bluuebunny/crossref_metadata_2025_split huggingface dataset:
Genetic evaluation of disorders of sex development: current practice and novel gene discovery
Authors: Kremen Jessica , Chan Yee-Ming 
Published: November 2018

Purpose of review
As the pace of genetic discovery accelerates, genetic sequencing is increasingly applied to rare disease such as DSD (differences or disorders of sex development,) which has led to an increase in the number of novel variant-containing candidate genes identified. In this review, we will discuss several candidate genes which have recently been proposed as causative of DSD, as well as novel work in understanding gene regulation in the mouse gonad that may have implications for the DSD phenotype in humans.

Recent findings
We performed a comprehensive search of PubMed through August 2018 to identify relevant peer-reviewed publications from 2017 to 2018 on DSD genetics.

Summary
Seminal work has identified a critical gonadal enhancer of Sox9 in a mouse model. This enhancer is located in a region which had previously been implicated in both XX and XY DSD, though the specific enhancer and its role in Sox9 gene expression had not been defined. Novel candidate genes in XY gonadal dysgenesis (SOX8, ESR2) and XX ovotesticular DSD (NR2F2) have been described.
Short article: Sequence variations of PKHD1 underlie congenital hepatic fibrosis in a Chinese family
Authors: Yang Ni , Leng Yunji , Dai Shundong , Chen Chen , Liu Chunfeng , Cao Lihua 
Published: November 2018

Objective
Congenital hepatic fibrosis (CHF) is a developmental disorder of the portobiliary system characterized by hepatic fibrosis, portal hypertension, and renal cystic disease. The aim of our study was to identify the disease-causing gene of a Chinese family with CHF.

Patients and methods
Whole-exome sequencing was performed in the family with CHF and variants were confirmed by Sanger sequencing. Online bioinformatics tools were used to evaluate the pathogenicity of the missense variants. Liver specimens were reviewed to confirm the histopathological diagnosis.

Results
The compound heterozygous variants c.7994T>C, p.(Leu2665Pro) and c.8518C>T, p.(Arg2840Cys) in PKHD1 were identified in a Chinese family with CHF by whole-exome sequencing. Liver histomorphology was reviewed to confirm the diagnosis of CHF.

Conclusion
We have identified variations in PKHD1 in a Chinese family with CHF. Our study extends the mutation spectrum of CHF and provides information for genetic counseling of patients’ family members.
Diaper Use Increases the Risk of Buttock and Perineal Abscesses
Authors: Pappano Dante , Radu Heather , Sexton Michelle 
Published: November 2018

Objectives
Over the last decade, there has been a notable increase in the incidence of abscesses. Children in the diaper-wearing age group are disproportionately affected, and most of these abscesses occur in the buttock and perineal region. Using case-control methodology, we sought to determine if diaper use itself is an independent risk factor for abscess formation.

Methods
Cases were patients, at least 2 years of age but less than 4 years, who presented to the emergency department with a complaint of a buttock or perineal abscess. Age-matched controls presented to the emergency department for unrelated reasons. Caregivers of subjects responded to a survey regarding diaper use (toilet trained, for sleep only, or all day), type and brand of diaper, and diaper hygiene-related factors.

Results
We enrolled 465 patients (93 cases, 372 controls). Fully toilet trained children were less likely to have buttock and perineal abscess than their sleep-only and all-day diaper-wearing peers. Limiting diaper use to naptime and overnights (sleep only) did not confer protection against abscesses. Diaper hygiene–related factors did not affect the risk of abscess formation. Female sex was also identified as a strong risk factor for buttock and perineal abscess formation.

Conclusions
Diaper use is a potentially modifiable risk factor for buttock and perineal abscess formation in young children.
A Lodged Barramundi Fish-Bone Stabbing the Piriform Fossa in a Child
Authors: Goldman Ran D. , Gurberg Joshua , Paul Moxham J. 
Published: November 2018

Abstract
Unintentional ingestion of a fish bone is common in children, especially among families with high consumption of seafood. Complications in children are extremely rare. We describe a 3-year-old healthy boy who had a large bone of Barramundi fish lodged in his upper esophagus causing significant distress. Soft tissue neck radiograph revealed a mildly thickened epiglottis and bulbous and hypertrophied adenoid soft tissue. A 21-mm foreign body was noticed. A flexible fiberoptic laryngoscopy revealed a large fish bone emerging from the left piriform fossa and arcing over the left arytenoid to hover over the posterior glottis. The bone was removed during anesthesia induction before a rigid esophagoscopy. The fish-bone entry point was seen stabbing through the edge of the piriform fossa and running down alongside the esophagus, without causing a through and through perforation. Fish bone ingestion can cause significant complications including perforation of the esophagus. Early suspicion of ingestion, radiological investigation, and swift management are important to ensure reduced complication rate in children.
An Update on End-Tidal CO2 Monitoring
Authors: Selby Samuel T. , Abramo Thomas , Hobart-Porter Nicholas 
Published: November 2018

Abstract
End-tidal CO2 (etCO2) monitoring is not a new modality in the pediatric emergency department (PED) and emergency department. It is the standard of care during certain procedures such as intubations and sedations and can be used in variety of clinical situations. However, etCO2 may be underused in the PED setting. The implementation of etCO2 monitoring may be accomplished many ways, but a foundation of capnography principles specifically in ventilation, cardiac output, and current literature regarding its application is essential to successful implementation. It is the intention of this article to briefly review the principles of etCO2 monitoring and its clinical applications in the PED setting.
The biofilm in bacterial vaginosis: implications for epidemiology, diagnosis and treatment: 2018 update
Authors: Verstraelen Hans , Swidsinski Alexander 
Published: November 2018

Purpose of review
Bacterial vaginosis is conventionally appreciated as a temporary community disturbance of the vaginal microbiota, though really involving self-organization as a resilient biofilm community. We will briefly review here how recent findings on this matter may affect practice and research in this field.

Recent findings
The rapidly expanding literature base on the vaginal microbiome is largely based on 16S ribosomal ribonucleic acid (rRNA) and cpn60 gene sequencing, with few studies accounting thus far for spatial microbiota organization. The putative sexually transmitted disease profile of bacterial vaginosis inferred from epidemiologic research, may concur with its biofilm nature, notably involving spread of dispersed cells or cell aggregates between hosts. De novo biofilm formation in response to prolonged vaginal ecosystem pressure should be considered a pathogenetic model as well. Biofilm assays may not only aid epidemiologic research, but also add to monitoring therapeutic efficacy of novel treatments. Therapeutic research thus far is largely confined to inhibition of in-vitro biofilm formation, though a recent innovative clinical trial involved a combinational approach of metronidazole and a surfactant, specifically aiming for the biofilm.

Summary
Bacterial vaginosis research will further benefit from biofilm assays complementing taxonomy-based data, and this already translates in a novel treatment paradigm.
Lymphoganuloma venereum in the Western world, 15 years after its re-emergence: new perspectives and research priorities
Authors: de Vries Henry J.C. 
Published: November 2018

Purpose of review
Lymphogranuloma venereum (LGV) is a serious sexually transmitted infection caused by Chlamydia trachomatis. If left untreated LGV can cause irreversible late sequelae. LGV is endemic among a high-risk population of men who have sex with men (MSM), and largely reported in Western metropoles.

Recent findings
Although the majority of LGV patients are HIV positive, in recent years the proportion of HIV-negative MSM with LGV is rising. This could indicate a shift toward lower risk populations. Apart from a few European countries, no proper LGV surveillance efforts have been implemented so far. Moreover, a considerable proportion of the infections are asymptomatic. As a result, the true magnitude of the LGV epidemic is underestimated.
Depending on the stage and location of infection, LGV manifests in a variety of clinical presentations. Among MSM, anorectal infections are overreported as opposed to genital LGV infections in a ratio of 15 to 1, respectively. Therefore, other modes of transmission apart from anal sex are here discussed.

Summary
To improve surveillance, cheaper and more practical screening methods are needed. Moreover, randomized clinical trials are needed to evaluate more simple treatment modalities as opposed to the currently recommended 3-week course of doxycycline.
Can a complex adaptive systems perspective support the resiliency of the heart failure patient – informal caregiver dyad?
Authors: Nimmon Laura , Kimel Gil , Lingard Lorelei , Bates Joanna 
Published: November 2018

Purpose of review
A holistic palliative approach for heart failure care emphasizes supporting nonprofessional informal caregivers. Informal caregivers play a vital role caring for heart failure patients. However, caregiving negatively affects informal caregivers’ well being, and in turn heart failure patients’ health outcomes. This opinion article proposes that complex adaptive systems (CAS) theory applied to heart failure models of care can support the resiliency of the heart failure patient – informal caregiver dyad.

Recent findings
Heart failure care is enacted within a complex system composed of patients, their informal caregivers and a variety of health professionals. In a national study, we employed a CAS perspective to explore how all parts of the heart failure team function interdependently in emergent and adaptive ways. Salient in our data were the severe vulnerability of elderly heart failure patients and their long-term partners who suffered from a chronic illness. Novel approaches are needed that can quickly adapt and reorganize care when unpredictable disturbances occur in the couples’ functional capacity.

Summary
The linear protocol-driven care models that shape heart failure guidelines, training and care delivery initiatives do not adequately capture heart failure patients’ social environment. CAS is a powerful theoretical tool that can render visible the most vulnerable members of the heart failure team, and incite robust specialized holistic palliative heart failure care models.
Salt in freshwaters: causes, effects and prospects - introduction to the theme issue
Authors: Cañedo-Argüelles Miguel , Kefford Ben , Schäfer Ralf 
Published: December 2018

Humans are globally increasing the salt concentration of freshwaters (i.e. freshwater salinization), leading to significant effects at the population, community and ecosystem level. The present theme issue focuses on priority research questions and delivers results that contribute to shaping the future research agenda on freshwater salinization as well as fostering our capacity to manage salinization. The issue is structured along five topics: (i) the estimation of future salinity and evaluation of the relative contribution of the different drivers; (ii) the physiological responses of organisms to alterations in ion concentrations with a specific focus on the osmophysiology of freshwater insects and the responses of different organisims to seawater intrusion; (iii) the impact of salinization on ecosystem functioning, also considering the connections between riparian and stream ecosystems; (iv) the role of context in moderating the response to salinization. The contributions scrutinise the role of additional stressors, biotic interactions, the identify of the ions and their ratios, as well as of the biogeographic and evolutionary context; and (v) the public discourse on salinization and recommendations for management and regulation. In this paper we introduce the general background of salinization, outline research gaps and report key findings from the contributions to this theme issue.
This article is part of the theme issue ‘Salt in freshwaters: causes, ecological consequences and future prospects’.
Predicting current and future background ion concentrations in German surface water under climate change
Authors: Le Trong Dieu Hien , Kattwinkel Mira , Schützenmeister Klaus , Olson John R. , Hawkins Charles P. , Schäfer Ralf B. 
Published: December 2018

Salinization of surface waters is a global environmental issue that can pose a regional risk to freshwater organisms, potentially leading to high environmental and economic costs. Global environmental change including climate and land use change can increase the transport of ions into surface waters. We fit both multiple linear regression (LR) and random forest (RF) models on a large spatial dataset to predict Ca2+(266 sites), Mg2+(266 sites), and(357 sites) ion concentrations as well as electrical conductivity (EC—a proxy for total dissolved solids with 410 sites) in German running water bodies. Predictions in both types of models were driven by the major factors controlling salinity including geologic and soil properties, climate, vegetation and topography. The predictive power of the two types of models was very similar, with RF explaining 71–76% of the spatial variation in ion concentrations and LR explaining 70–75% of the variance. Mean squared errors for predictions were all smaller than 0.06. The factors most strongly associated with stream ion concentrations varied among models but rock chemistry and climate were the most dominant. The RF model was subsequently used to forecast the changes in EC that were likely to occur for the period of 2070 to 2100 in response to just climate change—i.e. no additional effects of other anthropogenic activities. The future forecasting shows approximately 10% and 15% increases in mean EC for representative concentration pathways 2.6 and 8.5 (RCP2.6 and RCP8.5) scenarios, respectively.This article is part of the theme issue ‘Salt in freshwaters: causes, ecological consequences and future prospects’.
Biological interactions mediate context and species-specific sensitivities to salinity
Authors: Bray J. P. , Reich J. , Nichols S. J. , Kon Kam King G. , Mac Nally R. , Thompson R. , O'Reilly-Nugent A. , Kefford B. J. 
Published: December 2018

Toxicants have both sub-lethal and lethal effects on aquatic biota, influencing organism fitness and community composition. However, toxicant effects within ecosystems may be altered by interactions with abiotic and biotic ecosystem components, including biological interactions. Collectively, this generates the potential for toxicant sensitivity to be highly context dependent, with significantly different outcomes in ecosystems than laboratory toxicity tests predict. We experimentally manipulated stream macroinvertebrate communities in 32 mesocosms to examine how communities from a low-salinity site were influenced by interactions with those from a high-salinity site along a gradient of salinity. Relative to those from the low-salinity site, organisms from the high-salinity site were expected to have greater tolerance and fitness at higher salinities. This created the potential for both salinity and tolerant-sensitive organism interactions to influence communities. We found that community composition was influenced by both direct toxicity and tolerant-sensitive organism interactions. Taxon and context-dependent responses included: (i) direct toxicity effects, irrespective of biotic interactions; (ii) effects that were owing to the addition of tolerant taxa, irrespective of salinity; (iii) toxicity dependent on sensitive-tolerant taxa interactions; and (iv) toxic effects that were increased by interactions. Our results reinforce that ecological processes require consideration when examining toxicant effects within ecosystems.
This article is part of the theme issue ‘Salt in freshwaters: causes, ecological consequences and future prospects’.
Temperature affects acute mayfly responses to elevated salinity: implications for toxicity of road de-icing salts
Authors: Jackson John K. , Funk David H. 
Published: December 2018

Salinity in freshwater ecosystems has increased significantly at numerous locations throughout the world, and this increase often reflects the use or production of salts from road de-icing, mining/oil and gas drilling activities, or agricultural production. When related to de-icing salts, highest salinity often occurs in winter when water temperature is often low relative to mean annual temperature at a site. Our study examined acute (96 h) responses to elevated salinity (NaCl) concentrations at five to seven temperature treatments (5–25°C) for four mayfly species (Baetidae:Neocloeon triangulifer,Procloeon fragile; Heptageniidae:Maccaffertium modestum; Leptophlebiidae:Leptophlebia cupida) that are widely distributed across eastern North America. Based on acute LC50s at 20°C,P. fragilewas most sensitive (LC50 = 767 mg l−1, 1447 µS cm−1), followed byN. triangulifer(2755 mg l−1, 5104 µS cm−1),M. modestum(2760 mg l−1, 5118 µS cm−1) andL. cupida(4588 mg l−1, 8485 µS cm−1). Acute LC50s decreased as temperature increased for all four species (n= 5–7,R2= 0.65–0.88,p= 0.052–0.002). Thus, acute salt toxicity is strongly temperature dependent for the mayfly species we tested, which suggests that brief periods of elevated salinity during cold seasons or in colder locations may be ecologically less toxic than predicted by standard 20 or 25°C laboratory bioassays.This article is part of the theme issue ‘Salt in freshwaters: causes, ecological consequences and future prospects’.
Neutrophil Elastase Activates Macrophage MMPs, Promotes Cell Adhesion and Cytokine Production Via Integrin-Src Kinases Pathway
Authors: Krotova Karina , Khodayari Nazli , Oshins Regina , Aslanidi George , Brantly Mark L. 
Published: December 2018

ABSTRACTThere are a number of diseases characterized by the presence of neutrophil elastase (NE) activity in tissues including cystic fibrosis and alpha-1-antitrypsin deficiency induced lung destruction. It is generally accepted that NE actively contributes to this pathological process, but the precise mechanisms has yet to be determined. We hypothesized that NE activates the macrophages (M□) pro-inflammatory program. We demonstrate that following NE exposure, monocyte-derived M□ release proteolytic activity composed of several matrix metalloproteinases (MMPs) which could contribute to extracellular matrix (ECM) degradation. NE upregulates expression of M□ derived pro-inflammatory cytokines including TNFα, IL-1β, and IL-8. Thus, NE-activated M□ can contribute to tissue destruction through the proteolytic activity of metalloproteinases and by supporting chronic inflammation through expression of pro-inflammatory cytokines. We also demonstrate that NE increases M□ adhesion that is attenuated by antibodies specific to integrin subunits. We show that the effects of NE on M□ can be mediated through an activation of integrin pathways. In support of integrin involvement, we demonstrate that NE activates the Src kinase family, a hallmark of integrin signaling activation. Moreover, pretreatment of macrophages with a specific Src kinase inhibitor, PP2, completely prevents NE-induced inflammatory cytokine production. Taken together these findings indicate that NE has effect on lung destruction that extends beyond direct proteolytic degradation of matrix proteins.
Transverse chromatic offsets with pupil displacements in the human eye: Sources of variability and methods for real-time correction
Authors: Boehm Alexandra E. , Privitera Claudio M. , Schmidt Brian P. , Roorda Austin 
Published: December 2018

AbstractTracking SLO systems equipped to perform retinally targeted stimulus delivery typically use near-IR wavelengths for retinal imaging and eye tracking and visible wavelengths for stimulation. The lateral offsets between wavelengths caused by transverse chromatic aberration (TCA) must be carefully corrected in order to deliver targeted stimuli to the correct location on the retina. However, both the magnitude and direction of the TCA offset is dependent on the position of the eye’s pupil relative to the incoming beam, and thus can change dynamically within an experimental session without proper control of the pupil position. The goals of this study were twofold: 1) To assess sources of variability in TCA alignments as a function of pupil displacements in an SLO and 2) To demonstrate a novel method for real-time correction of chromatic offsets. To summarize, we found substantial between- and within-subject variability in TCA in the presence of monochromatic aberrations. When adaptive optics was used to fully correct for monochromatic aberrations, variability both within and between observers was minimized. In a second experiment, we demonstrate that pupil tracking can be used to update stimulus delivery in the SLO in real time to correct for variability in chromatic offsets with pupil displacements.
Characterizing smoking-induced transcriptional heterogeneity in the human bronchial epithelium at single-cell resolution
Authors: Duclos Grant E. , Teixeira Vitor H. , Autissier Patrick , Gesthalter Yaron B. , Reinders-Luinge Marjan A. , Terrano Robert , Dumas Yves M. , Liu Gang , Mazzilli Sarah A. , Brandsma Corry-Anke , van den Berge Maarten , Janes Sam M. , Timens Wim , Lenburg Marc E. , Spira Avrum , Campbell Joshua D. , Beane Jennifer 
Published: December 2018

ABSTRACTThe human bronchial epithelium is composed of multiple, distinct cell types that cooperate to perform functions, such as mucociliary clearance, that defend against environmental insults. While studies have shown that smoking alters bronchial epithelial function and morphology, the precise effects of this exposure on specific cell types are not well-understood. We used single-cell RNA sequencing to profile bronchial epithelial cells from six never- and six current smokers. Unsupervised analyses identified thirteen cell clusters defined by unique combinations of nineteen distinct gene sets. Expression of a set of toxin metabolism genes localized to ciliated cells from smokers. Smoking-induced airway remodeling was characterized by a loss of club cells and extensive goblet cell hyperplasia. Finally, we identified a novel peri-goblet epithelial subpopulation in smokers that expressed a marker of bronchial premalignant lesions. Our data demonstrates that smoke exposure drives a complex landscape of cellular and molecular alterations in the human bronchial epithelium that may contribute to the onset of smoking-associated lung diseases.
Ccube: A fast and robust method for estimating cancer cell fractions
Authors: Yuan Ke , Macintyre Geoff , Liu Wei ,   PCAWG-11 working group, Markowetz Florian 
Published: December 2018

AbstractEstimating and clustering cancer cell fractions of genomic alterations are central tasks for studying intratumour heterogeneity. We present Ccube, a probabilistic framework for inferring the cancer cell fraction of somatic point mutations and the subclonal composition from whole-genome sequencing data. We develop a variational inference method for model fitting, which allows us to handle samples with large number of the variants (more than 2 million) while quantifying uncertainty in a Bayesian fashion. Ccube is available at https://github.com/keyuan/ccube.