bluuebunny/crossref_metadata_2025 huggingface dataset:
Large scale microbiome profiling in the cloud
Authors: Valdes Camilo , Stebliankin Vitalii , Narasimhan Giri
Published: May 2019

Motivation

Bacterial metagenomics profiling for metagenomic whole sequencing (mWGS) usually starts by aligning sequencing reads to a collection of reference genomes. Current profiling tools are designed to work against a small representative collection of genomes, and do not scale very well to larger reference genome collections. However, large reference genome collections are capable of providing a more complete and accurate profile of the bacterial population in a metagenomics dataset. In this paper, we discuss a scalable, efficient and affordable approach to this problem, bringing big data solutions within the reach of laboratories with modest resources.

Results

We developed Flint, a metagenomics profiling pipeline that is built on top of the Apache Spark framework, and is designed for fast real-time profiling of metagenomic samples against a large collection of reference genomes. Flint takes advantage of Spark’s built-in parallelism and streaming engine architecture to quickly map reads against a large (170 GB) reference collection of 43 552 bacterial genomes from Ensembl. Flint runs on Amazon’s Elastic MapReduce service, and is able to profile 1 million Illumina paired-end reads against over 40 K genomes on 64 machines in 67 s—an order of magnitude faster than the state of the art, while using a much larger reference collection. Streaming the sequencing reads allows this approach to sustain mapping rates of 55 million reads per hour, at an hourly cluster cost of $8.00 USD, while avoiding the necessity of storing large quantities of intermediate alignments.

Availability and implementation

Flint is open source software, available under the MIT License (MIT). Source code is available at https://github.com/camilo-v/flint.

Supplementary information

Supplementary data are available at Bioinformatics online.
Model-based optimization of subgroup weights for survival analysis
Authors: Richter Jakob , Madjar Katrin , Rahnenführer Jörg
Published: May 2019

Motivation

To obtain a reliable prediction model for a specific cancer subgroup or cohort is often difficult due to limited sample size and, in survival analysis, due to potentially high censoring rates. Sometimes similar data from other patient subgroups are available, e.g. from other clinical centers. Simple pooling of all subgroups can decrease the variance of the predicted parameters of the prediction models, but also increase the bias due to heterogeneity between the cohorts. A promising compromise is to identify those subgroups with a similar relationship between covariates and target variable and then include only these for model building.

Results

We propose a subgroup-based weighted likelihood approach for survival prediction with high-dimensional genetic covariates. When predicting survival for a specific subgroup, for every other subgroup an individual weight determines the strength with which its observations enter into model building. MBO (model-based optimization) can be used to quickly find a good prediction model in the presence of a large number of hyperparameters. We use MBO to identify the best model for survival prediction of a specific subgroup by optimizing the weights for additional subgroups for a Cox model. The approach is evaluated on a set of lung cancer cohorts with gene expression measurements. The resulting models have competitive prediction quality, and they reflect the similarity of the corresponding cancer subgroups, with both weights close to 0 and close to 1 and medium weights.

Availability and implementation

mlrMBO is implemented as an R-package and is freely available at http://github.com/mlr-org/mlrMBO.
Omadacycline: A Modernized Tetracycline
Authors: Gallagher Jason C
Published: May 2019

When tetracyclines were introduced in the 1940s, these antibiotics offered a broad spectrum of activity against multiple types of pathogens. However, their utility waned after the selection of tetracycline resistance in the pathogens against which they were effective. Omadacycline is a semisynthetic aminomethylcycline antibacterial derived from the tetracycline class of antibiotics that is unaffected by these resistance mechanisms. It has an appropriate spectrum of activity for community-acquired infections, including those caused by many resistant organisms. Omadacycline offers a well-tolerated treatment for acute bacterial skin and skin structure infections and community-acquired bacterial pneumonia. Omadacycline has minimal known drug–drug interactions, and should be administered in a fasting state, avoiding dairy and cation-containing products for at least 4 hours after dosing. It does not require dose adjustments for sex, age, or hepatic or renal impairment, and has a safety profile similar to that of other oral tetracyclines. Because omadacycline can be administered effectively orally, it can help reduce hospitalization costs associated with intravenous antibiotic administration. This special supplement to Clinical Infectious Diseases offers an in-depth examination of omadacycline development, including discussions of pharmacokinetic and pharmacodynamic trials, spectrum of activity and preclinical data, early clinical trials, phase III clinical trials, and an integrated safety summary.
Microbiology and Preclinical Review of Omadacycline
Authors: Karlowsky James A , Steenbergen Judith , Zhanel George G
Published: May 2019

Omadacycline is a novel aminomethylcycline antimicrobial and semisynthetic derivative of tetracycline. In vitro, omadacycline displays potent activity against gram-positive and many gram-negative bacteria, including methicillin-resistant Staphylococcus aureus, Streptococcus pneumoniae, β-hemolytic streptococci, vancomycin-resistant Enterococcus, and Enterobacteriaceae. Omadacycline is also active against atypical and anaerobic pathogens, including Legionella pneumophila, Mycoplasma spp., Ureaplasma spp., Bacteroides spp., and Clostridioides difficile. This review outlines the microbiology and preclinical studies of omadacycline, including its mechanism of action; spectrum of activity; protein binding; activity in the presence of surfactant, serum, normal, and pH-adjusted urine, or bacterial biofilms; postantibiotic effect; pharmacodynamic properties; and in vitro and in vivo efficacy. The results of in vitro and in vivo animal studies support the observations made in phase III clinical trials and the clinical development of omadacycline.
Validation of distinct pathogenic patterns in a cohort of membranoproliferative glomerulonephritis patients by cluster analysis
Authors: Garam Nóra , Prohászka Zoltán , Szilágyi Ágnes , Aigner Christof , Schmidt Alice , Gaggl Martina , Sunder-Plassmann Gere , Bajcsi Dóra , Brunner Jürgen , Dumfarth Alexandra , Cejka Daniel , Flaschberger Stefan , Flögelova Hana , Haris Ágnes , Hartmann Ágnes , Heilos Andreas , Mueller Thomas , Rusai Krisztina , Arbeiter Klaus , Hofer Johannes , Jakab Dániel , Sinkó Mária , Szigeti Erika , Bereczki Csaba , Janko Viktor , Kelen Kata , Reusz György S , Szabó Attila J , Klenk Nóra , Kóbor Krisztina , Kojc Nika , Knechtelsdorfer Maarten , Laganovic Mario , Lungu Adrian Catalin , Meglic Anamarija , Rus Rina , Kersnik-Levart Tanja , Macioniene Ernesta , Miglinas Marius , Pawłowska Anna , Stompór Tomasz , Podracka Ludmila , Rudnicki Michael , Mayer Gert , Rysava Romana , Reiterova Jana , Saraga Marijan , Seeman Tomáš , Zieg Jakub , Sládková Eva , Szabó Tamás , Capitanescu Andrei , Stancu Simona , Tisljar Miroslav , Galesic Kresimir , Tislér András , Vainumäe Inga , Windpessl Martin , Zaoral Tomas , Zlatanova Galia , Csuka Dorottya
Published: May 2019

Background

A novel data-driven cluster analysis identified distinct pathogenic patterns in C3-glomerulopathies and immune complex-mediated membranoproliferative glomerulonephritis. Our aim was to replicate these observations in an independent cohort and elucidate disease pathophysiology with detailed analysis of functional complement markers.

Methods

A total of 92 patients with clinical, histological, complement and genetic data were involved in the study, and hierarchical cluster analysis was done by Ward method, where four clusters were generated.

Results

High levels of sC5b-9 (soluble membrane attack complex), low serum C3 levels and young age at onset (13 years) were characteristic for Cluster 1 with a high prevalence of likely pathogenic variations (LPVs) and C3 nephritic factor, whereas for Cluster 2—which is not reliable because of the small number of cases—strong immunoglobulin G staining, low C3 levels and high prevalence of nephritic syndrome at disease onset were observed. Low plasma sC5b-9 levels, decreased C3 levels and high prevalence of LPV and sclerotic glomeruli were present in Cluster 3, and patients with late onset of the disease (median: 39.5 years) and near-normal C3 levels in Cluster 4. A significant difference was observed in the incidence of end-stage renal disease during follow-up between the different clusters. Patients in Clusters 3–4 had worse renal survival than patients in Clusters 1–2.

Conclusions

Our results confirm the main findings of the original cluster analysis and indicate that the observed, distinct pathogenic patterns are replicated in our cohort. Further investigations are necessary to analyse the distinct biological and pathogenic processes in these patient groups.
The Association Between Self-Reported and Performance-Based Physical Function With Activities of Daily Living Disability in the Canadian Longitudinal Study on Aging
Authors: Mayhew Alexandra J , Griffith Lauren E , Gilsing Anne , Beauchamp Marla K , Kuspinar Ayse , Raina Parminder
Published: May 2019

Background

Physical function limitations precede disability and are a target to prevent or delay disability in aging adults. The objective of this article was to assess the relationship between self-report and performance-based measures of physical function with disability.

Methods

Baseline data (2012–2015) from the Canadian Longitudinal Study on Aging (n = 51,338) was used. Disability was defined as having a limitation for at least one of 14 activities of daily living. Physical function was measured using 14 questions across three domains (upper body, lower body, and dexterity) and five performance-based tests (gait speed, timed up and go, single leg stance, chair rise, and grip strength). Logistic regression was used to assess the relationship between physical function operationalized as (i) at least one limitation, (ii) presence or absence of limitations in each individual domain/test, and (iii) number of domains/tests with limitations, with disability.

Results

In the 21,241 participants with self-reported function data, the odds of disability were 1.87 (95% CI: 1.56–2.24), 6.78 (5.68–8.08), and 14.43 (11.50–18.1) for one, two, and three limited domains, respectively. In the 30,097 participants with performance-based measures of function, the odds of disability ranged from 1.53 (1.33–1.76) for one test limited to 14.91 (11.56–19.26) for all five tests limited.

Conclusions

Both performance-based and self-report measures of physical function were associated with disability. Each domain and performance test remained associated with disability after adjustment for the other domains and tests. Disability risk was higher when the number of self-report domains and performance-based limitations increased.
Prader–Willi syndrome imprinting centre deletion mice have impaired baseline and 5-HT2CR-mediated response inhibition
Authors: Davies Jennifer R , Wilkinson Lawrence S , Isles Anthony R , Humby Trevor
Published: May 2019

Prader–Willi syndrome (PWS) is a neurodevelopmental disorder caused by deletion or inactivation of paternally expressed imprinted genes on human chromosome 15q11–q13. In addition to endocrine and developmental issues, PWS presents with behavioural problems including stereotyped behaviour, impulsiveness and cognitive deficits. The PWS genetic interval contains several brain-expressed small nucleolar (sno) RNA species that are subject to genomic imprinting, including snord115 that negatively regulates post-transcriptional modification of the serotonin 2C receptor (5-HT2CR) pre-mRNA potentially leading to a reduction in 5-HT2CR function. Using the imprinting centre deletion mouse model for PWS (PWSICdel) we have previously shown impairments in a number of behaviours, some of which are abnormally sensitive to 5-HT2CR-selective drugs. In the stop-signal reaction time task test of impulsivity, PWSICdel mice showed increased impulsivity relative to wild-type (WT) littermates. Challenge with the selective 5-HT2CR agonist WAY163909 reduced impulsivity in PWSICdel mice but had no effect on WT behaviour. This behavioural dissociation in was also reflected in differential patterns of immunoreactivity of the immediate early gene c-Fos, with a blunted response to the drug in the orbitofrontal cortex of PWSICdel mice, but no difference in c-Fos activation in the nucleus accumbens. These findings suggest specific facets of response inhibition are impaired in PWSICdel mice and that abnormal 5-HT2CR function may mediate this dissociation. These data have implications for our understanding of the aetiology of PWS-related behavioural traits and translational relevance for individuals with PWS who may seek to control appetite with the new obesity treatment 5-HT2CR agonist lorcaserin.
Is Strategic Studies Rationalist, Materialist, and A-Critical? Reconnecting Security and Strategy
Authors: Vennesson Pascal
Published: May 2019

Between the 1940s and the 1960s, strategy was at the heart of security studies and closely intertwined with International Relations (IR). Over the past three decades, however, the study of strategy has been relegated to a secondary position in the international security subfield and marginalized in IR theorizing. One important source of this disconnect is the challenge mounted by critical security advocates, who sought to reorient the study of security away from strategic studies. They reached into the philosophy of science and pulled out three familiar dichotomies, rationalism/constructivism, materialism/idealism, and problem-solving/critical theorizing, that they could utilize within security debates. Specifically, they argue that strategic studies leaves out too much of what is really important for security and world politics because it is rationalist, materialist, and retains an uncritical view of knowledge production. In this article, I turn the critical security conventional wisdom on its head and show that strategic studies, exemplified by the ideas of Carl von Clausewitz and Thomas Schelling, actually transcends these dichotomies and hence offers an indispensable source of insights for both security studies and IR.
EpiAlignment: alignment with both DNA sequence and epigenomic data
Authors: Lu Jia , Cao Xiaoyi , Zhong Sheng
Published: May 2019

Comparative epigenomics, which subjects both epigenome and genome to interspecies comparison, has become a powerful approach to reveal regulatory features of the genome. Thus elucidated regulatory features surpass the information derived from comparison of genomic sequences alone. Here, we present EpiAlignment, a web-based tool to align genomic regions with both DNA sequence and epigenomic data. EpiAlignment takes DNA sequence and epigenomic profiles derived by ChIP-seq from two species as input data, and outputs the best semi-global alignments. These alignments are based on EpiAlignment scores, computed by a dynamic programming algorithm that accounts for both sequence alignment and epigenome similarity. For timely response, the EpiAlignment web server automatically initiates up to 140 computing threads depending on the size of user input data. For users’ convenience, we have pre-compiled the comparable human and mouse epigenome datasets in matched cell types and tissues from the Roadmap Epigenomics and ENCODE consortia. Users can either upload their own data or select pre-compiled datasets as inputs for EpiAlignment analyses. Results are presented in graphical and tabular formats where the entries can be interactively expanded to visualize additional features of these aligned regions. EpiAlignment is available at https://epialign.ucsd.edu/.
Building Arc Crust: Plutonic to Volcanic Connections in an Extensional Oceanic Arc, the Southern Alisitos Arc, Baja California
Authors: Morris Rebecca A , DeBari Susan M , Busby Cathy , Medynski Sarah , Jicha Brian R
Published: May 2019

The ∼50 km long Rosario segment of the Cretaceous Alisitos oceanic arc terrane provides undeformed three-dimensional exposures of the upper 7 km of an oceanic extensional arc, where crustal generation processes are recorded in both the volcanic and underlying plutonic rocks. These exceptional exposures allow for the study of the physical and chemical links between the rock units and help constrain the differentiation processes active during the growth and evolution of arc crust. This study focuses on the southern third of the Rosario segment, previously referred to as the southern volcano-bounded basin, and its plutonic underpinnings. Upper crustal rocks in the Rosario segment consist of a 3–5 km thick volcanic–volcaniclastic section with hypabyssal intrusions. Plutons intrude these units at various levels along-strike, but at each intrusive contact the transition is complete over a distance of <150 m, where stoped volcanic blocks are present. There is striking compositional overlap in whole-rock and mineral chemistry between the plutonic and volcanic units, suggesting a comagmatic source. Whole-rock geochemistry shows coherent trends in major and trace elements in mafic to intermediate compositions, but less coherent trends above 63 wt % SiO2. Units are predominantly low-K with flat rare earth element patterns, and show large ion lithophile element enrichment and high field strength element depletion. Initial Nd and Pb isotope ratios overlap for all units and imply no cratonic continental involvement. This agrees with low Sr/Y ratios of all rock types, indicative of thin, immature oceanic arc crust. Modeling results show that closed-system fractional crystallization drove crustal differentiation from mafic to intermediate compositions, but open-system processes likely occurred to produce some of the felsic compositions. Differentiation occurred in a two-step fractionation process. Step 1, from basaltic andesite to andesite, fractionated an anhydrous gabbroic cumulate (∼40% crystallization). Step 2, from andesite to rhyolite, fractionated a hydrous amphibole cumulate (∼65% crystallization, total), which is similar to what fluid dynamical models suggest for production of rhyolite (between 50–70% crystallization). Our results can be used as a reference model for differentiation processes relating to the growth of the middle and upper crust within active extensional arc systems. The Rosario segment plutonic rocks may be analogous to the low-velocity zone (Vp = 6·0–6·5 km s–1) imaged within the extensional Izu–Bonin arc. The chemistry of the plutonic and volcanic rocks is most similar to those of volcanic rocks in the Izu–Bonin active rift.
Irregular parameter dependence of numerical results in tensor renormalization group analysis
Authors: Kadoh Daisuke , Kuramashi Yoshinobu , Ueno Ryoichiro
Published: May 2019

We study the parameter dependence of numerical results obtained by the tensor renormalization group. We often observe irregular behavior as the parameters are varied with the method. Using the two-dimensional Ising model we explicitly show that the sharp cutoff used in the truncated singular value decomposition causes this unwanted behavior when the level crossing happens between singular values below and above the truncation order as the parameters are varied. We also test a smooth cutoff, instead of the sharp one, as a truncation scheme and discuss its effects.
Dash for Cash: Monthly Market Impact of Institutional Liquidity Needs
Authors: Etula Erkko , Rinne Kalle , Suominen Matti , Vaittinen Lauri
Published: May 2019

We present broad-based evidence that the monthly payment cycle induces systematic patterns in liquid markets around the globe. First, we document temporary increases in the costs of debt and equity capital that coincide with key dates associated with month-end cash needs. Second, we present direct and indirect evidence on the role of institutions in the genesis of these patterns and derive estimates of the associated costs borne by market participants. Third, and finally, we investigate the limits to arbitrage that prevent markets from functioning efficiently. Our results indicate that many investors and their agents, including mutual funds, suffer from liquidity-related trading.

Received January 16, 2018; editorial decision January 2, 2019 by Editor Robin Greenwood. Authors have furnished an Internet Appendix, which is available on the Oxford University Press Web site next to the link to the final published paper online.
Latent Trade Diversification and Its Relevance for Macroeconomic Stability
Authors: Lederman Daniel , Pienknagura Samuel , Rojas Diego
Published: May 2019

This paper examines the economic implications of a novel concept of trade diversification—latent diversification. In contrast to traditional measures, latent diversification accounts for potential movements of factors of production into activities where the country has previous exporting experience, hence presenting an additional margin through which countries can respond to shocks. The paper shows that the gap between traditional measures of diversification and latent diversification is sizeable and that latent diversification is in its own right an important determinant of macroeconomic stability. More diversified latent export baskets are associated with lower terms-of-trade volatility and, in turn, lower GDP per capita volatility, even after controlling for the degree of contemporaneous export diversification and other country characteristics.
Mitochondrial genome reorganization provides insights into the relationship between oribatid mites and astigmatid mites (Acari: Sarcoptiformes: Oribatida)
Authors: Li Wei-Ning , Xue Xiao-Feng
Published: May 2019

Oribatida s.l. represents one of the most species-rich mite lineages, including two recognized groups: oribatid mites (Oribatida s.s., non-astigmatan oribatids) and astigmatid mites (Astigmata). However, the relationship between these two groups has been debated. Here, we sequenced the complete mitochondrial (mt) genome of one oribatid mite and one astigmatid mite, retrieved complete mt genomes of three oribatid mites, and compared them with two other oribatid mites and 12 astigmatid mites sequenced previously. We find that gene orders in the mt genomes of both oribatid mites and astigmatid mites are rearranged relative to the hypothetical ancestral arrangement of the arthropods. Based on the shared derived gene clusters in each mt genome group, rearranged mt genomes are roughly divided into two groups corresponding to each mite group (oribatid mites or astigmatid mites). Phylogenetic results show that Astigmata nested in Oribatida. The monophyly of Astigmata is recovered, while paraphyly of Oribatida s.s. is observed. Our results show that rearranged gene orders in the mt genomes characterize various lineages of oribatid mites and astigmatid mites, and have potential phylogenetic information for resolving the high-level (cohort or supercohort) phylogeny of Oribatida.
Tubal Ligation and Age at Natural Menopause
Authors: Ainsworth Alessandra J. , Baumgarten Sarah C. , Bakkum-Gamez Jamie N. , Vachon Celine M. , Weaver Amy L. , Laughlin-Tommaso Shannon K.
Published: May 2019

OBJECTIVE:

To determine the effect of tubal ligation on age at natural menopause, as a marker of long-term ovarian function.

METHODS:

Three preexisting population-based cohorts were included in this cross-sectional study. Data from each cohort was analyzed separately. The cohorts were restricted to women who never smoked and had reached natural menopause, without prior hysterectomy or oophorectomy. The following variables were collected: race, age at menarche, age at menopause, history of hysterectomy or oophorectomy, gravidity and parity, tobacco use, and ever use of hormonal contraception. The type of tubal ligation and age at tubal ligation were manually abstracted in cohort 1. For cohorts 2 and 3, history of tubal ligation was obtained from an institutional form, completed by patient report. The primary outcome, age at natural menopause, was compared between the two groups (those with and without a history of tubal ligation).

RESULTS:

Inclusion criteria was met by 555 women from cohort 1, 1,816 women from cohort 2, and 1,534 women from cohort 3. Baseline characteristics did not differ between cohorts. The percentage with tubal ligation was the same in all cohorts: 26.0%, 25.5%, and 25.0%, respectively. Women with a tubal ligation were more likely to have had at least one pregnancy and to have used hormonal contraception compared with women without a tubal ligation. There was no significant difference in age at natural menopause in women who underwent tubal ligation (50.1, 49.9, 50.0 years, respectively) compared with those who did not (50.7, 49.6, 50.0 years, respectively). The type of tubal ligation (cohort 1 only) had no effect on age at menopause.

CONCLUSIONS:

Tubal ligation did not affect age at natural menopause in the three large cohorts included in this study.
Pregnancy-Associated Death in Utah
Authors: Smid Marcela C. , Stone Nicole M. , Baksh Laurie , Debbink Michelle P. , Einerson Brett D. , Varner Michael W. , Gordon Adam J. , Clark Erin A. S.
Published: May 2019

OBJECTIVE:

Drug-induced deaths, defined as intentional or unintentional consumption of illicit substances or diverted medications leading to death, are the leading cause of death for reproductive-age women in the United States. Our objective was to describe pregnancy-associated deaths attributed to drug-induced causes to identify opportunities for intervention.

METHODS:

Using the Utah Perinatal Morality Review Committee database, we performed a retrospective cohort study of all pregnancy-associated deaths—death of a woman during pregnancy or within 1 year from the end of pregnancy—from 2005 to 2014. We performed a detailed descriptive analysis of women with drug-induced deaths. We compared characteristics of women with drug-induced and other pregnancy-associated deaths.

RESULTS:

From 2005 to 2014, 136 pregnancy-associated deaths were identified. Drug-induced death was the leading cause of pregnancy-associated death (n=35, 26%) and 89% occurred in the postpartum period. More specifically, those with a drug-induced death were more likely to die in the late postpartum period, defined as death occurring within 43 days to 1 year of the end of the pregnancy, (n=28/35, 80%) compared with women whose deaths were from other pregnancy-associated causes (n=34/101, 34%) (P<.001). The majority of drug-induced deaths were attributed to opioids (n=27/35, 77%), prescription opioids (n=21/35, 60%), and polysubstance use (n=29/35, 83%). From 2005 to 2014, the pregnancy-associated mortality ratio increased 76%, from 23.3 in 2005 to 41.0 in 2014. During this same time period, the drug-induced pregnancy-associated mortality ratio increased 200%, from 3.9 in 2005 to 11.7 in 2014.

CONCLUSION:

Drug-induced death is the leading cause of pregnancy-associated death in Utah and occurs primarily in the late postpartum period. Interventional studies focused on identifying and treating women at risk of drug-induced death are urgently needed.
What Is New in Hysterectomy for Benign Gynecologic Disorders?
Authors: Famuyide Abimbola O.
Published: May 2019

This month we focus on current research in hysterectomy for benign gynecologic disorders. Dr. Famuyide discusses four recent publications, which are concluded with a “bottom-line” that is the take-home message. A complete reference for each can be found on Box 1 on this page along with direct links to abstracts.
Understanding Articular Cartilage Injury and Potential Treatments
Authors: Borrelli Joseph , Olson Steven A. , Godbout Charles , Schemitsch Emil H. , Stannard James P. , Giannoudis Peter V.
Published: May 2019

The goals of all orthopaedic surgeons treating articular cartilage injuries have been anatomic reduction and stable fixation of the articular cartilage surface with restoration of limb alignment and/or reestablishment of the joint stability, all while minimizing the risk of surgical complications. Recent developments in the study of articular cartilage injury have shown that there is a robust cellular response to joint injury. This response has been shown to involve the synoviocytes, chondrocytes, and osteocytes in and around the injured joint and if these responses are left unchecked, they can lead to the development of posttraumatic osteoarthritis (PTOA). Therefore, to predictably and successfully treat articular cartilage injuries, it is not sufficient to just restore articular congruity, limb alignment, and joint stability, but we must also recognize and attempt to mitigate this associated cellular response. Understanding not only the mechanical aspects of these joint injuries but also the biological aspects is paramount to giving our patients the best opportunity to heal their injuries, recover full function, and avoid the potential devastating development of PTOA. Gone is the simplistic view that if one can achieve articular congruity after intraarticular fracture, as well as joint stability after ligamentous injury, that our patients will do just fine. This review sheds new light on the molecular response to cartilage injury, how residual joint incongruity and instability affect the joint's ability to recover from injury, and how chondrocyte apoptosis in response to injury can influence joint. This article then briefly reviews how cellular and growth factors may be beneficial to the treatment of articular cartilage injury and how ultimately cartilage regeneration may be used in the future to salvage the joints ravaged by PTOA in response to injury.
A New and More Sensitive View for the Detection of Syndesmotic Instability
Authors: Gosselin-Papadopoulos Nayla , Hébert-Davies Jonah , Laflamme Georges-Yves , Ménard Jérémie , Leduc Stéphane , Nault Marie-Lyne
Published: May 2019

Objectives:

We hypothesize that a single syndesmotic view, capturing both sagittal and coronal tibiofibular displacement, will be more sensitive than a mortise view to detect syndesmotic instability.

Methods:

Ten fresh frozen human lower limbs were used to test the new syndesmotic view with simulated syndesmosis injury. The anteroinferior tibiofibular ligament, interosseous membrane, and posteroinferior tibiofibular ligament were sectioned sequentially. At each stage, the syndesmosis was tested using the external rotation stress (ERS) test and lateral stress test (LST). For each stress condition, a true mortise view and the new syndesmotic view were performed. Medial clear space and tibiofibular clear space (TFCS) were measured on a mortise view, and TFCS was measured on a syndesmotic view (TFCS-s). Wilcoxon signed-rank tests were used to compare measurements.

Results:

Syndesmotic view enabled instability detection with a 2-ligament dissection at a mean increase in TFCS-s of 2.37 mm (P = 0.021) and 1.98 mm (P = 0.011), using the ERS and LST, respectively. TFCS on the mortise view was significantly different only with a complete injury. Medial clear space did not vary significantly with injury increments. Sensitivity was 66% and 61% using ERS and LST, respectively, for the TFCS-s, compared with 27% and 33%, respectively, for the TFCS. Specificity was similar for TFCS and TFCS-s.

Conclusions:

This study was able to demonstrate that the syndesmotic view is more sensitive than the mortise view in detecting syndesmotic instability in a cadaveric model. It is particularly helpful to uncover instability secondary to an incomplete syndesmosis injury requiring fixation.
Encountering Patient Suicide During Psychiatric Training: An Integrative, Systematic Review
Authors: Leaune Edouard , Ravella Noémie , Vieux Maxime , Poulet Emmanuel , Chauliac Nicolas , Terra Jean-Louis
Published: May 2019

Background/aim

Patient suicide is an adversity that can be considered an “occupational hazard.” It has been identified as one of the most stressful adverse events during psychiatric training. The aim of this study was to systematically review the literature assessing the impact of patient suicide on trainees.

Methods

We conducted a systematic review on the MEDLINE, Science Direct, Scopus, and Web of Science databases. Studies that reported prevalence of patient suicide, quantitative or qualitative assessment of psychological and professional impacts, coping strategies, and support or educational and postvention programs were deemed eligible for inclusion.

Results

Of the 1994 articles identified, 22 were included. The literature on the topic was scarce, and the quality of the studies was moderate. No article dealt with nonpsychiatric residents. During their training, 46.4% of psychiatric trainees encountered at least one patient suicide. The traumatic impact was significantly more intense in trainees compared to senior physicians. A negative impact on their professional practice was reported by 17% to 39% of trainees. Formal institutional support for the affected trainees was described as having major shortcomings, and informal support from peers and families was reported as the most helpful response. However, 52% of impacted trainees considered encountering patient suicide a useful and beneficial experience.

Conclusion

The frequent posttraumatic symptoms and the negative professional consequences following patient suicide are worrying phenomena that highlight the need to improve suicide prevention and postvention programs during psychiatric training. Identifying trainees with personal vulnerability factors should be a major concern during the postvention process.
Improving neuropsychiatric symptoms following stroke using virtual reality
Authors: De Luca Rosaria , Manuli Alfredo , De Domenico Carmen , Lo Voi Emanuele , Buda Antonio , Maresca Giuseppa , Bramanti Alessia , Calabrò Rocco Salvatore
Published: May 2019

Rationale:

Post-stroke cognitive impairment occurs frequently in patients with stroke, with a 20% to 80% prevalence. Anxiety is common after stroke, and is associated with a poorer quality of life. The use of standard relaxation techniques in treating anxiety in patients undergoing post-stroke rehabilitation have shown some positive effects, whereas virtual reality seems to have a role in the treatment of anxiety disorders, especially when associated to neurological damage.

Patients concerns:

A 50-year-old woman, smokers, affected by hypertension and right ischemic stroke in the chronic phase (i.e., after 12 months by cerebrovascular event), came to our observation for a severe anxiety state and a mild cognitive deficit, mainly involving attention and visuo-executive processes, besides a mild left hemiparesis.

Diagnosis:

Anxiety in a patient with ischemic stroke.

Interventions:

Standard relaxation techniques alone in a common clinical setting or the same psychological approach in an immersive virtual environment (i.e., Computer Assisted Rehabilitation Environment – CAREN).

Outcomes:

The patient's cognitive and psychological profile, with regard to attention processes, mood, anxiety, and coping strategies, were evaluated before and after the 2 different trainings. A significant improvement in the functional and behavioral outcomes were observed only at the end of the combined approach.

Lessons:

The immersive virtual reality environment CAREN might be useful to improve cognitive and psychological status, with regard to anxiety symptoms, in post-stroke individuals.
Utilization of the directional balloon technique to improve the effectiveness of percutaneous kyphoplasty in the treatment of osteoporotic vertebral compression fractures and reduction of bone cement leakage
Authors: Wang Pu , Li Jin , Song Zukun , Peng Zhan , Wang Guangye
Published: May 2019

Background:

This article evaluates the effectiveness of a new directional balloon technique in the treatment of osteoporotic vertebral compression fractures (OVCFs).

Methods:

From September 2015 to April 2017, 100 patients with single-segment OVCFs treated using percutaneous kyphoplasty were available for complete data assessment. Among these, 51 cases were treated with the traditional nondirectional balloon technique (group 1) and 49 cases were treated with the directional balloon technique (group 2). Operative time, blood loss, and X-ray exposure time were compared between the 2 groups. The visual analogue score (VAS), Oswestry disability index (ODI), and Roland Morris disability (RMD) scores, and wedge-shaped and kyphosis angles were measured at 3 days and 1, 3, 6, and 12 months, respectively, after surgery.

Results:

There were no significant differences in blood loss or the amount of bone cement injected between the 2 groups; however, operative times, X-ray exposure times, and leakage rates of bone cement, especially type C in group 2, were significantly lower in group 2 than those in group 1. VAS, ODI, and RMD scores, and wedge-shaped and kyphosis angles at each time point after surgery were significantly higher than those before surgery. However, the improvement in VAS, ODI, and RMD scores in group 2 was only significantly better than those in group 1 at 3 days after surgery.

Conclusion:

The utilization of the directional balloon technique in the treatment of OVCFs using percutaneous kyphoplasty can not only reduce the operation time, the radiation, and the bone cement leakage, but also improve the early curative effect.
The effect of vitamin D3 on blood pressure in people with vitamin D deficiency
Authors: He Silu , Hao Xiyuan
Published: May 2019

Objective:

To evaluate the effect of vitamin D3 on blood pressure in people with vitamin D deficiency.

Methods:

Randomized controlled trials (RCTs) were electronically searched databases including CNKI, VIP, WanFang Data, the Cochrane Library, PubMed, and EMbase which were about oral vitamin D3 among people with vitamin D deficiency from inception to December 2017. Two reviewers independently screened literature according to the inclusion and extracted data; meta-analysis was performed using RevMan5.3.

Results:

A total of 17 RCTs with 22 arms involving 1687 participants were included. The results of meta-analysis showed that, there were no significant differences between the vitamin D deficiency group and the control group on the level of change in systolic pressure (ΔSBP) [weighted mean difference (WMD) = −1.94, 95% confidence interval (CI) (−3.93,0.04) P = .06] and on the level of change in diastolic pressure (ΔDBP) [WMD = −0.50, 95% CI (−1.17, 0.17) P = .14]. The results of subgroups showed that, there were statistically significant differences in the age of >50 years subgroup on ΔSBP [WMD = −2.32, 95% CI (−4.39, −0.25) P = .03]; there were statistically significant differences in the hypertension subgroup on ΔSBP [WMD = −6.58, 95% CI (−8.72, −4.44) P <.00001]; there were statistically significant differences in the hypertension subgroup on ΔDBP [WMD = −3.07, 95% CI (−4.66, −1.48) P = .0002]; there were statistically significant differences in the body mass index (BMI) >30 subgroup on ΔSBP [WMD = −3.51, 95% CI (−5.96, −1.07) P = .005].

Conclusion:

Oral vitamin D3 has no significant effect on blood pressure in people with vitamin D deficiency. It reduces systolic blood pressure in people with vitamin D deficiency that was older than 50 years old or obese. It reduces systolic blood pressure and diastolic pressure in people with both vitamin D deficiency and hypertension.
Delirium induced by tigecycline treatment for Acinetobacter baumannii infection
Authors: Zheng Xiaoying , Jiang Huiming , Xue Lifen , Qiu Feng , Zhu Shenyin , Li Xinyu
Published: May 2019

Rationale:

Tigecycline is a broad-spectrum antimicrobial agent structurally belong to tetracyclines and covers against many multidrug-resistant organisms. Arising clinical cases reporting its adverse drug reactions have emerged alongside with the increasing off label use globally. By literature review, delirium caused by tigecycline has not been reported yet. We present what we believe to be the first case of tigecycline-induced delirium.

Patient concerns:

A 77-year-old male patient with end-stage renal disease was hospitalized due to acute exacerbation of chronic obstructive pulmonary disease.

Diagnosis:

The patient developed delirium after infused with a loading dose of tigecycline for pulmonary infection.

Interventions:

All potential causes inducing delirium were evaluated and the symptoms improved soon after discontinuation of tigecycline. He experienced delirium once again after reusing tigecycline for the exacerbation of the pulmonary infection even without a loading dose. Tigecycline was discontinued and the symptoms quickly relieved.

Outcomes:

According to the Naranjo adverse drug reaction probability scale, tigecycline was the probable cause of his delirium.

Lessons:

Clinicians should be aware of this potential adverse effect of tigecycline. We recommend that clinicians monitor patients for signs and symptoms of delirium during treatment with tigecycline.
Efficacy, safety, and in-hospital outcomes of subcutaneous versus transvenous implantable defibrillator therapy
Authors: Chen Chao-Feng , Jin Chao-Lun , Liu Mei-Jun , Xu Yi-Zhou
Published: May 2019

Background:

Lead-related complication is an important drawback of trans-venous implantable cardioverter-defibrillators (TV-ICD). The subcutaneous ICD (S-ICD) was developed to overcome ICD lead associated complications; however, whether the S-ICD confers enhanced clinical benefits compared with TV-ICD remains unclear. The present systematic review and meta-analysis aimed to assess TV-ICD and S-ICD for safety, efficacy, and in-hospital outcomes in the prevention of sudden cardiac death (SCD) in patients not requiring pacing.

Methods:

The Medline, PubMed, EmBase, and Cochrane Library databases were searched for studies comparing TV-ICD and S-ICD.

Results:

A total of 9 eligible studies, including 5 propensity-matched case–control, 3 retrospective, and 1 cross-sectional studies were identified, assessing 7361 patients in all. Pool analyses demonstrated that SICD were associated with lower lead-related complication rates [odds ratio (OR) = 0.13; 95% confidence interval [CI] 0.05–0.33; I
2 = 0%], and S-ICD was more beneficial in terms of reducing ICD shocks [OR = 0.48; 95% CI 0.32–0.72, I
2 = 4%]. In addition, the patients administered S-ICD tend to have shorter length of hospital stay after implantation (SMD = −0.06; 95% CI −0.11 to 0.00, I
2 = 0%) and reduce total complication rates (OR = 0.72; 95% CI 0.50–1.03; I
2 = 18%), non-decreased quality of life (QoL). Moreover, both devices appeared to perform equally well with respect to infection rate and death.

Conclusions:

Available overall data suggested that S-ICD is associated with reducing lead-related complications, ICD shocks. In addition, S-ICD has tendency to shorten hospitalization and reduce total complications, although the difference is no significant. Equivalent death rate, infection, and QoL were found between 2 groups. Therefore, S-ICD could be considered an alternative approach to TV-ICD in appropriate patients for SCD prevention.
Decision analysis about the cost-effectiveness of different in vitro fertilization-embryo transfer protocol under considering governments, hospitals, and patient
Authors: Pan Wei , Tu Haiting , Jin Lei , Hu Cheng , Li Yuehan , Wang Renjie , Huang Weiming , Liao ShuJie
Published: May 2019

Objective:

The aim of this study was to explore the benefits of in vitro fertilization (IVF) for patients and hospitals under different protocols and if IVF treatment should be incorporated into health care.

Perspective:

The government should consider including IVF treatment in health insurance. Hospitals and patients could obtain the best benefit by following the hospital's recommended protocol.

Setting:

This retrospective study was conducted from January 2014 to August 2017 at an academic hospital.

Methods:

A total of 7440 patients used gonadotropin-releasing hormone agonists (GnRHa) protocol, 2619 patients used, gonadotropin-releasing hormone antagonists (GnRHant) protocol, and 1514 patients used GnRHa ultra-long protocol. Primary outcomes were live birth rate (LBR), cost-effectiveness, hospital revenue, and government investment.

Results:

The cycle times for the GnRHa protocol and the GnRHa ultra-long protocol were significantly higher than the GnRHant protocol. Patients who were ≤29 years chose the GnRHant protocol. The cost of a successful cycle was 67,579.39 ± 9,917.55 ¥ and LBR was 29.25%. Patients who were >30 years had the GnRHa protocol as the dominant strategy, as it was more effective at lower costs and higher LBR. When patients were >30 to ≤34 years, the cost of a successful cycle was 66,556.7 ± 8,448.08 ¥ and the LBR was 31.05%. When patients were >35 years, the cost of a successful cycle was 83,297.92 ± 10,918.05 ¥ and the LBR was 25.07%. The government reimbursement for a cycle ranged between 11,372.12 ± 2,147.71 ¥ and 12,753.67 ± 1,905.02 ¥.

Conclusions:

The government should consider including IVF treatment in health insurance. Hospitals recommend the GnRHant protocol for patients <29 years old and the GnRHa protocol for patients >30 years old, to obtain the best benefits. Patients could obtain the best benefit by using the protocol recommended by the hospital.
Local infiltration with cocktail analgesics during 2 level lumbar spinal fusion surgery
Authors: Ren Zhinan , Li Zheng , Li Shugang , Sheng Lin , Xu Derong , Chen Xin , Wu William Ka Kei , Chan Matthew T.V. , Ho Jeffery
Published: May 2019

Background:

Despite introducing novel analgesics, pain management for spine surgery remains a challenge. Multimodal pain control has recently gained popularity in surgical spine care. We proposed a novel management approach using multimodal cocktail analgesics. Injection to skin surrounding surgical incision site will be given perioperatively. This study evaluates the safety and efficacy of cocktail analgesic injection on pain management following lumbar spinal fusion surgery.

Methods:

Thirty-six patients with degenerative lumbar spinal diseases on the waiting list for lumbar spinal fusion surgery will be recruited. Patients will be randomly assigned to receive either cocktail analgesic injection or sterile saline before surgical wound closure. All patients will routinely receive postoperative intravenous patient-controlled analgesia (IV-PCA) with sufentanil on an as-needed basis without a basal dose. The primary outcome is perceived pain intensity as measured by visual analog pain score. Secondary outcomes include sufentanil consumption, time to first use of IV-PCA, rescue analgesics consumption, and the presence of adverse effects. Findings of this interventional trial will provide novel evidence supporting the superior effect of cocktail analgesic injection during surgery.

Trial registration number:

ChiCTR-IPR-17013094.