bluuebunny/crossref_metadata_2025 huggingface dataset:
Smcr8 deficiency disrupts axonal transport-dependent lysosomal function and promotes axonal swellings and gain of toxicity in C9ALS/FTD mouse models
Authors: Liang Chen , Shao Qiang , Zhang Wei , Yang Mei , Chang Qing , Chen Rong , Chen Jian-Fu
Published: October 2019

G4C2 repeat expansions in an intron of C9ORF72 cause the most common familial amyotrophic lateral sclerosis and frontotemporal dementia (collectively, C9ALS/FTD). Mechanisms and mediators of C9ALS/FTD pathogenesis remain poorly understood. C9orf72 and Smcr8 form a protein complex. Here, we show that expression of Smcr8, like C9orf72, is reduced in C9ALS/FTD mouse models and patient tissues. Since Smcr8 is highly conserved between human and mouse, we evaluated the effects of Smcr8 downregulation in mice. Smcr8 knockout (KO) mice exhibited motor behavior deficits, which resemble those of C9ALS/FTD mouse models, and displayed axonal swellings in their spinal cords and neuromuscular junctions. These deficits are caused by impaired autophagy-lysosomal functions due to disrupted axonal transport in mutant motor neurons. Consistent with its interaction with C9orf72 and their downregulation in patient tissues, Smcr8 deficiency exacerbated autophagy-lysosomal impairment in C9orf72 KO mice. The disease relevance of Smcr8 downregulation was reflected by exacerbated axonal swellings and gain of toxicity pathology arising from Smcr8 haploinsufficiency in a mouse model of C9ALS/FTD. Thus, our in vivo studies suggested that Smcr8 deficiency impairs axonal transport dependent autophagy-lysosomal function and exacerbates axonal degeneration and gain of toxicity in C9ALS/FTD mouse models.
Functional characterization of a novel PBX1 de novo missense variant identified in a patient with syndromic congenital heart disease
Authors: Alankarage Dimuthu , Szot Justin O , Pachter Nick , Slavotinek Anne , Selleri Licia , Shieh Joseph T , Winlaw David , Giannoulatou Eleni , Chapman Gavin , Dunwoodie Sally L
Published: October 2019

Pre-B cell leukemia factor 1 (PBX1) is an essential developmental transcription factor, mutations in which have recently been associated with CAKUTHED syndrome, characterized by multiple congenital defects including congenital heart disease (CHD). During analysis of a whole-exome-sequenced cohort of heterogeneous CHD patients, we identified a de novo missense variant, PBX1:c.551G>C p.R184P, in a patient with tetralogy of Fallot with absent pulmonary valve and extra-cardiac phenotypes. Functional analysis of this variant by creating a CRISPR-Cas9 gene-edited mouse model revealed multiple congenital anomalies. Congenital heart defects (persistent truncus arteriosus and ventricular septal defect), hypoplastic lungs, hypoplastic/ectopic kidneys, aplastic adrenal glands and spleen, as well as atretic trachea and palate defects were observed in the homozygous mutant embryos at multiple stages of development. We also observed developmental anomalies in a proportion of heterozygous embryos, suggestive of a dominant mode of inheritance. Analysis of gene expression and protein levels revealed that although Pbx1 transcripts are higher in homozygotes, amounts of PBX1 protein are significantly decreased. Here, we have presented the first functional model of a missense PBX1 variant and provided strong evidence that p.R184P is disease-causal. Our findings also expand the phenotypic spectrum associated with pathogenic PBX1 variants in both humans and mice.
Vacuum-assisted venous drainage in adult cardiac surgery: a propensity-matched study
Authors: Gao Sizhe , Li Yongnan , Diao Xiaolin , Yan Shujie , Liu Gang , Liu Mingyue , Zhang Qiaoni , Zhao Wei , Ji Bingyang
Published: October 2019

OBJECTIVES

Conventional cardiopulmonary bypass with gravity drainage leads inevitably to haemodilution. Vacuum-assisted venous drainage (VAVD) utilizes negative pressure in the venous reservoir, allowing active drainage with a shortened venous line to reduce the priming volume. The goal of this study was to analyse the efficacy and safety of VAVD.

METHODS

Data on 19 687 patients (18 681 with gravity drainage and 1006 with VAVD) who underwent cardiac operations between 1 January 2015 and 31 January 2018 were retrospectively collected from a single centre. Propensity matching identified 1002 matched patient pairs with VAVD and gravity drainage for comparison of blood product transfusion rate, major morbidities and in-hospital mortality rates.

RESULTS

The blood transfusion rate of the VAVD group was lower than that of the gravity drainage group (28.1% vs 35% for red blood cells, 13% vs 18% for fresh frozen plasma and 0.1% vs 1.8% for platelets; P = 0.0009, 0.0020 and <0.0001, respectively). The mean difference (95% confidence interval) between the groups for red blood cells, fresh frozen plasma and platelets was −6.9% (−11.0% to −2.8%), −5.0% (−8.1% to −1.8%) and −1.7% (−2.5% to −0.9%), respectively. No difference was observed regarding the major morbidities of cerebrovascular accidents, acute kidney injury, hepatic failure and perioperative myocardial infarction and the in-hospital deaths between the 2 groups.

CONCLUSIONS

VAVD was associated with a reduction in blood product transfusions, and an increase in the risk of major morbidities and in-hospital deaths of the VAVD group was not observed.
Clinical significance of presenting syndromes on outcome after coronary artery bypass grafting
Authors: Bin Mahmood Syed Usman , Mori Makoto , Yousef Sameh , Mullan Clancy W , Mangi Abeel A , Geirsson Arnar
Published: October 2019

OBJECTIVES

Evidence of an association between postoperative survival and the presenting syndrome following coronary artery bypass grafting (CABG) is limited. Our goal was to evaluate whether the presenting symptoms of acute coronary syndrome (ACS) or stable ischaemic heart disease were associated with mid-term survival in patients undergoing CABG.

METHODS

We performed a single-centre retrospective study involving consecutive CABG operations from 2011 to 2016. Post-discharge survival was ascertained via patient-level data linkage with the State of Connecticut vital statistics. Baseline and postoperative variables were compared between the two groups. The multivariate Cox proportional hazard model, adjusted for demographics and comorbidity, was used to show whether the presenting syndrome category was independently associated with mid-term survival.

RESULTS

A total of 1631 patients were included: 794 with stable ischaemic heart disease and 837 with ACS. Patients with ACS who underwent CABG showed more comorbidities. The overall 30-day mortality rate was 1.8% (ACS 2.3% vs stable ischaemic heart disease 1.3%; P = 0.12). In-hospital, postoperative outcomes revealed higher rates of prolonged ventilation (11.7% vs 4.8%; P < 0.001), pneumonia (6.6% vs 3.9%; P = 0.016) and stay in the intensive care unit (3.7 ± 4.0 vs 3.2 ± 2.7 days; P = 0.014) in patients with ACS. The overall mean duration of the long-term follow-up period was 27.9 ± 16.5 months, during which 117 deaths occurred. The multivariable Cox proportional hazard model adjusted for demographics and comorbidity showed that ACS was not a predictor of mid-term mortality [hazard ratio (HR) 1.26, 95% confidence interval (CI) 0.84–1.90; P = 0.26]. Other significant predictors were cardiogenic shock (HR 2.12, 95% CI 1.04–4.33; P = 0.039) and history of congestive heart failure (HR 1.78, 95% CI 1.18–2.69; P = 0.0062).

CONCLUSIONS

The presenting syndrome was not an independent predictor of the mid-term mortality rate. The results indicate that the classification of the presenting syndrome may be fluid and that clinical decision-making for postoperative care of patients who have CABG directed by category of presenting syndrome needs careful consideration. These data should be interpreted in the context of the limitations of this study.
A Cluster of Colistin- and Carbapenem-Resistant Klebsiella pneumoniae Carrying blaNDM-1 and mcr-8.2
Authors: Ma Ke , Feng Yu , Liu Lu , Yao Zhihong , Zong Zhiyong
Published: October 2019

Background

Klebsiella pneumoniae resistant to both carbapenems and colistin imposes severe challenges for management. In this study, we report a cluster of 5 carbapenem-resistant K pneumoniae clinical strains belonging to ST1 and K57 types, 4 of which were also resistant to colistin, from 2 hospitals.

Methods

The 5 strains were subjected to whole-genome sequencing (WGS) using the short-read Illumina HiSeq platform, and 2 strains were also selected for long-read WGS using MinION. Clonal relatedness of the 5 strains was determined based on single-nucleotide polymorphisms (SNPs). Conjugation experiments were performed to obtain self-transmissible plasmids.

Results

All 5 strains carried the carbapenemase-encoding gene blaNDM-1, whereas the 4 colistin-resistant strains also harbored a new variant of the mcr-8 colistin resistance gene, namely, mcr-8.2. MCR-8.2 differs from MCR-8.1 by four amino acid substitutions (A51V, A232S, N365Y, and N480K). mcr-8.2 was located on a large, hybrid, nonself-transmissible plasmid containing IncQ, IncR, and IncFII replicons, whereas blaNDM-1 was carried by self-transmissible IncX3 plasmids. Phylogenetic analysis based on SNPs revealed that the 5 strains were likely to have a common origin.

Conclusions

Both the intra- and interhospital transfer of strains carrying mcr-8 and blaNDM-1 were identified, which represents an emerging threat for clinical management and infection control.
The role of organizational and professional cultures in medication safety: a scoping review of the literature
Authors: Machen Samantha , Jani Yogini , Turner Simon , Marshall Martin , Fulop Naomi J
Published: October 2019

Purpose

This scoping review explores what is known about the role of organizational and professional cultures in medication safety. The aim is to increase our understanding of ‘cultures’ within medication safety and provide an evidence base to shape governance arrangements.

Data sources

Databases searched are ASSIA, CINAHL, EMBASE, HMIC, IPA, MEDLINE, PsycINFO and SCOPUS.

Study selection

Inclusion criteria were original research and grey literature articles written in English and reporting the role of culture in medication safety on either organizational or professional levels, with a focus on nursing, medical and pharmacy professions. Articles were excluded if they did not conceptualize what was meant by ‘culture’ or its impact was not discussed.

Data extraction

Data were extracted for the following characteristics: author(s), title, location, methods, medication safety focus, professional group and role of culture in medication safety.

Results of data synthesis

A total of 1272 citations were reviewed, of which, 42 full-text articles were included in the synthesis. Four key themes were identified which influenced medication safety: professional identity, fear of litigation and punishment, hierarchy and pressure to conform to established culture. At times, the term ‘culture’ was used in a non-specific and arbitrary way, for example, as a metaphor for improving medication safety, but with little focus on what this meant in practice.

Conclusions

Organizational and professional cultures influence aspects of medication safety. Understanding the role these cultures play can help shape both local governance arrangements and the development of interventions which take into account the impact of these aspects of culture.
A unique mechanism for thiolation of serum albumins by disulphide molecules
Authors: Nakashima Fumie , Shibata Takahiro , Uchida Koji
Published: October 2019

Protein S-thiolation is a reversible oxidative modification that serves as an oxidative regulatory mechanism for certain enzymes and binding proteins with reactive cysteine residues. It is generally believed that the thiolation occurs at free sulphydryl group of cysteine residues. Meanwhile, despite the fact that disulphide linkages, serving structural and energetic roles in proteins, are stable and inert to oxidative modification, a recent study shows that the thiolation could also occur at protein disulphide linkages when human serum albumin (HSA) was treated with disulphide molecules, such as cystine and homocystine. A chain reaction mechanism has been proposed for the thiolation at disulphide linkages, in which free cysteine (Cys34) is involved in the reaction with disulphide molecules to form free thiols (cysteine or homocysteine) that further react with protein disulphide linkages to form the thiolated cysteine residues in the protein. This review focuses on the recent finding of this unique chain reaction mechanism of protein thiolation.
Leiomyosarcoma of the superior mesenteric artery: a case report
Authors: Striano Augusto , Esposito Francesco , Crafa Francesco
Published: October 2019

Arterial leiomyosarcoma (A-LMS) is a very rare tumour and no cases originating from the superior mesenteric artery (SMA) have been described. We present a case of A-LMS originating from distal part of SMA and incorporating superior mesenteric vein (SMV). SMA and SMV were prepared along their course by laparotomy. Prior to resection, the superior mesenteric vessels were clamped, and intra-operative infrared angiography after intravenous injection of indocyanine green was performed. Once confirmed the vitality of the bowel, mass resection including the distal portion of the SMA and SMV was executed. The postoperative course was uneventful. Histology confirmed initial diagnosis. Six months after surgery no recurrence was highlighted. This is the first case of A-LMS originating from SMA, successfully treated without any intestinal resection or vascular reconstruction. The use of near-infrared angiography associated with a preoperative angiographic workup is indispensable for the success of the surgery.
Signatures of an eccentric disc cavity: Dust and gas in IRS 48
Authors: Calcino Josh , Price Daniel J , Pinte Christophe , van der Marel Nienke , Ragusa Enrico , Dipierro Giovanni , Cuello Nicolás , Christiaens Valentin
Published: October 2019

We test the hypothesis that the disc cavity in the ‘transition disc’ Oph IRS 48 is carved by an unseen binary companion. We use 3D dust–gas smoothed-particle hydrodynamics simulations to demonstrate that marginally coupled dust grains concentrate in the gas overdensity that forms in the cavity around a low binary mass ratio binary. This produces high contrast ratio dust asymmetries at the cavity edge similar to those observed in the disc around IRS 48 and other transition discs. This structure was previously assumed to be a vortex. However, we show that the observed velocity map of IRS 48 displays a peculiar asymmetry that is not predicted by the vortex hypothesis. We show the unusual kinematics are naturally explained by the non-Keplerian flow of gas in an eccentric circumbinary cavity. We further show that perturbations observed in the isovelocity curves of IRS 48 may be explained as the product of the dynamical interaction between the companion and the disc. The presence of an ∼0.4 M⊙ companion at an ∼10 au separation can qualitatively explain these observations. High spatial resolution line and continuum imaging should be able to confirm this hypothesis.
Leavers and remainers: galaxies split by group-exit
Authors: Choque-Challapa Nelvy , Smith Rory , Candlish Graeme , Peletier Reynier , Shin Jihye
Published: October 2019

The disruption of substructure in galaxy clusters likely plays an important role in shaping the cluster population given that a significant fraction of cluster galaxies today have spent time in a previous host system, and thus may have been pre-processed. Once inside the cluster, group galaxies face the combined environmental effects from group and cluster – so-called post-processing. We investigate these concepts by tracking the evolution of satellites and their hosts after entering the cluster and find that tidal forces during their first pericentric passage are very efficient at breaking up groups, preferentially removing satellites at larger distances from their hosts. 92.2 per cent of satellites whose host has passed pericentre will leave their host by z = 0, typically no later than half a Gyr after pericentric passage. We find satellites leave with high velocities, and quickly separate to large distances from their hosts, making their identification within the cluster population challenging. Those few satellites ($\sim 7.8{{\ \rm per\ cent}}$) that remain bound to their hosts after a pericentric passage are typically found close to their host centres. This implies that substructure seen in clusters today is very likely on first infall into the cluster, and yet to pass pericentre. This is even more likely if the substructure is extended, with satellites beyond R200 of their host. We find the cluster dominates the tidal mass-loss and destruction of satellites, and is responsible for rapidly halting the accretion of new satellites on to hosts once they reach 0.6–0.8R200 radii from the cluster.
Narrow-band Hα imaging of nearby Wolf–Rayet galaxies
Authors: Paswan A , Saha Kanak , Omar A
Published: October 2019

We present narrow-band Hα imaging of nearby Wolf–Rayet (WR) galaxies known as a subset of starburst galaxies. The Hα images have been used to show morphology of star-forming regions in galaxies, which leads to speculate that the studied galaxies have most likely experienced merger or interaction with low luminous dwarf galaxies or H i clouds. We further derive the Hα-based star formation rates (SFRs) in galaxies using our Hα observations. These SFRs are well correlated with SFRs derived using other indicators at far-ultraviolet, far-infrared, and 1.4-GHz radio wavebands. It is noticed that the infrared excess (IRX) method gives the best SFR estimates, consistent with different models predication. These models also predict that the sample galaxies have probably gone through a continuous star formation at least for 1 Gyr over which the recent (<10 Myr) star formation has taken place in WR phase. This study presents main-sequence (MS) relation for nearby WR galaxies for the first time. This derived MS relation is found to be similar to previously known MS relation for normal nearby star-forming galaxies, suggesting that WR systems evolve in a similar fashion as normal star-forming galaxies evolve.
TBC1D20 deficiency induces Sertoli cell apoptosis by triggering irreversible endoplasmic reticulum stress in mice
Authors: Chang Wen-Lin , Cui Lina , Gu Yanli , Li Minghua , Ma Qian , Zhang Zeng , Ye Jing , Zhang Fangting , Yu Jing , Gui Yaoting
Published: October 2019

Male ‘blind sterile’ mice with the causative TBC1 domain family member 20 (TBC1D20) deficiency are infertile with excessive germ cell apoptosis and spermatogenesis arrest at the spermatid stage. Sertoli cells are characterised as ‘nurse cells’ essential for normal spermatogenesis, but the role and corresponding molecular mechanisms of TBC1D20 deficiency in Sertoli cells of mice are not clear to date. In the present study, the histopathology of the testis and Sertoli cell proliferation and apoptosis were determined, and the corresponding molecular mechanisms were investigated by western blotting. Our data showed that TBC1D20 exhibits a testis-abundant expression pattern, and its expression level is positively associated with spermatogenesis. TBC1D20 is assembled in the Golgi and endoplasmic reticulum and is widely expressed by various germ cell subtypes and Sertoli cells. TBC1D20 deficiency in Sertoli cells led to an excessive apoptosis ratio and G1/S arrest. The increased apoptosis of TBC1D20-deficient Sertoli cells resulted from caspase-12 activation. TBC1D20-deficient Sertoli cells had an abnormal Golgi-endoplasmic reticulum structure, which led to endoplasmic reticulum stress, resulting in cell cycle arrest and excessive apoptosis. It suggested that TBC1D20 deficiency triggers irreversible endoplasmic reticulum stress resulting in G1/S arrest and excessive apoptosis in TBC1D20-deficient Sertoli cells, and TBC1D20 deficiency in Sertoli cells may also contribute to the infertility phenotype in ‘blind sterile’ male mice.
EuRBPDB: a comprehensive resource for annotation, functional and oncological investigation of eukaryotic RNA binding proteins (RBPs)
Authors: Liao Jian-You , Yang Bing , Zhang Yu-Chan , Wang Xiao-Juan , Ye Yushan , Peng Jing-Wen , Yang Zhi-Zhi , He Jie-Hua , Zhang Yin , Hu KaiShun , Lin De-Chen , Yin Dong
Published: October 2019

RNA binding proteins (RBPs) are a large protein family that plays important roles at almost all levels of gene regulation through interacting with RNAs, and contributes to numerous biological processes. However, the complete list of eukaryotic RBPs including human is still unavailable. Here, we systematically identified RBPs in 162 eukaryotic species based on both computational analysis of RNA binding domains (RBDs) and large-scale RNA binding proteomic data, and established a comprehensive eukaryotic RBP database, EuRBPDB (http://EuRBPDB.syshospital.org). We identified a total of 311 571 RBPs with RBDs (corresponding to 6368 ortholog groups) and 3,651 non-canonical RBPs without known RBDs. EuRBPDB provides detailed annotations for each RBP, including basic information and functional annotation. Moreover, we systematically investigated RBPs in the context of cancer biology based on published literatures, PPI-network and large-scale omics data. To facilitate the exploration of the clinical relevance of RBPs, we additionally designed a cancer web interface to systematically and interactively display the biological features of RBPs in various types of cancers. EuRBPDB has a user-friendly web interface with browse and search functions, as well as data downloading function. We expect that EuRBPDB will be a widely-used resource and platform for both the communities of RNA biology and cancer biology.
ZAR1 and ZAR2 are required for oocyte meiotic maturation by regulating the maternal transcriptome and mRNA translational activation
Authors: Rong Yan , Ji Shu-Yan , Zhu Ye-Zhang , Wu Yun-Wen , Shen Li , Fan Heng-Yu
Published: October 2019

Zar1 was one of the earliest mammalian maternal-effect genes to be identified. Embryos derived from Zar1-null female mice are blocked before zygotic genome activation; however, the underlying mechanism remains unclear. By knocking out Zar1 and its homolog Zar2 in mice, we revealed a novel function of these genes in oocyte meiotic maturation. Zar1/2-deleted oocytes displayed delayed meiotic resumption and polar body-1 emission and a higher incidence of abnormal meiotic spindle formation and chromosome aneuploidy. The grown oocytes of Zar1/2-null mice contained decreased levels of many maternal mRNAs and displayed a reduced level of protein synthesis. Key maturation-associated changes failed to occur in the Zar1/2-null oocytes, including the translational activation of maternal mRNAs encoding the cell-cycle proteins cyclin B1 and WEE2, as well as maternal-to-zygotic transition (MZT) licensing factor BTG4. Consequently, maternal mRNA decay was impaired and MZT was abolished. ZAR1/2 bound mRNAs to regulate the translational activity of their 3′-UTRs and interacted with other oocyte proteins, including mRNA-stabilizing protein MSY2 and cytoplasmic lattice components. These results countered the traditional view that ZAR1 only functions after fertilization and highlight a previously unrecognized role of ZAR1/2 in regulating the maternal transcriptome and translational activation in maturing oocytes.
The static and dynamic structural heterogeneities of B-DNA: extending Calladine–Dickerson rules
Authors: Dans Pablo D , Balaceanu Alexandra , Pasi Marco , Patelli Alessandro S , Petkevičiūtė Daiva , Walther Jürgen , Hospital Adam , Bayarri Genís , Lavery Richard , Maddocks John H , Orozco Modesto
Published: October 2019

We present a multi-laboratory effort to describe the structural and dynamical properties of duplex B-DNA under physiological conditions. By processing a large amount of atomistic molecular dynamics simulations, we determine the sequence-dependent structural properties of DNA as expressed in the equilibrium distribution of its stochastic dynamics. Our analysis includes a study of first and second moments of the equilibrium distribution, which can be accurately captured by a harmonic model, but with nonlocal sequence-dependence. We characterize the sequence-dependent choreography of backbone and base movements modulating the non-Gaussian or anharmonic effects manifested in the higher moments of the dynamics of the duplex when sampling the equilibrium distribution. Contrary to prior assumptions, such anharmonic deformations are not rare in DNA and can play a significant role in determining DNA conformation within complexes. Polymorphisms in helical geometries are particularly prevalent for certain tetranucleotide sequence contexts and are always coupled to a complex network of coordinated changes in the backbone. The analysis of our simulations, which contain instances of all tetranucleotide sequences, allow us to extend Calladine–Dickerson rules used for decades to interpret the average geometry of DNA, leading to a set of rules with quantitative predictive power that encompass nonlocal sequence-dependence and anharmonic fluctuations.
Gene knockdown in malaria parasites via non-canonical RNAi
Authors: Hentzschel Franziska , Mitesser Vera , Fraschka Sabine Anne-Kristin , Krzikalla Daria , Carrillo Elena Herrera , Berkhout Ben , Bártfai Richárd , Mueller Ann-Kristin , Grimm Dirk
Published: October 2019

The lack of endogenous RNAi machinery in the malaria parasite Plasmodium hampers gene annotation and hence antimalarial drug and vaccine development. Here, we engineered rodent Plasmodium berghei to express a minimal, non-canonical RNAi machinery that solely requires Argonaute 2 (Ago2) and a modified short hairpin RNA, so-called AgoshRNA. Using this strategy, we achieved robust and specific gene knockdown throughout the entire parasite life cycle. We also successfully silenced the endogenous gene perforin-like protein 2, phenocopying a full gene knockout. Transcriptionally restricting Ago2 expression to the liver stage further enabled us to perform a stage-specific gene knockout. The RNAi-competent Plasmodium lines reported here will be a valuable resource for loss-of-function phenotyping of the many uncharacterized genes of Plasmodium in low or high throughput, without the need to engineer the target gene locus. Thereby, our new strategy and transgenic Plasmodium lines will ultimately benefit the discovery of urgently needed antimalarial drug and vaccine candidates. Generally, the ability to render RNAi-negative organisms RNAi-competent by mere introduction of two components, Ago2 and AgoshRNA, is a unique paradigm that should find broad applicability in other species.
Associations of ABO blood type and galactose-deficient immunoglobulin A1 with adverse outcomes in patients with IgA nephropathy
Authors: Wang Manliu , Lv Jicheng , Chen Pei , Yu Guizhen , Shi Sufang , Liu Lijun , Zhou Xujie , Xu Damin , Zhao Minghui , Zhang Hong
Published: October 2019

Background

Both ABO blood group antigens and pathogenic immunoglobulin A1 (IgA1) in patients with IgA nephropathy (IgAN) are influenced by modifications of N-acetylgalactosamine and galactose. The purpose of this study was to assess whether ABO blood type is associated with galactose-deficient IgA1 (Gd-IgA1) in the progression of kidney disease in patients with IgAN.

Methods

We enrolled 1313 IgAN patients with a median of 44 months follow-up and measured the plasma Gd-IgA1 levels. Multivariate Cox regression models were used to estimate the association between all variables and adverse outcomes. Using the propensity score matching method, 718 IgAN patients with blood type either A or B were selected, and their data were used to assess the association of blood type and Gd-IgA1/serum complement 3 (sC3) with outcomes.

Results

We found that the risk of adverse outcomes was significantly higher in patients with blood type A than in those with type B (hazard ratio = 1.82, 95% confidence interval 1.23–2.71; P = 0.003) after multivariate adjustment. The Gd-IgA1 levels showed trends similar to the multivariate-adjusted event-free curves for the blood types. However, this higher risk of adverse outcomes in type A than in type B patients was no longer significant after the addition of Gd-IgA1/sC3 to the model.

Conclusions

IgAN patients with blood type A had a higher risk of adverse outcomes than those with type B, and this risk was associated with Gd-IgA1/sC3. Thus, the ABO blood type may provide a reference for the prognostic factors for individuals with IgAN.
Genome-Wide Identification of Cassava Serine/Arginine-Rich Proteins: Insights into Alternative Splicing of Pre-mRNAs and Response to Abiotic Stress
Authors: Gu Jinbao , Ma Siya , Zhang Yuna , Wang Dong , Cao Shuqing , Wang Zhen-Yu
Published: October 2019

Serine/arginine-rich (SR) proteins have an essential role in the splicing of pre-messenger RNA (pre-mRNA) in eukaryote. Pre-mRNA with introns can be alternatively spliced to generate multiple transcripts, thereby increasing adaptation to the external stress conditions in planta. However, pre-mRNA of SR proteins can also be alternatively spliced in different plant tissues and in response to diverse stress treatments, indicating that SR proteins might be involved in regulating plant development and adaptation to environmental changes. We identified and named 18 SR proteins in cassava and systematically studied their splicing and transcriptional changes under tissue-specific and abiotic stress conditions. Fifteen out of 18 SR genes showed alternative splicing in the tissues. 45 transcripts were found from 18 SR genes under normal conditions, whereas 55 transcripts were identified, and 21 transcripts were alternate spliced in some SR genes under salt stress, suggesting that SR proteins might participate in the plant adaptation to salt stress. We then found that overexpression of MeSR34 in Arabidopsis enhanced the tolerance to salt stress through maintaining reactive oxygen species homeostasis and increasing the expression of calcineurin B-like proteins (CBL)–CBL-interacting protein kinases and osmotic stress-related genes. Therefore, our findings highlight the critical role of cassava SR proteins as regulators of RNA splicing and salt tolerance in planta.
Characterizing and Understanding the Low Back Pain Experience Among Persons with Lower Limb Loss
Authors: Butowicz Courtney M , Silfies Sheri P , Vendemia Jennifer , Farrokhi Shawn , Hendershot Brad D
Published: October 2019

Objective

This study preliminarily characterizes and compares the impact of lower limb loss and development of chronic low back pain (cLBP) on psychosocial factors, as well as the relationship between these factors and low back pain–related functional disability.

Design

Cross-sectional study.

Methods

Participants were adults, active duty or retired military, with traumatic lower limb loss with and without chronic low back pain. Psychosocial factors and low back pain–related functional disability were measured using common clinical self-report questionnaires. The presence of psychosocial factors was compared between those with and without cLBP using multivariate analysis of covariance (P < 0.05), and correlations determined relationships between psychosocial factors and cLBP-related functional disability.

Results

There were no statistically significant differences among psychosocial factors between those with vs without cLBP (F(4, 13) = 0.81, P = 0.54, η2= 0.19). Employment status (ρ = 0.43, P = 0.02), anxiety (ρ = 0.45, P = 0.04), and kinesiophobia (ρ = 0.47, P = 0.04) were moderately associated with low back pain–related disability.

Conclusions

Psychological (i.e., anxiety) and social (i.e., employment status) factors may influence how persons with traumatic lower limb loss respond to self-reported measures of low back pain–related disability. The findings suggest that the Modified Oswestry Disability Index identifies cLBP-related functional disability in the context of lower limb loss. These results support the interdependence among biological, psychological, and social factors, which should be collectively considered during the development of rehabilitative strategies to treat secondary musculoskeletal conditions within this population.
An Age of Promises: British Election Manifestos and Addresses 1900–97
Authors: Thackeray David , Toye Richard
Published: October 2019

This article explores the issue of electoral promises in twentieth-century Britain—how they were made, how they were understood, and how they evolved across time. It does so through a study of general election manifestos (issued by political parties) and election addresses (issued on behalf of individual candidates). The premise of the article is that exploring the act of making promises illuminates the development of political communication and democratic representation, and that considering the print culture and circulation history aspects of addresses and manifestos helps us understand the relationship between the process of pledging and actual policy outcomes. The article further argues that the Labour Party was an innovator that helped push changes in the ways in which policies were promoted to the electorate. It posits that the years 1900–97 saw an important but slow and contested shift towards a more programmatic form of politics. This did not always favour policies of state expansion, but it did favour promises of state action.
Cuticular wax coverage and its transpiration barrier properties in Quercus coccifera L. leaves: does the environment matter?
Authors: Bueno Amauri , Sancho-Knapik Domingo , Gil-Pelegrín Eustaquio , Leide Jana , Peguero-Pina José Javier , Burghardt Markus , Riederer Markus
Published: October 2019

Plants prevent uncontrolled water loss by synthesizing, depositing and maintaining a hydrophobic layer over their primary aerial organs—the plant cuticle. Quercus coccifera L. can plastically respond to environmental conditions at the cuticular level. When exposed to hot summer conditions with high vapour-pressure deficit (VPD) and intense solar radiation (Mediterranean atmospheric conditions; MED), this plant species accumulates leaf cuticular waxes even over the stomata, thereby decreasing transpirational water loss. However, under mild summer conditions with moderate VPD and regular solar radiation (temperate atmospheric conditions; TEM), this effect is sharply reduced. Despite the ecophysiological importance of the cuticular waxes of Q. coccifera, the wax composition and its contribution to avoiding uncontrolled dehydration remain unknown. Thus, we determined several leaf traits for plants exposed to both MED and TEM conditions. Further, we qualitatively and quantitatively investigated the cuticular lipid composition by gas chromatography. Finally, we measured the minimum leaf conductance (gmin) as an indicator of the efficacy of the cuticular transpiration barrier. The MED leaves were smaller, stiffer and contained a higher load of cuticular lipids than TEM leaves. The amounts of leaf cutin and cuticular waxes of MED plants were 1.4 times and 2.6 times higher than that found for TEM plants, respectively. In detail, MED plants produced higher amounts of all compound classes of cuticular waxes, except for the equivalence of alkanoic acids. Although MED leaves contained higher cutin and cuticular wax loads, the gmin was not different between the two habitats. Our findings suggest that the qualitative accumulation of equivalent cuticular waxes might compensate for the higher wax amount of MED plants, thereby contributing equally to the efficacy of the cuticular transpirational barrier of Q. coccifera. In conclusion, we showed that atmospheric conditions profoundly affect the cuticular lipid composition of Q. coccifera leaves, but do not alter its transpiration barrier properties.
The value of PAs in hospital medical staff governance
Authors: DePalma Sondra M.
Published: October 2019

Regulatory and accrediting standards require hospitals to have a medical staff responsible for quality of care, patient safety, and clinician self-governance. PAs are on about 20% of hospital medical staffs in the United States and the number is growing.
Updated guidelines for chronic obstructive pulmonary disease
Authors: Dunn Bethany
Published: October 2019

The 2017 Global Initiative for Chronic Obstructive Lung Disease guidelines for the evaluation and management of chronic obstructive pulmonary disease revise the assessment tool used to evaluate patients, implement a new pharmacologic algorithm focusing on escalation/de-escalation therapy, and recommend new combination inhaled medications. The guidelines also address nonpharmacologic treatments and the importance of identifying and properly managing comorbidities. This article highlights these important changes to clinical practice.
A clinical review of viral hepatitis
Authors: Loader Michelle , Moravek Rudolph , Witowski Sarah E. , Driscoll Lynette M.
Published: October 2019

Viral hepatitis remains a significant public health problem in the United States, despite advances in antiviral therapy and effective vaccines. According to the CDC, about 20,000 deaths each year are attributed to viral hepatitis, and 5 million people are chronically infected and at risk for serious liver disease and hepatocellular cancer. This article reviews the three most common causes of viral hepatitis, screening guidelines, clinical features, medical management, approaches for primary prevention, and the natural history of untreated disease.
Implementation of an Opioid Reduction Protocol for Simple Outpatient Neurosurgical Procedures
Authors: Eley Nicholas , Sikora Matt , Wright Anna K. , Leveque Jean-Christophe
Published: October 2019

Study Design.

Quality improvement with before and after evaluation of the intervention.

Objective.

To evaluate postoperative opioid utilization at a high-volume tertiary referral center following implementation of an opioid reduction protocol for simple outpatient neurosurgical procedures.

Summary of Background Data.

The opioid epidemic has been well-publicized both in the scientific and lay press over the last few years. As a response to this crisis many state-wide and national medical groups have sought to develop opioid prescribing guidelines for both acute and chronic pain states. Some guidelines have studied opioid prescribing in orthopedic procedures but have primarily limited their recommendations to simple outpatient orthopedic joint procedures. Although, it is not clear that these opioid prescribing reductions are directly translatable to neurosurgical procedures.

Methods.

We implemented an opioid reduction protocol geared towards the postoperative management for simple outpatient neurosurgical procedures and measured the effect on number of pills and total morphine equivalent dose (MED) prescribed, postoperative readmissions, refill requests, and conversion to long-term opiate use.

Results.

Our study population was 246 patients, with 109 patients in the pre-intervention (PRE) group and 137 patients in the post-intervention (POST) group. The vast majority of patients in both groups were discharged with an opioid prescription (93% PRE, 91% POST, P = 0.87). The POST group had significantly lower total discharge opioid medication quantity (52 tabs PRE, 27 tabs POST, P < 0.001), discharge day MED (51.3 PRE, 45.3 POST, P = 0.01), and total discharge MED (287 PRE, 149 POST, P < 0.001).

Conclusion.

A standardized discharge protocol for postoperative neurosurgery can lead to significant reductions in opioid discharge quantity without compromising patient safety or increasing the utilization of hospital resources through readmissions, refill requests, or clinic phone calls. This study provides an example of a feasible and effective discharge prescription regimen that may be generalizable to some of the most common outpatient neurosurgical procedures.

Level of Evidence: 3
Trends in Comorbidities and Complications Among Patients Undergoing Inpatient Spine Surgery
Authors: Wilson Lauren A. , Fiasconaro Megan , Liu Jiabin , Bekeris Janis , Poeran Jashvant , Kim David H. , Girardi Federico , Sama Andrew , Memtsoudis Stavros G.
Published: October 2019

Study Design.

Retrospective database study.

Objective.

We sought to identify trends in demographics, comorbidities, and postoperative complications among patients undergoing ACDF and PLF.

Summary of Background Data.

As demand for anterior cervical discectomy and fusion (ACDF) and posterior lumbar fusion (PLF) surgery continues to increase, it is important to understand changes in the healthcare system and patient populations undergoing these procedures.

Methods.

We identified 220,520 ACDF and 151,547 PLF surgeries (2006–2016; Premier Healthcare database). Annual proportions or medians were calculated for patient and hospital characteristics, and (Elixhauser) comorbidities. Postoperative complications, including blood transfusions, cardiovascular, pulmonary, renal, or wound complications, hemorrhage, stroke, sepsis, thromboembolism, delirium, inpatient falls, and mortality, were reported per 1000 inpatient days. Trends were assessed by Cochran–Armitage tests and linear regression for binary and continuous variables, respectively.

Results.

The median age of patients undergoing ACDF and PLF increased significantly from 2006 to 2016 (50 to 57 yr and 58 to 61 yr, respectively; P < 0.001) coinciding with an increasing comorbidity burden (30.2% to 47.9% and 44.9% to 55.7%, respectively representing the share of patients with ≥2 Elixhauser comorbidities; P < 0.001). Overall rate of any complication experienced a significant decline after both ACDF (24.5 to 20.8 per 1000 inpatient days; P = 0.002) and PLF (30.5 to 23.1 per 1000 inpatient days; P < 0.001).

Conclusions.

The comorbidity burden of patients undergoing ACDF and PLF increased substantially from 2006 to 2016, however without a corresponding increase in overall complication rate. Understanding these changes can help guide future practice, advise in the allocation of resources, and inform future areas of research.

Level of Evidence: 3
Inflammatory Cells in Atypical Eruption of Lymphocyte Recovery Carry the Same Mutations as Neoplastic Myeloid Cells
Authors: Prieto-Torres Lucía , Chamizo Cristina , Salgado Rocio Nieves , Atance Mireia , Soto Carlos , Alonso Domínguez Juan Manuel , Arquero Teresa , Piris Miguel Angel , Requena Luis , Rodriguez-Pinilla Socorro María
Published: October 2019

Cutaneous eruption of lymphocyte recovery (ELR) during bone marrow (BM) aplasia recovery after intensive chemotherapy has been reported in very few patients. The presence of skin rashes in patients with acute leukemia who are undergoing intensive chemotherapy and BM transplantation is a diagnostic challenge because of the clinical similarity between drug eruptions, infiltrates related to the relapse of the underlying disease, cutaneous graft-versus-host disease, and ELR. IDH1 mutations have been identified as a recurrent genetic anomaly in acute myeloid leukemia and myelodysplastic syndromes. However, until now, this IDH1 mutation has not been reported as being shared by myeloid cells and non-neoplastic inflammatory cells in this clinical setting. Here, we present the rare case of a woman diagnosed with myelodysplastic syndrome that evolved into an acute myelogenous leukemia with leukemic cutaneous infiltrate. The patient developed ELR after the intensive chemotherapy administered before BM transplantation. The IDH1 mutation was identified in BM cells and in myeloid and inflammatory cells in skin biopsies before allogeneic BM transplantation. We discuss the main aspects of the differential diagnosis of these cutaneous reactions in leukemic patients and the biological significance of the IDH1 mutation.
Distinct Salivary Gland Features in Sjögren's Syndrome and Lupus Erythematosus Sialadenite
Authors: Bologna Sheyla B. , Cavalcante Wanessa S. , Florezi Giovanna P. , Souza Milena M. , Nico Marcello M. S. , Lourenço Silvia V.
Published: October 2019

Background:

Primary Sjögren's syndrome (pSS) is an important cause of xerostomia, and the presence of this symptom in lupus erythematosus (LE) is usually referred to as secondary SS. Although these diseases share many clinical and laboratory aspects, the histopathological changes of minor salivary glands (MSG) have been widely evaluated to determine whether this damage is specific for each disease. Based on this query, the aim of this study was to analyze morphological findings of minor salivary glands in pSS or LE.

Methods:

Two groups of 30 (MSG) from patients with pSS and LE were histopathologically evaluated, and the results were statistically analyzed using the two-tailed Fisher exact test.

Results:

The morphological changes were distinct among the groups and statistically significant. In pSS, the most evident features were the focal lymphocytic ductal aggression, with the focus score ≥1 and the periductal fibroplasia, while in LE, perivascular inflammatory infiltrate, spongiosis of ductal cells not associated with the exocytosis, and hyalinization of the periductal basement membrane were detected.

Conclusions:

These results indicated that in each disorder, MSG have their specific morphological changes, which lead to xerostomia, and the impairment of MSG in LE is probably due to a lupus sialadenitis.
Unusual Case of Nail Unit Melanoma
Authors: Pisano Catherine , Shu Nova , Sharma Sanjay , Soldano Anthony , Keeling Brett
Published: October 2019

We present a case of a nail unit melanoma with chondroid differentiation that was initially misdiagnosed as a benign chondroid neoplasm. A 67-year-old Caucasian woman presented to an outside dermatologist with a tender subungual nodule on the right index finger with overlying nail plate changes that had been present and enlarging for 1 year. Initial histopathological evaluation rendered a diagnosis of benign chondroid neoplasm. On arrival to our institution, magnetic resonance imaging was performed, and the lesion appeared consistent with a glomus tumor. Plastic surgery performed a surgical resection with intraoperative frozen sections revealing a hypocellular cartilaginous mass, but pathology was unable to comment on the presence of malignant cells. On permanent sectioning of the excised lesion, a lentiginous proliferation of melanocytes overlying a dermal aggregate of atypical cells with conspicuous mitoses embedded in a chondroid matrix was seen. A panel of immunohistochemical stains was performed, including SOX-10, HMB-45, S-100, MITF and MART1 was performed with SOX-10, HMB-45, and S-100 staining the junctional melanocytes and dermal cells, rendering a diagnosis of primary chondroid melanoma.
Screening for Anemia in Children with Down Syndrome
Authors: Mittal Shruti , Boan Andrea D. , Pereira-Smith Silvia , LaRosa Angela
Published: October 2019

Objective:

As part of the 2011 American Academy of Pediatrics (AAP) health supervision guidelines for children with Down syndrome (DS), annual screening for iron deficiency anemia is recommended between the ages of 1 and 18 years, but the evidence supporting this recommendation is limited. This study aimed to assess the prevalence of anemia in patients with DS between the ages of 1 and 18 years to provide additional evidence for the AAP 2011 guideline recommendations for annual hemoglobin and ferritin screening in patients with DS.

Methods:

A retrospective cohort study was completed by obtaining data from the electronic health record (EHR) for patients meeting the following inclusion criterion: a diagnosis of DS in patients aged 1 to 18 years seen at our institution with hemoglobin drawn between July 2012 and 2016. Data were analyzed by the Fisher exact test and χ2 test.

Results:

A total of 200 patients were identified. 22.5% had anemia, defined as a hemoglobin concentration less than 2 SDs for normed age. The National Health and Nutrition Examination Survey (2007–2010) reported prevalence of anemia for children aged 1 to 5 years is 3.2% when compared with 18.7% in our sample. Of the 45 children with anemia, 5% had a microcytic, 67.5% a normocytic, and 27.5% a macrocytic anemia. Only 10 received a diagnosis of anemia in the EHR.

Conclusion:

The prevalence of anemia in this cohort of children with DS is significantly higher than that in the general population, supporting the AAP guidelines for an annual screening until the age of 18 years.