bluuebunny/crossref_metadata_2025 huggingface dataset:
Two-Day ABPM-Derived Indices and Mortality in Hemodialysis Patients
Authors: Viazzi Francesca , Cappadona Francesca , Leoncini Giovanna , Ratto Elena , Gonnella Annalisa , Bonino Barbara , Verzola Daniela , Garibotto Giacomo , Pontremoli Roberto
Published: October 2019

BACKGROUND

Blood pressure (BP) and arterial stiffness are known cardiovascular risk factors in hemodialysis (HD) patients. This study examines the prognostic significance of 44-hour BP circadian rhythm and ambulatory arterial stiffness index (AASI) in this population.

METHODS

A total of 80 HD patients underwent 44-hour ambulatory BP monitoring (ABPM) with a TM-2430 monitor during a standard midweek interdialytic interval and followed up for 4.5 ± 1.7 years. The end point was all-cause mortality.

RESULTS

About 76% of participants were hypertensive (40% uncontrolled), 62% were nondippers, and 23% risers during the first interdialytic day, whereas 73% and 44% in the second day, respectively. During follow-up, 31 patients (40%) died. These showed higher pulse pressure (PP) and AASI44 and AASI of the second interdialytic period. The incidence of all-cause mortality was higher in HD patients with AASI44 > median, i.e. >0.54 (interquartile range = 14) (54% vs. 28%, χ 2 = 5.3, P = 0.021) when compared with those with lower AASI44. Second, but not first-day ABPM-derived parameters, namely nondipping (log-rank χ 2 = 6.10, P = 0.0134) or reverse dipping status (log-rank χ 2 = 5.32, P = 0.210) and arterial stiffness index (log-rank χ 2 = 6.61, P = 0.0101) were significantly related to greater mortality.

CONCLUSIONS

These findings indicate a strong relationship between arterial stiffness and cardiovascular risk and support a wider use of 44-hour ABPM recording for risk stratification in HD patients.
Genetic monogamy despite frequent extrapair copulations in “strictly monogamous” wild jackdaws
Authors: Gill Lisa F , van Schaik Jaap , von Bayern Auguste M P , Gahr Manfred L
Published: October 2019

“Monogamy” refers to different components of pair exclusiveness: the social pair, sexual partners, and the genetic outcome of sexual encounters. Avian monogamy is usually defined socially or genetically, whereas quantifications of sexual behavior remain scarce. Jackdaws (Corvus monedula) are considered a rare example of strict monogamy in songbirds, with lifelong pair bonds and little genetic evidence for extrapair (EP) offspring. Yet jackdaw copulations, although accompanied by loud copulation calls, are rarely observed because they occur visually concealed inside nest cavities. Using full-day nest-box video surveillance and on-bird acoustic bio-logging, we directly observed jackdaw sexual behavior and compared it to the corresponding genetic outcome obtained via molecular parentage analysis. In the video-observed nests, we found genetic monogamy but frequently detected forced EP sexual behavior, accompanied by characteristic male copulation calls. We, thus, challenge the long-held notion of strict jackdaw monogamy at the sexual level. Our data suggest that male mate guarding and frequent intrapair copulations during the female fertile phase, as well as the forced nature of the copulations, could explain the absence of EP offspring. Because EP copulation behavior appeared to be costly for both sexes, we suggest that immediate fitness benefits are an unlikely explanation for its prevalence. Instead, sexual conflict and dominance effects could interact to shape the spatiotemporal pattern of EP sexual behavior in this species. Our results call for larger-scale investigations of jackdaw sexual behavior and parentage and highlight the importance of combining social, sexual, and genetic data sets for a more complete understanding of mating systems.
Microhabitat complexity influences fear acquisition in fathead minnows
Authors: Crane Adam L , Ferrari Maud C O , Rivera-Hernández Ita A E , Brown Grant E
Published: October 2019

Habitat varies in structure, with animals often preferring a certain degree of microhabitat complexity that facilitates fitness-related activities such as predator avoidance. Environments with high predation risk can induce elevated baseline fear and neophobia in prey, but whether microhabitat complexity influences the acquisition of neophobia has yet to be reported. Here, we tested whether exposure to predation risk induces different levels of fear in microhabitats that differed in complexity. We exposed fathead minnows, Pimephales promelas, to predation risk repeatedly (12 times over 4 days) in the form of damage-released chemical alarm cues (compared to water control) in tanks with vertical plant structure distributed either throughout the tank (complex habitat) or clumped together (simple habitat). Then, we tested minnows before and after exposure to a novel odor in tanks with either the same microhabitat complexity (i.e., familiar habitats) or in tanks with novel habitat that had different substrate structure and no vertical structure. Minnows in the complex habitat showed less overall movement one day after the background risk period, whereas individuals in the simple habitat showed reduced movement regardless of prior risk exposure. We observed stronger effects in the novel habitat, where background risk in both simple and complex habitats caused neophobia. However, individuals from the simple background habitat showed higher baseline fear behaviors. Hence, for minnows, low microhabitat complexity appears to lead to elevated fear, which remains even after a habitat change.
BCrystal: an interpretable sequence-based protein crystallization predictor
Authors: Elbasir Abdurrahman , Mall Raghvendra , Kunji Khalid , Rawi Reda , Islam Zeyaul , Chuang Gwo-Yu , Kolatkar Prasanna R , Bensmail Halima
Published: October 2019

Motivation

X-ray crystallography has facilitated the majority of protein structures determined to date. Sequence-based predictors that can accurately estimate protein crystallization propensities would be highly beneficial to overcome the high expenditure, large attrition rate, and to reduce the trial-and-error settings required for crystallization.

Results

In this study, we present a novel model, BCrystal, which uses an optimized gradient boosting machine (XGBoost) on sequence, structural and physio-chemical features extracted from the proteins of interest. BCrystal also provides explanations, highlighting the most important features for the predicted crystallization propensity of an individual protein using the SHAP algorithm. On three independent test sets, BCrystal outperforms state-of-the-art sequence-based methods by more than 12.5% in accuracy, 18% in recall and 0.253 in Matthew’s correlation coefficient, with an average accuracy of 93.7%, recall of 96.63% and Matthew’s correlation coefficient of 0.868. For relative solvent accessibility of exposed residues, we observed higher values to associate positively with protein crystallizability and the number of disordered regions, fraction of coils and tripeptide stretches that contain multiple histidines associate negatively with crystallizability. The higher accuracy of BCrystal enables it to accurately screen for sequence variants with enhanced crystallizability.

Availability and implementation

Our BCrystal webserver is at https://machinelearning-protein.qcri.org/ and source code is available at https://github.com/raghvendra5688/BCrystal.

Supplementary information

Supplementary data are available at Bioinformatics online.
Cancer classification of single-cell gene expression data by neural network
Authors: Kim Bong-Hyun , Yu Kijin , Lee Peter C W
Published: October 2019

Motivation

Cancer classification based on gene expression profiles has provided insight on the causes of cancer and cancer treatment. Recently, machine learning-based approaches have been attempted in downstream cancer analysis to address the large differences in gene expression values, as determined by single-cell RNA sequencing (scRNA-seq).

Results

We designed cancer classifiers that can identify 21 types of cancers and normal tissues based on bulk RNA-seq as well as scRNA-seq data. Training was performed with 7398 cancer samples and 640 normal samples from 21 tumors and normal tissues in TCGA based on the 300 most significant genes expressed in each cancer. Then, we compared neural network (NN), support vector machine (SVM), k-nearest neighbors (kNN) and random forest (RF) methods. The NN performed consistently better than other methods. We further applied our approach to scRNA-seq transformed by kNN smoothing and found that our model successfully classified cancer types and normal samples.

Availability and implementation

Cancer classification by neural network.

Supplementary information

Supplementary data are available at Bioinformatics online.
SOLart: a structure-based method to predict protein solubility and aggregation
Authors: Hou Qingzhen , Kwasigroch Jean Marc , Rooman Marianne , Pucci Fabrizio
Published: October 2019

Motivation

The solubility of a protein is often decisive for its proper functioning. Lack of solubility is a major bottleneck in high-throughput structural genomic studies and in high-concentration protein production, and the formation of protein aggregates causes a wide variety of diseases. Since solubility measurements are time-consuming and expensive, there is a strong need for solubility prediction tools.

Results

We have recently introduced solubility-dependent distance potentials that are able to unravel the role of residue–residue interactions in promoting or decreasing protein solubility. Here, we extended their construction by defining solubility-dependent potentials based on backbone torsion angles and solvent accessibility, and integrated them, together with other structure- and sequence-based features, into a random forest model trained on a set of Escherichia coli proteins with experimental structures and solubility values. We thus obtained the SOLart protein solubility predictor, whose most informative features turned out to be folding free energy differences computed from our solubility-dependent statistical potentials. SOLart performances are very good, with a Pearson correlation coefficient between experimental and predicted solubility values of almost 0.7 both in cross-validation on the training dataset and in an independent set of Saccharomyces cerevisiae proteins. On test sets of modeled structures, only a limited drop in performance is observed. SOLart can thus be used with both high-resolution and low-resolution structures, and clearly outperforms state-of-art solubility predictors. It is available through a user-friendly webserver, which is easy to use by non-expert scientists.

Availability and implementation

The SOLart webserver is freely available at http://babylone.ulb.ac.be/SOLART/.

Supplementary information

Supplementary data are available at Bioinformatics online.
Freezing of gait: understanding the complexity of an enigmatic phenomenon
Authors: Weiss Daniel , Schoellmann Anna , Fox Michael D , Bohnen Nicolaas I , Factor Stewart A , Nieuwboer Alice , Hallett Mark , Lewis Simon J G
Published: October 2019

Diverse but complementary methodologies are required to uncover the complex determinants and pathophysiology of freezing of gait. To develop future therapeutic avenues, we need a deeper understanding of the disseminated functional-anatomic network and its temporally associated dynamic processes. In this targeted review, we will summarize the latest advances across multiple methodological domains including clinical phenomenology, neurogenetics, multimodal neuroimaging, neurophysiology, and neuromodulation. We found that (i) locomotor network vulnerability is established by structural damage, e.g. from neurodegeneration possibly as result from genetic variability, or to variable degree from brain lesions. This leads to an enhanced network susceptibility, where (ii) modulators can both increase or decrease the threshold to express freezing of gait. Consequent to a threshold decrease, (iii) neuronal integration failure of a multilevel brain network will occur and affect one or numerous nodes and projections of the multilevel network. Finally, (iv) an ultimate pathway might encounter failure of effective motor output and give rise to freezing of gait as clinical endpoint. In conclusion, we derive key questions from this review that challenge this pathophysiological view. We suggest that future research on these questions should lead to improved pathophysiological insight and enhanced therapeutic strategies.
Evolutionary modifications in human brain connectivity associated with schizophrenia
Authors: van den Heuvel Martijn P , Scholtens Lianne H , de Lange Siemon C , Pijnenburg Rory , Cahn Wiepke , van Haren Neeltje E M , Sommer Iris E , Bozzali Marco , Koch Kathrin , Boks Marco P , Repple Jonathan , Pievani Michela , Li Longchuan , Preuss Todd M , Rilling James K
Published: October 2019

See Vértes and Seidlitz (doi:10.1093/brain/awz353) for a scientific commentary on this article.

Is schizophrenia a by-product of human brain evolution? By comparing the human and chimpanzee connectomes, van den Heuvel et al. demonstrate that connections unique to the human brain show greater involvement in schizophrenia pathology. Modifications in service of higher-order brain functions may have rendered the brain more vulnerable to dysfunction.
Looking beyond the face area: lesion network mapping of prosopagnosia
Authors: Cohen Alexander L , Soussand Louis , Corrow Sherryse L , Martinaud Olivier , Barton Jason J S , Fox Michael D
Published: October 2019

Face blindness can occur after injury to a variety of brain locations, and yet the regions critical for face recognition remain unclear. Cohen et al. show that lesions that cause face blindness map to a specific brain network, and use this to predict subclinical deficits in an independent lesion cohort.
Diagnostic criteria for small fibre neuropathy in clinical practice and research
Authors: Devigili Grazia , Rinaldo Sara , Lombardi Raffaella , Cazzato Daniele , Marchi Margherita , Salvi Erika , Eleopra Roberto , Lauria Giuseppe
Published: October 2019

Definitive diagnostic criteria for small fibre neuropathy have yet to be established, with implications both for clinical practice and for the design of clinical trials. Devigili et al. demonstrate that a combined approach – with clinical, functional and structural assessment of small nerve fibres – improves the reliability of diagnosis.
LncRNA CRNDE acts as an oncogene in cervical cancer through sponging miR-183 to regulate CCNB1 expression
Authors: Bai Xiaoxia , Wang Wendong , Zhao Peng , Wen Jie , Guo Xuedong , Shen Tao , Shen Junhua , Yang Xiaofu
Published: October 2019

Studies have identified a series of lncRNAs that contributed to various tumors, although the underlying mechanisms remain largely unclear. We proposed a ceRNA network and investigate relations among lncRNA/miRNA/mRNA in cervical cancer (CC). The genes of differential expression and lncRNA/miRNA/mRNA network were identified by combining TCGA, miRcode, starBase, miRTarBase, miRDB, TargetScan and STRING databases. Meanwhile, the function enrichment was recognized with Gene Ontology and Kyoto Encyclopedia of Genes and Genomes. Quantitative real time-PCR (qRT-PCR) was performed to determine colorectal neoplasia differentially expressed (CRNDE) expression in CC tissues and cell lines. The effects of CRNDE on the CC biological functions and cyclin B1 (CCNB1) expression were detected by conducting in vitro and in vivo experiments. Quantitative real time-PCR, western blot and dual-luciferase reporter assay were used to predict the target of miR-183. Furthermore, rescue experiments were conducted to further confirm the regulation of CCNB1 by CRNDE. Systematic analyses of bioinformatics from several databases predicted that CRNDE, miR-183 and CCNB1 were in the same network path. Their expressions were up-regulated in CC tissues and cells. Silencing CRNDE-inhibited cell proliferation, migration and invasion, restricted solid tumor growth and promoted cell apoptosis. Moreover, our results suggested that miR-183 targeted the CCNB1 3′UTR and regulated its expression. Additionally, miR-183 mimic could inverse the antitumor function of CRNDE inhibition and partially eliminated the attenuated expression of CCNB1 induced by silencing CRNDE, indicating that CRNDE could positively regulate CCNB1 expression by sponging miR-183. Our study highlighted a role for the CRNDE/miR-183/CCNB1-axis in CC and offered a promising diagnostic strategy for CC treatment.
Key Aspects of Neurovascular Control Mediated by Specific Populations of Inhibitory Cortical Interneurons
Authors: Lee L , Boorman L , Glendenning E , Christmas C , Sharp P , Redgrave P , Shabir O , Bracci E , Berwick J , Howarth C
Published: October 2019

Inhibitory interneurons can evoke vasodilation and vasoconstriction, making them potential cellular drivers of neurovascular coupling. However, the specific regulatory roles played by particular interneuron subpopulations remain unclear. Our purpose was therefore to adopt a cell-specific optogenetic approach to investigate how somatostatin (SST) and neuronal nitric oxide synthase (nNOS)-expressing interneurons might influence the neurovascular relationship. In mice, specific activation of SST- or nNOS-interneurons was sufficient to evoke hemodynamic changes. In the case of nNOS-interneurons, robust hemodynamic changes occurred with minimal changes in neural activity, suggesting that the ability of blood oxygen level dependent functional magnetic resonance imaging (BOLD fMRI) to reliably reflect changes in neuronal activity may be dependent on type of neuron recruited. Conversely, activation of SST-interneurons produced robust changes in evoked neural activity with shallow cortical excitation and pronounced deep layer cortical inhibition. Prolonged activation of SST-interneurons often resulted in an increase in blood volume in the centrally activated area with an accompanying decrease in blood volume in the surrounding brain regions, analogous to the negative BOLD signal. These results demonstrate the role of specific populations of cortical interneurons in the active control of neurovascular function.
Long-term Memory Upscales Volume of Postsynaptic Densities in the Process that Requires Autophosphorylation of αCaMKII
Authors: Śliwińska Małgorzata Alicja , Cały Anna , Borczyk Malgorzata , Ziółkowska Magdalena , Skonieczna Edyta , Chilimoniuk Magdalena , Bernaś Tytus , Giese K Peter , Radwanska Kasia
Published: October 2019

It is generally accepted that formation and storage of memory relies on alterations of the structure and function of brain circuits. However, the structural data, which show learning-induced and long-lasting remodeling of synapses, are still very sparse. Here, we reconstruct 1927 dendritic spines and their postsynaptic densities (PSDs), representing a postsynaptic part of the glutamatergic synapse, in the hippocampal area CA1 of the mice that underwent spatial training. We observe that in young adult (5 months), mice volume of PSDs, but not the volume of the spines, is increased 26 h after the training. The training-induced growth of PSDs is specific for the dendritic spines that lack smooth endoplasmic reticulum and spine apparatuses, and requires autophosphorylation of αCaMKII. Interestingly, aging alters training-induced ultrastructural remodeling of dendritic spines. In old mice, both the median volumes of dendritic spines and PSDs shift after training toward bigger values. Overall, our data support the hypothesis that formation of memory leaves long-lasting footprint on the ultrastructure of brain circuits; however, the form of circuit remodeling changes with age.
Cytomegalovirus Seropositivity Is Associated With Increased Microbial Translocation in People Living With Human Immunodeficiency Virus and Uninfected Controls
Authors: Ramendra Rayoun , Isnard Stéphane , Lin John , Fombuena Brandon , Ouyang Jing , Mehraj Vikram , Zhang Yonglong , Finkelman Malcolm , Costiniuk Cecilia , Lebouché Bertrand , Chartrand-Lefebvre Carl , Durand Madeleine , Tremblay Cécile , Ancuta Petronela , Boivin Guy , Routy Jean-Pierre
Published: October 2019

Background

Cytomegalovirus (CMV) seropositivity and anti-CMV immunoglobulin G (IgG) levels are associated with adverse health outcomes in elderly populations. Among people living with human immunodeficiency virus (PLWH), CMV seropositivity has been associated with persistent CD8 T-cell elevation and increased risk of developing non-AIDS comorbidities despite long-term antiretroviral therapy (ART). Herein, we investigated whether CMV seropositivity and elevation of anti-CMV IgG levels were associated with increased epithelial gut damage, microbial translocation, and systemic inflammation.

Methods

A total of 150 PLWH (79 ART-naive and 71 ART-treated) were compared to 26 without human immunodeficiency virus (HIV) infection (uninfected controls). Plasma markers of HIV disease progression, epithelial gut damage, microbial translocation, nonspecific B-cell activation, anti-CMV and anti–Epstein-Barr virus (EBV) IgG levels, and proinflammatory cytokines were measured.

Results

CMV seropositivity and elevated anti-CMV IgG levels were associated with markers of epithelial gut damage, microbial translocation, and inflammation in PLWH and participants without HIV infection. In contrast, total nonspecific IgG, immunoglobulin M, immunoglobulin A, and anti-EBV IgG levels were not associated with these markers. CMV seropositivity was associated with markers of epithelial gut damage, microbial translocation, and inflammation independent of sociodemographic and behavioral characteristics of the study population.

Conclusions

CMV-seropositive people with and without HIV had increased epithelial gut damage, microbial translocation, and inflammation. Furthermore, anti-CMV IgG levels were independently associated with increased epithelial gut damage and microbial translocation. CMV coinfection may partially explain persistent gut damage, microbial translocation, and inflammation in ART-treated PLWH.
Treatment Options for Carbapenem-resistant Gram-negative Bacterial Infections
Authors: Doi Yohei
Published: October 2019

Antimicrobial resistance has become one of the greatest threats to public health, with rising resistance to carbapenems being a particular concern due to the lack of effective and safe alternative treatment options. Carbapenem-resistant gram-negative bacteria of clinical relevance include the Enterobacteriaceae, Pseudomonas aeruginosa, Acinetobacter baumannii, and more recently, Stenotrophomonas maltophilia. Colistin and tigecycline have been used as first-line agents for the treatment of infections caused by these pathogens; however, there are uncertainties regarding their efficacy even when used in combination with other agents. More recently, several new agents with activity against certain carbapenem-resistant pathogens have been approved for clinical use or are reaching late-stage clinical development. They include ceftazidime-avibactam, ceftolozane-tazobactam, meropenem-vaborbactam, imipenem-cilastatin-relebactam, plazomicin, eravacycline, and cefiderocol. In addition, fosfomycin has been redeveloped in a new intravenous formulation. Data regarding the clinical efficacy of these new agents specific to infections caused by carbapenem-resistant pathogens are slowly emerging and appear to generally favor newer agents over previous best available therapy. As more treatment options become widely available for carbapenem-resistant gram-negative infections, the role of antimicrobial stewardship will become crucial in ensuring appropriate and rationale use of these new agents.
Weight Gain Following Initiation of Antiretroviral Therapy: Risk Factors in Randomized Comparative Clinical Trials
Authors: Sax Paul E , Erlandson Kristine M , Lake Jordan E , Mccomsey Grace A , Orkin Chloe , Esser Stefan , Brown Todd T , Rockstroh Jürgen K , Wei Xuelian , Carter Christoph C , Zhong Lijie , Brainard Diana M , Melbourne Kathleen , Das Moupali , Stellbrink Hans-Jürgen , Post Frank A , Waters Laura , Koethe John R
Published: October 2019

Background

Initiation of antiretroviral therapy (ART) often leads to weight gain. While some of this weight gain may be an appropriate return-to-health effect, excessive increases in weight may lead to obesity. We sought to explore factors associated with weight gain in several randomized comparative clinical trials of ART initiation.

Methods

We performed a pooled analysis of weight gain in 8 randomized controlled clinical trials of treatment-naive people living with human immunodeficiency virus (HIV) initiating ART between 2003 and 2015, comprising >5000 participants and 10 000 person-years of follow-up. We used multivariate modeling to explore relationships between demographic factors, HIV disease characteristics, and ART components and weight change following ART initiation.

Results

Weight gain was greater in more recent trials and with the use of newer ART regimens. Pooled analysis revealed baseline demographic factors associated with weight gain including lower CD4 cell count, higher HIV type 1 RNA, no injection drug use, female sex, and black race. Integrase strand transfer inhibitor use was associated with more weight gain than were protease inhibitors or nonnucleoside reverse transcriptase inhibitors (NNRTIs), with dolutegravir and bictegravir associated with more weight gain than elvitegravir/cobicistat. Among the NNRTIs, rilpivirine was associated with more weight gain than efavirenz. Among nucleoside/nucleotide reverse transcriptase inhibitors, tenofovir alafenamide was associated with more weight gain than tenofovir disoproxil fumarate, abacavir, or zidovudine.

Conclusions

Weight gain is ubiquitous in clinical trials of ART initiation and is multifactorial in nature, with demographic factors, HIV-related factors, and the composition of ART regimens as contributors. The mechanisms by which certain ART agents differentially contribute to weight gain are unknown.
Congestion-Free Transient Plane (CFTP) Using Bandwidth Sharing During Link Failures in SDN
Authors: Vanamoorthy Muthumanikandan , Chinnaiah Valliyammai
Published: October 2019

Software-defined networking (SDN) is an emerging trend where the control plane and the data plane are separated from each other, culminating in effective bandwidth utilization. This separation also allows multi-vendor interoperability. Link failure is a major problem in networking and must be detected as soon as possible because when a link fails the path becomes congested and packet loss occurs, delaying the delivery of packets to the destination. Backup paths must be configured immediately when a failure is detected in the network to speed up packet delivery, avoid congestion and packet loss and provide faster convergence. Various SDN segment protection algorithms that efficiently reduce CPU cycles and flow table entries exist, but each has drawbacks. An independent transient plane technique can be used to reduce packet loss but is not as efficient when multiple flows try to share the same link. The proposed work focuses on reducing congestion, providing faster convergence with minimal packet loss and effectively utilizing link bandwidth using bandwidth-sharing techniques. An analysis and related studies show that this method performs better and offers a more reliable network without loss, while simultaneously ensuring the swift delivery of data packets toward the destination without congestion, compared to the other existing schemes.
Post-apocalyptic humanism in Hesiod, Mary Shelley, and Olaf Stapledon
Authors: Payne Mark
Published: October 2019

This paper considers the role of anachronism in large scale narratives of speculative fiction. Mary Shelley's The Last Man and Olaf Stapledon's Last and First Men signal in their titles an ambition to deal with humankind totally and all inclusively. Both authors look to Hesiod as a model for their projects: the Greek poet's account of successive creations and destructions of humankind at the hands of the gods offers a way of narrating human being as both a local cosmic occurrence that has been and one day will be no longer, and as a life form that has persisted with distinctive orientations and commitments through its various local incarnations. The question of anachronism is thus given maximum scope. Rather than a question about accuracy in the representation of local historical details, anachronism emerges as an interrogation of what we recognize and acknowledge as ourselves in the horizon of deep time.
Thymectomy in ocular myasthenia gravis before generalization results in a higher remission rate
Authors: Li Feng , Li Zhongmin , Chen Yanli , Bauer Gero , Uluk Deniz , Elsner Aron , Swierzy Marc , Ismail Mahmoud , Meisel Andreas , Rückert Jens-C
Published: October 2019

OBJECTIVES

This study aimed to compare the outcomes of patients with ocular myasthenia gravis (OMG) who underwent thymectomy before generalization with the outcomes of those who underwent thymectomy after generalization.

METHODS

We retrospectively reviewed patients who underwent robotic thymectomy for myasthenia gravis between January 2003 and February 2018. Patients who presented with purely ocular symptoms at myasthenia gravis onset were eligible for inclusion. Exclusion criteria were patients who were lost to follow-up and patients who underwent re-thymectomy. Patients with OMG who developed generalization before thymectomy were categorized into gOMG group and those who did not were categorized into OMG group. The primary outcome was complete stable remission according to the Myasthenia Gravis Foundation of America Post-Intervention Status (MGFA-PIS).

RESULTS

One hundred and sixty-five (66 males and 99 females) out of 596 patients with myasthenia gravis were eligible for inclusion. Of these, there were 73 and 92 patients undergoing thymectomy before and after the generalization of OMG, respectively. After propensity score matching, a data set of 130 patients (65 per group) was formed and evaluating results showed no statistical differences between the 2 groups. The estimated cumulative probabilities of complete stable remission at 5 years were 49.5% [95% confidence interval (CI) 0.345–0.611] in the OMG group and 33.4% (95% CI 0.176–0.462) in the gOMG group (P = 0.0053). Similar results were also found in patients with non-thymomatous subgroup [55 patients per group, OMG vs gOMG, 53.5% (95% CI 0.370–0.656) vs 28.9% (95% CI 0.131–0.419), P = 0.0041].

CONCLUSIONS

Thymectomy in OMG before generalization might result in a higher rate of complete stable remission than thymectomy after generalization.
Reduced biventricular contractility during exercise in adults with small, unrepaired ventricular septal defects: an echocardiographic study
Authors: Maagaard Marie , Heiberg Johan , Redington Andrew N , Hjortdal Vibeke E
Published: October 2019

OBJECTIVES

Small ventricular septal defects are often considered to be without long-term haemodynamic consequences and so the majority remains unrepaired. However, we recently showed reduced functional capacity and altered right ventricular morphology in adults with small, unrepaired ventricular septal defects. The underlying mechanisms behind these findings remain unclear, and so, biventricular contractility during exercise was evaluated.

METHODS

Adults with small, unrepaired ventricular septal defects and healthy controls were examined with echocardiography during supine bicycle exercise with increasing workload. Tissue velocity Doppler was used for evaluating isovolumetric acceleration and systolic velocities during exercise.

RESULTS

In total, 34 patients with ventricular septal defects, a median shunt- ratio of 1.2 (26 ± 6 years), and 28 healthy peers (27 ± 5 years) were included. Right ventricular isovolumetric acceleration was lower in patients as compared with controls at rest (97 ± 40 vs 158 ± 43 cm/s2, P = 0.01) and at peak heart rate (222 ± 115 vs 410 ± 120 cm/s2, P < 0.01). Peak systolic velocities were similar at rest, but differed with exercise (13 ± 3 vs 16 ± 3 cm/s, P = 0.02). Left ventricular isovolumetric acceleration was lower in patients as compared with controls throughout the test (P < 0.01). Septal isovolumetric acceleration was similar at rest, but reduced during increasing exercise as compared with controls (220 ± 108 vs 303 ± 119 cm/s2, P = 0.03). Left ventricular isovolumetric acceleration was negatively correlated with the shunt- ratio, and right ventricular and septal peak systolic velocities were positively correlated with lower functional capacity.

CONCLUSIONS

Altered biventricular contractility is present during exercise in adults with small, unrepaired ventricular septal defects. These results add to the growing number of studies showing that long-term outcome in unrepaired ventricular septal defects may not be benign.
‘Much land and water have I and my sweet companion run over…’: newly discovered letters from Muzio Clementi to Gottfried Christoph Härtel
Authors: Sala Luca Lévi
Published: October 2019

Three newly discovered letters from Muzio Clementi to Gottfried Christoph Härtel make a valuable addition to the known corpus of his correspondence with the Leipzig publisher. Held at the Staatsbibliothek zu Berlin (Mus. Slg. Härtel 28–30), these three letters originate in the early years of the second lengthy international trip that Clementi undertook, encompassing the end of 1804 and the first months of 1805, a period when he moved through Germany and settled for a while in Berlin before leaving for his honeymoon in Italy, prior to returning to Berlin. Since the bulk of the extant correspondence between Clementi and Härtel dates from between 1815 and 1822, these letters offer new knowledge about aspects of Clementi’s friendship and business relationship with the German publisher, and about some details of Clementi’s own private life.
Have Changes in Gender Segregation and Occupational Closure Contributed to Increasing Wage Inequality in Germany, 1992–2012?
Authors: Witte Nils
Published: October 2019

Wage inequality continued to increase through the 1990s and 2000s in post-industrial economies. This article contributes to the debate on occupations and inequality by assessing the role of occupational segregation and occupational closure for understanding the increase in inequality. Using employee data for West Germany in 1992 and 2012 and based on decompositions of unconditional quantile regressions the article investigates the contribution of changes in both occupational characteristics to changes in the wage structure. Our findings suggest that both the employment increase in more closed occupations and increased rewards in these occupations have contributed to wage increases across the distribution, especially in the lower half of the wage distribution. Our results further suggest disproportional wage increases in female-dominated occupations at the bottom of the distribution and disproportional wage decreases in male-dominated occupations at the top. If these occupational characteristics had remained at 1992 levels, then 90/10 wage inequality would have been 25 per cent higher in 2012. Thus, changes in occupational characteristics have contributed to wage compression in the observation period.
The association between patterns of atrial fibrillation, anticoagulation, and cardiovascular events
Authors: Atar Dan , Berge Eivind , Le Heuzey Jean-Yves , Virdone Saverio , Camm A John , Steffel Jan , Gibbs Harry , Goldhaber Samuel Z , Goto Shinya , Kayani Gloria , Misselwitz Frank , Stepinska Janina , Turpie Alexander G G , Bassand Jean-Pierre , Kakkar Ajay K ,   for the GARFIELD-AF Investigators
Published: October 2019

Aims

Guidelines do not recommend to take pattern of atrial fibrillation (AF) into account for the indication of anticoagulation (AC). We assessed AF pattern and the risk of cardiovascular events during 2-years of follow-up.

Methods and results

We categorized AF as paroxysmal, persistent, or permanent in 29 181 patients enrolled (2010–15) in the Global Anticoagulant Registry In the FIELD of AF (GARFIELD-AF). We used multivariable Cox regression to assess the risks of stroke/systemic embolism (SE) and death across patterns of AF, and whether this changed with AC on outcomes. Atrial fibrillation pattern was paroxysmal in 14 344 (49.2%), persistent in 8064 (27.6%), and permanent 6773 (23.2%) patients. Median CHA2DS2-VASc, GARFIELD-AF, and HAS-BLED scores assessing the risk of stroke/SE and/or bleeding were similar across AF patterns, but the risk of death, as assessed by the GARFIELD-AF risk calculator, was higher in non-paroxysmal than in paroxysmal AF patterns. During 2-year follow-up, after adjustment, non-paroxysmal AF patterns were associated with significantly higher rates of all-cause death, stroke/SE, and new/worsening congestive heart failure (CHF) than paroxysmal AF in non-anticoagulated patients only. In anticoagulated patients, a significantly higher risk of death but not of stroke/SE and new/worsening CHF persisted in non-paroxysmal compared with paroxysmal AF patterns.

Conclusion

In non-anticoagulated patients, non-paroxysmal AF patterns were associated with higher risks of stroke/SE, new/worsening HF and death than paroxysmal AF. In anticoagulated patients, the risk of stroke/SE and new/worsening HF was similar across all AF patterns. Thus AF pattern is no longer prognostic for stroke/SE when patients are treated with anticoagulants.

Clinical Trial Registration

URL: http://www.clinicaltrials.gov. Unique identifier: NCT01090362.
Attenuation in the mantle wedge beneath super-volcanoes of the Taupo Volcanic Zone, New Zealand
Authors: Eberhart-Phillips Donna , Bannister Stephen , Reyners Martin
Published: October 2019

The Taupo Volcanic Zone has a 120-km-long section of rhyolitic volcanism, within which is a 60-km-long area of supervolcanoes. The underlying subducted slab has along-strike heterogeneity due to the Hikurangi Plateau's prior subduction history. We studied 3-D Qs (1/attenuation) using t* spectral decay from local earthquakes to 370-km depth. Selection emphasized those events with data quality to sample the low Qs mantle wedge, and Qs inversion used varied linking of nodes to obtain resolution in regions of sparse stations, and 3-D initial model. The imaged mantle wedge has a 250-km-long 150-km-wide zone of low Qs (<300) at 65–85 km depth which includes two areas of very low Qs (<120). The most pronounced low Qs feature underlies the Mangakino and Whakamaru super-eruptive calderas, with inferred melt ascending under the central rift structure. The slab is characterized by high Qs (1200–2000), with a relatively small area of reduction in Qs (<800) underlying Taupo at 65-km depth, and adjacent to the mantle wedge low Qs. This suggests abundant dehydration fluids coming off the slab at specific locations and migrating near-vertically upward to the volcanic zone. The seismicity in the subducted slab has a patch of dense seismicity underlying the rhyolitic volcanic zone, consistent with locally abundant fractures and fluid flux. The relationship between the along-arc and downdip slab heterogeneity and dehydration implies that patterns of volcanism may be strongly influenced by large initial outer rise hydration which occurred while the edge of the Hikurangi Plateau hindered subduction. A second very low Qs feature is 50-km west above the 140-km-depth slab. The distinction suggests involvement of a second dehydration peak at that depth, consistent with some numerical models.
Preferred conformations of lipooligosaccharides and oligosaccharides of Moraxella catarrhalis
Authors: Gao Ya , Lee Jumin , Widmalm Göran , Im Wonpil
Published: October 2019

Moraxella catarrhalis (M. catarrhalis) is a pathogenic gram-negative bacterium that causes otitis media and sinusitis in children. Three major serotypes A, B and C are identified to account for approximately 95% of the clinical isolates. Understanding the conformational properties of different serotypes of M. catarrhalis provides insights into antigenic determinants. In this work, all-atom molecular dynamics simulations were conducted for M. catarrhalis lipooligosaccharide (LOS) bilayer systems and oligosaccharides (OS) in water solution to investigate the conformational similarities and differences of three serotypes. For up to 10 neutral monosaccharides in the core part, the conformational ensembles described by the pair-wise root mean square deviation distributions are similar among the three serotypes of either the LOS or OS. At the central β-($1\to4$)-linkage, anti-$\psi$ conformation in conjunction with the gauche-gauche (g−) conformation of the central trisubstituted glucosyl residue is observed as the dominant conformation to sustain the structural characteristics of M. catarrhalis three types, which is further supported by calculated transglycosidic ${}^3{J}_{C,H}\Big({\psi}_H\Big)$ of serotype A in comparison to experimental data. Interestingly, the conformational variability of three serotypes is more restricted for the OS in water solution than that in the LOS bilayer systems. The LOS–LOS interactions in the bilayer systems are responsible for the increased conformational diversity despite of tight packing. Solvent-accessible surface area analysis suggests that a trisaccharide attached to the β-($1\to 6$)-linked sugar in all three serotypes of LOS could be the common epitope and have the possibility to interact with antibodies.
Online STI information seeking behaviour and condom use intentions among young Facebook users in Malaysia
Authors: Mohamad Shakir Sharina Mahavera , Wong Li Ping , Lim Abdullah Khatijah , Adam Phillipe
Published: October 2019

The Internet has opened pathways for youth to find sexual health information which was not easily available to them in the past. Studies have shown that seeking sexual health information online may potentially influence an individuals’ decision-making to change their sexual health behaviours. However, there is a gap in research on the associations of seeking online sexually transmitted infection (STI) information with STI prevention among young people, particularly in Malaysia. This study investigated the associations of seeking STI information online with the intentions of condom use among young adult online users in Malaysia. A cross-sectional online survey was conducted among Malaysian youth aged 18–25 years old who were recruited through Facebook. In total, 1530 respondents completed the survey, identifying 874 respondents who had sought STI information online. The majority of respondents had intentions to use condoms as protection against STI. Respondents who sought online STI information were significantly more likely to have the intention to use condoms compared to respondents who did not seek online STI information (OR = 1.33, 95% CI = 1.01–1.76, p = 0.040). Online STI information has the potential to increase access to STI information among young online users in Malaysia amid the stigma surrounding sex-related issues. Providing accurate STI information online from reliable sources may equip young people who have Internet access with awareness of sexual health protective behaviours such as condom use. It is recommended to facilitate Internet access to reach sectors of the population that currently do not have access, as the Internet is useful in STI prevention.
Point of Care Exome Sequencing Reveals Allelic and Phenotypic Heterogeneity Underlying Mendelian disease in Qatar
Authors: Fakhro Khalid A , Robay Amal , Rodrigues-Flores Juan L , Mezey Jason G , Al-Shakaki Alya A , Chidiac Omar , Stadler Dora , Malek Joel A , Imam Abu Bakr , Sheikh Arwa , Azzam Asmaa , Janahi Ibrahim , Khanjar Izzat , Osman Kamal , Ziki Maen Abu , Mahmah Mohamed Adnan , Selim Mohamed , Numeiri Nuha , Ali Rehab , Lakhani Shenela , Butt Fizza , Omran Tawfeg Ben , Crystal Ronald G
Published: October 2019

The effectiveness of next generation sequencing at solving genetic disease has motivated the rapid adoption of this technology into clinical practice around the world. In this study, we use whole exome sequencing (WES) to assess 48 patients with Mendelian disease from 30 serial families as part of the “Qatar Mendelian Disease pilot program” – a coordinated multi-center effort to build capacity and clinical expertise in genetic medicine in Qatar. By enrolling whole families (parents plus available siblings), we demonstrate significantly improved discriminatory power for candidate variant identification over trios for both de novo and recessive inheritance patterns. For the same index cases, we further demonstrate that even in the absence of families, variant prioritization is improved up to 8-fold when a modest set of population-matched controls is used vs large public databases, stressing the poor representation of Middle Eastern alleles in presently available databases. Our in-house pipeline identified candidate disease variants in 27 of 30 families (90%), 23 of which (85%) harbor novel pathogenic variants in known disease genes, pointing to significant allelic heterogeneity and founder mutations underlying Mendelian disease in the Middle East. For 6 of these families, the clinical presentation was only partially explained by the candidate gene, suggesting phenotypic expansion of known syndromes. Our pilot study demonstrates the utility of WES for Middle Eastern populations, the dramatic improvement in variant prioritization conferred by enrolling population-matched controls and/or enrolling additional unaffected siblings at the point-of-care, and 25 novel disease-causing alleles, relevant to newborn and premarital screening panels in regional populations.
Imprinting effects of UBE3A loss on synaptic gene networks and Wnt signaling pathways
Authors: Lopez S Jesse , Laufer Benjamin I , Beitnere Ulrika , Berg Elizabeth L , Silverman Jill L , O’Geen Henriette , Segal David J , LaSalle Janine M
Published: October 2019

Ubiquitin E3 ligase 3A (UBE3A) encodes an E3 ubiquitin ligase whose loss from the maternal allele causes the neurodevelopmental disorder Angelman syndrome (AS). Previous studies of UBE3A function have not examined full Ube3a deletion in mouse, the complexity of imprinted gene networks in brain nor the molecular basis of systems-level cognitive dysfunctions in AS. We therefore utilized a systems biology approach to elucidate how UBE3A loss impacts the early postnatal brain in a novel CRISPR/Cas9-engineered rat Angelman model of a complete Ube3a deletion. Strand-specific transcriptome analysis of offspring from maternally or paternally inherited Ube3a deletions revealed the expected parental expression patterns of Ube3a sense and antisense transcripts by postnatal day 2 (P2) in hypothalamus and day 9 (P9) in cortex, compared to wild-type littermates. The dependency of genome-wide effects on parent-of-origin, Ube3a genotype and time (P2 and P9) was investigated through transcriptome (RNA sequencing of cortex and hypothalamus) and methylome (whole-genome bisulfite sequencing of hypothalamus). Weighted gene co-expression and co-methylation network analyses identified co-regulated networks in maternally inherited Ube3a deletion offspring enriched in postnatal developmental processes including Wnt signaling, synaptic regulation, neuronal and glial functions, epigenetic regulation, ubiquitin, circadian entrainment and splicing. Furthermore, we showed that loss of the paternal Ube3a antisense transcript resulted in both unique and overlapping dysregulated gene pathways with maternal loss, predominantly at the level of differential methylation. Together, these results provide a holistic examination of the molecular impacts of UBE3A loss in brain, supporting the existence of interactive epigenetic networks between maternal and paternal transcripts at the Ube3a locus.