bluuebunny/crossref_metadata_2025_split huggingface dataset:
Unbiased pangenome graphs
Authors: Garrison Erik , Guarracino Andrea 
Published: November 2022

Abstract

Motivation
Pangenome variation graphs model the mutual alignment of collections of DNA sequences. A set of pairwise alignments implies a variation graph, but there are no scalable methods to generate such a graph from these alignments. Existing related approaches depend on a single reference, a specific ordering of genomes or a de Bruijn model based on a fixed k-mer length. A scalable, self-contained method to build pangenome graphs without such limitations would be a key step in pangenome construction and manipulation pipelines.

Results
We design the seqwish algorithm, which builds a variation graph from a set of sequences and alignments between them. We first transform the alignment set into an implicit interval tree. To build up the variation graph, we query this tree-based representation of the alignments to reduce transitive matches into single DNA segments in a sequence graph. By recording the mapping from input sequence to output graph, we can trace the original paths through this graph, yielding a pangenome variation graph. We present an implementation that operates in external memory, using disk-backed data structures and lock-free parallel methods to drive the core graph induction step. We demonstrate that our method scales to very large graph induction problems by applying it to build pangenome graphs for several species.

Availability and implementation
seqwish is published as free software under the MIT open source license. Source code and documentation are available at https://github.com/ekg/seqwish. seqwish can be installed via Bioconda https://bioconda.github.io/recipes/seqwish/README.html or GNU Guix https://github.com/ekg/guix-genomics/blob/master/seqwish.scm.
Active learning for efficient analysis of high-throughput nanopore data
Authors: Guan Xiaoyu , Li Zhongnian , Zhou Yueying , Shao Wei , Zhang Daoqiang 
Published: November 2022

AbstractMotivationAs the third-generation sequencing technology, nanopore sequencing has been used for high-throughput sequencing of DNA, RNA, and even proteins. Recently, many studies have begun to use machine learning technology to analyze the enormous data generated by nanopores. Unfortunately, the success of this technology is due to the extensive labeled data, which often suffer from enormous labor costs. Therefore, there is an urgent need for a novel technology that can not only rapidly analyze nanopore data with high-throughput, but also significantly reduce the cost of labeling. To achieve the above goals, we introduce active learning to alleviate the enormous labor costs by selecting the samples that need to be labeled. This work applies several advanced active learning technologies to the nanopore data, including the RNA classification dataset (RNA-CD) and the Oxford Nanopore Technologies barcode dataset (ONT-BD). Due to the complexity of the nanopore data (with noise sequence), the bias constraint is introduced to improve the sample selection strategy in active learning. Results: The experimental results show that for the same performance metric, 50% labeling amount can achieve the best baseline performance for ONT-BD, while only 15% labeling amount can achieve the best baseline performance for RNA-CD. Crucially, the experiments show that active learning technology can assist experts in labeling samples, and significantly reduce the labeling cost. Active learning can greatly reduce the dilemma of difficult labeling of high-capacity nanopore data. We hope active learning can be applied to other problems in nanopore sequence analysis.Availability and implementationThe main program is available at https://github.com/guanxiaoyu11/AL-for-nanopore.Supplementary informationSupplementary data are available at Bioinformatics online.
PoDCall: positive droplet calling and normalization of droplet digital PCR DNA methylation data
Authors: Jeanmougin Marine , Brodal Hans Petter , Dietrichson Pharo Heidi , Vedeld Hege Marie , Lind Guro Elisabeth 
Published: November 2022

Abstract

Motivation
Droplet digital PCR (ddPCR) holds great promises for investigating DNA methylation with high sensitivity. Yet, the lack of methods for analyzing ddPCR DNA methylation data has resulted in users processing the data manually at the expense of standardization.

Results
PoDCall is an R package performing automated calling of positive droplets, quantification and normalization of methylation levels in ddPCR experiments. A Shiny application provides users with an intuitive and interactive interface to access PoDCall functionalities.

Availability and implementation
The PoDCall R package is freely available on Bioconductor at https://bioconductor.org/packages/PoDCall/. The Shiny application can be executed from the R console using the wrapper function PoDCall::podcallShiny().

Supplementary information
Supplementary data are available at Bioinformatics online.
Systematic identification of biochemical networks in cancer cells by functional pathway inference analysis
Authors: Badshah Irbaz I , Cutillas Pedro R 
Published: November 2022

AbstractMotivationPathway inference methods are important for annotating the genome, for providing insights into the mechanisms of biochemical processes and allow the discovery of signalling members and potential new drug targets. Here, we tested the hypothesis that genes with similar impact on cell viability across multiple cell lines belong to a common pathway, thus providing a conceptual basis for a pathway inference method based on correlated anti-proliferative gene properties.MethodsTo test this concept, we used recently available large-scale RNAi screens to develop a method, termed functional pathway inference analysis (FPIA), to systemically identify correlated gene dependencies.ResultsTo assess FPIA, we initially focused on PI3K/AKT/MTOR signalling, a prototypic oncogenic pathway for which we have a good sense of ground truth. Dependencies for AKT1, MTOR and PDPK1 were among the most correlated with those for PIK3CA (encoding PI3Kα), as returned by FPIA, whereas negative regulators of PI3K/AKT/MTOR signalling, such as PTEN were anti-correlated. Following FPIA, MTOR, PIK3CA and PIK3CB produced significantly greater correlations for genes in the PI3K-Akt pathway versus other pathways. Application of FPIA to two additional pathways (p53 and MAPK) returned expected associations (e.g. MDM2 and TP53BP1 for p53 and MAPK1 and BRAF for MEK1). Over-representation analysis of FPIA-returned genes enriched the respective pathway, and FPIA restricted to specific tumour lineages uncovered cell type-specific networks. Overall, our study demonstrates the ability of FPIA to identify members of pro-survival biochemical pathways in cancer cells.Availability and implementationFPIA is implemented in a new R package named ‘cordial’ freely available from https://github.com/CutillasLab/cordial.Supplementary informationSupplementary data are available at Bioinformatics online.
On the statistical role of inexact matching in observational studies
Authors: Guo Kevin , Rothenhäusler Dominik 
Published: November 2022

Summary
In observational causal inference, exact covariate matching plays two statistical roles: (i) it effectively controls for bias due to measured confounding; (ii) it justifies assumption-free inference based on randomization tests. In this paper we show that inexact covariate matching does not always play these same roles. We find that inexact matching often leaves behind statistically meaningful bias, and that this bias renders standard randomization tests asymptotically invalid. We therefore recommend additional model-based covariate adjustment after inexact matching. In the framework of local misspecification, we prove that matching makes subsequent parametric analyses less sensitive to model selection or misspecification. We argue that gaining such robustness is the primary statistical role of inexact matching.
Patient-Centered Access to IBD Care: A Qualitative Study
Authors: Heisler Courtney , Rohatinsky Noelle , Mirza Raza M , Kits Olga , Zelinsky Sandra , Veldhuyzen van Zanten Sander , Nguyen Geoffrey , McCurdy Jeffrey , MacMillan Mark , Lakatos Peter L , Targownik Laura , Fowler Sharyle , Rioux Kevin , Jones Jennifer 
Published: November 2022

Abstract

Background
Canada has the highest global age-adjusted incidence and prevalence rates of inflammatory bowel disease (IBD). Due to IBD patient volumes and limited resources, challenges to timely access to specialty care have emerged. To address this gap, the aim of this paper was to understand the experiences and perspectives of persons living with IBD with a focus on accessing health care.

Methods
Using a qualitative descriptive approach, patients diagnosed with IBD (≥18 years of age) were purposively sampled from rural and urban gastroenterology clinics and communities across Canada. Co-facilitated by a researcher and patient research partner, 14 focus groups were recorded, transcribed, and coded for themes. Thematic analysis was used to ascertain the congruence or discordance of IBD specialty care access experiences.

Results
A total of 63 individuals participated in the study. The majority of participants were female (41/63, 65%) and from urban/suburban regions (33/63, 52%), with a mean age of 48.39 (range 16–77 years). The analysis generated three main themes: (1) need for patient to be partner, (2) adapting IBD care access to individual context, and (3) patient-defined care priorities should guide access to IBD care.

Conclusions
The complexity of specialty care access for IBD patients cannot be underestimated. It is vital to possess a robust understanding of healthcare system structures, processes, and the impact of these factors on accessing care. Using a patient-centered exploration of barriers and facilitators, IBD specialty care access in Canada can be better understood and improved on provincial and national levels.
Phenomapping in heart failure with preserved ejection fraction: insights, limitations, and future directions
Authors: Peters Anthony E , Tromp Jasper , Shah Sanjiv J , Lam Carolyn S P , Lewis Gregory D , Borlaug Barry A , Sharma Kavita , Pandey Ambarish , Sweitzer Nancy K , Kitzman Dalane W , Mentz Robert J 
Published: November 2022

Abstract
Heart failure with preserved ejection fraction (HFpEF) is a heterogeneous entity with complex pathophysiology and manifestations. Phenomapping is the process of applying statistical learning techniques to patient data to identify distinct subgroups based on patterns in the data. Phenomapping has emerged as a technique with potential to improve the understanding of different HFpEF phenotypes. Phenomapping efforts have been increasing in HFpEF over the past several years using a variety of data sources, clinical variables, and statistical techniques. This review summarizes methodologies and key takeaways from these studies, including consistent discriminating factors and conserved HFpEF phenotypes. We argue that phenomapping results to date have had limited implications for clinical care and clinical trials, given that the phenotypes, as currently described, are not reliably identified in each study population and may have significant overlap. We review the inherent limitations of aggregating and utilizing phenomapping results. Lastly, we discuss potential future directions, including using phenomapping to optimize the likelihood of clinical trial success or to drive discovery in mechanisms of the disease process of HFpEF.
Pericardial effusion and tamponade in the context of herpes zoster: a novel occurrence
Authors: Easton Aleisha , Joret Maximilian , Xian Susan , Ternouth Ian 
Published: November 2022

Abstract

Background
Pericarditis and pericardial effusion are relatively common hospital presentations, which rarely result in cardiac tamponade. The aetiology is often undetermined and presumed idiopathic or viral. This article reviews varicella zoster virus (VZV)–associated pericardial effusion and peri/myopericarditis and constitutes the first report of VZV-associated cardiac tamponade in the adult population.

Case summary
We report the case of a 59-year-old woman who presented to hospital with pleuritic chest pain, haemodynamic instability, and a recent herpes zoster rash in the left T1 distribution. Computed tomography revealed a large pericardial effusion, and echocardiography showed features of cardiac tamponade. The patient was treated with pericardial drainage. Aspirate analysis revealed abundant polynuclear cells and histocytes with no organism. Polymerase chain reaction did not determine a cause.

Discussion
There are 13 reported cases of VZV-associated peri/myopericarditis in adults in the literature published in the English language. Of these, only three patients had a pericardial effusion. Aetiological diagnosis of an effusion is challenging and rarely made on virological grounds but rather on clinical features. Varicella zoster virus–associated pericardial effusion should be considered in patients presenting with haemodynamic instability and a dermatomal rash affecting the C3–C5 and T1–T4 distributions.
Foliar Residual Toxicity of Insecticides to Brassica Pests and Their Natural Enemies
Authors: Anjum Farida , Wright Denis J 
Published: November 2022

Abstract
Overuse of pesticides can result in the development of resistance, secondary pest outbreaks, and pest resurgence due to a reduction in natural enemies. The present study compares the residual toxicity of lambda-cyhalothrin, a relatively nonselective insecticide, with abamectin, indoxacarb, and spinosad, compounds which have been reported to be less harmful to arthropod natural enemies. Two key cosmopolitan pests of crucifer crops, (Plutella xylostella) and (Myzus persicae), and two of their respective hymenopteran parasitoids, (Cotesia vestalis) and (Aphidius colemani) were used as representative pests and natural enemies. The pyrethroid lambda-cyhalothrin was found to be the most persistent toxicant against both pest and both parasitoid species tested, while the lactones abamectin and spinosad were the least persistent toxicants. A leaf wax stripping technique was used to compare the contact toxicity of insecticide residues against adult C. vestalis and A. colemani in the epicuticular wax layer. For each compound, removal of epicuticular wax reduced the 24 h residual toxicity (LC50) of fresh deposits (day 0) by about an order of magnitude against C. vestalis. A second residual toxicity experiment showed that removal of epicuticular wax significantly reduced the residual toxicity of each compound against A. colemani at 0, 7, and 14 d after application, with little or no detectable residual activity for the oxadiazine indoxacarb or abamectin/spinosad respectively after 14 d. The present data supports the view that in addition to the intrinsic toxicity of insecticides to natural enemies, differences in their persistence as foliar residues should also be considered in IPM systems.
AVA inversion for novel fluid indicator considering consolidation parameter
Authors: Yang Wenqiang , Yang Zhifang , Zong Zhaoyun , Sun Qianhao , Yan Xinfei 
Published: November 2022

Abstract
Geofluid identification from seismic data are crucial for understanding reservoir characteristics. However, fluid indicators based on elastic parameter combinations show strong ambiguity in terms of geofluid identification. Although the effective pore-fluid bulk modulus proves to be the superior fluid indicator in geofluid discrimination, it is limited to empirical models such as the critical porosity model. The consolidation parameter model can evaluate the consolidation and compaction of sediments and is widely used due to its better applicability. Therefore, a novel fluid indicator considering consolidation parameter is proposed and a boundary-constrained inversion strategy for geofluid identification is developed. First, the novel fluid indicator is defined based on the poroelasticity theory. Then, the linearized AVA (amplitude variation with angle) approximation equation related to the new fluid indicator is derived to directly link seismic data and properties of pore-filling materials. The model analysis verifies the accuracy of the derived approximation equation at moderate incident angles, which can be used for parameter prediction by pre-stack seismic inversion. Furthermore, the contribution of each attribute of the novel equation to the reflectivity is analyzed to validate the feasibility of new fluid indicator inversion. Finally, a boundary-constrained AVA pre-stack inversion method is presented to enhance the robustness of the inversion results of the model parameter. The reliability of the improved method is proved by accurate inversion results of synthetic seismic records. After determining the consolidation parameter using well-log data combined with BGT (Biot–Gassmann Theory), the field data further demonstrated that the proposed approach is accurate and effective.
Transmission of SARS-CoV-2 Delta variant from an infected aircrew member on a short-haul domestic flight, Australia 2021
Authors: Williamson Kirsten M , Butler Michelle , Elton Benjamin , Taylor Joanne , Islam Fakhrul , Douglas Michael P , Kirk Martyn D , Durrheim David N 
Published: November 2022

Abstract
In June 2021, when COVID-19 incidence in Australia was low, a COVID-19 (Delta variant) cluster occurred on an 81-minute domestic flight, with an aircrew member as the likely source. Outbreak investigation demonstrated that SARS-CoV-2 may be transmitted during short-haul flights and that mask use protected against infection.
Outliers in the Ep,z – Eγ relation of Fermi-GBM long-duration gamma-ray bursts
Authors: Jiang Lu-Yao , Wang Yun , Wei Da-Ming , Ren Jia , Xie Lang , Li Jing 
Published: November 2022

ABSTRACT
Long gamma-ray bursts (GRBs) are typically associated with massive star core collapse, while the short GRBs are associated with compact binary mergers. However, recent evidence indicates that some peculiar long-duration bursts may correspond to compact binary mergers origins. In this paper, we use the data of the Fermi Gamma-ray Burst Monitor to search for peculiar long-duration bursts which may be from compact binary mergers based on outlier events in the $E_{p,z}\!-\!E_{\gamma ,\rm iso}$ relation. We obtained 10 outlier events by systematically analysing bursts with $T_{90}\gt 4.2 \rm \ s$ from 2008 August to 2021 July. In order to determine whether these outlier events were from compact binary mergers, we analysed their properties, including spectral lag, hardness ratio, and energy-hardness parameter. Based on the distributions of T90 − HR and T90 − Ep, we calculated the probability of outlier events belonging to the short GRBs. Our analysis indicates that GRB 120304B is likely to arise from the merger of a neutron star and a massive white dwarf. GRB 150210A is likely to arise from massive star core collapse. The other eight GRBs are fuzzy bursts that have both long and short GRBs properties. Additionally, we find that outlier samples have relatively high Ep and low fluences.
Investigating RNA–protein recognition mechanisms through supervised molecular dynamics (SuMD) simulations
Authors: Pavan Matteo , Bassani Davide , Sturlese Mattia , Moro Stefano 
Published: November 2022

AbstractRibonucleic acid (RNA) plays a key regulatory role within the cell, cooperating with proteins to control the genome expression and several biological processes. Due to its characteristic structural features, this polymer can mold itself into different three-dimensional structures able to recognize target biomolecules with high affinity and specificity, thereby attracting the interest of drug developers and medicinal chemists. One successful example of the exploitation of RNA’s structural and functional peculiarities is represented by aptamers, a class of therapeutic and diagnostic tools that can recognize and tightly bind several pharmaceutically relevant targets, ranging from small molecules to proteins, making use of the available structural and conformational freedom to maximize the complementarity with their interacting counterparts. In this scientific work, we present the first application of Supervised Molecular Dynamics (SuMD), an enhanced sampling Molecular Dynamics-based method for the study of receptor–ligand association processes in the nanoseconds timescale, to the study of recognition pathways between RNA aptamers and proteins, elucidating the main advantages and limitations of the technique while discussing its possible role in the rational design of RNA-based therapeutics.
Changing landscape of living kidney donation and the role of telemedicine
Authors: Al Ammary Fawaz , Muzaale Abimereki D. , Tantisattamoa Ekamol , Hanna Ramy M. , Reddy Uttam G. , Bunnapradist Suphamai , Kalantar-Zadeh Kamyar 
Published: November 2022

Purpose of review
There has been a decline in living kidney donation over the last two decades. Donors from low-income families or racial/ethnic minorities face greater disproportionate geographic, financial, and logistical barriers to completing lengthy and complex evaluations. This has contributed to the decreased proportion of these subgroups. The authors view telemedicine as a potential solution to this problem.

Recent findings
Since the initial decline of donors in 2005, biologically related donors have experienced a lack of growth across race/ethnicity. Conversely, unrelated donors have emerged as the majority of donors in recent years across race/ethnicity, except for unrelated black donors. Disparities in access to living kidney donation persist. Telemedicine using live-video visits can overcome barriers to access transplant centers and facilitate care coordination. In a U.S. survey, nephrologists, surgeons, coordinators, social workers, and psychologists/psychologists across transplant centers are favorably disposed to use telemedicine for donor evaluation/follow-up beyond the coronavirus disease 2019 pandemic. However, with the waning of relaxed telemedicine regulations under the Public Health Emergency, providers perceive payor policy and out-of-state licensing as major factors hindering telemedicine growth prospects.

Summary
Permanent federal and state policies that support telemedicine services for living kidney donation can enhance access to transplant centers and help overcome barriers to donor evaluation.
Practicing health equity in involuntary discharges to overcome disparities in dialysis and kidney patient care
Authors: Edwards Dawn P. , Kalantar-Zadeh Kamyar , Streja Elani , Ahdoot Rebecca S. , Norris Keith C. , Molony Donald 
Published: November 2022

Purpose of review
Potential causes and consequences of involuntary discharge (IVD) of patients from dialysis facilities are widely unknown. So, also are the extent of racial disparities in IVDs and their impact on health equity.

Recent findings
Under the current End-Stage Renal Disease (ESRD) program
Conditions for Coverage (CFC), there are limited justifications for IVDs. The ESRD Networks oversee dialysis quality and safety including IVDs in US dialysis facilities, with support from the Agency for Healthcare Quality and Research (AHRQ) and other stakeholders. Whereas black Americans constitute a third of US dialysis patients, they are even more overrepresented in the planned and executed IVDs. Cultural gaps between patients and dialysis staff, psychosocial and regional factors, structural racism in kidney care, antiquated ESRD policies, unintended consequences of quality incentive programs, other perverse incentives, and failed patient–provider communications are among potential contributors to IVDs.

Summary
Practicing health equity in kidney care may be negatively impacted by IVDs. Accurate analyses of patterns and trends of involuntary discharges, along with insights from well designed AHRQ surveys and qualitative research with mixed method approaches are urgently needed. Pilot and feasibility programs should be designed and tested, to address the root causes of IVDs and related racial disparities.