bluuebunny/crossref_metadata_2025 huggingface dataset:
Integrating Neuropsychology into Interprofessional Geriatrics Clinics
Authors: Brunette Amanda M , Rycroft Sarah Seligman , Colvin Leigh , Schwartz Andrea Wershof , Driver Jane A , Nothern Alexandra , Harrington Mary Beth , Jackson Colleen E
Published: September 2021

Interprofessional healthcare teams are increasingly viewed as a clinical approach to meet the complex medical, psychological, and psychosocial needs of older adult patients. Despite the fact that older adults are at risk for cognitive difficulties, neuropsychologists are not routinely included on Geriatrics consult teams. The primary aim of this paper is to highlight the utility of neuropsychology within an interprofessional Geriatrics consult clinic. To address this aim, we describe specific benefits to patient care that may be associated with the inclusion of neuropsychologists on Geriatrics consult teams, including differential diagnosis, enhanced patient care, and reduced barriers to care. We provide a description of the integration of neuropsychology within a Veterans Health Administration (VA) interprofessional Geriatrics consult clinic team in order to illustrate the implementation of this model.
MAResNet: predicting transcription factor binding sites by combining multi-scale bottom-up and top-down attention and residual network
Authors: Han Ke , Shen Long-Chen , Zhu Yi-Heng , Xu Jian , Song Jiangning , Yu Dong-Jun
Published: September 2021

Accurate identification of transcription factor binding sites is of great significance in understanding gene expression, biological development and drug design. Although a variety of methods based on deep-learning models and large-scale data have been developed to predict transcription factor binding sites in DNA sequences, there is room for further improvement in prediction performance. In addition, effective interpretation of deep-learning models is greatly desirable. Here we present MAResNet, a new deep-learning method, for predicting transcription factor binding sites on 690 ChIP-seq datasets. More specifically, MAResNet combines the bottom-up and top-down attention mechanisms and a state-of-the-art feed-forward network (ResNet), which is constructed by stacking attention modules that generate attention-aware features. In particular, the multi-scale attention mechanism is utilized at the first stage to extract rich and representative sequence features. We further discuss the attention-aware features learned from different attention modules in accordance with the changes as the layers go deeper. The features learned by MAResNet are also visualized through the TMAP tool to illustrate that the method can extract the unique characteristics of transcription factor binding sites. The performance of MAResNet is extensively tested on 690 test subsets with an average AUC of 0.927, which is higher than that of the current state-of-the-art methods. Overall, this study provides a new and useful framework for the prediction of transcription factor binding sites by combining the funnel attention modules with the residual network.
Genome optimization via virtual simulation to accelerate maize hybrid breeding
Authors: Cheng Qian , Jiang Shuqing , Xu Feng , Wang Qian , Xiao Yingjie , Zhang Ruyang , Zhao Jiuran , Yan Jianbing , Ma Chuang , Wang Xiangfeng
Published: September 2021

The employment of doubled-haploid (DH) technology in maize has vastly accelerated the efficiency of developing inbred lines. The selection of superior lines has to rely on genotypes with genomic selection (GS) model, rather than phenotypes due to the high expense of field phenotyping. In this work, we implemented ‘genome optimization via virtual simulation (GOVS)’ using the genotype and phenotype data of 1404 maize lines and their F1 progeny. GOVS simulates a virtual genome encompassing the most abundant ‘optimal genotypes’ or ‘advantageous alleles’ in a genetic pool. Such a virtually optimized genome, although can never be developed in reality, may help plot the optimal route to direct breeding decisions. GOVS assists in the selection of superior lines based on the genomic fragments that a line contributes to the simulated genome. The assumption is that the more fragments of optimal genotypes a line contributes to the assembly, the higher the likelihood of the line favored in the F1 phenotype, e.g. grain yield. Compared to traditional GS method, GOVS-assisted selection may avoid using an arbitrary threshold for the predicted F1 yield to assist selection. Additionally, the selected lines contributed complementary sets of advantageous alleles to the virtual genome. This feature facilitates plotting the optimal route for DH production, whereby the fewest lines and F1 combinations are needed to pyramid a maximum number of advantageous alleles in the new DH lines. In summary, incorporation of DH production, GS and genome optimization will ultimately improve genomically designed breeding in maize.

Short abstract: Doubled-haploid (DH) technology has been widely applied in maize breeding industry, as it greatly shortens the period of developing homozygous inbred lines via bypassing several rounds of self-crossing. The current challenge is how to efficiently screen the large volume of inbred lines based on genotypes. We present the toolbox of genome optimization via virtual simulation (GOVS), which complements the traditional genomic selection model. GOVS simulates a virtual genome encompassing the most abundant ‘optimal genotypes’ in a breeding population, and then assists in selection of superior lines based on the genomic fragments that a line contributes to the simulated genome. Availability of GOVS (https://govs-pack.github.io/) to the public may ultimately facilitate genomically designed breeding in maize.
IntelliPy: a GUI for analyzing IntelliCage data
Authors: Ruffini Nicolas , Müller Marianne B , Schmitt Ulrich , Gerber Susanne
Published: September 2021

The IntelliCage systems offer the possibility to conduct long-term behavioral experiments on mice in social groups without human intervention. Although this setup provides new findings, only about 150 studies with the IntelliCage system have been published in the last two decades, which is also caused by the challenging problems of processing and handling the large and heterogeneous amounts of captured data. This application note introduces the Python-GUI IntelliPy, especially designed for users not very experienced in using programming languages. IntelliPy allows users to quickly analyze the IntelliCage output in a user-friendly way, thus making the systems more accessible to a broader audience.

Availability and implementation

https://github.com/NiRuff/IntelliPy.

Supplementary information

Supplementary data are available at Bioinformatics online.
ACES: Analysis of Conservation with an Extensive list of Species
Authors: Padhi Evin M , Ng Jeffrey K , Mehinovic Elvisa , Sams Eleanor I , Turner Tychele N
Published: September 2021

Motivation

An abundance of new reference genomes is becoming available through large-scale sequencing efforts. While the reference FASTA for each genome is available, there is currently no automated mechanism to query a specific sequence across all new reference genomes.

Results

We developed ACES (Analysis of Conservation with an Extensive list of Species) as a computational workflow to query specific sequences of interest (e.g. enhancers, promoters, exons) against reference genomes with an available reference FASTA. This automated workflow generates BLAST hits against each of the reference genomes, a multiple sequence alignment file, a graphical fragment assembly file and a phylogenetic tree file. These data files can then be used by the researcher in several ways to provide key insights into conservation of the query sequence.

Availability and implementation

ACES is available at https://github.com/TNTurnerLab/ACES

Supplementary information

Supplementary data are available at Bioinformatics online.
CNN-PepPred: an open-source tool to create convolutional NN models for the discovery of patterns in peptide sets—application to peptide–MHC class II binding prediction
Authors: Junet Valentin , Daura Xavier
Published: September 2021

The ability to unveil binding patterns in peptide sets has important applications in several biomedical areas, including the development of vaccines. We present an open-source tool, CNN-PepPred, that uses convolutional neural networks to discover such patterns, along with its application to peptide–HLA class II binding prediction. The tool can be used locally on different operating systems, with CPUs or GPUs, to train, evaluate, apply and visualize models.

Availability and implementation

CNN-PepPred is freely available as a Python tool with a detailed User’s Guide at https://github.com/ComputBiol-IBB/CNN-PepPred. The site includes the peptide sets used in this study, extracted from IEDB (www.iedb.org).

Supplementary information

Supplementary data are available at Bioinformatics online.
Panache: a web browser-based viewer for linearized pangenomes
Authors: Durant Éloi , Sabot François , Conte Matthieu , Rouard Mathieu
Published: September 2021

Motivation

Pangenomics evolved since its first applications on bacteria, extending from the study of genes for a given population to the study of all of its sequences available. While multiple methods are being developed to construct pangenomes in eukaryotic species there is still a gap for efficient and user-friendly visualization tools. Emerging graph representations come with their own challenges, and linearity remains a suitable option for user-friendliness.

Results

We introduce Panache, a tool for the visualization and exploration of linear representations of gene-based and sequence-based pangenomes. It uses a layout similar to genome browsers to display presence absence variations and additional tracks along a linear axis with a pangenomics perspective.

Availability and implementation

Panache is available at github.com/SouthGreenPlatform/panache under the MIT License.
Sciviewer enables interactive visual interrogation of single-cell RNA-Seq data from the Python programming environment
Authors: Kotliar Dylan , Colubri Andrés
Published: September 2021

Motivation

Visualizing two-dimensional embeddings (such as UMAP or tSNE) is a useful step in interrogating single-cell RNA sequencing (scRNA-Seq) data. Subsequently, users typically iterate between programmatic analyses (including clustering and differential expression) and visual exploration (e.g. coloring cells by interesting features) to uncover biological signals in the data. Interactive tools exist to facilitate visual exploration of embeddings such as performing differential expression on user-selected cells. However, the practical utility of these tools is limited because they don’t support rapid movement of data and results to and from the programming environments where most of the data analysis takes place, interrupting the iterative process.

Results

Here, we present the Single-cell Interactive Viewer (Sciviewer), a tool that overcomes this limitation by allowing interactive visual interrogation of embeddings from within Python. Beyond differential expression analysis of user-selected cells, Sciviewer implements a novel method to identify genes varying locally along any user-specified direction on the embedding. Sciviewer enables rapid and flexible iteration between interactive and programmatic modes of scRNA-Seq exploration, illustrating a useful approach for analyzing high-dimensional data.

Availability and implementation

Code and examples are provided at https://github.com/colabobio/sciviewer.
PaReBrick: PArallel REarrangements and BReaks identification toolkit
Authors: Zabelkin Alexey , Yakovleva Yulia , Bochkareva Olga , Alexeev Nikita
Published: September 2021

Motivation

High plasticity of bacterial genomes is provided by numerous mechanisms including horizontal gene transfer and recombination via numerous flanking repeats. Genome rearrangements such as inversions, deletions, insertions and duplications may independently occur in different strains, providing parallel adaptation or phenotypic diversity. Specifically, such rearrangements might be responsible for virulence, antibiotic resistance and antigenic variation. However, identification of such events requires laborious manual inspection and verification of phyletic pattern consistency.

Results

Here, we define the term ‘parallel rearrangements’ as events that occur independently in phylogenetically distant bacterial strains and present a formalization of the problem of parallel rearrangements calling. We implement an algorithmic solution for the identification of parallel rearrangements in bacterial populations as a tool PaReBrick. The tool takes a collection of strains represented as a sequence of oriented synteny blocks and a phylogenetic tree as input data. It identifies rearrangements, tests them for consistency with a tree, and sorts the events by their parallelism score. The tool provides diagrams of the neighbors for each block of interest, allowing the detection of horizontally transferred blocks or their extra copies and the inversions in which copied blocks are involved. We demonstrated PaReBrick’s efficiency and accuracy and showed its potential to detect genome rearrangements responsible for pathogenicity and adaptation in bacterial genomes.

Availability and implementation

PaReBrick is written in Python and is available on GitHub: https://github.com/ctlab/parallel-rearrangements.

Supplementary information

Supplementary data are available at Bioinformatics online.
Phylogenomics of alligator lizards elucidate diversification patterns across the Mexican Transition Zone and support the recognition of a new genus
Authors: Blair Christopher , Bryson Robert W , García-Vázquez Uri O , Nieto-Montes De Oca Adrián , Lazcano David , Mccormack John E , Klicka John
Published: September 2021

Genomic data continue to advance our understanding of species limits and biogeographic patterns. However, there is still no consensus regarding appropriate methods of phylogenomic analysis that make the best use of these heterogeneous data sets. In this study, we used thousands of ultraconserved element (UCE) loci from alligator lizards in the genus Gerrhonotus to compare and contrast species trees inferred using multiple contemporary methods and provide a time frame for biological diversification across the Mexican Transition Zone (MTZ). Concatenated maximum likelihood (ML) and Bayesian analyses provided highly congruent results, with differences limited to poorly supported nodes. Similar topologies were inferred from coalescent analyses in Bayesian Phylogenetics and Phylogeography and SVDquartets, albeit with lower support for some nodes. All divergence times fell within the Miocene, linking speciation to local Neogene vicariance and/or global cooling trends following the mid-Miocene Climatic Optimum. We detected a high level of genomic divergence for a morphologically distinct species restricted to the arid mountains of north-eastern Mexico, and erected a new genus to better reflect evolutionary history. In summary, our results further advocate leveraging the strengths and weaknesses of concatenation and coalescent methods, provide evidence for old divergences for alligator lizards, and indicate that the MTZ continues to harbour substantial unrecognized diversity.
Partial separability and functional graphical models for multivariate Gaussian processes
Authors: Zapata J , Oh S Y , Petersen A
Published: September 2021

The covariance structure of multivariate functional data can be highly complex, especially if the multivariate dimension is large, making extensions of statistical methods for standard multivariate data to the functional data setting challenging. For example, Gaussian graphical models have recently been extended to the setting of multivariate functional data by applying multivariate methods to the coefficients of truncated basis expansions. However, compared with multivariate data, a key difficulty is that the covariance operator is compact and thus not invertible. This paper addresses the general problem of covariance modelling for multivariate functional data, and functional Gaussian graphical models in particular. As a first step, a new notion of separability for the covariance operator of multivariate functional data is proposed, termed partial separability, leading to a novel Karhunen–Loève-type expansion for such data. Next, the partial separability structure is shown to be particularly useful in providing a well-defined functional Gaussian graphical model that can be identified with a sequence of finite-dimensional graphical models, each of identical fixed dimension. This motivates a simple and efficient estimation procedure through application of the joint graphical lasso. Empirical performance of the proposed method for graphical model estimation is assessed through simulation and analysis of functional brain connectivity during a motor task.
Frailty is associated with increased waiting time for relevant process-of-care measures; findings from the Emergency Laparoscopic and Laparotomy Scottish audit (ELLSA)
Authors: Ramsay Euan A. , Carter Ben , Soiza Roy L. , Duffy Siobhan , Moug Susan J. , Myint Phyo K.
Published: September 2021

This paper using Scottish audit data found that frailty was associated with longer waiting times at almost all stages of the preoperative emergency general surgical pathway. Frailty and ASA fitness grade were also good indicators of mortality in this cohort.
Continent ileostomy: short- and long-term outcomes of a forgotten procedure
Authors: Ecker Nils Karl Josef , Möslein Gabriela , Ecker Karl-Wilhelm
Published: September 2021

Background

Continent ileostomy (CI) aims to provide control of gas and faecal evacuation; however, it is rarely performed. This paper reports on outcomes of CI in a large single-surgeon series.

Methods

All consecutive patients who underwent CI between 1986 and 2015 were reviewed. Patients were classified according to the CI procedure (single stage versus two stage) and according to the underlying disease conditions (inflammatory bowel disease (IBD) versus no IBD). Primary outcome measures were early mortality and complications requiring surgical revision within 30 days (group Ia), those requiring surgical revision within 1–12 months (group Ib), and long-term complications after more than 12 months (group II). Secondary outcome measures were pouch survival and quality of life (QoL) assessed using questionnaires for occupational, sports, sexual, and travel activities; patients undergoing CI after conversion from ileostomy. Analyses were performed using descriptive statistics and Kaplan–Meier curves for the long-term outcomes.

Results

Sixty-two consecutive patients (28 men, 34 women) who underwent CI were reviewed, including 48 with IBD, and 14 without inflammatory conditions. Mean(s.d.) follow-up was 14.4 (9.5) (range 1–30) years. Twenty-seven patients (44 per cent) developed group I complications, of which 25 were corrected successfully. Two patients dropped out of the analysis: one who died from sepsis and the other owing to pouch loss attributed to unsolvable nipple complications. Of the remaining 60 patients, 23 (38 per cent) developed between one and five group II complications. The cumulative probability of reoperation was 54. per cent at 25 years. Overall, pouch survival was achieved in 90 per cent. The two-stage approach led to significantly fewer complications in group Ia (single stage versus two stage: 8 of 25 versus 2 of 37; P = 0.005), whereas complication rates in group Ib (5 of 23 versus 14 of 37) and group II (9 of 23 versus 14 of 37) were similar. Four CIs failed because of IBD complications. CI pouch and function were preserved in all patients without IBD, whereas in the group with IBD 2 of 31 with ulcerative colitis and 2 of 17 with Crohn’s colitis lost the CI owing to severe intractable inflammatory complications. In 16 patients who had conversion from ileostomy to CI, QoL improved significantly above precolectomy levels in all domains

Conclusions

CI remains an alternative to conventional ileostomy. Although affected by high reoperation rates, it has the benefit of a high rate of pouch survival.
Called to the Crisis: The Experiences of Hospital-Based Social Workers Providing on-Call Services
Authors: Fox Mim , Hopkins Dominque , Crehan Scott
Published: September 2021

Social workers who are based in hospitals regularly participate in on-call services whereby they respond to crisis or emergency presentations outside of usual working hours. A social work research team across four metropolitan hospitals in a Local Heath District in Sydney, Australia, investigated the experience of participating in an on-call service and the impact this had on the wellbeing of the social workers involved. By utilising a Participatory Action Research methodology that included in-depth interviews and reflective co-analysis, the findings showed evidence of risk for on-call social workers, as well as two key protective factors that mitigate the anxiety associated with night time and crisis work. These factors are preparation for participation in an on-call service, and timely and effective support whilst working outside of normal working hours. This research offers suggested strategies for translation into other hospital social work departments who undertake on-call services.
Sphingolipid changes in Parkinson L444P GBA mutation fibroblasts promote α-synuclein aggregation
Authors: Galvagnion Céline , Marlet Frederik Ravnkilde , Cerri Silvia , Schapira Anthony H V , Blandini Fabio , Di Monte Donato A
Published: September 2021

Intraneuronal accumulation of aggregated α-synuclein is a pathological hallmark of Parkinson’s disease. Therefore, mechanisms capable of promoting α-synuclein deposition bear important pathogenetic implications. Mutations of the glucocerebrosidase 1 (GBA) gene represent a prevalent Parkinson’s disease risk factor. They are associated with loss of activity of a key enzyme involved in lipid metabolism, glucocerebrosidase, supporting a mechanistic relationship between abnormal α-synuclein–lipid interactions and the development of Parkinson pathology.

In this study, the lipid membrane composition of fibroblasts isolated from control subjects, patients with idiopathic Parkinson’s disease and Parkinson's disease patients carrying the L444P GBA mutation (PD-GBA) was assayed using shotgun lipidomics.

The lipid profile of PD-GBA fibroblasts differed significantly from that of control and idiopathic Parkinson’s disease cells. It was characterized by an overall increase in sphingolipid levels. It also featured a significant increase in the proportion of ceramide, sphingomyelin and hexosylceramide molecules with shorter chain length and a decrease in the percentage of longer-chain sphingolipids. The extent of this shift was correlated to the degree of reduction of fibroblast glucocerebrosidase activity. Lipid extracts from control and PD-GBA fibroblasts were added to recombinant α-synuclein solutions. The kinetics of α-synuclein aggregation were significantly accelerated after addition of PD-GBA extracts as compared to control samples. Amyloid fibrils collected at the end of these incubations contained lipids, indicating α-synuclein–lipid co-assembly. Lipids extracted from α-synuclein fibrils were also analysed by shotgun lipidomics. Data revealed that the lipid content of these fibrils was significantly enriched by shorter-chain sphingolipids. In a final set of experiments, control and PD-GBA fibroblasts were incubated in the presence of the small molecule chaperone ambroxol. This treatment restored glucocerebrosidase activity and sphingolipid levels and composition of PD-GBA cells. It also reversed the pro-aggregation effect that lipid extracts from PD-GBA fibroblasts had on α-synuclein.

Taken together, the findings of this study indicate that the L444P GBA mutation and consequent enzymatic loss are associated with a distinctly altered membrane lipid profile that provides a biological fingerprint of this mutation in Parkinson fibroblasts. This altered lipid profile could also be an indicator of increased risk for α-synuclein aggregate pathology.
Metabolome-wide association study of occupational exposure to benzene
Authors: Rothman Nathaniel , Vermeulen Roel , Zhang Luoping , Hu Wei , Yin Songnian , Rappaport Stephen M , Smith Martyn T , Jones Dean P , Rahman Mohammad , Lan Qing , Walker Douglas I
Published: September 2021

Benzene is a recognized hematotoxin and leukemogen; however, its mechanism of action in humans remain unclear. To provide insight into the processes underlying benzene hematotoxicity, we performed high-resolution metabolomic profiling of plasma collected from a cross-sectional study of 33 healthy workers exposed to benzene (median 8-h time-weighted average exposure; 20 ppma), and 25 unexposed controls in Shanghai, China. Metabolic features associated with benzene were identified using a metabolome-wide association study (MWAS) that tested for the relationship between feature intensity and benzene exposure. MWAS identified 478 mass spectral features associated with benzene exposure at false discovery rate < 20%. Comparison to a list of 13 known benzene metabolites and metabolites predicted using a multi-component biotransformation algorithm showed five metabolites were detected, which included the known metabolites phenol and benzene diolepoxide. Metabolic pathway enrichment identified 41 pathways associated with benzene exposure, with altered pathways including carnitine shuttle, fatty acid metabolism, sulfur amino acid metabolism, glycolysis, gluconeogenesis and branched chain amino acid metabolism. These results suggest disruption to fatty acid uptake, energy metabolism and increased oxidative stress, and point towards pathways related to mitochondrial dysfunction, which has previously been linked to benzene exposure in animal models and human studies. Taken together, these results suggest benzene exposure is associated with disruption of mitochondrial pathways, and provide promising, systems biology biomarkers for risk assessment of benzene-induced hematotoxicity in humans.
Age Differences of the Hierarchical Cognitive Control and the Frontal Rostro–Caudal Functional Brain Activation
Authors: Yao Zai-Fu , Hsieh Shulan
Published: September 2021

Age-related differences in the functional hierarchical organization of the frontal lobe remain unclear. We adopted task-related functional magnetic resonance imaging (fMRI) to investigate age differences in the functional hierarchical organization of the frontal lobe. Behavioral results report both reaction time and efficiency declined as the levels of abstraction increased in the selection of a set of stimulus–response mappings in older adults compared with young adults. fMRI findings suggest trends of the hierarchical organization along the rostro–caudal axis in both groups, and brain–behavior correlation further suggests neural dedifferentiation in older adults when performing at the highest level of control demands experiment. Behavioral performances and age difference overactivations at the highest level of control demands were both associated with working memory capacity, suggesting the working memory capacity is important for processing the highest task demands. Region-of-interest analysis revealed age differences in brain overactivation and common activation across experiments in the primary motor cortex, parietal lobule, and the fusiform gyrus may serve as shared mechanisms underlying tasks that are required for the selection of stimulus–response mapping sets. Overall, older adults reflect maladaptive overactivation in task-irrelevant regions that are detrimental to performance with the highest control demands.
Individualized Functional Subnetworks Connect Human Striatum and Frontal Cortex
Authors: Gordon Evan M , Laumann Timothy O , Marek Scott , Newbold Dillan J , Hampton Jacqueline M , Seider Nicole A , Montez David F , Nielsen Ashley M , Van Andrew N , Zheng Annie , Miller Ryland , Siegel Joshua S , Kay Benjamin P , Snyder Abraham Z , Greene Deanna J , Schlaggar Bradley L , Petersen Steven E , Nelson Steven M , Dosenbach Nico U F
Published: September 2021

The striatum and cerebral cortex are interconnected via multiple recurrent loops that play a major role in many neuropsychiatric conditions. Primate corticostriatal connections can be precisely mapped using invasive tract-tracing. However, noninvasive human research has not mapped these connections with anatomical precision, limited in part by the practice of averaging neuroimaging data across individuals. Here we utilized highly sampled resting-state functional connectivity MRI for individual-specific precision functional mapping (PFM) of corticostriatal connections. We identified ten individual-specific subnetworks linking cortex—predominately frontal cortex—to striatum, most of which converged with nonhuman primate tract-tracing work. These included separable connections between nucleus accumbens core/shell and orbitofrontal/medial frontal gyrus; between anterior striatum and dorsomedial prefrontal cortex; between dorsal caudate and lateral prefrontal cortex; and between middle/posterior putamen and supplementary motor/primary motor cortex. Two subnetworks that did not converge with nonhuman primates were connected to cortical regions associated with human language function. Thus, precision subnetworks identify detailed, individual-specific, neurobiologically plausible corticostriatal connectivity that includes human-specific language networks.
A Dual, Systematic Approach to Malaria Diagnostic Biomarker Discovery
Authors: Yerlikaya Seda , Owusu Ewurama D A , Frimpong Augustina , DeLisle Robert Kirk , Ding Xavier C
Published: September 2021

Background

The emergence and spread of Plasmodium falciparum parasites that lack HRP2/3 proteins and the resulting decreased utility of HRP2-based malaria rapid diagnostic tests (RDTs) prompted the World Health Organization and other global health stakeholders to prioritize the discovery of novel diagnostic biomarkers for malaria.

Methods

To address this pressing need, we adopted a dual, systematic approach by conducting a systematic review of the literature for publications on diagnostic biomarkers for uncomplicated malaria and a systematic in silico analysis of P. falciparum proteomics data for Plasmodium proteins with favorable diagnostic features.

Results

Our complementary analyses led us to 2 novel malaria diagnostic biomarkers compatible for use in an RDT format: glyceraldehyde 3-phosphate dehydrogenase and dihydrofolate reductase-thymidylate synthase.

Conclusions

Overall, our results pave the way for the development of next-generation malaria RDTs based on new antigens by identifying 2 lead candidates with favorable diagnostic features and partially de-risked product development prospects.
Rapid Genomic Characterization and Global Surveillance of Klebsiella Using Pathogenwatch
Authors: Argimón Silvia , David Sophia , Underwood Anthony , Abrudan Monica , Wheeler Nicole E , Kekre Mihir , Abudahab Khalil , Yeats Corin A , Goater Richard , Taylor Ben , Harste Harry , Muddyman Dawn , Feil Edward J , Brisse Sylvain , Holt Kathryn , Donado-Godoy Pilar , Ravikumar K L , Okeke Iruka N , Carlos Celia , Aanensen David M ,   NIHR Global Health Research Unit on Genomic Surveillance of Antimicrobial Resistance, Fabian Bernal Johan , Arevalo Alejandra , Fernanda Valencia Maria , Osma Castro Erik C D , Nagaraj Geetha , Shamanna Varun , Govindan Vandana , Prabhu Akshata , Sravani D , Shincy M R , Rose Steffimole , Ravishankar K N , Oaikhena Anderson O , Afolayan Ayorinde O , Ajiboye Jolaade J , Ewomazino Odih Erkison , Lagrada Marietta L , Macaranas Polle Krystle V , Olorosa Agnettah M , Gayeta June M , Masim Melissa Ana L , Herrera Elmer M , Molloy Ali , Stelling John
Published: September 2021

Background

Klebsiella species, including the notable pathogen K. pneumoniae, are increasingly associated with antimicrobial resistance (AMR). Genome-based surveillance can inform interventions aimed at controlling AMR. However, its widespread implementation requires tools to streamline bioinformatic analyses and public health reporting.

Methods

We developed the web application Pathogenwatch, which implements analytics tailored to Klebsiella species for integration and visualization of genomic and epidemiological data. We populated Pathogenwatch with 16 537 public Klebsiella genomes to enable contextualization of user genomes. We demonstrated its features with 1636 genomes from 4 low- and middle-income countries (LMICs) participating in the NIHR Global Health Research Unit (GHRU) on AMR.

Results

Using Pathogenwatch, we found that GHRU genomes were dominated by a small number of epidemic drug-resistant clones of K. pneumoniae. However, differences in their distribution were observed (eg, ST258/512 dominated in Colombia, ST231 in India, ST307 in Nigeria, ST147 in the Philippines). Phylogenetic analyses including public genomes for contextualization enabled retrospective monitoring of their spread. In particular, we identified hospital outbreaks, detected introductions from abroad, and uncovered clonal expansions associated with resistance and virulence genes. Assessment of loci encoding O-antigens and capsule in K. pneumoniae, which represent possible vaccine candidates, showed that 3 O-types (O1–O3) represented 88.9% of all genomes, whereas capsule types were much more diverse.

Conclusions

Pathogenwatch provides a free, accessible platform for real-time analysis of Klebsiella genomes to aid surveillance at local, national, and global levels. We have improved representation of genomes from GHRU participant countries, further facilitating ongoing surveillance.
Methodology to Determine Cause of Death for Stillbirths and Neonatal Deaths Using Automated Case Reports and a Cause-of-Death Panel
Authors: Hwang Kay S , Parlberg Lindsay , Aceituno Anna , Moore Janet L , Goudar Shivaprasad S , Sunder Tikmani Shiyam , Saleem Sarah , Guruprasad Gowdar , Revankar Amit , Habib Zaheer , Dhaded Sangappa M , Yogesh Kumar S , Raghoji Chaitali , Kusugur Varun , Pujar Sneharoopa , Roujani Sana , McClure Elizabeth M , Goldenberg Robert L
Published: September 2021

Background

Review of data from multiple sources is often necessary to determine cause of death for stillbirths and neonatal deaths, especially in low- to middle-income countries (LMICs) where available data may vary. The minimally invasive tissue sampling (MITS) procedure provides granular histologic and microbiologic data that clinical reports and verbal autopsies cannot provide. Expert panel evaluation of data from individual deaths can be resource-intensive but remains essential to accurately infer causes of death.

Methods

The Project to Understand and Research Preterms and Stillbirths in South Asia (PURPOSe) study uses review panels to evaluate causes of death in 2 LMICs. To make the process manageable, a subset of the study variables was selected with professional input and organized into case reports. Case reports include clinical information, laboratory results, fetal or neonatal organ histology and polymerase chain reaction results from tissue obtained by MITS. Panelists evaluated the complete case report forms and then determined the cause of death based on available data.

Results

Computerized case reports averaged 2 to 3 pages. Approximately 6 to 8 cases were reviewed and discussed per 1-hour panel meeting. All panelists were provided the same information; missing data were noted. This limited bias between panelists and across meetings. Study teams notably took ownership of data quality.

Conclusions

Standardized case reports for cause-of-death determination panel evaluation improve the efficiency of the review process, clarify available information, and limit bias across panelists, time, and location.
Minimally Invasive Tissue Sampling Findings in 12 Patients With Coronavirus Disease 2019
Authors: Rakislova Natalia , Rodrigo-Calvo Maria Teresa , Marimon Lorena , Ribera-Cortada Inmaculada , Ismail Mamudo R , Carrilho Carla , Fernandes Fabiola , Ferrando Melania , Sanfeliu Esther , Castillo Paola , Guerrero José , Ramírez-Ruz José , Saez de Gordoa Karmele , López Del Campo Ricardo , Bishop Rosanna , Ortiz Estrella , Muñoz-Beatove Abel , Vila Jordi , Hurtado Juan Carlos , Navarro Mireia , Maixenchs Maria , Delgado Vima , Aldecoa Iban , Martinez-Pozo Antonio , Castro Pedro , Menéndez Clara , Bassat Quique , Martinez Miguel J , Ordi Jaume
Published: September 2021

Background

Minimally invasive tissue sampling (MITS), a postmortem procedure that uses core needle biopsy samples and does not require opening the body, may be a valid alternative to complete autopsy (CA) in highly infectious diseases such as coronavirus disease-19 (COVID-19). This study aimed to (1) compare the performance of MITS and CA in a series of COVID-19 deaths and (2) evaluate the safety of the procedure.

Methods

From October 2020 to February 2021, MITS was conducted in 12 adults who tested positive before death for COVID-19, in a standard, well-ventilated autopsy room, where personnel used reinforced personal protective equipment. In 9 cases, a CA was performed after MITS. A thorough histological evaluation was conducted, and the presence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was evaluated by real-time reverse-transcription polymerase chain reaction (RT-PCR) and immunohistochemistry.

Results

The diagnoses provided by MITS and CA matched almost perfectly. In 9 patients, COVID-19 was in the chain of events leading to death, being responsible for diffuse alveolar damage and mononuclear T-cell inflammatory response in the lungs. No specific COVID-19 features were identified. Three deaths were not related to COVID-19. All personnel involved in MITS repeatedly tested negative for COVID-19. SARS-CoV-2 was identified by RT-PCR and immunohistochemistry in the MITS samples, particularly in the lungs.

Conclusions

MITS is useful for evaluating COVID-19–related deaths in settings where a CA is not feasible. The results of this simplified and safer technique are comparable to those of CA.
Colocalization of Radicular Pain and Erythema Migrans in Patients With Bannwarth Syndrome Suggests a Direct Spread of Borrelia Into the Central Nervous System
Authors: Ogrinc Katarina , Kastrin Andrej , Lotrič-Furlan Stanka , Bogovič Petra , Rojko Tereza , Maraspin Vera , Ružić-Sabljić Eva , Strle Klemen , Strle Franc
Published: September 2021

Background

There is a general assumption that after deposition into skin, Lyme borreliae disseminate hematogenously to other organs, resulting in extracutaneous manifestations of Lyme borreliosis, including Lyme neuroborreliosis. However, our experience over the past 40 years, along with several published case reports that observed colocalization of radicular pain and erythema migrans (EM) in patients with borrelial meningoradiculoneuritis (Bannwarth syndrome), argues against hematogenous dissemination in Lyme neuroborreliosis.

Methods

We compared the location of EM in 112 patients with Bannwarth syndrome to 12315 EM patients without neurological involvement. Moreover, we assessed the colocalization of EM and radicular pain in patients with Bannwarth syndrome.

Results

Compared to >12000 EM patients without neurological involvement, patients with Bannwarth syndrome had a significantly higher frequency of EM on head/neck (6% vs 1%; P=.0005) and trunk (47% vs 24%; P<.0001), similar frequency on arms (16% vs 16%; P=.91), but lower frequency on legs (30% vs 59%; P<.0001). Moreover, in 79% (89/112) of patients the site of EM matched the dermatomes of radicular pain. The odds for a congruent location of EM and radicular pain were highly significant with the highest odds ratios (OR) observed for head (OR=221), followed by neck (OR=159), legs (OR=69), arms (OR=48), and trunk (OR=33).

Conclusions

The greater frequency of EM on head/neck and trunk and the colocalization of EM with radicular pain in patients with Bannwarth syndrome suggest that central nervous system involvement in Lyme neuroborreliosis is due to a retrograde spread of borrelia from skin to the spinal cord via peripheral nerves.
Tribute to Domenico Mario Nuti
Authors: Ellman Michael
Published: September 2021

This article is a tribute to the late D.M.Nuti who died at the end of 2020. It details his contributions to economic theory, economic policy, the analysis of actually existing socialism, transition economics and economic systems. It also draws attention to his role as a teacher and manager of research. He linked economists in Rome, Florence, Warsaw, Budapest, London and Cambridge. Influenced by Kalecki and the Cambridge Keynesians, he devoted his life to the study of variants of socialism and ended up advocating an updated version of social democracy. This would replace the perverted social democracy of Blair and Schroder.
0/2 h-Algorithm for Rapid Triage of Suspected Myocardial Infarction Using a Novel High-Sensitivity Cardiac Troponin I Assay
Authors: Wildi Karin , Boeddinghaus Jasper , Nestelberger Thomas , Lopez-Ayala Pedro , Yufera Sanchez Ana , Okamura Bernhard , Shrestha Samyut , Rohner Jennifer , Miró Òscar , Martinez-Nadal Gemma , Martin-Sanchez F Javier , Koechlin Luca , Twerenbold Raphael , Christ Michael , Kawecki Damian , Rubini Giménez Maria , Keller Dagmar I , Mueller Christian ,   for the APACE investigators, Wussler Desiree , Strebel Ivo , Bakula Adam , Frey Simon , Gualandro Danielle M , Zimmermann Tobias , Puelacher Christian , du Fay de Lavallaz Jeanne , Potlukova Eliska , Diebold Matthias , Geigy Nicolas , Rentsch Katharina , Mitrovic Sandra , Fuenzalida Carolina , Glarner Noemi , Morawiec Beata , Breidthardt Tobias , Freese Michael , López Beatriz , Calderón Sofia , Adrada Esther Rodriguez , Ganovská Eva , Parenica Jiri , von Eckardstein Arnold , Campodarve Isabel , Gea Joaquim
Published: September 2021

Background

We aimed to derive and validate a 0/2 h-algorithm using the new high-sensitivity cardiac troponin I (hs-cTnI)-VITROS assay (VITROS® Immunodiagnostic Products hs-Troponin I Reagent Pack, Ortho Clinical Diagnostics) for rapid rule-out/in of non-ST-segment elevation myocardial infarction (NSTEMI).

Methods

The final diagnosis was centrally adjudicated by 2 independent cardiologists according to the fourth universal definition of myocardial infarction (MI) among 1888 patients presenting to the emergency department with acute chest pain. hs-cTnI-VITROS concentrations were measured at presentation and at 2 h in a blinded fashion. The optimal assay-specific thresholds for the hs-cTnI-VITROS 0/2 h-algorithm were derived in a randomly selected 70% of the cohort and validated in the remaining 30%.

Results

NSTEMI was the final diagnosis in 216/1322 (16.3%) patients of the derivation cohort. Rule-out was defined as baseline hs-cTnI concentrations of <1 ng/L in patients presenting with chest pain onset >3 h or a baseline hs-cTnI concentration of <2 ng/L and an absolute change of <3 ng/L within 2 h. Thresholds for rule-in were either ≥40 ng/L at presentation or an absolute change within 2 h of ≥ 5ng/L. In the derivation cohort, these thresholds ruled-out 50.8% of patients with a negative predictive value (NPV) and sensitivity of 99.7% (95% Confidence Interval (CI), 98.8–99.9%) and 99.1% (95% CI, 96.7–99.9%), and ruled-in 17.9% with a positive predictive value (PPV) of 79.2% (95% CI, 74.3–83.5%). In the validation cohort, NSTEMI was the final diagnosis in 91/566 (16.1%) patients. The derived 0/2 h-algorithm ruled-out 46.3% of patients with a NPV and sensitivity of 100% (95% CI, 95.6–100%) and 100% (95% CI, 96.0–100%), and ruled-in 18.9% with a PPV of 73.8% (95% CI, 66.1–80.3%) in the validation cohort.

Conclusion

hs-cTnI-VITROS concentrations at presentation combined with absolute changes within the first 2 h allowed safe rule-out and accurate rule-in of NSTEMI in two-thirds of unselected patients presenting with acute chest pain to the emergency department.

Trial registration

www.clinicaltrials.gov: NCT0047058
Structural Racism and Race Discrimination
Authors: Atrey Shreya
Published: September 2021

What is the relationship between ‘racism’ and ‘race discrimination’? The paper explores this question. It shows that once we look beyond racism understood colloquially as individual bigotry, to racism understood in a structural sense as embedded in the social, economic, cultural and political dimensions of the State itself, it is possible to locate racism in the practice of discrimination law, within the category of race discrimination. Yet, discrimination law frequently fails to grasp structural racism. The paper reveals how this happens and in turn shows how race discrimination can be infiltrated with a structural view of racism. The overall purpose is to establish that discrimination law fails to be relevant in the face of contemporary forms of racism in the absence of a structural view.
Acute Gastroenteritis in the Etiology of Inflammatory Bowel Disease: Systematic Review and Meta-analysis
Authors: Di Re Angelina , Liang Yi , Gosselink Martijn Pieter , Ctercteko Grahame
Published: September 2021

Background

Inflammatory bowel disease (IBD) consists of a spectrum of disorders including ulcerative colitis and Crohn’s disease, with a rising incidence worldwide. However, despite this prevalence the etiology of IBD remains uncertain. It has been suggested that an episode of gastroenteritis may precipitate IBD.

Methods

Studies were identified using a literature search of Pubmed/Medline and Embase/Ovid. This review was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. The primary outcome was incidence of new-onset IBD after gastroenteritis. Secondary outcomes included incidence of IBD after bacterial, viral, and parasitic gastrointestinal infections.

Results

Eleven studies (n = 923 608 patients) were included. Four studies assessed patients with gastroenteritis, subsequently developing IBD as the primary outcome. Patients with gastroenteritis had a higher incidence of subsequent IBD but this did not reach statistical significance (odds ratio [OR] 3.81, 95% CI 0.52–27.85, P = .19). Seven studies examined the incidence of antecedent gastroenteritis (primary outcome) in patients with a confirmed diagnosis of IBD, compared to the controlled population. There was no difference between incidence of antecedent gastroenteritis across the 2 population groups (OR 1.07, 95% CI 0.55–2.08, P = .85). There was no association between IBD and bacterial, viral, or parasitic infections.

Conclusions

In summary, our meta-analysis has shown that there is considerable heterogeneity in the literature regarding the role of gastroenteritis in the development of IBD. Further higher quality studies need to be performed to ascertain the true nature of this.
Integration of multiple imaging platforms to uncover cardiovascular defects in adult zebrafish
Authors: Bensimon-Brito Anabela , Boezio Giulia L M , Cardeira-da-Silva João , Wietelmann Astrid , Ramkumar Srinath , Lundegaard Pia R , Helker Christian S M , Ramadass Radhan , Piesker Janett , Nauerth Arno , Mueller Clemens , Stainier Didier Y R
Published: September 2021

Aims

Mammalian models have been instrumental in investigating adult heart function and human disease. However, electrophysiological differences with human hearts and high costs motivate the need for non-mammalian models. The zebrafish is a well-established genetic model to study cardiovascular development and function; however, analysis of cardiovascular phenotypes in adult specimens is particularly challenging as they are opaque.

Methods and results

Here, we optimized and combined multiple imaging techniques including echocardiography, magnetic resonance imaging, and micro-computed tomography to identify and analyse cardiovascular phenotypes in adult zebrafish. Using alk5a/tgfbr1a mutants as a case study, we observed morphological and functional cardiovascular defects that were undetected with conventional approaches. Correlation analysis of multiple parameters revealed an association between haemodynamic defects and structural alterations of the heart, as observed clinically.

Conclusion

We report a new, comprehensive, and sensitive platform to identify otherwise indiscernible cardiovascular phenotypes in adult zebrafish.