerized tomography (CT) can be utilized to calculate a measure of TLC (TLCCT). The clinical utility of TLCCT is not certain. We sought to determine, in a clinical setting, whether TLCCT correlates with TLCpleth across a range of lung diseases and scanning techniques. In addition, we determined whether TLCCT affects the interpretation of pulmonary function tests.

Subjects and Methods:

Records of 118 of 148 consecutive lung transplant recipients were reviewed and determined to have coinciding pulmonary function tests, including plethysmography as well as volumetric chest CT performed supine during full inspiration. CT images acquired with a wide range of scanning protocols were analyzed using CALIPER, a software program for lung and trachea extraction from a CT volume and volumetric tissue characterization of the lung. Segmentation of the lung was achieved by using completely automated dynamic thresholding and region-growing techniques developed to extract the relatively low-density lung and tracheal anatomy from the CT data set without user intervention.

Results:

TLCpleth and TLCCT were strongly related with a correlation coefficient of 0.88 (P<0.001). The efficacy of the CT-derived measure was not influenced by specific lung diagnoses, age, height, body mass index, or spirometric parameters. TLCCT did not misidentify any diagnosis of restrictive lung disease, nor hyperinflation.

Conclusions:

In a clinical setting, CT segmentation analysis provides a favorable determination of TLC compared with traditional plethysmography. The technique has general applicability across varying CT data acquisition protocols, lung diseases, and patient characteristics. TLCCT may substitute for TLCpleth in pulmonary function interpretation and may be preferable for some patients in whom plethysmography is difficult to perform, such as transplant subjects with severe pulmonary fibrosis.
MEG May Reveal Hidden Population of Spikes in Epilepsy With Porencephalic Cyst/Encephalomalacia
Authors: Kakisaka Yosuke , Wang Zhong I. , Shibata Sumiya , Takahashi Yoko , Mosher John C. , Alexopoulos Andreas V. , Burgess Richard C.
Published: November 2016

Porencephalic cyst/encephalomalacia is often associated with intractable epilepsy. A limited number of studies reported magnetoencephalography's (MEG's) potential to help construct treatment strategy for epilepsies associated with porencephalic cyst/encephalomalacia. The authors present here simultaneous electroencephalography (EEG) and MEG findings in three adult patients with pediatric-onset epilepsy due to porencephalic cyst/encephalomalacia. There were two types of spikes: one type was detected by MEG only (EEG−/MEG+), and the other detected by both EEG and MEG (EEG+/MEG+). Both types were seen in all three cases. The EEG−/MEG+ spikes all formed tight clusters; in contrast, the majority of EEG+/MEG+ spikes formed loose clusters. These data suggest that MEG may be helpful to better identify spike populations in epilepsy patients with porencephalic cyst/encephalomalacia. If hidden spike populations were to be found by MEG, this information would affect the interpretation of patient's pathophysiology and planning of intracranial electrode placement.
Shifting microbial communities sustain multi-year iron reduction and methanogenesis in ferruginous sediment incubations
Authors: Bray Marcus S. , Wu Jieying , Reed Benjamin C. , Kretz Cecilia B. , Belli Keaton M. , Simister Rachel L. , Henny Cynthia , Stewart Frank J. , DiChristina Thomas J. , Brandes Jay A. , Fowle David A. , Crowe Sean A. , Glass Jennifer B.
Published: November 2016

Reactive Fe(III) minerals can influence methane (CH4) emissions by inhibiting microbial methanogenesis or by stimulating anaerobic CH4oxidation. The balance between Fe(III) reduction, methanogenesis, and methane oxidation in ferruginous Archean and Paleoproterozoic oceans would have controlled CH4fluxes to the atmosphere, thereby regulating the capacity for CH4to warm the early Earth under the Faint Young Sun. We studied CH4and Fe cycling in anoxic incubations of ferruginous sediment from the ancient ocean analogue Lake Matano, Indonesia over three successive transfers (500 days total). Iron reduction, methanogenesis, methane oxidation, and microbial taxonomy were monitored in treatments amended with ferrihydrite or goethite. After three dilutions, Fe(III) reduction persisted only in bottles with ferrihydrite. Enhanced CH4production was observed in the presence of goethite, highlighting the potential for reactive Fe(III)-oxides to inhibit methanogenesis. Supplementing the media with hydrogen, nickel and selenium did not stimulate methanogenesis. There was limited evidence for Fe(III)-dependent CH4oxidation, although some incubations displayed CH4-stimulated Fe(III)-reduction. 16S rRNA profiles continuously changed over the course of enrichment, with ultimate dominance of unclassified members of the order Desulfuromonadales in all treatments. Microbial diversity decreased markedly over the course of incubation, with subtle differences between ferrihydrite and goethite amendments. These results suggest that Fe(III)-oxide mineralogy and availability of electron donors could have led to spatial separation of Fe(III)-reducing and methanogenic microbial communities in ferruginous marine sediments, potentially explaining the persistence of CH4as a greenhouse gas throughout the first half of Earth history.
Functional transcriptomics in diverse intestinal epithelial cell types reveals robust gut microbial sensitivity of microRNAs in intestinal stem cells
Authors: Peck Bailey C. E. , Mah Amanda T. , Pitman Wendy A. , Ding Shengli , Lund P. Kay , Sethupathy Praveen
Published: November 2016

Gut microbiota play an important role in regulating the development of the host immune system, metabolic rate, and at times, disease pathogenesis. The factors and mechanisms that mediate communication between microbiota and the intestinal epithelium are poorly understood. We provide novel evidence that microbiota may control intestinal epithelial stem cell (IESC) proliferation in part through microRNAs (miRNAs). We demonstrate that miRNA profiles differ dramatically across functionally distinct cell types of the mouse jejunal intestinal epithelium and that miRNAs respond to microbiota in a highly cell-type specific manner. Importantly, we also show that miRNAs in IESCs are more prominently regulated by microbiota compared to miRNAs in any other intestinal epithelial cell (IEC) subtype. We identify miR-375 as one miRNA that is significantly suppressed by the presence of microbiota in IESCs. Using a novel method to knockdown gene and miRNA expressionex vivoenteroids, we demonstrate that we can knockdown gene expression in Lgr5+IESCs. Furthermore, when we knockdown miR-375 in IESCs, we observe significantly increased proliferative capacity. Understanding the mechanisms by which microbiota regulate miRNA expression in IESCs and other IEC subtypes will elucidate a critical molecular network that controls intestinal homeostasis and, given the heightened interest in miRNA-based therapies, may offer novel therapeutic strategies in the treatment of gastrointestinal diseases associated with altered IESC function.
Structure-based alignment of human caspase recruitment domains provides a framework for understanding their function
Authors: Boyle Joseph P. , Monie Tom
Published: November 2016

Intracellular signalling is driven by protein-protein interactions. Members of the Death Domain superfamily mediate protein-protein interactions in both cell death and innate immune signalling pathways. They drive the formation of macromolecular complexes that act as a scaffold for protein recruitment and downstream signal transduction. Death Domain family members have low sequence identity, complicating their identification and predictions of their structure and function. We have taken all known human caspase recruitment domains (CARDs), a subfamily of the Death Domain superfamily, and generated a structure-guided sequence alignment. This alignment has enabled the identification of 14 positions that define the hydrophobic core and present a template for the identification of novel CARD sequences. We identify a conserved salt bridge in over half of all human CARDs and find a subset of CARDs likely to be regulated by tyrosine phosphorylation in their type I interface. Our alignment highlights that the CARDs of NLRC3 and NLRC5 are likely to be pseudodomains that have lost some of their original functionality. Together these studies demonstrate the benefits of structure-guided sequence alignments in understanding protein functionality.
A lottery simulation model for predicting cancer risk based on the strength and abundance of individual mutations
Authors: Wolfe Alexander J , Giangreco Adam
Published: November 2016

Models for predicting an individual’s risk of developing cancer are complicated by a lack of well-conserved mutations present in most types of disease. To address this challenge we developed a simple lottery simulation of cancer development based solely on the abundance and relative survival advantage of mutations present within individual stem or progenitor cells. In simulations requiring few mutations or that involve mutations exhibiting a strong survival advantage cancers develop in our simulation in a progressive manner amenable to oncogene-based risk prediction. In contrast, in simulations involving numerous mutations that lack a strong survival advantage, a stochastic process of neutral drift and punctuated equilibrium determines eventual tumour formation. In these situations, the development of cancer is largely attributable to the rate of mutational variability amongst progenitor cells rather than the identity and relative survival advantage of the mutations present at any single time point. These results suggest that measuring rates of stem cell mutational variability represents an important component of predicting an individual’s risk of developing cancer.
Functional constraints on replacing an essential gene with its ancient and modern homologs
Authors: Kacar Betül , Garmendia Eva , Tunçbağ Nurcan , Andersson Dan I. , Hughes Diarmaid
Published: November 2016

The complexity hypothesis posits that network connectivity and protein function are two important determinants of how a gene adapts to and functions in a foreign genome. Genes encoding proteins that carry out essential informational tasks in the cell, in particular where multiple interaction partners are involved, are less likely to be transferable to a foreign organism. Here we investigated the constraints on transfer of a gene encoding a highly conserved informational protein, translation elongation factor Tu (EF-Tu), by systematically replacing the endogenoustufAgene in theEscherichia coligenome with its extant and ancestral homologs. The extant homologs representedtufvariants from both near and distant homologous organisms. The ancestral homologs represented phylogenetically resurrectedtufsequences dating from 0.7 to 3.6 bya. Our results demonstrate that all of the foreigntufgenes are transferable to theE. coligenome, provided that an additional copy of the EF-Tu gene,tufB, remains present in theE. coligenome. However, when thetufBgene was removed, only the variants obtained from the γ-proteobacterial family (extant and ancestral), supported growth. This demonstrates the limited functional interchangability ofE. coli tufwith its homologs. Our data show a linear correlation between relative bacterial fitness and the evolutionary distance of the extanttufhomologs inserted into theE. coligenome. Our data and analysis also suggest that the functional conservation of protein activity, and its network interactivity, act to constrain the successful transfer of this essential gene into foreign bacteria.
biMM: Efficient estimation of genetic variances and covariances for cohorts with high-dimensional phenotype measurements
Authors: Pirinen Matti , Benner Christian , Marttinen Pekka , Järvelin Marjo-Riitta , Rivas Manuel A. , Ripatti Samuli
Published: November 2016

Genetic research utilizes a decomposition of trait variances and covariances into genetic and environmental parts. Our software package biMM is a computationally efficient implementation of a bivariate linear mixed model for settings where hundreds of traits have been measured on partially overlapping sets of individuals.

Availability

Implementation in R freely available atwww.iki.fi/mpirinen.
The type IVa pilus machinery is pre-installed during cell division
Authors: Carter Tyson , Buensuceso Ryan N.C. , Tammam Stephanie , Lamers Ryan P. , Harvey Hanjeong , Howell P. Lynne , Burrows Lori L.
Published: November 2016

Type IV pili (T4aP) are ubiquitous microbial appendages used for adherence, twitching motility, DNA uptake, and electron transfer. Many of these functions depend on dynamic assembly and disassembly of the pilus by a megadalton-sized, cell envelope-spanning protein complex located at the poles of rod-shaped bacteria. How the T4aP assembly complex becomes integrated into the cell envelope in the absence of dedicated peptidoglycan (PG) hydrolases is unknown. After ruling out potential involvement of housekeeping PG hydrolases in installation of the T4aP machinery inP. aeruginosa, we discovered that key components of inner (PilMNOP) and outer (PilQ) membrane subcomplexes are recruited to future sites of cell division. Mid-cell recruitment of a fluorescently tagged alignment subcomplex component, mCherry-PilO, depended on PilQ secretin monomers – specifically, their N-terminal PG-binding AMIN domains. PilP, which connects PilO to PilQ, was required for recruitment, while PilM, which is structurally similar to divisome component FtsA, was not. Recruitment preceded secretin oligomerization in the outer membrane, as loss of the PilQ pilotin, PilF, had no effect on localization. These results were confirmed in cells chemically blocked for cell division prior to outer membrane invagination. The hub protein FimV and a component of the Polar Organelle Coordinator complex – PocA – were independently required for mid-cell recruitment of PilO and PilQ. Together, these data reveal an integrated, energy-efficient strategy for the targeting and pre-installation – rather than retrofit – of the T4aP system into nascent poles, without the need for dedicated PG-remodelling enzymes.
SOFIA: an R package for enhancing genetic visualization with Circos
Authors: Diaz-Garcia Luis , Covarrubias-Pazaran Giovanny , Schlautman Brandon , Zalapa Juan
Published: November 2016

Visualization of data from any stage of genetic and genomic research is one of the most useful approaches for detecting potential errors, ensuring accuracy and reproducibility, and presentation of the resulting data. Currently software such as Circos, ClicO FS, and RCircos, among others, provide tools for plotting a variety of genetic data types in a concise manner for data exploration and presentation. However, each of the programs have one or more disadvantages that limit their usability in data exploration or construction of publication quality figures, such as inflexibility in formatting and configuration, reduced image quality, lack of potential for automation, or requirements of high-level computational expertise. Therefore, we developed the R package SOFIA, which leverages the capabilities of Circos by manipulating data, preparing configuration files, and running the Perl-native Circos directly from the R environment with minimal user intervention. The advantages of integrating both R and Circos into SOFIA are numerous. R is a very powerful, mid-level programming language widely used among the genetic and genomic research community, while Circos has proven to be a novel software for arranging genomic data to create aesthetical publication quality circular figures. Producing Circos figures in R with SOFIA is simple, requires minimal coding experience, even for complex figures that incorporate high-dimensional genetic information, and allows simultaneous analysis and visual exploration of genomic and genetic data in a single programming environment.
Overcoming evolved resistance to population-suppressing homing-based gene drives
Authors: Marshall John M. , Buchman Anna , Sánchez C. Héctor M. , Akbari Omar S.
Published: November 2016

The use of homing-based gene drive systems to modify or suppress wild populations of a given species has been proposed as a solution to a number of significant ecological and public health related problems, including the control of mosquito-borne diseases. The recent development of a CRISPR-Cas9-based homing system for the suppression ofAnopheles gambiae, the main African malaria vector, is encouraging for this approach; however, with current designs, the slow emergence of homing-resistant alleles is expected to result in suppressed populations rapidly rebounding, as homing-resistant alleles have a significant fitness advantage over functional, population-suppressing homing alleles. To explore this concern, we develop a mathematical model to estimate tolerable rates of homing-resistant allele generation to suppress a wild population of a given size. Our results suggest that, to achieve meaningful population suppression, tolerable rates of resistance allele generation are orders of magnitude smaller than those observed for current designs for CRISPR-Cas9-based homing systems. To remedy this, we propose a homing system architecture in which guide RNAs (gRNAs) are multiplexed, increasing the effective homing rate and decreasing the effective resistant allele generation rate. Modeling results suggest that the size of the population that can be suppressed increases exponentially with the number of multiplexed gRNAs and that, with six multiplexed gRNAs, a mosquito species could potentially be suppressed on a continental scale. We also demonstrate successful multiplexingin vivoinDrosophila melanogasterusing a ribozyme-gRNA-ribozyme (RGR) approach – a strategy that could readily be adapted to engineer stable, homing-based suppression drives in relevant organisms.
The dynamic landscape of fission yeast meiosis alternative-splice isoforms
Authors: Kuang Zheng , Boeke Jef D. , Canzar Stefan
Published: November 2016

Alternative splicing increases the diversity of transcriptomes and proteomes in metazoans. The extent to which alternative splicing is active and functional in unicellular organisms is less understood. Here, we exploit a single-molecule long-read sequencing technique and develop an open-source software program called SpliceHunter to characterize the transcriptome in the meiosis of fission yeast. We reveal 14,353 alternative splicing events in 17,669 novel isoforms at different stages of meiosis, including antisense and read-through transcripts. Intron retention is the major type of alternative splicing, followed by alternate “intron in exon.” Seven hundred seventy novel transcription units are detected; 53 of the predicted proteins show homology in other species and form theoretical stable structures. We report the complexity of alternative splicing along isoforms, including 683 intra-molecularly co-associated intron pairs. We compare the dynamics of novel isoforms based on the number of supporting full-length reads with those of annotated isoforms and explore the translational capacity and quality of novel isoforms. The evaluation of these factors indicates that the majority of novel isoforms are unlikely to be both condition-specific and translatable but consistent with the possibility of biologically functional novel isoforms. Moreover, the co-option of these unusual transcripts into newly born genes seems likely. Together, the results of this study highlight the diversity and dynamics at the isoform level in the sexual development of fission yeast.
Extending the single-crystal quartz pressure gauge up to hydrostatic pressure of 19 GPa
Authors: Scheidl Katharina S. , Kurnosov Alexander , Trots Dmytro M. , Boffa Ballaran Tiziana , Angel Ross J. , Miletich Ronald
Published: November 2016

In situ high-pressure diffraction experiments on single-crystal α-quartz under quasi-hydrostatic conditions up to 19 GPa were performed with diamond-anvil cells. Isotropic pressures were calibrated through the ruby-luminescence technique. A 4:1 methanol–ethanol mixture and the densified noble gases helium and neon were used as pressure media. The compression data revealed no significant influence of the pressure medium at room temperature on the high-pressure behavior of α-quartz. In order to describe its compressibility for use as a pressure standard, a fourth-order Birch–Murnaghan equation of state (EoS) with parameters K
T0 = 37.0 (3) GPa, K
T0′ = 6.7 (2) and K
T0′′ = −0.73 (8) GPa−1 was applied to fit the data set of 99 individual data points. The fit of the axial compressibilities yields M
T0 = 104.5 (8) GPa, M
T0′ = 13.7 (4), M
T0′′ = −1.04 (11) GPa−1 (a axis) and M
T0 = 141 (3) GPa, M
T0′ = 21 (2), M
T0′′ = 8.4 (6) GPa−1 (c axis), confirming the previously reported anisotropy. Assuming an estimated standard deviation of 0.0001% in the quartz volume, an uncertainty of 0.013 GPa can be expected using the new set of EoS parameters to determine the pressure.
Pushing the limits of crystallography
Authors: Wolny Janusz , Buganski Ireneusz , Kuczera Pawel , Strzalka Radoslaw
Published: November 2016

A very serious concern of scientists dealing with crystal structure refinement, including theoretical research, pertains to the characteristic bias in calculated versus measured diffraction intensities, observed particularly in the weak reflection regime. This bias is here attributed to corrective factors for phonons and, even more distinctly, phasons, and credible proof supporting this assumption is given. The lack of a consistent theory of phasons in quasicrystals significantly contributes to this characteristic bias. It is shown that the most commonly used exponential Debye–Waller factor for phasons fails in the case of quasicrystals, and a novel method of calculating the correction factor within a statistical approach is proposed. The results obtained for model quasiperiodic systems show that phasonic perturbations can be successfully described and refinement fits of high quality are achievable. The standard Debye–Waller factor for phonons works equally well for periodic and quasiperiodic crystals, and it is only in the last steps of a refinement that different correction functions need to be applied to improve the fit quality.
Crystal structure of diethylammonium aniline-4-sulfonate anilinium-4-sulfonate
Authors: Toure Assane , Diop Libasse , Diop Cheikh Abdoul Khadir , Oliver Allen G.
Published: November 2016

The title compound, C4H12N+·C6H6NO3S−·C6H7NO3S, consists of an ion pair and a zwitterionic neutral molecule. The cation adopts an extended conformation [C—C—N—C torsion angles = 177.1 (3) and −178.4 (3)°]. In the crystal, the components are linked by N—H...O and N—H...N hydrogen bonds, generating a three-dimensional network, which is consolidated by weak C—H...O interactions.