bluuebunny/crossref_metadata_2025 huggingface dataset:
Race, Ethnicity, Health Insurance, and Mortality in Older Survivors of Critical Illness
Authors: Baldwin Matthew R. , Sell Jessica L. , Heyden Nina , Javaid Azka , Berlin David A. , Gonzalez Wendy C. , Bach Peter B. , Maurer Mathew S. , Lovasi Gina S. , Lederer David J.
Published: March 2017

Objectives:

To determine whether minority race or ethnicity is associated with mortality and mediated by health insurance coverage among older (≥ 65 yr old) survivors of critical illness.

Design:

A retrospective cohort study.

Setting:

Two New York City academic medical centers.

Patients:

A total of 1,947 consecutive white (1,107), black (361), and Hispanic (479) older adults who had their first medical-ICU admission from 2006 through 2009 and survived to hospital discharge.

Interventions:

None.

Measurements and Main Results:

We obtained demographic, insurance, and clinical data from electronic health records, determined each patient’s neighborhood-level socioeconomic data from 2010 U.S. Census tract data, and determined death dates using the Social Security Death Index. Subjects had a mean (sd) age of 79 years (8.6 yr) and median (interquartile range) follow-up time of 1.6 years (0.4–3.0 yr). Blacks and Hispanics had similar mortality rates compared with whites (adjusted hazard ratio, 0.92; 95% CI, 0.76–1.11 and adjusted hazard ratio, 0.92; 95% CI, 0.76–1.12, respectively). Compared to those with commercial insurance and Medicare, higher mortality rates were observed for those with Medicare only (adjusted hazard ratio, 1.43; 95% CI, 1.03–1.98) and Medicaid (adjusted hazard ratio, 1.30; 95% CI, 1.10–1.52). Medicaid recipients who were the oldest ICU survivors (> 82 yr), survivors of mechanical ventilation, and discharged to skilled-care facilities had the highest mortality rates (p-for-interaction: 0.08, 0.03, and 0.17, respectively).

Conclusions:

Mortality after critical illness among older adults varies by insurance coverage but not by race or ethnicity. Those with federal or state insurance coverage only had higher mortality rates than those with additional commercial insurance.
Hormonal manipulation with finasteride or oral contraception does not influence incidence of renal cell carcinoma
Authors: Kabra Aashish , Gelfond Jonathan , Liss Michael A.
Published: March 2017

Androgens have been suspected to be involved in the initiation of renal cell carcinoma because of a two-fold increased risk in men compared with women. To investigate the role of self-reported finasteride or oral contraceptive use in the Prostate, Lung, Colorectal, and Ovarian (PCLO) to determine whether the androgen receptor reduces renal cancer development. We query the PCLO trial for predictor variables from the baseline questionnaire and follow-up questionnaires enquiring medication use, specifically the use of 5-α reductase inhibitors (dutasteride or finasteride) and oral contraceptive therapy. The primary outcome of this study was the incidence of renal cancer. Statistical analysis included Student’s t-test for continuous variables, χ
2, or Fisher’s exact tests for dichotomous or categorical variables, and multivariable analysis using Cox proportional hazards models. Eight percent (n=6117/73 694) of men in the PCLO trial reported the use of finasteride. 52 (10.6%) of the 492 men diagnosed with renal cancer had self-reported exposure to finasteride and this was not significant in univariable analysis (52/6169; 0.84% vs. 440/66 454; 0.67%, P=0.12) or multivariable main effects analysis (hazard ratio: 1.12; 95% confidence interval: 0.83–1.5; P=0.47). Approximately 54% of women (n=40 997/75 989) in the PCLO trial reported the use of oral contraceptives by questionnaire. 136 (52.1%) of the 261 women diagnosed with renal cancer had self-reported exposure to oral contraceptive therapy and this was not significant in univariable analysis (136/40 997; 0.33% vs. 125/34 992; 0.36%, P=0.36) or in multivariable main effects analysis (hazard ratio: 1.03; 95% confidence interval: 0.97–1.1; P=0.30). Self-reported use of finasteride or oral contraceptives is not associated with a reduced incidence of renal cancer.
Functionality of Patients 75 Years and Older Undergoing Mohs Micrographic Surgery: A Multicenter Study
Authors: Regula Christie G. , Alam Murad , Behshad Ramona , Glashofer Marc , Hanke C. William , Harmon Christopher , Johnson Ryan , Kent David , Lee Patrick , Lawrence Naomi
Published: March 2017

BACKGROUND

Mohs surgery is indisputably a highly effective treatment for nonmelanoma skin cancers. In the current health care environment, physicians are challenged to provide high quality, efficacious care in a manner that is mindful of the patient's general health and well-being. We have used a functional assessment to evaluate older patients who present for Mohs surgery.

OBJECTIVE

The purpose of this study is to categorize the functional status, using the Karnofsky Performance Status (KPS) Scale, of patients 75 years and older undergoing Mohs surgery of a nonmelanoma skin cancer and to identify distinguishing characteristics of lower functioning patients.

METHODS

Patients 75 years and older undergoing Mohs surgery for nonmelanoma skin cancer at 8 separate geographically diverse sites were included. Patient and tumor characteristics were recorded. Physicians scored subjects on the KPS scale and administered a questionnaire to categorize the symptoms and impact of their skin cancer.

RESULTS

A total of 291 subjects completed the study. The average KPS score was 90.1. 93.1% of our subjects had a KPS score of ≥70. Subjects with a KPS score <70 were more likely to be older with larger symptomatic tumors.

CONCLUSION

The vast majority of patients 75 years and older undergoing Mohs surgery are highly functioning. Lower functioning patients are older with larger symptomatic tumors that negatively impact their lives.
The Clinical and Histological Effect of a Low-Fluence Q-Switched 1,064-nm Neodymium:Yttrium-Aluminum-Garnet Laser for the Treatment of Melasma and Solar Lentigenes in Asians: Prospective, Randomized, and Split-Face Comparative Study
Authors: Kaminaka Chikako , Furukawa Fukumi , Yamamoto Yuki
Published: March 2017

BACKGROUND

The low-fluence Q-switched 1,064-nm neodymium:yttrium-aluminum-garnet laser (QSNYL) is popular for melasma treatment among Asians.

OBJECTIVE

This study was to evaluate the clinical and histological effects of the low-fluence QSNYL for treatment of melasma and solar lentigenes.

MATERIALS AND METHODS

In this randomized split-face clinical study, 22 patients with melasma or solar lentigo received low-fluence QSNYL weekly for 10 sessions on one cheek. The treatment efficacy was determined by Mexameter skin colorimetry, physician and patient assessment, and by evaluating histological changes.

RESULTS

The treated sides had statistically significant reductions in the melanin and erythema indices (EI); 50.0% of melasma and 62.5% of solar lentigo patients had >50% clearance after the final treatment. The increased EI, vascularity, and mast cell activity in patients with melasma and large-sized solar lentigo showed no improvement. The recurrence rates were 16.7% and 12.7% for melasma and solar lentigo, respectively. Postinflammatory hyperpigmentation developed in 1 patient, but no serious side effects were noted.

CONCLUSION

Low-fluence QSNYL is effective in treating melasma and small type solar lentigo in Asians. The authors' study also demonstrated that lesion thickness, vascularity, and mast cell activity can be used to predict the efficacy of the treatment of these lesions.
Therapeutic Drug Monitoring of Biopharmaceuticals May Benefit From Pharmacokinetic and Pharmacokinetic–Pharmacodynamic Modeling
Authors: Passot Christophe , Pouw Mieke F. , Mulleman Denis , Bejan-Angoulvant Theodora , Paintaud Gilles , Dreesen Erwin , Ternant David
Published: March 2017

Biopharmaceuticals, especially monoclonal antibodies, have been increasingly used to treat several chronic inflammatory diseases. Due to the complexity of their pharmacokinetics and concentration–effect relationship, therapeutic drug monitoring (TDM) has been used to optimize their dosing regimen. Up to date, several decisional algorithms have been developed to provide tools for monoclonal antibodies' therapeutic drug monitoring. However, these algorithms are unable to determine the individual optimal dosing scheme. The aim of this article is to deal with population pharmacokinetic (PK) and pharmacokinetic–pharmacodynamic (PK-PD) modeling. Allowing the quantification of the variability of the dose-concentration–response relationship, population pharmacokinetic–pharmacodynamic modeling may be a valuable tool to determine the optimal dosing scheme. Based on population modeling, Bayesian estimators may be developed to optimize dosing schemes for each patient using limited sampling strategies. These estimators may allow accurate dosing adjustment for each patient individually.
Drug Efficacy Monitoring in Pharmacotherapy of Multiple Sclerosis With Biological Agents
Authors: Caldano Marzia , Raoul William , Rispens Theo , Bertolotto Antonio
Published: March 2017

Multiple sclerosis is a heterogenous disease. Although several EMA-approved disease-modifying treatments including biopharmaceuticals are available, their efficacy is limited, and a certain percentage of patients are always nonresponsive. Drug efficacy monitoring is an important tool to identify these nonresponsive patients early on. Currently, detection of antidrug antibodies and quantification of biological activity are used as methods of efficacy monitoring for interferon beta and natalizumab therapies. For natalizumab and alemtuzumab treatments, drug level quantification could be an essential component of the overall disease management. Thus, utilization and development of strategies to determine treatment response are vital aspects of multiple sclerosis management given the tremendous clinical and economic promise of this tool.
Comparison of Plasma, Saliva, and Hair Levetiracetam Concentrations
Authors: Karaś-Ruszczyk Katarzyna , Kuczyńska Julita , Sienkiewicz-Jarosz Halina , Kurkowska-Jastrzębska Iwona , Bienkowski Przemyslaw , Restel Magdalena , Samochowiec Jerzy , Mierzejewski Pawel
Published: March 2017

Background:

Previous findings revealed high correlations between serum/plasma and saliva levetiracetam concentrations, indicating saliva as an alternative matrix for monitoring levetiracetam therapy. Levetiracetam concentration in the hair, which could reflect long-term drug exposure and patients' compliance, has not been systematically tested, as yet. The aim of this study was to determine the correlation between plasma, saliva, and hair levetiracetam concentrations in 47 patients with epilepsy.

Methods:

Plasma, saliva, and hair levetiracetam concentrations were measured by liquid chromatography–tandem mass spectrometry with positive ionization.

Results:

Levetiracetam saliva and plasma concentrations were highly correlated (r = 0.93). Plasma concentrations were not influenced by sex, age, and other concomitant antiepileptic drugs. Levetiracetam hair concentrations correlated with plasma concentrations (r = 0.36) but not daily dose (mg/kg). Drug hair concentrations were not influenced by hair color or treatment (dyed).

Conclusions:

The results tend to indicate that saliva may be a reliable alternative to plasma for monitoring levetiracetam concentrations. Levetiracetam can also be detected in human hair.
QUANTIFICATION OF RETINAL VESSEL TORTUOSITY IN DIABETIC RETINOPATHY USING OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY
Authors: Lee Hyungwoo , Lee Minsub , Chung Hyewon , Kim Hyung Chan
Published: March 2017

Purpose:

To investigate the association of vessel tortuosity with severity of diabetic retinopathy (DR) using optical coherence tomography angiography.

Methods:

We retrospectively analyzed 30 healthy eyes and 121 eyes of diabetic subjects with no DR, mild nonproliferative DR (NPDR), moderate to severe NPDR and proliferative DR (PDR). Binarized images were used to quantify the vessel tortuosity, vessel density, foveal avascular zone (FAZ) area, and FAZ acircularity. The vessels were divided vertically as superficial retinal layer and deep retinal layer, and horizontally as circular areas with 3 mm and 1.5 mm diameters. Analysis of variance was performed for multiple comparisons. Correlation analysis evaluated the association between the quantified parameters.

Results:

Compared with healthy eyes, vessel tortuosity increased as DR severity was more in NPDR, but decreased in PDR (P = 0.033). The decrease in vessel density and the increase in both FAZ area and FAZ acircularity were consistent, while DR approached PDR. Among all parameters, statistically significant difference between no DR and mild NPDR was observed only in vessel tortuosity, especially within the 1.5 mm area of superficial retinal layer (P = 0.011). Correlations of vessel tortuosity with FAZ area and acircularity were confined to the 3 mm and 1.5 mm areas of superficial retinal layer (r = −0.185, P = 0.023 for FAZ area; r = 0.268, P = 0.001 for FAZ acircularity), while vessel density strongly correlated with FAZ parameters in the superficial retinal layer and deep retinal layer.

Conclusion:

Vessel tortuosity increased as the stage of NPDR was more severe, but decreased in PDR. The vessel tortuosity determined using optical coherence tomography angiography might be a useful parameter indicating the progression to PDR, circumventing the risk from invasive conventional angiography.
Effects of Corneal Scars and Their Treatment With Rigid Contact Lenses on Quality of Vision
Authors: de Jong Bram , van der Meulen Ivanka J. E. , van Vliet Johannes M. J. , Lapid-Gortzak Ruth , Nieuwendaal Carla P. , van den Berg Thomas J. T. P.
Published: March 2017

Objectives:

To study the effects of corneal scars and the treatment of these scars with rigid gas-permeable (RGP) contact lenses on quality of vision including straylight. Visual effects were related to scar characteristics such as size and grade.

Methods:

Straylight and best-corrected visual acuity were measured in 23 patients with corneal scars during and after RGP contact lens wear. Contralateral eyes were used as controls, and age-normal values in case of bilateral scars. Straylight measurements were performed using the compensation comparison method of the Oculus C-Quant instrument.

Results:

Scarred eye straylight values were 1.53 log(s) without contact lens and 1.60 log(s) with contact lens (P=0.043). Healthy eyes without contact lens had a mean straylight value of 1.13 log(s), corresponding to age-normal values. Contact lens wear increased straylight in healthy eyes to 1.26 log(s) (P<0.001). Visual acuity improved from 0.66 logarithm of minimal angle of resolution (logMAR) to 0.19 logMAR with contact lens wear in eyes with a corneal scar (P<0.001).

Conclusions:

Corneal scars can have a strong effect on quality of vision by diminishing visual acuity and increasing straylight. The increase in straylight from corneal scars on its own can lead to a serious visual handicap. Contact lens treatment did not improve straylight, but showed a slight worsening. As the recovery of visual acuity with contact lens wear far exceeded straylight increase, contact lenses remain a clinically useful treatment option in most patients with corneal scars.
Mid-Term Follow-Up of Minimally Invasive Multivessel Coronary Artery Bypass Grafting
Authors: Rodriguez Maria Lorena , Lapierre Harry R. , Sohmer Benjamin , Glineur David , Ruel Marc
Published: March 2017

Objective

Minimally invasive coronary artery bypass grafting (MICS CABG) through a small left thoracotomy is a novel technique for surgical coronary revascularization, which is increasingly being adopted around the world. This study aimed to describe the characteristics and mid-term outcomes of a series of MICS CABG to identify areas for improvement.

Methods

A prospective longitudinal study was performed on the 306 MICS CABG patients operated on by a single surgeon from 2005 to 2015. Minimally invasive coronary artery bypass grafting used a small left thoracotomy to enable coronary revascularization with a similar configuration to an open sternotomy technique, with left internal thoracic artery harvesting, and hand-sewn proximal radial/saphenous and distal anastomoses, under direct visualization. We compared patients who were operated on during the first and second halves of the series to ascertain the impact of a learning curve on outcomes.

Results

The mean ± SD age was 62 ± 9 years, 87% were male, and 23% had three-vessel disease. Off-pump coronary artery bypass was performed in 80%, and the median number of grafts was 2 (range 1–4). Sternotomy conversion occurred in 3.3%, reoperation for bleeding in 2%, and unplanned, emergency CPB conversion in 1%. Superficial thoracotomy infection, atrial fibrillation, and left-sided pleural effusion requiring drainage were encountered in 2%, 1%, and 1%, respectively. There were no perioperative stroke, myocardial infarction, or death. At a mean ± SD follow-up of 2.8 ± 2.5 years, 97.4% of patients were free from major adverse cardiac and cerebrovascular events. Between the first and latter half of the series, there was a decrease in the rate of conversion to sternotomy (5.2%–1.3%, P = 0.05) and in the mid-term need for repeat revascularization (11% vs 2.6%, P = 0.03). Overall repeat revascularization rate was 2.5% per year. The intensive care unit and hospital lengths of stay (1.6 ± 1.5 vs 1.4 ± 0.9, P = 0.2, and 6.1 ± 2.6 vs 5.6 ± 1.8, P = 0.4) were not statistically different.

Conclusions

Minimally invasive coronary artery bypass grafting can be safely initiated as a minimally invasive, multivessel alternative to open surgical coronary revascularization, with excellent mid-term results. Learning phase effects were not observed with regard to overall procedural safety, but rather in terms of improved freedom from conversion to sternotomy and from repeat revascularization.
Development of the Irritable Bowel Syndrome Cognitive Affective Scale: a brief self-report measure for clinical and research settings
Authors: Ballou Sarah , Keefer Laurie
Published: March 2017

Objectives

Measures of cognitive-affective processes believed to underlie Irritable Bowel Syndrome (IBS) symptom expression are used widely in both clinical and research settings. When combined, these measures can be time-consuming and it is not clear whether they evaluate distinct or overlapping constructs. With this study, we seek to identify the most critical cognitive-affective components contributing toward the expression of IBS and to identify which items in these constructs might be streamlined into a single, brief self-report measure.

Patients and methods

This measure was developed according to Food and Drug Administration guidelines for patient-reported outcome development. First, authors consolidated existing cognitive-affective measures (visceral sensitivity, anxiety sensitivity, and pain catastrophization) into a single questionnaire. Second, a principal components factor analysis was carried out on the basis of responses from a sample of participants with IBS. Third, on the basis of the results of the factor analysis, items were reduced to the final brief self-report measure and preliminary validity/reliability analyses (Cronbach’s α, correlation with other related constructs) were carried out.

Results

An initial, 44-item measure was created. In all, 179 patients with ROME-III IBS completed an online survey. Principal component analysis and item reduction yielded a 15-item scale with three factors: pain catastrophization, visceral hypervigilance, and extraintestinal hypervigilance. The final three factors showed comparable internal consistencies (α>0.90), concurrent validity, and predictive validity compared with the original 44 items.

Conclusion

Although more research is warranted, the 15 items identified appear to provide an accurate measure of two important cognitive-affective constructs in the IBS population.
MicroRNAs and lipid metabolism
Authors: Aryal Binod , Singh Abhishek K. , Rotllan Noemi , Price Nathan , Fernández-Hernando Carlos
Published: March 2017

Purpose of review

Work over the past decade has identified the important role of microRNAs (miRNAS) in regulating lipoprotein metabolism and associated disorders including metabolic syndrome, obesity, and atherosclerosis. This review summarizes the most recent findings in the field, highlighting the contribution of miRNAs in controlling LDL-cholesterol (LDL-C) and HDL-cholesterol (HDL-C) metabolism.

Recent findings

A number of miRNAs have emerged as important regulators of lipid metabolism, including miR-122 and miR-33. Work over the past 2 years has identified additional functions of miR-33 including the regulation of macrophage activation and mitochondrial metabolism. Moreover, it has recently been shown that miR-33 regulates vascular homeostasis and cardiac adaptation in response to pressure overload. In addition to miR-33 and miR-122, recent GWAS have identified single-nucleotide polymorphisms in the proximity of miRNA genes associated with abnormal levels of circulating lipids in humans. Several of these miRNAs, such as miR-148a and miR-128-1, target important proteins that regulate cellular cholesterol metabolism, including the LDL receptor (LDLR) and the ATP-binding cassette A1 (ABCA1).

MicroRNAs have emerged as critical regulators of cholesterol metabolism and promising therapeutic targets for treating cardiometabolic disorders including atherosclerosis. Here, we discuss the recent findings in the field, highlighting the novel mechanisms by which miR-33 controls lipid metabolism and atherogenesis, and the identification of novel miRNAs that regulate LDL metabolism. Finally, we summarize the recent findings that identified miR-33 as an important noncoding RNA that controls cardiovascular homeostasis independent of its role in regulating lipid metabolism.
Pediatric intestinal failure-associated liver disease
Authors: Courtney Cathleen M. , Warner Brad W.
Published: March 2017

Purpose of review

The goal of this review is to provide updates on the definition, pathophysiology, treatment, and prevention of intestinal failure-associated liver disease (IFALD) that are relevant to care of pediatric patients.

Recent findings

Current literature emphasizes the multifactorial nature of IFALD. The pathogenesis is still largely unknown; however, molecular pathways have been identified. Key to these pathways are proinflammatory cytokines involved in hepatic inflammation and bile acids synthesis such as Toll-like receptor 4 and farnesoid X receptor, respectively. Research for prevention and treatment is aimed at alleviating risk factors associated with IFALD, principally those associated with parental nutrition. Multiple nutrients and amino acids are relevant to the development of IFALD, but lipid composition has been the primary focus. Lipid emulsions with a lower ratio of omega-6-to-omega-3 polyunsaturated fatty acids (FAs) appear to improve bile flow and decrease intrahepatic inflammation. Long-term consequences of these alternative lipid emulsions are yet to be determined.

IFALD remains the greatest contributor of mortality in patients with intestinal failure. Many factors contribute to its development, namely, alterations in the gut microbiome, sepsis, and lack of enteral intake. Novel combinations of lipid formulations are promising alternatives to purely soy-based formulas to reduce cholestasis.
High-flow nasal cannula therapy beyond the perinatal period
Authors: Lee Michael , Nagler Joshua
Published: March 2017

Purpose of review

High-flow nasal cannula (HFNC) is emerging as a means of oxygen delivery and respiratory support for a range of conditions outside the perinatal period. We aim to review the mechanisms of action and advantages of HFNC and to summarize current findings regarding clinical benefit in specific pediatric disease processes and in patients with significant respiratory distress.

Recent findings

Currently published studies outside the neonatal population demonstrate both safety and efficacy of this mode of respiratory support. Retrospective and prospective observational trials have shown improvements in oxygenation and respiratory distress, as well as reductions in the need for intubation in select patient populations. Randomized controlled trials are ongoing.

HFNC is emerging as a means of oxygen delivery and respiratory support across a wide range of pediatric conditions. Available data suggest that it is well tolerated by children and can have a favorable effect on clinical outcomes. Future research will better define optimal patient populations and best practices for use.
Pulmonary manifestations of rheumatologic diseases
Authors: Cidon Michal , Bansal Manvi , Hartl Dominik
Published: March 2017

Purpose of review

The present review intends to provide an overview of the diversity and complexity of pulmonary manifestations of rheumatologic diseases and gaps in knowledge to effectively manage them.

Recent findings

Diffuse lung disease in children with rheumatologic diseases represents a heterogeneous group of autoimmune disorders. Despite their significant morbidity and mortality, we have limited understanding about their pathogenesis. Here, we provide an overview of the pathophysiology and current management approach of these disorders, highlighting tools which assist with diagnosis, risk stratification and therapy. In this context, we address the need to develop a standardized approach to diagnose at-risk patients with rheumatologic disease and to predict their progression and the need to develop robust studies which evaluate the factors and interventions that influence pulmonary disease outcome.

Diffuse lung disease in children with rheumatologic diseases represents a heterogeneous group of severe autoimmune disorders. By adopting a collaborative research approach among multicenters to help diagnose, risk stratify, and understand disease progression, effective management decisions can be optimized to improve clinical outcome.
A Case of ALL Developing Posterior Reversible Encephalopathy Secondary to Hyponatremia
Authors: Eroglu Nilgun , Bahadir Aysenur , Erduran Erol
Published: March 2017

Posterior reversible encephalopathy syndrome (PRES), may be due to different causes. It may develop secondary to hypertension, renal decompensation, electrolyte imbalance, and chemotherapeutic drugs. We describe a case of acute lymphoblastic leukemia in which PRES developed secondary to hyponatremia despite being normotensive during receipt of chemotherapy. Magnetic resonance imaging findings were suggestive of PRES. Partial diffusion restriction was observed in lesions in the bilateral occipitoparietal regions and the cerebellum. The patient was treated with appropriate medications with the resolution of his stroke-like symptoms. No neurological deficit was observed and clinical condition improved. The patient continued with chemotherapy. Early diagnosis and treatment of this syndrome is important in terms of preventing neurological sequelae. Cases of secondary PRES developing for several etiological reasons have been reported in induction therapy, but no pediatric cases of PRES developing secondary to hyponatremia despite being normotensive while receiving chemotherapy in acute lymphoblastic leukemia have previously been reported.
Prevention of gastrointestinal side-effects in paediatric oncology: what are the guidelines?
Authors: Cheng Karis K.F.
Published: March 2017

Purpose of review

Gastrointestinal side-effects, particularly with regard to alimentary tract mucositis and chemotherapy-induced nausea and vomiting (CINV), continue to be frequent and debilitating symptomatic conditions among children and adolescents receiving cytotoxic cancer therapy. Further avenues of progress for mucositis and CINV prevention in paediatric oncology setting are warranted.

Recent findings

The current article reviews the major guidelines and literature published in 2016 pertaining to the prevention of mucositis and CINV. Considerable professional organizational efforts have been made to develop consensus-based or evidence-based guidelines that periodically update to define basic standards of mucositis and CINV prevention. There are a few published works in 2016 that may contribute to the emerging evidence on prevention of mucositis and CINV in the paediatric setting for future guideline updates.

The concomitant use of 5-HT3 receptor antagonist and dexamethasone are effective to prevent acute and delayed CINV in children who are to receive highly or moderately emetogenic chemotherapy. Optimal control of acute and delayed CINV can prevent anticipatory CINV. Oral care protocols would be beneficial to prevent mucositis in children across all cancer treatment modalities. Cryotherapy or low-level light therapy may be applied to cooperative children undergoing chemotherapy or haematological stem cell transplant conditioning regimens with a high rate of mucositis.
Towards the complete proteinaceous regulome of Acinetobacter baumannii
Authors: Casella Leila G , Weiss Andy , Pérez-Rueda Ernesto , Antonio Ibarra J , Shaw Lindsey N
Published: March 2017

The emergence of Acinetobacter baumannii strains, with broad multidrug-resistance phenotypes and novel virulence factors unique to hypervirulent strains, presents a major threat to human health worldwide. Although a number of studies have described virulence-affecting entities for this organism, very few have identified regulatory elements controlling their expression. Previously, our group has documented the global identification and curation of regulatory RNAs in A. baumannii. As such, in the present study, we detail an extension of this work, the performance of an extensive bioinformatic analysis to identify regulatory proteins in the recently annotated genome of the highly virulent AB5075 strain. In so doing, 243 transcription factors, 14 two-component systems (TCSs), 2 orphan response regulators, 1 hybrid TCS and 5 σ factors were found. A comparison of these elements between AB5075 and other clinical isolates, as well as a laboratory strain, led to the identification of several conserved regulatory elements, whilst at the same time uncovering regulators unique to hypervirulent strains. Lastly, by comparing regulatory elements compiled in this study to genes shown to be essential for AB5075 infection, we were able to highlight elements with a specific importance for pathogenic behaviour. Collectively, our work offers a unique insight into the regulatory network of A. baumannii strains, and provides insight into the evolution of hypervirulent lineages.
UBiT2: a client-side web-application for gene expression data analysis
Authors: Fan Jean , Fan David , Slowikowski Kamil , Gehlenborg Nils , Kharchenko Peter
Published: March 2017

We present a purely client-side web-application, UBiT2 (User-friendly BioInformatics Tools), that provides installation-free, offline alignment, analysis, and visualization of RNA-sequencing as well as qPCR data. Analysis modules were designed with single cell transcriptomic analysis in mind. Using just a browser, users can perform standard analyses such as quality control, filtering, hierarchical clustering, principal component analysis, differential expression analysis, gene set enrichment testing, and more, all with interactive visualizations and exportable publication-quality figures. We apply UBiT2 to recapitulate findings from single cell RNA-seq and Fluidigm Biomark
TM
multiplex RT-qPCR gene expression datasets. UBiT2 is available at http://pklab.med.harvard.edu/jean/ubit2/index.html with open-source code available at https://github.com/JEFworks/ubit2.
Thermal decomposition of the amino acids glycine, cysteine, aspartic acid, asparagine, glutamic acid, glutamine, arginine and histidine
Authors: Weiss Ingrid M. , Muth Christina , Drumm Robert , Kirchner Helmut O.K.
Published: March 2017

Calorimetry, thermogravimetry and mass spectrometry were used to follow the thermal decomposition of the eight amino acids G, C, D, N, E, Q, R and H between 185°C and 280°C. Endothermic heats of decomposition between 72 and 151 kJ/mol are needed to form 12 to 70%volatile products. This process is neither melting nor sublimation. With exception of cysteine they emit mainly H2O, some NH3 and no CO2. Cysteine produces CO2 and little else. The reactions are described by polynomials, AA ^ a (NH3) + b (H2O) + c (CO2) + d (H2S) + e (residue), with integer or half integer coefficients. The solid monomolecular residues are rich in peptide bonds.
Estimation of genomic prediction accuracy from reference populations with varying degrees of relationship
Authors: Hong Lee S. , Clark Sam , van der Werf Julius H.J.
Published: March 2017

Genomic prediction is emerging in a wide range of fields including animal and plant breeding, risk prediction in human precision medicine and forensic. It is desirable to establish a theoretical framework for genomic prediction accuracy when the reference data consists of information sources with varying degrees of relationship to the target individuals. A reference set can contain both close and distant relatives as well as ‘unrelated’ individuals from the wider population in the genomic prediction. The various sources of information were modeled as different populations with different effective population sizes (Ne). Both the effective number of chromosome segments (Me) andNeare considered to be a function of the data used for prediction. We validate our theory with analyses of simulated as well as real data, and illustrate that the variation in genomic relationships with the target is a predictor of the information content of the reference set. With a similar amount of data available for each source, we show that close relatives can have a substantially larger effect on genomic prediction accuracy than lesser related individuals. We also illustrate that when prediction relies on closer relatives, there is less improvement in prediction accuracy with an increase in training data or marker panel density. We release software that can estimate the expected prediction accuracy and power when combining different reference sources with various degrees of relationship to the target, which is useful when planning genomic prediction (before or after collecting data) in animal, plant and human genetics.
Toxicity of chlordane at early developmental stage of zebrafish
Authors: Xiong Jingxuan
Published: March 2017

Chlordane is highly toxic organochlorine pesticides that have been widely used throughout the world for decades and posing adverse effects on the environment. Contents detected in tissue and blood samples have resulted in a raising concern for their potential effects on wildlife and humans. In this study, we investigate the potential effect of chlordane on the development of zebrafish embryos. Zebrafish larvae were treated with different concentrations (0, 25, 50, 100, 200 ng/L) of chlordane from 12 hours postfertilization (hpf). Different early stage parameters were observed at 1, 2, 3 and 4 day post-fertilization (dpf). Chlordane-exposed zebrafish larvae appeared significant lower survival rate, developmental and hatching time delay and decreased embryo productivity. The heartbeat rate and blood flow were decreased in a dose dependent manner. These results suggested that exposure to real life of chlordane led to direct morphological and phenotypic changes and effects systems related to development and reproduction even in short-term manner.
Light Sheet Theta Microscopy for High-resolution Quantitative Imaging of Large Biological Systems
Authors: Migliori Bianca , Datta Malika S. , Dupre Christophe , Apak Mehmet C. , Asano Shoh , Gao Ruixuan , Boyden Edward S. , Hermanson Ola , Yuste Rafael , Tomer Raju
Published: March 2017

Advances in tissue clearing and molecular labelling methods are enabling unprecedented optical access to large intact biological systems. These advances fuel the need for high-speed microscopy approaches to image large samples quantitatively and at high resolution. While Light Sheet Microscopy (LSM), with its high planar imaging speed and low photo-bleaching, can be effective, scaling up to larger imaging volumes has been hindered by the use of orthogonal light-sheet illumination. To address this fundamental limitation, we have developed Light Sheet Theta Microscopy (LSTM), which uniformly illuminates samples from same side as the detection objective, thereby eliminating limits on lateral dimensions without sacrificing imaging resolution, depth and speed. We present detailed characterization of LSTM, and show that this approach achieves rapid high-resolution imaging of large intact samples with superior uniform high-resolution than LSM. LSTM is a significant step in high-resolution quantitative mapping of structure and function of large intact biological systems.
Protein identification with a nanopore and a binary alphabet
Authors: Sampath G.
Published: March 2017

Protein sequences are recoded with a binary alphabet obtained by dividing the 20 amino acids into two subsets based on volume. A protein is identified from subsequences by database search. Computations on theHelicobacter pyloriproteome show that over 93% of binary subsequences of length 20 are correct at a confidence level exceeding 90%. Over 98% of the proteins can be identified, most have multiple identifiers so the false detection rate is low. Binary sequences of unbroken protein molecules can be obtained with a nanopore from current blockade levels proportional to residue volume; only two levels, rather than 20, need be measured to determine a residue’s subset. This procedure can be translated into practice with a sub-nanopore that can measure residue volumes with ~0.07 nm3resolution as shown in a recent publication. The high detector bandwidth required by the high speed of a translocating molecule can be reduced more than tenfold with an averaging technique, the resulting decrease in the identification rate is only 10%. Averaging also mitigates the homopolymer problem due to identical successive blockade levels. The proposed method is a proteolysis-free single-molecule method that can identify arbitrary proteins in a proteome rather than specific ones. This approach to protein identification also works if residue mass is used instead of mass; again over 98% of the proteins are identified by binary subsequences of length 20. The possibility of using this in mass spectrometry studies of proteins, in particular those with post-translational modifications, is under investigation.
Cytosolic ribosomes on the surface of mitochondria
Authors: Gold Vicki A. M. , Chroscicki Piotr , Bragoszewski Piotr , Chacinska Agnieszka
Published: March 2017

By electron cryo-tomography and subtomogram averaging, translation-arrested ribosomes were used to depict the clustered organisation of the TOM complex on the surface of mitochondria, corroborating earlier reports of localized translation. Ribosomes were shown to interact specifically with the TOM complex and nascent chain binding was crucial for ribosome recruitment and stabilization. Ribosomes were bound to the membrane in discrete clusters, often in the vicinity of the crista junctions. This interaction highlights how protein synthesis may be coupled with transport, and the importance of spatial organization for efficient mitochondrial protein import.
The cross-frequency mediation mechanism of intracortical information transactions
Authors: Pascual-Marqui RD , Faber P , Ikeda S , Ishii R , Kinoshita T , Kitaura Y , Kochi K , Milz P , Nishida K , Yoshimura M
Published: March 2017

1. Abstract

In a seminal paper by von Stein and Sarnthein (2000), it was hypothesized that “bottom-up” information processing of “content” elicits local, high frequency (beta-gamma) oscillations, whereas “top-down” processing is “contextual”, characterized by large scale integration spanning distant cortical regions, and implemented by slower frequency (theta-alpha) oscillations. This corresponds to a mechanism of cortical information transactions, wheresynchronization of beta-gamma oscillations between distant cortical regions ismediatedby widespread theta-alpha oscillations. It is the aim of this paper to express this hypothesis quantitatively, in terms of a model that will allow testing this type of information transaction mechanism. The basic methodology used here corresponds to statistical mediation analysis, originally developed by (Baron and Kenny 1986). We generalize the classical mediator model to the case of multivariate complex-valued data, consisting of the discrete Fourier transform coefficients of signals of electric neuronal activity, at different frequencies, and at different cortical locations. The “mediation effect” is quantified here in a novel way, as the product of “dual frequency RV-coupling coefficients”, that were introduced in (Pascual-Marqui et al 2016,http://arxiv.org/abs/1603.05343). Relevant statistical procedures are presented for testing the cross-frequency mediation mechanism in general, and in particular for testing the von Stein & Sarnthein hypothesis.
The readability of scientific texts is decreasing over time
Authors: Plavén-Sigray Pontus , Matheson Granville James , Schiffler Björn Christian , Thompson William Hedley
Published: March 2017

Clarity and accuracy of reporting are fundamental to the scientific process. The understandability of written language can be estimated using readability formulae. Here, in a corpus consisting of 707 452 scientific abstracts published between 1881 and 2015 from 122 influential biomedical journals, we show that the readability of science is steadily decreasing. Further, we demonstrate that this trend is indicative of a growing usage of general scientific jargon. These results are concerning for scientists and for the wider public, as they impact both the reproducibility and accessibility of research findings.
Marine fish intestine responds to ocean acidification producing more carbonate aggregates
Authors: Gregório Sílvia F. , Ruiz-Jarabo Ignacio , Carvalho Edison M , Fuentes Juan
Published: March 2017

Marine fish contribute to the carbon cycle by producing mineralized intestinal aggregates generated as by-products of their osmoregulation. Here we aimed at characterizing the control of intestinal aggregate production in the gilthead sea bream in response to near future increases of environmental CO2. Our results demonstrate that hypercapnia (800 and 1200 μatm CO2) elicits higher intestine epithelial HCO3−secretion and the subsequent parallel increase of intestinal aggregate production when compared to present values (400 μatm CO2). Intestinal gene expression analysis revealed the up-regulation of crucial transport mechanisms involved not only in the intestinal secretion cascade (Slc4a4, Slc26a3 and Slc26a6) of sea bream, but also in other mechanisms involved in intestinal ion uptake linked to water absorption such asNKCC2and theAquaporin 1b.These results highlight the important role of fish in the marine carbon cycle, and their potential growing impact of intestinal biomineralization processes in the scenario of ocean acidification.
Inflammatory Breast Cancer: a model for investigating cluster-based dissemination
Authors: Jolly Mohit Kumar , Boareto Marcelo , Debeb Bisrat G , Aceto Nicola , Farach-Carson Mary C , Woodward Wendy A , Levine Herbert
Published: March 2017

Metastases claim more than 90% of cancer-related patient deaths and are usually seeded by a subset of circulating tumor cells (CTCs) shed off from the primary tumor. In circulation, CTCs are found both as single cells and as clusters of cells. The clusters of CTCs, although many fewer in number, possess much higher metastatic potential as compared to that of individual CTCs. In this review, we highlight recent insights into molecular mechanisms that can enable the formation of these clusters - (a) hybrid epithelial/mesenchymal (E/M) phenotype of cells that couples their ability to migrate and adhere, and (b) intercellular communication that can spatially coordinate the cluster formation and provide survival signals to cancer cells. Building upon these molecular mechanisms, we also offer a possible mechanistic understanding of why clusters are endowed with a higher metastatic potential. Finally, we discuss the highly aggressive Inflammatory Breast Cancer (IBC) as an example of a carcinoma that can metastasize via clusters and corroborates the proposed molecular mechanisms.
The role of coherence in bacterial communication
Authors: Majumdar Sarangam , Roy Sisir
Published: March 2017

Bacteria within biofilms can coordinate their behavior through distinct from of communication mechanism1. The well-established cell - to - cell signaling process in bacteria is known as quorum sensing through chemical signaling molecules2-5. Recently, another cell- to - cell communication process based on ion channel mediated electrical signaling6has also been observed. In this article, we propose a novel approach to explain the role of coherence and phase synchronization in the cell – to – cell bacterial communication. The observable long – range coherent electrical signaling is species independent and it is caused by membrane – potential - dependent modulation of tumbling frequency7-9. Moreover, noise can play a constructive role in enhancing the synchronization of chaotic bacterial communication systems and noise associated with the opening and closing the gate of ion channel induce small kinetic viscosity that make a wave-like pattern in concentration profile of quorum sensing.
Modeling noise mechanisms in neuronal synaptic transmission
Authors: Singh Abhyudai
Published: March 2017

In the nervous system, communication occurs via synaptic transmission where signaling molecules (neurotransmitters) are released by the presynaptic neuron, and they influence electrical activity of another neuron (postsynaptic neuron). The inherent probabilistic release of neurotransmitters is a significant source of noise that critically impacts the timing of spikes (action potential) in the postsynaptic neuron. We develop a stochastic model that incorporates noise mechanisms in synaptic transmission, such as, random docking of neurotransmitter-filled vesicle to a finite number of docking sites, with each site having a probability of vesicle release upon arrival of an action potential. This random, burst-like release of neurotransmitters serves as an input to an integrate-and-fire model, where spikes in the postsynaptic neuron are triggered when its membrane potential reaches a critical threshold for the first time. We derive novel analytical results for the probability distribution function of spike timing, and systematically investigate how underlying model parameters and noise processes regulate variability in the inter-spike times. Interestingly, in some parameter regimes, independent arrivals of action potentials in the presynaptic neuron generate strong dependencies in the spike timing of the postsynaptic neuron. Finally, we argue that probabilistic release of neurotransmitters is not only a source of disturbance, but plays a beneficial role in synaptic information processing.