bluuebunny/crossref_metadata_2025 huggingface dataset:
Proximity-enhanced SuFEx chemical cross-linker for specific and multitargeting cross-linking mass spectrometry
Authors: Yang Bing , Wu Haifan , Schnier Paul D. , Liu Yansheng , Liu Jun , Wang Nanxi , DeGrado William F. , Wang Lei
Published: October 2018

Significance

Chemical cross-linking mass spectrometry is a powerful method to identify protein interaction partners. The cross-links also provide approximate interresidue distances, which can help model the structures of complexes. However, current cross-linking reagents react with only a limited set of amino acid residues and their very high reactivity can induce cross-links between sites that are distant in the native state of the interrogated proteins. We therefore developed a “plant-and-cast” strategy, in which a heterobifunctional cross-linker is “planted” onto surface Lys residues using a highly reactive succinimide ester. The half-reacted cross-linker then “casts” a much less reactive sulfonyl fluoride across the proximal surface resulting in cross-links to neighboring Ser, Thr, Tyr, His, or Lys sidechains in a proximity-enhanced reaction.
Relation between blood pressure and pulse wave velocity for human arteries
Authors: Ma Yinji , Choi Jungil , Hourlier-Fargette Aurélie , Xue Yeguang , Chung Ha Uk , Lee Jong Yoon , Wang Xiufeng , Xie Zhaoqian , Kang Daeshik , Wang Heling , Han Seungyong , Kang Seung-Kyun , Kang Yisak , Yu Xinge , Slepian Marvin J. , Raj Milan S. , Model Jeffrey B. , Feng Xue , Ghaffari Roozbeh , Rogers John A. , Huang Yonggang
Published: October 2018

Significance

Continuous, cuffless, and noninvasive blood pressure monitoring by measuring the pulse wave velocity is generally considered to be a promising technique for noninvasive measurements. Previously reported relations between blood pressure and pulse wave velocity relation involve unrealistic assumptions that do not hold for human arteries, and also rely on empirical expressions without any theoretical basis. Here, an analytical model without such assumptions or empirical expressions is established to yield a relation between blood pressure and pulse wave velocity that has general utility for future work in continuous, cuffless, and noninvasive blood pressure monitoring.
High temperature wear performance of Ti–6.5Al–3.5Mo–1.5Zr–0.3Si alloy subjected to laser shock peening
Authors: Ren Xudong , Tong Zhaopeng , Zhou Wangfan , Chen Lan , Ren Yunpeng , Dai Fengze , Ye Yunxia , Adu-Gyamfi Samuel , Yang Jinde , Li Lin
Published: October 2018

This paper investigates the influence of laser shock peening (LSP) parameters on surface integrities and high temperature wear performances of Ti–6.5Al–3.5Mo–1.5Zr–0.3Si alloy. Surface integrities include surface roughness, residual stress and micro-hardness are measured. High temperature wear performance of TC11 alloy with and without LSP are investigated. The results indicate that multiple LSP impacts can improve surface micro-hardness and induce compressive residual stress in the surface layer. Moreover, the friction coefficient and wear rate of TC11 alloy significantly decrease after LSP with optimised parameters. The improved wear performance is ascribed to the low surface roughness, higher surface micro-hardness and compressive residual stress induced by multiple LSP impacts in the surface layer.
mRNP architecture in translating and stress conditions reveals an ordered pathway of mRNP compaction
Authors: Khong Anthony , Parker Roy
Published: October 2018

Stress granules (SGs) are transient membraneless organelles of nontranslating mRNA–protein complexes (mRNPs) that form during stress. In this study, we used multiple single-molecule FISH probes for particular mRNAs to examine their SG recruitment and spatial organization. Ribosome runoff is required for SG entry, as long open reading frame (ORF) mRNAs are delayed in SG accumulation, indicating that the SG transcriptome changes over time. Moreover, mRNAs are ∼20× compacted from an expected linear length when translating and compact ∼2-fold further in a stepwise manner beginning at the 5′ end during ribosome runoff. Surprisingly, the 5′ and 3′ ends of the examined mRNAs were separated when translating, but in nontranslating conditions the ends of long ORF mRNAs become close, suggesting that the closed-loop model of mRNPs preferentially forms on nontranslating mRNAs. Compaction of ribosome-free mRNAs is ATP independent, consistent with compaction occurring through RNA structure formation. These results suggest that translation inhibition triggers an mRNP reorganization that brings ends closer, which has implications for the regulation of mRNA stability and translation by 3′ UTR elements and the poly(A) tail.
The S6 gate in regulatory Kv6 subunits restricts heteromeric K+ channel stoichiometry
Authors: Pisupati Aditya , Mickolajczyk Keith J. , Horton William , van Rossum Damian B. , Anishkin Andriy , Chintapalli Sree V. , Li Xiaofan , Chu-Luo Jose , Busey Gregory , Hancock William O. , Jegla Timothy
Published: October 2018

The Shaker-like family of voltage-gated K+ channels comprises four functionally independent gene subfamilies, Shaker (Kv1), Shab (Kv2), Shaw (Kv3), and Shal (Kv4), each of which regulates distinct aspects of neuronal excitability. Subfamily-specific assembly of tetrameric channels is mediated by the N-terminal T1 domain and segregates Kv1–4, allowing multiple channel types to function independently in the same cell. Typical Shaker-like Kv subunits can form functional channels as homotetramers, but a group of mammalian Kv2-related genes (Kv5.1, Kv6s, Kv8s, and Kv9s) encodes subunits that have a “silent” or “regulatory” phenotype characterized by T1 self-incompatibility. These channels are unable to form homotetramers, but instead heteromerize with Kv2.1 or Kv2.2 to diversify the functional properties of these delayed rectifiers. While T1 self-incompatibility predicts that these heterotetramers could contain up to two regulatory (R) subunits, experiments show a predominance of 3:1R stoichiometry in which heteromeric channels contain a single regulatory subunit. Substitution of the self-compatible Kv2.1 T1 domain into the regulatory subunit Kv6.4 does not alter the stoichiometry of Kv2.1:Kv6.4 heteromers. Here, to identify other channel structures that might be responsible for favoring the 3:1R stoichiometry, we compare the sequences of mammalian regulatory subunits to independently evolved regulatory subunits from cnidarians. The most widespread feature of regulatory subunits is the presence of atypical substitutions in the highly conserved consensus sequence of the intracellular S6 activation gate of the pore. We show that two amino acid substitutions in the S6 gate of the regulatory subunit Kv6.4 restrict the functional stoichiometry of Kv2.1:Kv6.4 to 3:1R by limiting the formation and function of 2:2R heteromers. We propose a two-step model for the evolution of the asymmetric 3:1R stoichiometry, which begins with evolution of self-incompatibility to establish the regulatory phenotype, followed by drift of the activation gate consensus sequence under relaxed selection to limit stoichiometry to 3:1R.
Identification of the Optimal Recipient Layer for Transplanted Fat: A Prospective Study on Breast Lipoaugmentation
Authors: Guo Xiaoshuang , Mu Dali , Xing Wenshan , Qu Yaping , Luan Jie
Published: October 2018

Background

Fat grafting has become a popular procedure in aesthetic and reconstructive surgeries due to its safety, minimal invasiveness, and favorable visual outcomes, although the volume retention rate is unpredictable.

Objectives

A prospective clinical study on lipoaugmentation of the breast was conducted to compare fat retention rates in the pectoralis muscle and the periglandular area.

Methods

This prospective study included 20 breasts from 11 patients who underwent primary lipoaugmentation. Volume retention rate and percentage augmentation among different recipient layers, as well as complications and patient satisfaction, were evaluated. Magnetic resonance imaging was performed preoperatively and at 1 day and 3 months postoperatively. Complications were recorded, and patient satisfaction was appraised through the use of the Breast-Q questionnaire.

Results

Breasts were injected with 207 ± 29 mL of fat, achieving overall volume retention rates of 56.63% ± 16.40%. The overall augmentation was 21.53% ± 10.27%. Volume retention rate was significantly higher (59.00% ± 13.84%) in the periglandular area than in the pectoralis muscle (47.21% ± 22.41%) (P = 0.04). Augmentation was significantly higher (32.13% ± 12.96%) in the periglandular area than in the pectoralis muscle (4.95% ± 4.23%) (P = 0.00). Pain and numbness were the only reported complications. The Breast-Q score increased significantly for the measures “satisfaction with breasts,” “psychosocial well-being,” and “sexual well-being.”

Conclusions

Fat transfer is a safe and acceptable method for aesthetic and reconstructive breast surgery. The periglandular area was a better recipient site than muscle for transferred fat.

Level of Evidence: 4
Integrative cancer patient stratification via subspace merging
Authors: Ding Hao , Sharpnack Michael , Wang Chao , Huang Kun , Machiraju Raghu
Published: October 2018

Motivation

Technologies that generate high-throughput omics data are flourishing, creating enormous, publicly available repositories of multi-omics data. As many data repositories continue to grow, there is an urgent need for computational methods that can leverage these data to create comprehensive clusters of patients with a given disease.

Results

Our proposed approach creates a patient-to-patient similarity graph for each data type as an intermediate representation of each omics data type and merges the graphs through subspace analysis on a Grassmann manifold. We hypothesize that this approach generates more informative clusters by preserving the complementary information from each level of omics data. We applied our approach to The Cancer Genome Atlas (TCGA) breast cancer dataset and show that by integrating gene expression, microRNA and DNA methylation data, our proposed method can produce clinically useful subtypes of breast cancer. We then investigate the molecular characteristics underlying these subtypes. We discover a highly expressed cluster of genes on chromosome 19p13 that strongly correlates with survival in TCGA breast cancer patients and validate these results in three additional breast cancer datasets. We also compare our approach with previous integrative clustering approaches and obtain comparable or superior results.

Availability and implementation

https://github.com/michaelsharpnack/GrassmannCluster

Supplementary information

Supplementary data are available at Bioinformatics online.
farPPI: a webserver for accurate prediction of protein-ligand binding structures for small-molecule PPI inhibitors by MM/PB(GB)SA methods
Authors: Wang Zhe , Wang Xuwen , Li Youyong , Lei Tailong , Wang Ercheng , Li Dan , Kang Yu , Zhu Feng , Hou Tingjun
Published: October 2018

Protein-protein interactions (PPIs) have been regarded as an attractive emerging class of therapeutic targets for the development of new treatments. Computational approaches, especially molecular docking, have been extensively employed to predict the binding structures of PPI-inhibitors or discover novel small molecule PPI inhibitors. However, due to the relatively ‘undruggable’ features of PPI interfaces, accurate predictions of the binding structures for ligands towards PPI targets are quite challenging for most docking algorithms. Here, we constructed a non-redundant pose ranking benchmark dataset for small-molecule PPI inhibitors, which contains 900 binding poses for 184 protein-ligand complexes. Then, we evaluated the performance of MM/PB(GB)SA approaches to identify the correct binding poses for PPI inhibitors, including two Prime MM/GBSA procedures from the Schrödinger suite and seven different MM/PB(GB)SA procedures from the Amber package. Our results showed that MM/PBSA outperformed the Glide SP scoring function (success rate of 58.6%) and MM/GBSA in most cases, especially the PB3 procedure which could achieve an overall success rate of ∼74%. Moreover, the GB6 procedure (success rate of 68.9%) performed much better than the other MM/GBSA procedures, highlighting the excellent potential of the GBNSR6 implicit solvation model for pose ranking. Finally, we developed the webserver of Fast Amber Rescoring for PPI Inhibitors (farPPI), which offers a freely available service to rescore the docking poses for PPI inhibitors by using the MM/PB(GB)SA methods.

Availability and implementation

farPPI web server is freely available at http://cadd.zju.edu.cn/farppi/.

Supplementary information

Supplementary data are available at Bioinformatics online.
Infectious Diseases Physicians: Improving and Protecting the Public’s Health: Why Equitable Compensation Is Critical
Authors: Zahn Matthew , Adalja Amesh A , Auwaerter Paul G , Edelson Paul J , Hansen Gail R , Hynes Noreen A , Jezek Amanda , MacArthur Rodger D , Manabe Yukari C , McGoodwin Colin , Duchin Jeffrey S
Published: October 2018

Infectious diseases (ID) physicians play a crucial role in public health in a variety of settings. Unfortunately, much of this work is undercompensated despite the proven efficacy of public health interventions such as hospital acquired infection prevention, antimicrobial stewardship, disease surveillance, and outbreak response. The lack of compensation makes it difficult to attract the best and the brightest to the field of ID, threatening the future of the ID workforce. Here, we examine compensation data for ID physicians compared to their value in population and public health settings and suggest policy recommendations to address the pay disparities that exist between cognitive and procedural specialties that prevent more medical students and residents from entering the field. All ID physicians should take an active role in promoting the value of the subspecialty to policymakers and influencers as well as trainees.
The Impact of a National Antimicrobial Stewardship Program on Antibiotic Prescribing in Primary Care: An Interrupted Time Series Analysis
Authors: Balinskaite Violeta , Johnson Alan P , Holmes Alison , Aylin Paul
Published: October 2018

Background

The Quality Premium was introduced in 2015 to financially reward local commissioners of healthcare in England for targeted reductions in antibiotic prescribing in primary care.

Methods

We used a national antibiotic prescribing dataset from April 2013 until February 2017 to examine the number of antibiotic items prescribed, the total number of antibiotic items prescribed per STAR-PU (specific therapeutic group age/sex-related prescribing units), the number of broad-spectrum antibiotic items prescribed, and broad-spectrum antibiotic items prescribed, expressed as a percentage of the total number of antibiotic items. To evaluate the impact of the Quality Premium on antibiotic prescribing, we used a segmented regression analysis of interrupted time series data.

Results

During the study period, over 140 million antibiotic items were prescribed in primary care. Following the introduction of the Quality Premium, antibiotic items prescribed decreased by 8.2%, representing 5933563 fewer antibiotic items prescribed during the 23 post-intervention months, as compared with the expected numbers based on the trend in the pre-intervention period. After adjusting for the age and sex distribution in the population, the segmented regression model also showed a significant relative decrease in antibiotic items prescribed per STAR-PU. A similar effect was found for broad-spectrum antibiotics (comprising 10.1% of total antibiotic prescribing), with an 18.9% reduction in prescribing.

Conclusions

This study shows that the introduction of financial incentives for local commissioners of healthcare to improve the quality of prescribing was associated with a significant reduction in both total and broad-spectrum antibiotic prescribing in primary care in England.
The Surface Quasi-geostrophic Equation With Random Diffusion
Authors: Buckmaster Tristan , Nahmod Andrea , Staffilani Gigliola , Widmayer Klaus
Published: October 2018

Consider the surface quasi-geostrophic equation with random diffusion, white in time. We show global existence and uniqueness in high probability for the associated Cauchy problem satisfying a Gevrey type bound. This article is inspired by a recent work of Glatt-Holtz and Vicol [16].
Immunotherapy-related adverse events (irAEs): extraction from FDA drug labels and comparative analysis
Authors: Wang QuanQiu , Xu Rong
Published: October 2018

Objectives

Immune checkpoint inhibitors (ICIs) have dramatically improved outcomes in cancer patients. However, ICIs are associated with significant immune-related adverse events (irAEs) and the underlying biological mechanisms are not well-understood. To ensure safe cancer treatment, research efforts are needed to comprehensively detect and understand irAEs.

Materials and methods

We manually extracted and standardized irAEs from The U.S Food and Drug Administration (FDA) drug labels for six FDA-approved ICIs. We compared irAE profile similarities among ICIs and 1507 FDA-approved non-ICI drugs. We investigated how irAEs have differential effects on human organs by classifying irAEs based on their targeted organ systems. Finally, we identified broad-spectrum (nontarget-specific) and narrow-spectrum (target-specific) irAEs.

Results

A total of 893 irAEs were extracted. 31.4% irAEs were shared among ICIs as compared to the 8.0% between ICIs and non-ICI drugs. irAEs were resulted from both on- and off-target effects: irAE profiles were more similar for ICIs with same target than different targets, demonstrating the on-target effects; irAE profile similarity for ICIs with the same target is less than 50%, demonstrating unknown off-target effects. ICIs significantly target many organ systems, including endocrine system (3.4-fold enrichment), metabolism (3.7-fold enrichment), immune system (3.6-fold enrichment), and autoimmune system (4.8-fold enrichment). We identified 21 broad-spectrum irAEs shared among all ICIs, 20 irAEs specific for PD-L1/PD-1 inhibition, and 28 irAEs specific for CTLA-4 inhibition.

Discussion and conclusion

Our study presents the first effort toward building a standardized database of irAEs. The extracted irAEs can serve as the gold standard for automatic irAE extractions from other data resources and set a foundation to understand biological mechanisms of irAEs.
Do Interviewers Moderate the Effect of Monetary Incentives on Response Rates in Household Interview Surveys?
Authors: Kibuchi Eliud , Sturgis Patrick , Durrant Gabriele B , Maslovskaya Olga
Published: October 2018

As citizens around the world become ever more reluctant to respond to survey interview requests, incentives are playing an increasingly important role in maintaining response rates. In face-to-face surveys, interviewers are the key conduit of information about the existence and level of any incentive offered and, therefore, potentially moderate the effectiveness with which an incentive translates nonproductive addresses into interviews. Yet, while the existing literature on the effects of incentives on response rates is substantial, little is currently known about the role of interviewers in determining whether or not incentives are effective. In this article, we apply multilevel models to three different face-to-face interview surveys from the United Kingdom, which vary in their sample designs and incentive levels, to assess whether some interviewers are more successful than others in using incentives to leverage cooperation. Additionally, we link the response outcome data to measures of interviewer characteristics to investigate whether interviewer variability on this dimension is systematically related to level of experience and demographic characteristics. Our results show significant and substantial variability between interviewers in the effectiveness of monetary incentives on the probability of cooperation across all three surveys. However, none of the interviewer characteristics considered are significantly associated with more or less successful interviewers.
Study Characteristics Influence the Efficacy of Substance Abuse Treatments: A Meta-analysis of Medications for Smoking Cessation
Authors: Klemperer Elias M , Hughes John R , Naud Shelly
Published: October 2018

Background

Understanding study characteristics’ influence on treatment efficacy could improve interpretation of trials’ outcomes. We examined study characteristics as predictors of outcomes in clinical trials of medications for tobacco use.

Methods

We obtained and analyzed data on 44 trials of nicotine gum, 37 trials of nicotine patch, 27 trials of varenicline, and 43 trials of bupropion from Cochrane reviews. We extracted and analyzed data for 15 study characteristics, odds ratios (ORs), and percent abstinent in control and medication conditions. We used general linear models to determine which study characteristics explained the variability among outcomes after controlling for medication characteristics.

Results

Study characteristics accounted for 12% of the variance in odds ratios among patch trials, 16% among gum trials, 16% among varenicline trials, and 34% among bupropion trials above and beyond medication characteristics. Patch and gum trials with industry funding had larger odds ratios than those without. Among patch trials, this appeared to be due to less abstinence in industry-funded trials’ control conditions. Bupropion trials published earlier had larger odds ratios, which appeared to be due to less abstinence in control conditions. The reason for study characteristics’ influence on varenicline trials was unclear.

Discussion

Study characteristics influenced the assessment of treatment efficacy above and beyond medication characteristics in smoking cessation trials. Our findings that study characteristics are associated with higher or lower efficacy does not suggest that the effect size under one versus another condition is the more valid outcome. Future studies are needed to determine which study characteristics reliably influence efficacy because this would help investigators and clinicians interpret trials.

Implications

Study characteristics influenced the estimates of treatment efficacy but individual characteristics’ influence on efficacy appeared to differ among different medications for smoking cessation. We encourage researchers to report study characteristics to improve interpretation of findings and systematic reviews, and to account for nontreatment-related variables to better estimate the efficacy of treatments.
Prevalence of Nonopioid and Opioid Prescriptions Among Commercially Insured Patients with Chronic Pain
Authors: Miller Gabrielle F , Guy Gery P , Zhang Kun , Mikosz Christina A , Xu Likang
Published: October 2018

Objective The increased use of opioids to treat chronic pain in the past 20 years has led to a drastic increase in opioid prescribing in the United States. The Centers for Disease Control and Prevention’s (CDC’s) Guideline for Prescribing Opioids for Chronic Pain recommends the use of nonopioid therapy as the preferred treatment for chronic pain. This study analyzes the prevalence of nonopioid prescribing among commercially insured patients with chronic pain.

Design Data from the 2014 IBM® MarketScan® databases representing claims for commercially insured patients were used. International Classification of Diseases, Ninth Revision, codes were used to identify patients with chronic pain. Nonopioid prescriptions included nonsteroidal anti-inflammatory drugs (NSAIDs), analgesics/antipyretics (e.g., acetaminophen), anticonvulsants, and antidepressant medications. The prevalence of nonopioid and opioid prescriptions was calculated by age, sex, insurance plan type, presence of a depressive or seizure disorder, and region.

Results In 2014, among patients with chronic pain, 16% filled only an opioid, 17% filled only a nonopioid prescription, and 28% filled both a nonopioid and an opioid. NSAIDs and antidepressants were the most commonly prescribed nonopioids among patients with chronic pain. Having prescriptions for only nonopioids was more common among patients aged 50–64 years and among female patients.

Conclusions This study provides a baseline snapshot of nonopioid prescriptions before the release of the CDC Guideline and can be used to examine the impact of the CDC Guideline and other evidence-based guidelines on nonopioid use among commercially insured patients with chronic pain.
Subgroups of quantum groups
Authors: Christodoulou Georgia
Published: October 2018

We investigate the notion of a subgroup of a quantum group. We suggest a general definition, which takes into account the work that has been done for quantum homogeneous spaces. We further restrict our attention to reductive subgroups, where some faithful flatness conditions apply. Furthermore, we proceed with a categorical approach to the problem of finding quantum subgroups. We translate all existing results into the language of module and monoidal categories and give another characterization of the notion of a quantum subgroup.
B cells in Sjögren’s syndrome: from pathophysiology to therapeutic target
Authors: Mielle Julie , Tison Alice , Cornec Divi , Le Pottier Laëtitia , Daien Claire , Pers Jacques-Olivier
Published: October 2018

Biological abnormalities associated with B lymphocytes are a hallmark of patients with primary Sjögren’s syndrome. Those patients present abnormal distribution of B lymphocytes in peripheral blood and B cells in exocrine glands. B cells produce auto-antibodies, cytokines and present antigens but can also suppressive functions. In this review, we will summarize current knowledge on B cells in primary Sjögren’s syndrome patients, demonstrate their critical role in the immunopathology of the disease and describe the past and current trials targeting B cells.
Punishment and reinforcement by opioid receptor agonists in a choice procedure in rats
Authors: Minervini Vanessa , Osteicoechea Daniela C. , Casalez Angelo , France Charles P.
Published: October 2018

Intravenous (i.v.) drug self-administration remains the ‘gold standard’ for assessing abuse potential of drugs. Failure of a drug to maintain self-administration might indicate merely the absence of positive-reinforcing effects but might also indicate presence of aversive effects. Sensitivity to aversive effects is thought to affect the initiation and maintenance of drug use as well as relapse. Choice procedures are used to study positive-reinforcing effects of drugs and to a much lesser extent to study punishing effects of drugs. Experiment 1 compared the μ-opioid receptor agonist remifentanil (0.001–0.01 mg/kg/infusion), the κ-opioid receptor agonist spiradoline (0.0056–0.056 mg/kg/infusion), and histamine (1.0 mg/kg/infusion) in rats choosing between a food pellet only and an i.v. infusion+a food pellet. To test whether a history with one punishing drug affects the punishing effects of a second drug, experiment 2 compared sensitivity with spiradoline in rats with and without a history of histamine punishment. All rats predominantly chose a pellet alone when histamine+a pellet was the alternative, and they predominantly chose remifentanil+a pellet over a pellet alone. In experiment 2, spiradoline was punishing in rats with a history of histamine punishment but not drug-naive rats. This food choice procedure is sensitive to reinforcing and punishing effects of different drugs in the same subjects, suggesting that the procedure is well-suited for studying drug mixtures (e.g. μ and κ agonists) and the impact of different physiological conditions (e.g. pain) on reinforcement and punishment.
Septic Cavernous Sinus Thrombosis Associated With Orbital Cellulitis: A Report of 6 Cases and Review of Literature
Authors: Branson Sara V. , McClintic Elysa , Yeatts R. Patrick
Published: October 2018

Purpose:

To describe risk factors, clinical parameters, treatment, and prognosis for patients with septic cavernous sinus thrombosis presenting with orbital cellulitis.

Methods:

Retrospective case series of 6 patients identified with septic cavernous sinus thrombosis and orbital cellulitis confirmed by magnetic resonance imaging at a tertiary care center from January 1980 to December 2016. Medical records were reviewed for demographics, risk factors, symptoms, etiology, radiographic diagnosis, complications, treatments, and outcomes. In addition, a literature review was performed from 2005 to 2018, and 119 cases of septic cavernous sinus thrombosis confirmed by imaging were included for aggregate comparison. This study adheres to the tenets of the Declaration of Helsinki, and institutional review board approval was obtained.

Results:

All 6 cases presented with headache, fever, ocular motility deficit, periorbital edema, and proptosis. The primary source of infection included sinusitis (n = 4) and bacteremia (n = 2). Identified microorganisms included methicillin resistant Staphylococcus aureus (n = 3) and Streptococcus anginosus (n = 1). All cases were treated with broad-spectrum intravenous antibiotics and anticoagulation, and one case underwent endoscopic sinus surgery. The mean time between initial presentation to diagnosis of cavernous sinus thrombosis was 2.8 days, and the average length of hospital admission was 21 days. The mortality rate was 0%, but 4 cases were discharged with neurological deficits including vision loss (n = 1) and ocular motility disturbance (n = 3). Literature review produced an additional 119 cases.

Conclusions:

Early diagnostic imaging with contrast-enhanced CT or MRI should be initiated in patients with risk factors and ocular symptoms concerning for cavernous sinus thrombosis. Treatment entails early administration of broad-spectrum intravenous antibiotics, anticoagulation, and surgical drainage when applicable.
Study on the Aging Dynamics of the Periorbital Region: From Observation to Knowledge of Physiopathology
Authors: De Biasio Fabrizio , Miotti Giovanni , Zingaretti Nicola , Castriotta Luigi , Parodi Pier Camillo
Published: October 2018

Purpose:

Several anatomical and physio-pathologic studies of eyelid region have allowed the creation of theories on facial tissues aging dynamics, which have not been clarified yet. We assessed the signs of aging in the region over the time by observing the characteristics in the same person at different times of his/her life.

Methods:

We compared the position of the main anatomical landmarks of the eyelid region of 80 patients by overlaying their photographs when they were 20, 40, and 60 years old. Then we made comparisons in the group of men (40 people) and in the group of women (40 people) and between men and women.

Results:

The medial portion of the eyebrow was higher in the photograph taken at 60 years of age than in the one taken at 20 years old in 56.2% of cases; it was higher in 47.5% of cases when comparing the images at 20 and 40. The lateral portion of the eyebrow was seen higher in women in the 20 to 40 group, and it was seen lower in men at 60 years in statistical significance. In more than half of the patients observed, there was not a real descent of the eyebrow and the presence of a more or less accentuated form of upper eyelid’s ptosis in the photograph at 60 (globally 47.5%, 55.0% of women and 40.0% of men). This condition was observed in 27.5% of the photographs at 40. There were changes in the horizontal dimension of the palpebral fissure (shortening in 53.7%, preserved in 33.7%, and increased in 12.5% of cases at 60 years old). The position of lateral canthus appeared lower in 40.0% of patients photographed at 60, but it was stable in those photographed at 40. The herniation of the upper eyelid bags was observed in 31.2% of the patients photographed at 60 years old but only in 13.7% at 40. Dermatochalasis of the upper eyelid was present in 67.5% of the people at 60 years old and in 55.0% of those seen when they were 40. Comparing men and women groups 20 to 40, dermatochalasis is more present in men than women at 40 years old with statistical significance. The eyelid-cheek junction was seen to be lower in 75.0% of cases at 60 and in 48.7% of cases at 40, and it is more represented in men than in women.

Conclusion:

We have highlighted some interesting elements, partly agreeing with the data already recorded by other authors’, and our data suggest an important role of the eyelid structures senescence and its impact on the surrounding structures.
Appraisal of the emergency nurse practitioner specialty role
Authors: Hoyt Karen Sue , Evans Dian Dowling , Wilbeck Jennifer , Ramirez Elda , Agan Donna , Tyler Diane , Schumann Lorna
Published: October 2018

The role of the Emergency Nurse Practitioner (ENP) has evolved as a specialty and is appreciated within the context of the 2008 Consensus Model document (APRN Consensus Work Group & National Council of State Boards of Nursing APRN Advisory Committee, 2008). The first in a series of five articles, this article describes the appraisal of the ENP role as well as the specialty and the distinctive role of the ENP. The second article, Emergency Nurse Practitioner Practice Analysis: Report and Implications of the Findings, presents research to support the scientific basis of emergency specialty practice and content validity for a national certification program. Article 3, Beyond Competencies; Practice Standards for Emergency Nurse Practitioners: A Model for Clinicians, Educators, and Employers, introduces a new conceptual model that defines the specialty of emergency care's knowledge, skills, and abilities identified by the ENP practice analysis as practice standards not traditional competencies. In Article 4, Proposed Standardized Educational Preparation for the Emergency Nurse Practitioner, essential content for ENP preparation within graduate, postgraduate, and doctoral programs. The fifth article, Envisioning the Future for ENPs: Implications for Clinical Practice, Education, Research, and Health Policy, describes how ENPs are envisioning and impacting the future of emergency care and how their evolution can serve as a model for development of other advanced practice nursing specialties.
Müllerian inhibiting substance/anti-Müllerian hormone as a fertility preservation agent
Authors: Pépin David , Sabatini Mary E. , Donahoe Patricia K.
Published: October 2018

Purpose of review

The nascent field of oncofertility is quickly gaining traction as novel experimental treatments are being developed, driving a renewed interest in Müllerian inhibiting substance (MIS) as an ovarian fertoprotectant.

Recent findings

MIS is unique in its mechanisms of ovarian protection by virtue of acting directly on granulosa cells of primordial follicles and for being a benign reproductive hormone, with few side effects. We will explore in this review how it may be utilized to protect the ovary from chemotherapy, or to enhance ovarian tissue cryopreservation therapy. We will also examine potential mechanisms of action of MIS across multiple cell types, as well as current limitations in our understanding of the pharmacology of recombinant MIS.

The usefulness of MIS as a fertoprotectant may be dependent on the mechanisms of gonadotoxicity of each chemotherapeutic. Further investigation is needed to determine how to best deliver and combine MIS treatment to existing fertility management strategies.
High incidence of hepatocellular carcinoma and postoperative complications in patients with nonalcoholic steatohepatitis as a primary indication for deceased liver transplantation
Authors: Kern Barbara , Feurstein Benedikt , Fritz Josef , Fabritius Cornelia , Sucher Robert , Graziadei Ivo , Bale Reto , Tilg Herbert , Zoller Heinz , Newsome Philip , Eschertzhuber Stephan , Margreiter Raimund , Öfner Dietmar , Schneeberger Stefan
Published: October 2018

Background and aims

Nonalcoholic steatohepatitis (NASH) is an increasingly prevalent indication for liver transplantation (LT) across the world. The relative outcomes following transplantation are poorly described in this cohort. We aimed to analyze the incidence and outcome of LT for NASH as compared with other indications.

Patients and methods

This is a retrospective analysis of 513 patients who underwent deceased-donor, adult LT between 2002 and 2012 as recorded at the Medical University of Innsbruck, Austria.

Results

The prevalence of NASH cirrhosis as indication for liver transplantation was 12.7% (65/513). Patient survival in patients with NASH was comparable to other indications, including alcohol-induced liver steatosis (ALD) and hepatitis C virus (HCV) (P=0.208). Patients with NASH were older, had a higher model of end-stage liver disease score and a higher BMI, but patient survival and graft survival were equivalent to other indications. Patients with hepatocellular carcinoma (HCC) as primary indication for liver transplantation showed significantly inferior overall survival as compared with the other indications (P=0.003). Patients with NASH had coexisting HCC in 53.7% of cases, whereas HCC in ALD, HCV and other indications was prevalent in 31.2, 47.7, and 34.5%, respectively (P<0.0001). Patients with NASH had a higher incidence of advanced HCCs (outside the Milan criteria) than patients with ALD, HCV, and other indications (P=0.034). Postoperative complications were significantly higher in the NASH cohort (P=0.048).

Conclusion

In this single-center LT database analysis, patients with NASH have a higher incidence and a more rapid progression of HCC as well as an increased incidence of postoperative complications. Our findings warrant confirmation by others.
An Immune Suppression-associated EBV-positive Anaplastic Large Cell Lymphoma With a BRAF V600E Mutation
Authors: Gru Alejandro A. , Williams Eli , Junkins-Hopkins Jacqueline M.
Published: October 2018

Iatrogenic lymphoproliferative disorders have been described in patients receiving immunosuppressive/immunomodulatory agents outside the transplantation setting. Novel biological agents such as TNF-α blockers and JAK-inhibitors have also proven to be effective in many disorders including rheumatoid arthritis, inflammatory bowel disease (ulcerative colitis and Crohn disease), psoriasis, and others. A significant dilemma exists in those lymphoproliferative disorders associated with immunosuppressants and rheumatologic conditions, that relies on whether the association of the process is with the medication or the underlying autoimmune condition. In the current case report, we describe an extraordinary case of Epstein-Barr virus–positive anaplastic large cell lymphoma, in association with rheumatoid arthritis and the use of JAK-inhibitors. Comprehensive molecular testing (fluorescence in situ hybridization, OncoScan microarray, pyrosequencing) was done comparing sequential biopsies in this patient from skin and lung, which revealed a driving mutation in theBRAF V600Egene, a crucial finding, given the potential use of targeted therapy in this pathway.
Paramyxovirus infections in hematopoietic cell transplant recipients
Authors: Batista Marjorie V. , El Haddad Lynn , Chemaly Roy F.
Published: October 2018

Purpose of review

In hematopoietic cell transplant (HCT) recipients, paramyxovirus infections are major viral respiratory tract infections that, if they progress to lower respiratory tract infections, are associated with reduced survival rates in this population. There are important knowledge gaps regarding treatment decisions for HCT recipients with these infections and in the identification of risk factors that predict infection severity. Here, we review recent data on paramyxovirus infections in HCT recipients focusing on risk factors, new diagnostic and prognostic tools, and management including new drugs and vaccines under development.

Recent findings

Multiplexed molecular assays associated with immunodeficiency scoring index for respiratory syncytial virus (RSV) have improved our understanding of the epidemiology of RSV and other paramyxovirus infections and the risk factors for worse outcomes. Novel antiviral drugs, monoclonal antibodies, and vaccines are under evaluation with mixed preliminary results.

Advances in our knowledge of paramyxovirus infections in HCT recipients in the last two decades contributed to better strategies for management and prevention of these infections. A widespread understanding of how to stratify HCT recipients with paramyxovirus infections who would benefit most from antiviral therapy remains to be ascertained. Vaccines and new drugs under development may mitigate the burden of paramyxovirus infections.
Three-Dimensional Analysis of the Correlation Between Soft Tissue and Bone of the Lower Face Using Three-Dimensional Facial Laser Scan
Authors: Kim Seok Hwan , Shin Ho Seong
Published: October 2018

Background:

The prime aims of this study were to establish cephalometric linear and angular normative values of the lower face using a three-dimensional (3D) analysis in Korean individuals, and validate whether the linear and angular measurements using 3D laser scanner are comparable with measurements using 3D computed tomography (CT).

Methods:

In this study, 40 Korean individuals aged between 18 and 60 years were enrolled. Using 3D CT scan and 3D laser scanner, linear and angular values of the lower face were measured and recorded. Statistical analysis was carried out to verify the concordance and correlation between two 3D imaging modalities.

Results:

The 40 samples consisted of 11 women with a mean age of 40.8 ± 14.5 years and 29 men with a mean age of 29.7 ± 15.0 years. The results demonstrated the difference between sex and the tendency of asymmetry on both sides. Among different methods of measuring angular values, the gonial angle (GA) between tragion’ (Tr’)-gonion’ (Go’)-menton’ (Me’) from 3D laser scanning and between articulate-gonion-menton from CT scan demonstrated a good concordance and a high correlation.

Conclusions:

The GA measured between Tr’-Go’-Me’ using a 3D facial laser scan was comparable with values from 3D CT scan. The reference points and the GA, which we assessed here for 3D laser scanning, can be a reliable alternative method evaluating mandibular angles for assessing patients and surgical planning in plastic and orthognathic surgery.
Approach to Half-Nose and Proboscis Lateralis
Authors: Horoz Ugur , Kuroki Tomoaki , Shimoyama Mami , Yoshimoto Shinya
Published: October 2018

Half-nose or heminasal aplasia is an extremely rare congenital malformation, which has a withering effect both on the patient and the family. Proboscis lateralis is a rare facial anomaly resulting in the incomplete development of one side of the nose, which was first defined in 1861 by Forster in his monograph. Proboscis lateralis, cleft nose, and nasal agenesis are rare anomalies; however, half-nose is also an extremely rare condition. In the formation of half-nose deformities, either a facial cleft or nasal dysplasia is the assumed theories of embryological origin. In the reconstruction of proboscis lateralis tissue, local flaps and forehead flaps can be used for a functional and esthetically acceptable structure. The expanded forehead flap has become commonly used in recent years. Estimating the cosmetic result of surgery is an extreme challenge because of the accompanying nasal growth of the transferred tissue and the nose. In this study, the authors report on the reconstruction of half-nose and proboscis lateralis deformity with clinical results.
Safety and Stability of Postponed Maxillomandibular Fixation After Intraoral Vertical Ramus Osteotomy
Authors: Kim Jun-Young , Park Jin Hoo , Jung Hwi-Dong , Jung Young-Soo
Published: October 2018

The purpose of this study was to evaluate the postoperative safety and long-term stability of bimaxillary orthognathic patients with postponed maxillomandibular fixation (MMF) after intraoral vertical ramus osteotomy.

A total of 61 patients (21 male and 40 female patients; average age [SD], 21.7 [4.7]) were enrolled. All patients underwent maxillary LeFort I osteotomy and bilateral intraoral vertical ramus osteotomy for mandibular prognathism. During the hospital stay, postoperative airway compromise was observed and patients underwent MMF with wire at the second postoperative day. Stability was evaluated by measuring the position at each period: preoperative (T0), 2-day postoperative (T1), and 1-year postoperative.

Postoperative dyspnea and respiratory distress were absent in all patients. The mean number of refixations in physiotherapy was 0.62 (0.86) and the mean duration of physiotherapy was 11.6 (5.5) days. The mean amount of mandibular setback was 12.56 (5.76) mm and menton movement 0.98 (2.36) mm superiorly (T1). The mean mandibular relapse at Pog was 0.87 (1.96) mm anteriorly. Menton showed 1.11 (1.41) mm superiorly movement 1-year postoperatively (T2).

Despite its many advantages, intraoral vertical ramus osteotomy requires a period of MMF which can lead to early discomfort and airway-related emergency. In this study, the physiotherapy procedure and postoperative long-term stability in the postponed MMF group were not different from those of an immediate MMF group studied previously. It therefore constitutes a viable option for oral breathers and other compromised patients.
Incomplete Ear Amputation
Authors: Zhang Chao , Teng Li , Xu Jia-Jie , Lu Jian-Jian , Xie Fang , Yang Li-Ya , Li Shu-Yuan , Wu Huan-Huan , Sun Heng , Yang Biao
Published: October 2018

Ear amputations are common in emergency departments as the auricle's protrusion from the lateral aspect of the head makes it particularly susceptible to trauma. Of the numerous approaches for auricle injuries, the classic methods include microsurgical replantation, primary reattachment, composite graft, retroauricular pocket principle,
1
secondary reconstruction with rib cartilage, and methods using postauricular flap. The success of the operation depends largely on choosing the appropriate surgical procedure since many factors can influence surgical outcome. There is no 1 gold standard technique to treat the variety of auricle injuries. Inappropriate choice of surgical approach can be detrimental to subsequent reconstructive surgery. Therefore, the initial choice of optimal surgical approach is particularly important. In this article, a rare report of left subtotal ear laceration with inferior lobule pedicle by nonmicrosurgical primary reattachment was presented. The operation obtained an ideal cosmetic effect.
Soft ethics, the governance of the digital and the General Data Protection Regulation
Authors: Floridi Luciano
Published: October 2018

The article discusses the governance of the digital as the new challenge posed by technological innovation. It then introduces a new distinction between
soft ethics
, which applies after legal compliance with legislation, such as the General Data Protection Regulation in the European Union, and
hard ethics
, which precedes and contributes to shape legislation. It concludes by developing an analysis of the role of digital ethics with respect to digital regulation and digital governance.

This article is part of the theme issue ‘Governing artificial intelligence: ethical, legal, and technical opportunities and challenges’.