bluuebunny/crossref_metadata_2025 huggingface dataset:
GPress: a framework for querying general feature format (GFF) files and expression files in a compressed form
Authors: Meng Qingxi , Ochoa Idoia , Hernaez Mikel
Published: June 2020

Motivation

Sequencing data are often summarized at different annotation levels for further analysis, generally using the general feature format (GFF) or its descendants, gene transfer format (GTF) and GFF3. Existing utilities for accessing these files, like gffutils and gffread, do not focus on reducing the storage space, significantly increasing it in some cases. We propose GPress, a framework for querying GFF files in a compressed form. GPress can also incorporate and compress expression files from both bulk and single-cell RNA-Seq experiments, supporting simultaneous queries on both the GFF and expression files. In brief, GPress applies transformations to the data which are then compressed with the general lossless compressor BSC. To support queries, GPress compresses the data in blocks and creates several index tables for fast retrieval.

Results

We tested GPress on several GFF files of different organisms, and showed that it achieves on average a 61% reduction in size with respect to gzip (the current de facto compressor for GFF files) while being able to retrieve all annotations for a given identifier or a range of coordinates in a few seconds (when run in a common laptop). In contrast, gffutils provides faster retrieval but doubles the size of the GFF files. When additionally linking an expression file, we show that GPress can reduce its size by more than 68% when compared to gzip (for both bulk and single-cell RNA-Seq experiments), while still retrieving the information within seconds. Finally, applying BSC to the data streams generated by GPress instead of to the original file shows a size reduction of more than 44% on average.

Availability and implementation

GPress is freely available at https://github.com/qm2/gpress.

Supplementary information

Supplementary data are available at Bioinformatics online.
Simulation, power evaluation and sample size recommendation for single-cell RNA-seq
Authors: Su Kenong , Wu Zhijin , Wu Hao
Published: June 2020

Motivation

Determining the sample size for adequate power to detect statistical significance is a crucial step at the design stage for high-throughput experiments. Even though a number of methods and tools are available for sample size calculation for microarray and RNA-seq in the context of differential expression (DE), this topic in the field of single-cell RNA sequencing is understudied. Moreover, the unique data characteristics present in scRNA-seq such as sparsity and heterogeneity increase the challenge.

Results

We propose POWSC, a simulation-based method, to provide power evaluation and sample size recommendation for single-cell RNA-sequencing DE analysis. POWSC consists of a data simulator that creates realistic expression data, and a power assessor that provides a comprehensive evaluation and visualization of the power and sample size relationship. The data simulator in POWSC outperforms two other state-of-art simulators in capturing key characteristics of real datasets. The power assessor in POWSC provides a variety of power evaluations including stratified and marginal power analyses for DEs characterized by two forms (phase transition or magnitude tuning), under different comparison scenarios. In addition, POWSC offers information for optimizing the tradeoffs between sample size and sequencing depth with the same total reads.

Availability and implementation

POWSC is an open-source R package available online at https://github.com/suke18/POWSC.

Supplementary information

Supplementary data are available at Bioinformatics online.
Using AnABlast for intergenic sORF prediction in the Caenorhabditis elegans genome
Authors: Casimiro-Soriguer C S , Rigual M M , Brokate-Llanos A M , Muñoz M J , Garzón A , Pérez-Pulido A J , Jimenez J
Published: June 2020

Motivation

Short bioactive peptides encoded by small open reading frames (sORFs) play important roles in eukaryotes. Bioinformatics prediction of ORFs is an early step in a genome sequence analysis, but sORFs encoding short peptides, often using non-AUG initiation codons, are not easily discriminated from false ORFs occurring by chance.

Results

AnABlast is a computational tool designed to highlight putative protein-coding regions in genomic DNA sequences. This protein-coding finder is independent of ORF length and reading frame shifts, thus making of AnABlast a potentially useful tool to predict sORFs. Using this algorithm, here, we report the identification of 82 putative new intergenic sORFs in the Caenorhabditis elegans genome. Sequence similarity, motif presence, expression data and RNA interference experiments support that the underlined sORFs likely encode functional peptides, encouraging the use of AnABlast as a new approach for the accurate prediction of intergenic sORFs in annotated eukaryotic genomes.

Availability and implementation

AnABlast is freely available at http://www.bioinfocabd.upo.es/ab/. The C.elegans genome browser with AnABlast results, annotated genes and all data used in this study is available at http://www.bioinfocabd.upo.es/celegans.

Supplementary information

Supplementary data are available at Bioinformatics online.
Is Childhood Obesity a Child Protection Concern?
Authors: Nelson Peter , Bissell Paul , Homer Catherine , Pollard Lee , Powell-Hoyland Vanessa
Published: June 2020

Childhood obesity is a key public health concern. Obesity has an impact on morbidity and mortality, child development, and has links to child sexual abuse. The costs of childhood obesity on the health service and society are well recognised. Whether childhood obesity should also be a child protection concern has divided commentators and professionals. They pose a juxtaposition questioning whether childhood obesity is a consequence of neglect and obese children should potentially be removed from parents who do not seek to reduce their child’s weight, whilst expressing resistance to a role focused on bodily surveillance. This research sought to identify existing practice, through interviews (N23) and focus groups (N3:24) with key professional stakeholders, from social care, health and education, in one area in the UK. The research aimed to explore the decision-making, views and experiences of those working with obesity and the child protection system. The data were subject to Framework Analysis. Key findings include multi-agency working, personal and professional standpoint, and the complex and nuanced impact of individual and agency thresholds on practice. The research demonstrates how the tensions surrounding a child protection paradigm impact on individual and agency practice, potentially inhibiting the support offered to service users.
Age-Related Compensatory Reconfiguration of PFC Connections during Episodic Memory Retrieval
Authors: Deng Lifu , Stanley Mathew L , Monge Zachary A , Wing Erik A , Geib Benjamin R , Davis Simon W , Cabeza Roberto
Published: June 2020

During demanding cognitive tasks, older adults (OAs) frequently show greater prefrontal cortex (PFC) activity than younger adults (YAs). This age-related increase in PFC activity is often associated with enhanced cognitive performance, suggesting functional compensation. However, the brain is a complex network of interconnected regions, and it is unclear how network connectivity of PFC regions differs for OAs versus YAs. To investigate this, we examined the age-related difference on the functional brain networks mediating episodic memory retrieval. YAs and OAs participants encoded and recalled visual scenes, and age-related differences in network topology during memory retrieval were investigated as a function of memory performance. We measured both changes in functional integration and reconfiguration in connectivity patterns. The study yielded three main findings. First, PFC regions were more functionally integrated with the rest of the brain network in OAs. Critically, this age-related increase in PFC integration was associated with better retrieval performance. Second, PFC regions showed stronger performance-related reconfiguration of connectivity patterns in OAs. Finally, the PFC reconfiguration increases in OAs tracked reconfiguration reductions in the medial temporal lobe (MTL)—a core episodic memory region, suggesting that PFC connectivity in OAs may be compensating for MTL deficits.
Development of an HPLC Method for the Determination of Meropenem/Vaborbactam in Biological and Aqueous Matrixes
Authors: Sutherland Christina A , Nicolau David P
Published: June 2020

A HPLC method was developed and validated to analyze meropenem and vaborbactam simultaneously in murine plasma and saline matrixes. A 60-μL volume of extracted sample was injected onto a 5-μm BDS Phenyl-Hypersil C18 reversed-phase column and analyzed with a UV detector set at 298 nm for the first 4.9 min and switched to 240 nm. The mobile phase contained a mixture of methanol and 25-mM sodium phosphate buffer set at a flow rate of 1.0 mL/min for the 16 min run time. Cefuroxime was used as the internal standard. The standard curves were linear over a range of 0.25–50 μg/mL. The precision and accuracy for 0.25 μg/mL (LLQ) in plasma for both compounds were <4.8% and >98.9%, respectively. Interday and intraday precision and accuracy for all QC plasma samples for both compounds were <6.2% and >95.7%, respectively. This methodology details a reproducible assay for both compounds using a single extraction with good accuracy and precision.
Social Distancing Alters the Clinical Course of COVID-19 in Young Adults: A Comparative Cohort Study
Authors: Bielecki Michel , Züst Roland , Siegrist Denise , Meyerhofer Daniele , Crameri Giovanni Andrea Gerardo , Stanga Zeno , Stettbacher Andreas , Buehrer Thomas Werner , Deuel Jeremy Werner
Published: June 2020

Background

Social distancing and stringent hygiene seem to be effective in reducing the number of transmitted virus particles, and therefore the infectivity, of coronavirus disease 2019 (COVID-19) and could alter the mode of transmission of the disease. However, it is not known if such practices can change the clinical course in infected individuals.

Methods

We prospectively studied an outbreak of COVID-19 in Switzerland among a population of 508 predominantly male soldiers with a median age of 21 years. We followed the number of infections in 2 spatially separated cohorts with almost identical baseline characteristics with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) before and after implementation of stringent social distancing.

Results

Of the 354 soldiers infected prior to the implementation of social distancing, 30% fell ill from COVID-19, while no soldier in a group of 154, in which infections appeared after implementation of social distancing, developed COVID-19 despite the detection of viral RNA in the nasal and virus-specific antibodies within this group.

Conclusions

Social distancing not only can slow the spread of SARS-CoV-2 in a cohort of young, healthy adults but it can also prevent the outbreak of COVID-19 while still inducing an immune response and colonizing nasal passages. Viral inoculum during infection or mode of transmission may be a key factor determining the clinical course of COVID-19.
A heart transplant after total artificial heart support: initial and long-term results
Authors: David Charles-Henri , Lacoste Philippe , Nanjaiah Prakash , Bizouarn Philippe , Lepoivre Thierry , Michel Magali , Pattier Sabine , Toquet Claire , Périgaud Christian , Mugniot Antoine , Al Habash Ousama , Petit Thierry , Groleau Nicolas , Rozec Bertrand , Trochu Jean Noel , Roussel Jean Christian , Sénage Thomas
Published: June 2020

OBJECTIVES

At our centre, the SynCardia temporary Total Artificial Heart (TAH-t) (SynCardia Systems, LLC, Tucson, AZ, USA) is used to provide long-term support for patients with biventricular failure as a bridge to a transplant. However, a heart transplant (HT) after such support remains challenging. The aim of this retrospective study was to assess the immediate and long-term results following an HT in the cohort of patients who had a TAH-t implant.

METHODS

A total of 73 patients were implanted with the TAH-t between 1988 and 2019 in our centre. Of these 73 consecutive patients, 50 (68%) received an HT and are included in this retrospective analysis of prospectively collected data.

RESULTS

In the selected cohort, in-hospital mortality after an HT was 10% (n = 5). The median intensive care unit stay was 33 days (range 5–278). The median hospital stay was 41 days (range 28–650). A partial or total pericardiectomy was performed during the HT procedure in 21 patients (42%) due to a severe pericardial reaction. Long-term survival rates after an HT at 5, 10 and 12 years were 79.1 ± 5.9% (n = 32), 76.5 ± 6.3% (n = 22) and 72.4 ± 7.1% (n = 12), respectively, which was similar to the long-term survival for a primary HT without TAH-t during the same period (n = 686). An HT performed within 3–6 months post-TAH-t implantation appeared to provide the best survival (P = 0.007). Eight (16%) patients required chronic dialysis during the subsequent follow-up period, with 3 patients requiring a kidney transplant.

CONCLUSIONS

The long-term outcomes with the SynCardia TAH-t as a bridge to transplant in patients with severe biventricular failure are very encouraging. Our review noted that an HT following TAH-t can be technically challenging, especially in the case of a severe pericardial reaction, with potential pitfalls that should be recognized preoperatively.
Why is preventing antibiotic resistance so hard? Analysis of failed resistance management
Authors: Zhou Shiwei , Barbosa Camilo , Woods Robert J
Published: June 2020

We describe the case of a patient with pancreatitis followed by intra-abdominal infection in which source control was not achieved. Antimicrobial therapy led to the emergence of resistance in multiple organisms through multiple population dynamics processes. While the initial insult was not due to infection, subsequent infections with resistant organisms contributed to a poor outcome for the patient. Though resistance evolution was a known risk, it was difficult to predict the next organism that would arise in the setting of antibiotic pressure and its resistance profile. This case illustrates the clinical challenge of antibiotic resistance that current approaches cannot readily prevent.

LAY SUMMARY

Why is antibiotic resistance management so complex? Distinct evolutionary processes unfold when antibiotic treatment is initiated that lead, separately and together, to the undesired outcome of antibiotic resistance. This clinical case exemplifies some of those processes and highlights the dire need for evolutionary risk assessments to be incorporated into clinical decision making.
Metagenomic analysis reveals significant differences in microbiome and metabolic profiles in the rumen of sheep fed low N diet with increased urea supplementation
Authors: Li Zhipeng , Shen Junshi , Xu Yixuan , Zhu Weiyun
Published: June 2020

Urea is a cost-effective replacement for feed proteins in ruminant diets. However, its metabolism by the rumen microbiome is not fully understood. Here, rumen contents were collected from 18 male sheep fed one of the following three treatments: a low N basal diet with no urea (UC, 0 g/kg dry matter (DM)), low urea (LU, 10 g/kg DM) and high urea (HU, 30 g/kg DM). Principal coordinate analysis showed that the microbial composition and functional profiles of the LU treatment significantly differed from the UC and HU treatments. The genera Prevotella, Succinivibrio, Succinatimonas and Megasphaera were higher in the LU rumen, while the genera Clostridium, Ruminococcus and Butyrivibrio were enriched in the UC and HU rumen. The aspartate–glutamate and arginine–proline metabolic pathways and valine, leucine and isoleucine biosynthesis were higher in the LU rumen. The cysteine and methionine metabolism, lysine degradation and fructose and pentose phosphate metabolism pathways were higher in the UC and HU rumen. The protozoa population in the HU treatment was higher than in the UC and LU treatments. These findings suggest that the rumen microbiome of sheep fed low N diet with different urea supplementation are significantly different.
Polyphasic taxonomic analysis of Sinimarinibacterium arenosum sp. nov., a halophilic bacterium isolated from marine sediment
Authors: Kim Jong-Hwa , Baek Jihye , Yoon Jung-Hoon , Sukhoom Ampaitip , Kim Wonyong
Published: June 2020

A Gram stain-negative, aerobic, motile, rod-shaped bacterial strain, designated CAU 1509T, was isolated from marine sediment, and its taxonomic position was determined using a polyphasic approach. Phylogenetic analysis based on 16S rRNA gene sequences revealed that strain CAU 1509T formed a distinct lineage within the genus Sinimarinibacterium with the highest 16S rRNA gene sequence similarity to Sinimarinibacterium flocculans NH6–24T (97.0%). Similar to another member of Sinimarinibacterium, ubiquinone-8 (Q-8) was the predominant quinone, whereas C16:0, summed feature 3 (C16:1ω7c/ω6c) and summed feature 8 (C18:1ω7c/ω6c) were the major cellular fatty acids. The major polar lipids were diphosphatidylglycerol, phosphatidylglycerol, phosphatidylethanolamine, an unidentified phospholipid, four unidentified glycolipids and three unidentified aminolipids. Strain CAU 1509T has a genome of 4.54 Mb, including 4251 coding sequences, 6 rRNAs and 50 tRNAs, with a genomic DNA G+C content of 63.2 mol%. Based on its phenotypic, chemotaxonomic and phylogenetic properties, strain CAU 1509T should be classified as a novel species of the genus Sinimarinibacterium, for which the name Sinimarinibacterium arenosum sp. nov. is proposed. The type strain is CAU 1509T (= KCTC 72000T = NBRC 113698T).
The transcription factor Leu3 shows differential binding behavior in response to changing leucine availability
Authors: Börlin Christoph S , Nielsen Jens , Siewers Verena
Published: June 2020

The main transcriptional regulator of leucine biosynthesis in the yeast Saccharomyces cerevisiae is the transcription factor Leu3. It has previously been reported that Leu3 always binds to its target genes, but requires activation to induce their expression. In a recent large-scale study of high-resolution transcription factor binding site identification, we showed that Leu3 has divergent binding sites in different cultivation conditions, thereby questioning the results of earlier studies. Here, we present a follow-up study using chromatin immunoprecipitation followed by sequencing (ChIP-seq) to investigate the influence of leucine supplementation on Leu3 binding activity and strength. With this new data set we are able to show that Leu3 exhibits changes in binding activity in response to changing levels of leucine availability.
Transcriptional profiling of Vibrio cholerae O1 following exposure to human anti- lipopolysaccharide monoclonal antibodies
Authors: Baranova Danielle E , Willsey Graham G , Levinson Kara J , Smith Carol , Wade Joseph , Mantis Nicholas J
Published: June 2020

Following an episode of cholera, a rapidly dehydrating, watery diarrhea caused by the Gram-negative bacterium, Vibrio cholerae O1, humans mount a robust anti-lipopolysaccharide (LPS) antibody response that is associated with immunity to subsequent re-infection. In neonatal mouse and rabbit models of cholera, passively administered anti-LPS polyclonal and monoclonal (MAb) antibodies reduce V. cholerae colonization of the intestinal epithelia by inhibiting bacterial motility and promoting vibrio agglutination. Here we demonstrate that human anti-LPS IgG MAbs also arrest V. cholerae motility and induce bacterial paralysis. A subset of those MAbs also triggered V. cholerae to secrete an extracellular matrix (ECM). To identify changes in gene expression that accompany antibody exposure and that may account for motility arrest and ECM production, we subjected V. cholerae O1 El Tor to RNA-seq analysis after treatment with ZAC-3 IgG, a high affinity MAb directed against the core/lipid A region of LPS. We identified > 160 genes whose expression was altered following ZAC-3 IgG treatment, although canonical outer membrane stress regulons were not among them. ompS (VCA1028), a porin associated with virulence and indirectly regulated by ToxT, and norR (VCA0182), a σ54-dependent transcription factor involved in late stages of infection, were two upregulated genes worth noting.
Population and Stand-Level Inference in Forest Inventory with Penalized Splines
Authors: Magnussen Steen , Stelzer Anne-Sophie , Kändler Gerald
Published: June 2020

Penalized splines have potential to decrease estimates of variance in forest inventories with a design-based population-level inference, and a model-based domain-level inference by decreasing the likelihood of a model misspecification. We provide examples with second-order (B2) B-splines and radial basis (RB) functions as extensions to a linear working model (WM). Bias was not prominent, yet greater with B2 and in particular with RB than with WM, and decreased with sample size. Important reductions in the variance of a population mean were achieved with both B2 and RB, but at the domain-level only with RB. The proposed regression estimator of variance generated estimates of variance being slightly smaller than the observed variance. A consistent and larger underestimation was seen with the popular difference estimator of variance.

Study Implications: Forest inventories supported by light detection and range (LiDAR) data require—in the estimation phase—a model for linking LiDAR metrics to attributes of interest. Formulating a parametric model can be a challenge and unsatisfactory if the goodness of fit varies across the range of the attribute of interest. A semiparametric model provides more flexibility and lessens the chance of a model misspecification, albeit with the potential of overfitting. A penalty directed at reducing overfitting is required. A flexible semiparametric model is potentially also better suited for applications to small areas like stands than a parametric model. We demonstrate that important reductions in variance are indeed possible, but also that they depend on the form of the nonparametric part of the chosen model and the level of inference (population versus domains). With regard to practical application, reliable estimates of forest attributes at stand-level are of special interest within the scope of forest-management planning, as silvicultural treatments are always stand-oriented, at least with small-scale forestry under Central European conditions, and stand-related volume (basal area, tree density) belongs to the set of relevant parameters for management decisions regarding harvest and regeneration measures.
Organic farming in India: a vision towards a healthy nation
Authors: Das Suryatapa , Chatterjee Annalakshmi , Pal Tapan Kumar
Published: June 2020

Food quality and safety are the two important factors that have gained ever-increasing attention in general consumers. Conventionally grown foods have immense adverse health effects due to the presence of higher pesticide residue, more nitrate, heavy metals, hormones, antibiotic residue, and also genetically modified organisms. Moreover, conventionally grown foods are less nutritious and contain lesser amounts of protective antioxidants. In the quest for safer food, the demand for organically grown foods has increased during the last decades due to their probable health benefits and food safety concerns. Organic food production is defined as cultivation without the application of chemical fertilizers and synthetic pesticides or genetically modified organisms, growth hormones, and antibiotics. The popularity of organically grown foods is increasing day by day owing to their nutritional and health benefits. Organic farming also protects the environment and has a greater socio-economic impact on a nation. India is a country that is bestowed with indigenous skills and potentiality for growth in organic agriculture. Although India was far behind in the adoption of organic farming due to several reasons, presently it has achieved rapid growth in organic agriculture and now becomes one of the largest organic producers in the world. Therefore, organic farming has a great impact on the health of a nation like India by ensuring sustainable development.
Neighborhood Effects on the Health of Chinese Older Adults: Beyond the Rural and Urban Dichotomy
Authors: Li Yuekang , Wang Yi , Morrow-Howell Nancy
Published: June 2020

Background and Objectives

The associations between physical frailty and depressive symptoms among older individuals were established in the existing literature. Taking the person–environment perspective, we argue that neighborhood environment could either buffer the stress derived from being physically vulnerable or worsen it by adding another layer of stressors in the environmental context when physical health declined. The objectives of this study were to explore to what extent the neighborhood-level characteristics moderate the relationship between physical frailty and depressive symptoms.

Research Design and Methods

Using the China Health and Retirement Longitudinal Study 2011 wave, 6,245 individuals aged 60 years and older were included for analyses. Multilevel mixed-effects models were fitted to examine the moderating effects of urbanicity and neighborhood-level socioeconomic status (SES) on the relationship between frailty and depressive symptoms among older adults, controlling for individual-level characteristics.

Results

Results showed a stronger relationship between deterioration in physical health and depressive symptoms in rural neighborhoods and neighborhoods with lower SES, after controlling for individual-level SES. Also, the moderating effects of the neighborhood-level socioeconomic factors remained after controlling for urbanicity, indicating that neighborhood SES works beyond the rural–urban contexts.

Discussion and Implications

Findings from this study demonstrate the important roles of neighborhood socioeconomic characteristics in reshaping, and the need to redefine, China’s rural–urban dichotomy. The findings also identified neighborhoods with low SES as potential targets for policy and practice to reduce the stress associated with health decline.
User innovation and network effects: the case of video games
Authors: Abrate Graziano , Menozzi Anna
Published: June 2020

New models of knowledge creation are emerging, where the user community is a major source of innovation development. But, how does user innovation impact on producer sales, and the other way round? In this article, the mutual benefits deriving from the user–producer interaction are analyzed in terms of network effects and on a basis of a unique panel dataset of weekly observations in the context of video games and their user-generated, free modifications. The estimates of a system of equations modeling the original good’s retail demand function and the user innovation dynamics show that user-generated complements spur the demand for the original product and smooth the consumer price sensitivity. User innovation increases with the crowd of complementors up to a certain threshold and decreases afterwards, thus following a non-monotonic pattern.
Bias factor, maximum bias and the E-value: insight and extended applications
Authors: Cusson Alexandre , Infante-Rivard Claire
Published: June 2020

Background

Unmeasured confounding can bias the relationship between exposure and outcome. Sensitivity analyses generate bias-adjusted measures but these are not much used; this may change with the availability of the E-value (for evidence for causality in observational studies), appealing for its ease of calculation. However, as currently proposed, the E-value has some practical limitations that may reduce its use.

Methods

We first provide some insight into the relationship between two established measures for unmeasured confounding: ‘the bias factor’ and the maximum value this bias factor can take (‘the B bias’). These measures are the statistical foundation for the E-value. We use them to develop new E-value formulas for situations when it is not currently applicable such as e.g. when, not unusually, a negative relation between unmeasured confounder and outcome and a positive one with exposure are postulated. We also provide E-values on the odds ratio scale because, currently, even when using the odds ratio as the study measure in the calculation of E-value, the result is to be interpreted as a relative risk, which is somewhat inconvenient.

Results

The additional formulas for the E-value measure make it applicable in all possible scenarios defined by the combined directions between unmeasured confounder and both the exposure and outcome. In addition, E-value measures can now be interpreted as odds ratios if the observed results are reported on the same scale.

Conclusions

The E-value is part of newer sensitivity analyses methods for unmeasured confounding. We provide insight into its structure, underscoring its advantages and limitations, and expand its applications.
Racial Disparity of Coronavirus Disease 2019 in African American Communities
Authors: Kullar Ravina , Marcelin Jasmine R , Swartz Talia H , Piggott Damani A , Macias Gil Raul , Mathew Trini A , Tan Tina
Published: June 2020

The coronavirus disease 2019 (COVID-19) pandemic has unveiled unsettling disparities in the outcome of the disease among African Americans. These disparities are not new but are rooted in structural inequities that must be addressed to adequately care for communities of color. We describe the historical context of these structural inequities, their impact on the progression of COVID-19 in the African American (black) community, and suggest a multifaceted approach to addressing these healthcare disparities. (Of note, terminology from survey data cited for this article varied from blacks, African Americans, or both; for consistency, we use African Americans throughout.)
Massive Release of CD9+ Microvesicles in Human Immunodeficiency Virus Infection, Regardless of Virologic Control
Authors: Poveda Eva , Tabernilla Andrés , Fitzgerald Wendy , Salgado-Barreira Ángel , Grandal Marta , Pérez Alexandre , Mariño Ana , Álvarez Hortensia , Valcarce Nieves , González-García Juan , Bernardino José Ignacio , Gutierrez Félix , Fujioka Hisashi , Crespo Manuel , Ruiz-Mateos Ezequiel , Margolis Leonid , Lederman Michael M , Freeman Michael L
Published: June 2020

Background

The role of extracellular vesicles (EVs) in human immunodeficiency virus (HIV) pathogenesis is unknown. We examine the cellular origin of plasma microvesicles (MVs), a type of ectocytosis-derived EV, the presence of mitochondria in MVs, and their relationship to circulating cell-free mitochondrial deoxyribonucleic acid (ccf-mtDNA) in HIV-infected patients and controls.

Methods

Five participant groups were defined: 30 antiretroviral therapy (ART)-naive; 30 ART-treated with nondetectable viremia; 30 elite controllers; 30 viremic controllers; and 30 HIV-uninfected controls. Microvesicles were quantified and characterized from plasma samples by flow cytometry. MitoTrackerDeepRed identified MVs containing mitochondria and ccf-mtDNA was quantified by real-time polymerase chain reaction.

Results

Microvesicle numbers were expanded at least 10-fold in all HIV-infected groups compared with controls. More than 79% were platelet-derived MVs. Proportions of MVs containing mitochondria (22.3% vs 41.6%) and MV mitochondrial density (706 vs 1346) were significantly lower among HIV-infected subjects than controls, lowest levels for those on ART. Microvesicle numbers correlated with ccf-mtDNA levels that were higher among HIV-infected patients.

Conclusions

A massive release of platelet-derived MVs occurs during HIV infection. Some MVs contain mitochondria, but their proportion and mitochondrial densities were lower in HIV infection than in controls. Platelet-derived MVs may be biomarkers of platelet activation, possibly reflecting pathogenesis even in absence of HIV replication.
Group Testing for Severe Acute Respiratory Syndrome– Coronavirus 2 to Enable Rapid Scale-up of Testing and Real-Time Surveillance of Incidence
Authors: Pilcher Christopher D , Westreich Daniel , Hudgens Michael G
Published: June 2020

High-throughput molecular testing for severe acute respiratory syndrome–coronavirus 2 (SARS-CoV-2) may be enabled by group testing in which pools of specimens are screened, and individual specimens tested only after a pool tests positive. Several laboratories have recently published examples of pooling strategies applied to SARS-CoV-2 specimens, but overall guidance on efficient pooling strategies is lacking. Therefore we developed a model of the efficiency and accuracy of specimen pooling algorithms based on available data on SAR-CoV-2 viral dynamics. For a fixed number of tests, we estimate that programs using group testing could screen 2–20 times as many specimens compared with individual testing, increase the total number of true positive infections identified, and improve the positive predictive value of results. We compare outcomes that may be expected in different testing situations and provide general recommendations for group testing implementation. A free, publicly-available Web calculator is provided to help inform laboratory decisions on SARS-CoV-2 pooling algorithms.
Autosomal recessive complete STAT1 deficiency caused by compound heterozygous intronic mutations
Authors: Sakata Sonoko , Tsumura Miyuki , Matsubayashi Tadashi , Karakawa Shuhei , Kimura Shunsuke , Tamaura Moe , Okano Tsubasa , Naruto Takuya , Mizoguchi Yoko , Kagawa Reiko , Nishimura Shiho , Imai Kohsuke , Le Voyer Tom , Casanova Jean-Laurent , Bustamante Jacinta , Morio Tomohiro , Ohara Osamu , Kobayashi Masao , Okada Satoshi
Published: June 2020

Autosomal recessive (AR) complete signal transducer and activator of transcription 1 (STAT1) deficiency is an extremely rare primary immunodeficiency that causes life-threatening mycobacterial and viral infections. Only seven patients from five unrelated families with this disorder have been so far reported. All causal STAT1 mutations reported are exonic and homozygous. We studied a patient with susceptibility to mycobacteria and virus infections, resulting in identification of AR complete STAT1 deficiency due to compound heterozygous mutations, both located in introns: c.128+2 T>G and c.542-8 A>G. Both mutations were the first intronic STAT1 mutations to cause AR complete STAT1 deficiency. Targeted RNA-seq documented the impairment of STAT1 mRNA expression and contributed to the identification of the intronic mutations. The patient’s cells showed a lack of STAT1 expression and phosphorylation, and severe impairment of the cellular response to IFN-γ and IFN-α. The case reflects the importance of accurate clinical diagnosis and precise evaluation, to include intronic mutations, in the comprehensive genomic study when the patient lacks molecular pathogenesis. In conclusion, AR complete STAT1 deficiency can be caused by compound heterozygous and intronic mutations. Targeted RNA-seq-based systemic gene expression assay may help to increase diagnostic yield in inconclusive cases after comprehensive genomic study.
Democratizing EHR analyses with FIDDLE: a flexible data-driven preprocessing pipeline for structured clinical data
Authors: Tang Shengpu , Davarmanesh Parmida , Song Yanmeng , Koutra Danai , Sjoding Michael W , Wiens Jenna
Published: June 2020

Objective

In applying machine learning (ML) to electronic health record (EHR) data, many decisions must be made before any ML is applied; such preprocessing requires substantial effort and can be labor-intensive. As the role of ML in health care grows, there is an increasing need for systematic and reproducible preprocessing techniques for EHR data. Thus, we developed FIDDLE (Flexible Data-Driven Pipeline), an open-source framework that streamlines the preprocessing of data extracted from the EHR.

Materials and Methods

Largely data-driven, FIDDLE systematically transforms structured EHR data into feature vectors, limiting the number of decisions a user must make while incorporating good practices from the literature. To demonstrate its utility and flexibility, we conducted a proof-of-concept experiment in which we applied FIDDLE to 2 publicly available EHR data sets collected from intensive care units: MIMIC-III and the eICU Collaborative Research Database. We trained different ML models to predict 3 clinically important outcomes: in-hospital mortality, acute respiratory failure, and shock. We evaluated models using the area under the receiver operating characteristics curve (AUROC), and compared it to several baselines.

Results

Across tasks, FIDDLE extracted 2,528 to 7,403 features from MIMIC-III and eICU, respectively. On all tasks, FIDDLE-based models achieved good discriminative performance, with AUROCs of 0.757–0.886, comparable to the performance of MIMIC-Extract, a preprocessing pipeline designed specifically for MIMIC-III. Furthermore, our results showed that FIDDLE is generalizable across different prediction times, ML algorithms, and data sets, while being relatively robust to different settings of user-defined arguments.

Conclusions

FIDDLE, an open-source preprocessing pipeline, facilitates applying ML to structured EHR data. By accelerating and standardizing labor-intensive preprocessing, FIDDLE can help stimulate progress in building clinically useful ML tools for EHR data.
Growing Trends in the Efficient and Selective Extraction of Compounds in Complex Matrices Using Molecularly Imprinted Polymers and Their Relevance to Toxicological Analysis
Authors: Mulder Haley A , Halquist Matthew S
Published: June 2020

In the world of forensic and clinical toxicology, proper sample preparation is one of the key steps in identification and quantification of drugs of abuse. Traditional extraction methods such as solid-phase extraction and liquid−liquid extraction are often laborious and nonselective for the target analytes being measured. Molecularly imprinted polymers (MIPs) can be synthesized for sample extraction and their versatility allows the polymer to be employed in off-line, benchtop extractions or on/in-line instrument extractions, offering a faster and more selective sample preparation without the risk of interfering matrix effects. This review details the synthesis and applications of MIP materials for the extraction of drug compounds from biological matrices in publications from 1994 to today.
Forest Ownership Patterns in the Western Upper Peninsula of Michigan, USA
Authors: Zupko Robert
Published: June 2020

Abstract In heavily forested rural areas, tax-incentivization programs are commonly employed to encourage timber production and harvesting activities. Because of growing interest in developing woody-biomass-based biofuels in the Western Upper Peninsula of Michigan, USA, we analyzed property records to determine who the regional actors are along with what role tax-incentivization programs may play. We found that a minority of entities collectively control 77 percent of the land in the region; however, family forest owners collectively own 23 percent of the land. Although tax-incentive programs are commonly used by commercial forests, the requirements of the primary program in Michigan program appear to preclude most family forests in the region. Accordingly, this study suggests that a greater understanding of reluctance of family forests to enroll in secondary programs is needed, or a lowering of forestland requirements to permit more family forests to enroll.

Study Implications

In heavily forested rural areas, the development of local forest resources has been suggested as a means of developing the local economy. One means of using the forest resources is through the development of woody-biomass-based biofuel or bioenergy programs. As these programs are dependent upon harvesting to supply the relevant feedstocks, tax-incentivization programs, such as Michigan’s Commercial Forest Land (CFL), may be used to encourage commercial timber production and overcome resistance to harvesting by nonindustrial private forest (NIPF) owners. These findings suggest such programs are likely to be well to fully subscribed by commercial forests. However, the implementation of these programs (ex., minimum of 40 ac. of forestland) may preclude a significant number of family forests from being able to enroll, which may be a contributing factor to low subscription rates. As a result, policymakers wishing to encourage enrollment by family forests in tax-incentivization programs should consider the practical realities of regional family ownership (i.e., average forestland acreage) in developing the programs.
Laparoscopic sigmoidectomy for sigmoid colon cancer with left-sided inferior vena cava and persistent descending mesocolon
Authors: Kawakami Masayo , Nakazato Hidetsugu , Tomiyama Takeshi , Tomori Takehiko , Miyagi Jun , Nagayoshi Seiji , Ohmine Yasushi
Published: June 2020

Left-sided inferior vena cava (IVC) is a rare congenital malformation, as is persistent descending mesocolon, a developmental anomaly in which the colonic mesentery does not fuse with the dorsal abdominal wall. Although these anomalies are mostly asymptomatic, they should be identified preoperatively to avoid iatrogenic injury. We report a case of sigmoid colon cancer in a patient with both anomalies. The patient was an 80-year-old man whose preoperative computed tomography (CT) scan showed that the IVC ascended vertically along the left side of the abdominal aorta, and the descending colon was at the abdominal midline. Coronal CT was particularly useful for visualizing these anomalies. With this better understanding of the malpositioned anatomy, we successfully performed laparoscopic sigmoidectomy with lymph node dissection. Careful evaluation of preoperative CT imaging based on a clear understanding of such anatomical anomalies is particularly important for performing safe laparoscopic surgery.
Non-local thermodynamical equilibrium abundance analysis of singly ionized praseodymium for the Sun
Authors: Shaltout Abdelrazek M K , Abdelkawy Ali G A , Beheary M M
Published: June 2020

Determinations of the solar abundance of praseodymium (Pr) depend critically on the local thermodynamical equilibrium (LTE) and non-local thermodynamical equilibrium (NLTE) techniques beyond the capabilities of a classical one-dimensional model atmosphere. Here, in this analysis, we adopt an atomic model atom of Pr consisting of 105 energy levels and 14 bound–bound transitions of singly ionized praseodymium (Pr ii) and the ground state of the Pr iii continuum limit. We briefly analyse the solar abundance of Pr taking the solar model atmospheres of Holweger & Müller (1974, Solar Physics, 39, 19) with the measured equivalent linewidths and invoking a microturbulent velocity treatment. We succeed in accurately selecting nearby clear sections of the spectrum for 14 spectral lines of Pr ii with the improved atomic data of high-quality oscillator strengths available from the laboratory measurements of several possible sources as well as accurate damping constants successfully determined from the literature. We find a Pr abundance revised to be downwards log ϵPr(NLTE) = 0.75 ± 0.09, which is in good agreement with the meteoritic value (log ϵPr = 0.76 ± 0.03). A comparison of the NLTE abundance corrections with the standard LTE analysis, log ϵPr(LTE) = 0.74 ± 0.08, reveals a positive correction of  +0.01 dex, estimated from the selected solar Pr ii lines. The Pr abundance value is clearly superior following the classical one-dimensional model atmospheres of Holweger & Müller, the absolute scales of gf-values, the microturbulent velocity and the adopted equivalent linewidths.
Broccoli: Combining Phylogenetic and Network Analyses for Orthology Assignment
Authors: Derelle Romain , Philippe Hervé , Colbourne John K
Published: June 2020

Orthology assignment is a key step of comparative genomic studies, for which many bioinformatic tools have been developed. However, all gene clustering pipelines are based on the analysis of protein distances, which are subject to many artifacts. In this article, we introduce Broccoli, a user-friendly pipeline designed to infer, with high precision, orthologous groups, and pairs of proteins using a phylogeny-based approach. Briefly, Broccoli performs ultrafast phylogenetic analyses on most proteins and builds a network of orthologous relationships. Orthologous groups are then identified from the network using a parameter-free machine learning algorithm. Broccoli is also able to detect chimeric proteins resulting from gene-fusion events and to assign these proteins to the corresponding orthologous groups. Tested on two benchmark data sets, Broccoli outperforms current orthology pipelines. In addition, Broccoli is scalable, with runtimes similar to those of recent distance-based pipelines. Given its high level of performance and efficiency, this new pipeline represents a suitable choice for comparative genomic studies. Broccoli is freely available at https://github.com/rderelle/Broccoli.
Functional changes in decidual mesenchymal stem/stromal cells are associated with spontaneous onset of labour
Authors: Wijaya Joan C , Khanabdali Ramin , Georgiou Harry M , Kokkinos Maria I , James Patrick F , Brennecke Shaun P , Kalionis Bill
Published: June 2020

Ageing and parturition share common pathways, but their relationship remains poorly understood. Decidual cells undergo ageing as parturition approaches term, and these age-related changes may trigger labour. Mesenchymal stem/stromal cells (MSCs) are the predominant stem cell type in the decidua. Stem cell exhaustion is a hallmark of ageing, and thus ageing of decidual MSCs (DMSCs) may contribute to the functional changes in decidual tissue required for term spontaneous labour. Here, we determine whether DMSCs from patients undergoing spontaneous onset of labour (SOL-DMSCs) show evidence of ageing-related functional changes compared with those from patients not in labour (NIL-DMSCs), undergoing Caesarean section. Placentae were collected from term (37–40 weeks of gestation), SOL (n = 18) and NIL (n = 17) healthy patients. DMSCs were isolated from the decidua basalis that remained attached to the placenta after delivery. DMSCs displayed stem cell-like properties and were of maternal origin. Important cell properties and lipid profiles were assessed and compared between SOL- and NIL-DMSCs. SOL-DMSCs showed reduced proliferation and increased lipid peroxidation, migration, necrosis, mitochondrial apoptosis, IL-6 production and p38 MAPK levels compared with NIL-DMSCs (P < 0.05). SOL- and NIL-DMSCs also showed significant differences in lipid profiles in various phospholipids (phosphatidylethanolamine, phosphatidylglycerol, phosphatidylinositol, phosphatidylserine), sphingolipids (ceramide, sphingomyelin), triglycerides and acyl carnitine (P < 0.05). Overall, SOL-DMSCs had altered lipid profiles compared with NIL-DMSCs. In conclusion, SOL-DMSCs showed evidence of ageing-related reduced functionality, accumulation of cellular damage and changes in lipid profiles compared with NIL-DMSCs. These changes may be associated with term spontaneous labour.
Crossmodal Aesthetics: How Music and Dance Can Match
Authors: Aasen Solveig
Published: June 2020

The relationship between music and dance can sometimes be a ‘match’, a remarkable fit between the audible manifestation that music is and the visual or kinaesthetic manifestation that dance is. A match between two things seems to require a common measure with respect to which the match obtains. What can this be for two so different phenomena as music and dance? I argue that the most promising answer is: movement. This answer will not be satisfactory unless the movement of music and the movement of dance are the same on some level. I suggest that they are: there are qualities of movement that guide both dancers and musicians when producing dance and music as perceptible phenomena. But the match in qualities is elusive, since the qualities are instantiated in different ways in music and dance, respectively.