bluuebunny/crossref_metadata_2025_split huggingface dataset:
Network inference with ensembles of bi-clustering trees
Authors: Pliakos Konstantinos , Vens Celine 
Published: October 2019

Abstract

Background
Network inference is crucial for biomedicine and systems biology. Biological entities and their associations are often modeled as interaction networks. Examples include drug protein interaction or gene regulatory networks. Studying and elucidating such networks can lead to the comprehension of complex biological processes. However, usually we have only partial knowledge of those networks and the experimental identification of all the existing associations between biological entities is very time consuming and particularly expensive. Many computational approaches have been proposed over the years for network inference, nonetheless, efficiency and accuracy are still persisting open problems. Here, we propose bi-clustering tree ensembles as a new machine learning method for network inference, extending the traditional tree-ensemble models to the global network setting. The proposed approach addresses the network inference problem as a multi-label classification task. More specifically, the nodes of a network (e.g., drugs or proteins in a drug-protein interaction network) are modelled as samples described by features (e.g., chemical structure similarities or protein sequence similarities). The labels in our setting represent the presence or absence of links connecting the nodes of the interaction network (e.g., drug-protein interactions in a drug-protein interaction network).

Results
We extended traditional tree-ensemble methods, such as extremely randomized trees (ERT) and random forests (RF) to ensembles of bi-clustering trees, integrating background information from both node sets of a heterogeneous network into the same learning framework. We performed an empirical evaluation, comparing the proposed approach to currently used tree-ensemble based approaches as well as other approaches from the literature. We demonstrated the effectiveness of our approach in different interaction prediction (network inference) settings. For evaluation purposes, we used several benchmark datasets that represent drug-protein and gene regulatory networks. We also applied our proposed method to two versions of a chemical-protein association network extracted from the STITCH database, demonstrating the potential of our model in predicting non-reported interactions.

Conclusions
Bi-clustering trees outperform existing tree-based strategies as well as machine learning methods based on other algorithms. Since our approach is based on tree-ensembles it inherits the advantages of tree-ensemble learning, such as handling of missing values, scalability and interpretability.
CLINE: a web-tool for the comparison of biological dendrogram structures
Authors: Allendes Osorio Rodolfo S. , Tripathi Lokesh P. , Mizuguchi Kenji 
Published: October 2019

Abstract

Background
When visually comparing the results of hierarchical clustering, the differences in the arrangements of components are of special interest. However, in a biological setting, identifying such differences becomes less straightforward, as the changes in the dendrogram structure caused by permuting biological replicates, do not necessarily imply a different biological interpretation. Here, we introduce a visualization tool to help identify biologically similar topologies across different clustering results, even in the presence of replicates.

Results
Here we introduce CLINE, an open-access web application that allows users to visualize and compare multiple dendrogram structures, by visually displaying the links between areas of similarity across multiple structures. Through the use of a single page and a simple user interface, the user is able to load and remove structures form the visualization, change some aspects of their display and set the parameters used to match cluster topology across consecutive pairs of dendrograms.

Conclusions
We have implemented a web-tool that allows the users to visualize different dendrogram structures, showing not only the structures themselves, but also linking areas of similarity across multiple structures. The software is freely available at http://mizuguchilab.org/tools/cline/. Also, the source code, documentation and installation instructions are available on GitHub at https://github.com/RodolfoAllendes/cline/.
Legofit: estimating population history from genetic data
Authors: Rogers Alan R. 
Published: October 2019

AbstractBackgroundOur current understanding of archaic admixture in humans relies on statistical methods with large biases, whose magnitudes depend on the sizes and separation times of ancestral populations. To avoid these biases, it is necessary to estimate these parameters simultaneously with those describing admixture. Genetic estimates of population histories also confront problems of statistical identifiability: different models or different combinations of parameter values may fit the data equally well. To deal with this problem, we need methods of model selection and model averaging, which are lacking from most existing software.ResultsThe Legofit software package allows simultaneous estimation of parameters describing admixture, and the sizes and separation times of ancestral populations. It includes facilities for data manipulation, estimation, analysis of residuals, model selection, and model averaging.ConclusionsLegofit uses genetic data to study the history of a subdivided population. It is unaffected by recent history and can therefore focus on the deep history of population size, subdivision, and admixture. It outperforms several statistical methods that have been widely used to study population history and should be useful in any species for which DNA sequence data is available from several populations.
Dynamic transcriptome sequencing and analysis during early development in the bighead carp (Hypophthalmichthys nobilis)
Authors: Fu Jianjun , Zhu Wenbin , Wang Lanmei , Luo Mingkun , Song Feibiao , Dong Zaijie 
Published: October 2019

AbstractBackgroundEarly development is a key process of the life history of fish. However, the relationship between the transcriptome and the dynamic regulation of early development is still uncharacterized in the bighead carp (Hypophthalmichthys nobilis). In the present study, we performed transcriptome analysis of six development stages inH. nobilis, aiming to understand the dynamic molecular regulation of early development in this fish.ResultsA total of 76,573 unigenes were assembled from clean sequence reads, with an average length of 1768 base. Among which, 41,742 (54.54%) unigenes were annotated to public protein databases, and an additional 59,014 simple sequence repeat (SSR) loci were identified among the unigenes. Furthermore, 30,199 differentially expressed transcripts (DETs) (fold change > 4 or < 0.25, and the false discovery rate FDR < 0.01) were observed in comparisons between the adjacent developmental stages, and nine expression patterns (profiles) were simulated using series-cluster analysis across six developmental stages. The unigenes expression level markedly increased after the DS1 stage (early blastula), and the numbers of DETs gradually decreased during subsequent development. The largest transcriptomic change (up- or down-regulated) was detected during the period from DS1 to DS2 (6-somite stage), which was enriched for many biological processes and metabolic pathways related to maternal to zygotic transition (MZT). Distinctly protein-protein interaction (PPI) networks were plotted for DETs during the period from DS1 to DS2. The genes (or proteins) from the same pathways were integrated together, and showed with obvious co-regulation patterns. In the series-cluster analysis, a remarkable profile of gene expression (profile_48) was identified that is probably related to the hatching duringH. nobilisdevelopment, and the strict co-expression of a hatching enzyme gene (hce1) with 33 other annotated genes was identified from this profile.ConclusionsThe results indicated that strict dynamic regulation occurs during the early development inH. nobilis, especially in embryogenesis before hatching. This study provides valuable new information and transcriptomic resources related toH. nobilisearly development, and for certain events such as MZT and hatching.
Direct-from-blood RNA sequencing identifies the cause of post-bronchoscopy fever
Authors: Ko Emily R. , Philipson Casandra W. , Burke Thomas W. , Cer Regina Z. , Bishop-Lilly Kimberly A. , Voegtly Logan J. , Tsalik Ephraim L. , Woods Christopher W. , Clark Danielle V. , Schully Kevin L. 
Published: October 2019

Abstract

Background
Antibiotic resistance is rising at disturbing rates and contributes to the deaths of millions of people yearly. Antibiotic resistant infections disproportionately affect those with immunocompromising conditions, chronic colonization, and frequent antibiotic use such as transplant patients or those with cystic fibrosis. However, clinicians lack the diagnostic tools to confidently diagnose and treat infections, leading to widespread use of empiric broad spectrum antimicrobials, often for prolonged duration.

Case presentation
A 22 year-old Caucasian female with cystic fibrosis received a bilateral orthotopic lung transplantation 5 months prior to the index hospitalization. She underwent routine surveillance bronchoscopy and was admitted for post-procedure fever. A clear cause of infection was not identified by routine methods. Imaging and bronchoscopic lung biopsy did not identify an infectious agent or rejection. She was treated with a prolonged course of antimicrobials targeting known colonizing organisms from prior bronchoalveolar lavage cultures (Pseudomonas, Staphylococcus aureus, and Aspergillus). However, we identified Stenotrophomonas maltophilia in two independent whole blood samples using direct-pathogen sequencing, which was not identified by other methods.

Conclusions
This case represents a common clinical conundrum: identification of infection in a high-risk, complex patient. Here, direct-pathogen sequencing identified a pathogen that would not otherwise have been identified by common techniques. Had results been clinically available, treatment could have been customized, avoiding a prolonged course of broad spectrum antimicrobials that would only exacerbate resistance. Direct-pathogen sequencing is poised to fill a diagnostic gap for pathogen identification, allowing early identification and customization of treatment in a culture-independent, pathogen-agnostic manner.
Bayesian modeling of spatiotemporal patterns of TB-HIV co-infection risk in Kenya
Authors: Otiende Verrah , Achia Thomas , Mwambi Henry 
Published: October 2019

Abstract

Background
Tuberculosis (TB) and Human Immunodeficiency Virus (HIV) diseases are globally acknowledged as a public health challenge that exhibits adverse bidirectional relations due to the co-epidemic overlap. To understand the co-infection burden we used the case notification data to generate spatiotemporal maps that described the distribution and exposure hypotheses for further epidemiologic investigations in areas with unusual case notification levels.

Methods
We analyzed the TB and TB-HIV case notification data from the Kenya national TB control program aggregated for forty-seven counties over a seven-year period (2012–2018). Using spatiotemporal poisson regression models within the Integrated Nested Laplace Approach (INLA) paradygm, we modeled the risk of TB-HIV co-infection. Six competing models with varying space-time formulations were compared to determine the best fit model. We then assessed the geographic patterns and temporal trends of coinfection risk by mapping the posterior marginal from the best fit model.

Results
Of the total 608,312 TB case notifications, 194,129 were HIV co-infected. The proportion of TB-HIV co-infection was higher in females (39.7%) than in males (27.0%). A significant share of the co-infection was among adults aged 35 to 44 years (46.7%) and 45 to 54 years (42.1%). Based on the Bayesian Defiance Information (DIC) and the effective number of parameters (pD) comparisons, the spatiotemporal model allowing space-time interaction was the best in explaining the geographical variations in TB-HIV coinfection. The model results suggested that the risk of TB-HIV coinfection was influenced by infrastructure index (Relative risk (RR) = 5.75, Credible Interval (Cr.I) = (1.65, 19.89)) and gender ratio (RR = 5.81e−04, Cr. I = (1.06e−04, 3.18e−03). The lowest and highest temporal relative risks were in the years 2016 at 0.9 and 2012 at 1.07 respectively. The spatial pattern presented an increased co-infection risk in a number of counties. For the spatiotemporal interaction, only a few counties had a relative risk greater than 1 that varied in different years.

Conclusions
We identified elevated risk areas for TB/HIV co-infection and fluctuating temporal trends which could be because of improved TB case detection or surveillance bias caused by spatial heterogeneity in the co-infection dynamics. Focused interventions and continuous TB-HIV surveillance will ensure adequate resource allocation and significant reduction of HIV burden amongst TB patients.
Active immunoprophyilaxis with uromune® decreases the recurrence of urinary tract infections at three and six months after treatment without relevant secondary effects
Authors: Ramírez Sevilla Cristóbal , Gómez Lanza Esther , Manzanera Juan Llopis , Martín Jose Antonio Romero , Sanz Miguel Ángel Barranco 
Published: October 2019

Abstract

Background
To prospectively analyze the efficacy of uromune® in the prevention of uncomplicated recurrent urinary tract infections at 3 and 6 months, and according to gender and menopause.

Methods
From September 2011 to December 2017 uromune® was administered sublingually every 24 h along 3 months to 784 patients with history of three or more uncomplicated urinary tract infections in the 12 months prior to the first visit.
The variables analyzed with statistical package system for science version 15.0 were age, gender, number of urinary tract infections with positive urine culture in the first consultation, and 3 and 6 months after the end of treatment.
The results with positive urine culture were registered at 3 and 6 months after the end of the treatment according to gender and also in the menopausal group with respect to pre-menopausal women.

Results
Mean age was 73.5 years. 82.7% were women and 94.3% menopausal.
The number of episodes of urinary tract infections in the 12 months prior to uromune® were 3 in 37.2%, 4 in 28.1%, 5 in 19.5%, 6 in 9.6%, 7 in 4%, 8 in 1.4%, 9 in 0.1% and 10 in 0.1%.
Three months after uromune® 44.1% had 0 urinary tract infections and 27.6% had 1. After 6 months the results were 0 urinary tract infections in 32.3% and 1 in 32.4%.
Women had 0 urinary tract infections after 3 months in 45.4% and 1 in 28.5%. At 6 months the female had 0 episodes in 32.7% and 1 in 33.2%.
Menopausal women had 0 urinary tract infections at 3 months in 46.5% and 1 in 28% and at 6 months scored 0 episodes in 33.6% and 1 in 32.9%.

Conclusions
Uromune® was highly effective to reduce the number of episodes of urinary tract infections at three and six months of follow-up. Uromune® reduced the number of episodes to zero or one in 71.7 and 64.7% at three and six months with minimal side effects.
The best results were observed in women over 50 years old.
Sublingual immunoprophylaxis with uromune® could be the treatment of first choice in the prevention of uncomplicated recurrent urinary tract infections according to the sample analyzed.
Death due to delirium: a case of a self-cut hemodialysis dialysis catheter - a case report
Authors: Brown Pierre Antoine , Magner Peter O. , Hiremath Swapnil , Clark Edward G. 
Published: October 2019

Abstract

Background
Neuropsychiatric conditions such as depression, delirium and cognitive impairment are common in patients with end-stage kidney disease (ESKD) and individuals suffering from ESKD are more likely to commit suicide than members of the general population. Self-harm gestures are not infrequent for ESKD patients suffering from depression, but not well described in other conditions.

Case presentation
We present a case of self-harm in a patient with ESKD suffering from acute delirium. A man in his mid-seventies was admitted with fungal peritoneal dialysis (PD) associated peritonitis. On the first day post operatively, he was found with absent vital signs due to exsanguination from newly inserted central catheter which he which had self-severed. He died a few days later as a result of the self-harm gesture.

Conclusion
This case highlights that delirium may lead to self-harm events in ESKD and identifies a few strategies to help reduce the risk of self-harm events.
Correlation between significant asymptomatic carotid artery stenosis and severity of peripheral arterial occlusive disease in the lower limb: a retrospective study on 200 patients
Authors: Pan Zhongjie , Wang Ruitao , Li Li , Zhang Hua 
Published: October 2019

Abstract

Background
The aim of this study was to evaluate the correlation between significant asymptomatic carotid artery stenosis (ACAS) and severity of peripheral arterial occlusive disease (PAOD) in the lower limb, and to investigate the risk factors for significant ACAS in patients with lower limb PAOD.

Methods
Two hundred patients with lower limb PAOD were retrospectively reviewed. Baseline data, medical history and potential risk factors were collected. Lower limb PAOD was classified as stage IIA, stage IIB, stage III and stage IV. The carotid artery stenosis was classified as significant ACAS and non-significant ACAS. Multiple logistic regression estimated odds ratio of the risk factors.

Results
Compared to patients with non-significant ACAS, the patients with significant ACAS were significantly older in age and had greater percentage of cigarette-smoking andalcohol beverage consumption, and higher levels of total cholesterol and fibrinogen. There was no significant difference in sex, diabetes, hypertension, coronary heart disease and triglyceride between the two groups. The prevalence rate of significant ACAS increased with the stage of lower limb PAOD and with age. Advanced age and hypercholesteremia were risk factors for significant ACAS in this cohort. The prevalence rate of stroke increased with ACAS stage.

Conclusion
The results suggested that the prevalence rate of significant ACAS was positively correlated with the severity of lower limb PAOD and age. Advanced age and hypercholesteremia appeared to be potential risk factors for significant ACAS in patients with lower limb PAOD.
Dynamic interaction of genetic risk factors and cocaine abuse in the background of Parkinsonism – a case report
Authors: Illés Anett , Balicza Péter , Molnár Viktor , Bencsik Renáta , Szilvási István , Molnar Maria Judit 
Published: October 2019

Abstract

Background
Parkinsonism is a complex multifactorial neurodegenerative disorder, in which genetic and environmental risk factors may both play a role. Among environmental risk factors cocaine was earlier ambiguously linked to Parkinsonism. Former single case reports described Parkinsonism in chronic cocaine users, but an epidemiological study did not confirm an increased risk of Parkinson’s disease. Here we report a patient, who developed Parkinsonism in young age after chronic cocaine use, in whom a homozygous LRRK2 risk variant was also detected.

Case presentation
The patient was investigated because of hand tremor, which started after a 1.5-year period of cocaine abuse. Neurological examination suggested Parkinsonism, and asymmetrical pathology was confirmed by the dopamine transporter imaging study. The genetic investigations revealed a homozygous risk allele in the LRRK2 gene. After a period of cocaine abstinence, the patient’s symptoms spontaneously regressed, and the dopamine transporter imaging also returned to near-normal.

Conclusions
This case report suggests that cocaine abuse indeed might be linked to secondary Parkinsonism and serves as an example of a potential gene-environmental interaction between the detected LRRK2 risk variant and cocaine abuse. The reversible nature of the DaTscan pathology is a unique feature of this case, and needs further evaluation, whether this is incidental or can be a feature of cocaine related Parkinsonism.
A prospective study of maternal postnatal depressive symptoms with infant-feeding practices in a Chinese birth cohort
Authors: Sha Tingting , Gao Xiao , Chen Cheng , Li Ling , Cheng Gang , Wu Xialing , Tian Qianling , Yang Fan , He Qiong , Yan Yan 
Published: October 2019

Abstract

Background
The first few weeks after childbirth are critical, as women may encounter lactation problems and postpartum depression during this period. However, it is still unclear whether early breastfeeding behaviours are related to the symptoms of postnatal depression (PND) in Chinese populations. Therefore, the current study aimed to investigate the association between symptoms of PND and infant feeding practices based on a large-scale Chinese cohort.

Methods
A prospective study of the community-based cohort was conducted from January 2015 to December 2016. Infant feeding outcomes, including exclusive/partial breastfeeding and formula feeding, were assessed according to the WHO guidelines. Symptoms of PND were assessed by the Edinburgh Postnatal Depression Scale at 4 weeks postpartum. Multivariate generalized estimating equation models were applied to investigate the associations between depressive symptoms and infant feeding behaviours.

Results
A total of 956 mother-infant pairs were included. Fifty-six mothers presented screen-positive symptoms of PND with a cut-off ≥10. The percentage of early breastfeeding initiation was 75.8%, while the average duration of exclusive breastfeeding was 3.90 ± 2.33 months. Postnatal depressive symptoms were associated with a shorter breastfeeding duration (8.02 vs. 6.32 months, P < 0.05) and earlier formula introduction (4.98 vs. 3.60 months, P < 0.05). After adjustments were made for covariates, postnatal depressive symptoms were associated with an increased risk of the discontinuation of exclusive and partial breastfeeding (β = − 0.049, P = 0.047 and β = − 0.082, P = 0.006, respectively). Compared to mothers without symptoms of PND, mothers with depressive symptoms were more likely to supplement formula for their infants in the first year of life (β =0.074, P = 0.016). These associations were still significant in the sensitivity analyses, using an EPDS cut-off of ≥13.

Conclusions
Our findings indicate that depressive symptoms at 4 weeks postpartum are associated with the cessation of exclusive and partial breastfeeding duration and the introduction of formula in the 12 months of delivery. Early psychosocial assessment and social support should be offered to mothers in the early postpartum period to indirectly prevent adverse breastfeeding outcomes.