bluuebunny/crossref_metadata_2025 huggingface dataset:
Thermally stratified free shear layers: Combined Kelvin–Helmholtz Rayleigh–Taylor instability
Authors: Sengupta Aditi , Joshi Bhavna , Verma Atul Kumar
Published: August 2022

A numerical investigation of Rayleigh–Taylor instability (RTI) with different unstable thermal stratifications, and coupled Kelvin–Helmholtz (KH) and RTI (referred to as KHRTI) is performed by solving the compressible Navier–Stokes equation. Two air masses having temperature differences of ΔT*=21.75 and 46.5 K [corresponding to Gay–Lussac numbers (Ga) of 0.073 and 0.156] are considered in an isolated box, initially separated by a non-conducting interface for studying RTI. For KHRTI, dimensionless tangential shear of ΔU=0.92 and 1.89 is additionally imposed on the two air masses with ΔT*=21.75 K. Onset propagation and fully developed stages of the instabilities are explored via time-resolved and instantaneous temperature and vorticity. For RTI, lower ΔT* case shows retarded growth of the mixing layer and a set of interpenetrating bubbles. The higher ΔT* case shows an accelerated growth of the mixing layer with alternating rows of spikes and bubbles. For KHRTI, flow is governed by KH dynamics at early times and RT dynamics at later times. To further understand the interaction between RT and KH mechanisms, a compressible enstrophy transport equation in Suman et al. [“A novel compressible enstrophy transport equation based analysis of instability of Magnus–Robins effects for very high rotation rates,” Phys. Fluids 34, 044114 (2022)] is used. Depending on Ga, either vortex stretching or compressibility contribution terms of the enstrophy transport are dominant for RTI. Depending on the shear imposed, either baroclinic torque or viscous terms are dominant for KHRTI.
Current status of and future opportunities for digital agriculture in Australia
Authors: Hansen B. D. , Leonard E. , Mitchell M. C. , Easton J. , Shariati N. , Mortlock M. Y. , Schaefer M. , Lamb D. W.
Published: August 2022

In Australia, digital agriculture is considered immature and its adoption ad hoc, despite a relatively advanced technology innovation sector. In this review, we focus on the technical, governance and social factors of digital adoption that have created a disconnect between technology development and the end user community (farmers and their advisors). Using examples that reflect both successes and barriers in Australian agriculture, we first explore the current enabling technologies and processes, and then we highlight some of the key socio-technical factors that explain why digital agriculture is immature and ad hoc. Pronounced issues include fragmentation of the innovation system (and digital tools), and a lack of enabling legislation and policy to support technology deployment. To overcome such issues and increase adoption, clear value propositions for change are necessary. These value propositions are influenced by the perceptions and aspirations of individuals, the delivery of digitally-enabled processes and the supporting legislative, policy and educational structures, better use/conversion of data generated through technology applications to knowledge for supporting decision making, and the suitability of the technology. Agronomists and early adopter farmers will play a significant role in closing the technology-end user gap, and will need support and training from technology service providers, government bodies and peer-networks. Ultimately, practice change will only be achieved through mutual understanding, ownership and trust. This will occur when farmers and their advisors are an integral part of the entire digital innovation system.
Predicted effects of simulated ambient warming and moisture on forage nutrient quality and community composition in Mongolian an arid grassland
Authors: Yoshihara Yu , Aoki Ryoga , Kinugasa Toshihiko , Sasaki Takehiro
Published: August 2022

Sustainable forage and livestock production in grazed grasslands are threatened by global climatic change. In this study, we examined how forage quality at the species and community levels in Mongolian drylands might be affected by warming and additional moisture. Four different treatments, a control, open-top chambers (OTCs) only, OTCs with heaters, and OTCs with additional watering, were set up in the field, and air and soil temperature and soil moisture were monitored. A vegetation survey was conducted and plants were harvested during summer, 1 and 2 years after experimental treatments were established. The harvested plant samples were separated into a dominant species (Stipa) or ‘other species’, and analysed to determine acid detergent fibre (ADF) and in vitro dry-matter digestibility (IVDMD). ADF was measured with the detergent method and the digestibility with the pepsin–cellulase assay. Overall, the warming treatments alone (OTC and OTC with heater) increased ADF 10% and 5% more than did the control at the species and community levels respectively, and decreased digestibility 12% and 11% below the control at the community level. Changes in plant nutritional value may have occurred as a result of changes in plant structure for some or all the plant species monitored, and an indirect effect of the shift in botanical species composition owing to warming. Unlike moist grassland, grass nutrition in arid grasslands was sensitive to treatments associated with the predicted effects of global warming as the results of changes in plant nutrition. It is therefore highly possible that Mongolian livestock production will be negatively affected as a result of ongoing global warming.
ER-resident STIM1/2 couples Ca
2+
entry by NMDA receptors to pannexin-1 activation
Authors: Patil Chetan S. , Li Hongbin , Lavine Natalie E. , Shi Ruoyang , Bodalia Ankur , Siddiqui Tabrez J. , Jackson Michael F.
Published: August 2022

Pannexin-1 (Panx1) is a large-pore ion and solute permeable channel highly expressed in the nervous system, where it subserves diverse processes, including neurite outgrowth, dendritic spine formation, and N-methyl D-aspartate (NMDA) receptor (NMDAR)-dependent plasticity. Moreover, Panx1 dysregulation contributes to neurological disorders, including neuropathic pain, epilepsy, and excitotoxicity. Despite progress in understanding physiological and pathological functions of Panx1, the mechanisms that regulate its activity, including its ion and solute permeability, remain poorly understood. In this study, we identify endoplasmic reticulum (ER)-resident stromal interaction molecules (STIM1/2), which are Ca
2+
sensors that communicate events within the ER to plasma membrane channels, as binding and signaling partners of Panx1. We demonstrate that Panx1 is activated to its large-pore configuration in response to stimuli that recruit STIM1/2 and map the interaction interface to a hydrophobic region within the N terminus of Panx1. We further characterize a Panx1 N terminus–recognizing antibody as a function-blocking tool able to prevent large-pore Panx1 activation by STIM1/2. Using either the function-blocking antibody or re-expression of Panx1 deletion mutants in Panx1 knockout (KO) neurons, we show that STIM recruitment couples Ca
2+
entry via NMDARs to Panx1 activation, thereby identifying a model of NMDAR-STIM-Panx1 signaling in neurons. Our study highlights a previously unrecognized and important role of the Panx1 N terminus in regulating channel activation and membrane localization. Considering past work demonstrating an intimate functional relation between NMDARs and Panx1, our study opens avenues for understanding activation modality and context-specific functions of Panx1, including functions linked to diverse STIM-regulated cellular responses.
Gender-diverse teams produce more novel and higher-impact scientific ideas
Authors: Yang Yang , Tian Tanya Y. , Woodruff Teresa K. , Jones Benjamin F. , Uzzi Brian
Published: August 2022

Science’s changing demographics raise new questions about research team diversity and research outcomes. We study mixed-gender research teams, examining 6.6 million papers published across the medical sciences since 2000 and establishing several core findings. First, the fraction of publications by mixed-gender teams has grown rapidly, yet mixed-gender teams continue to be underrepresented compared to the expectations of a null model. Second, despite their underrepresentation, the publications of mixed-gender teams are substantially more novel and impactful than the publications of same-gender teams of equivalent size. Third, the greater the gender balance on a team, the better the team scores on these performance measures. Fourth, these patterns generalize across medical subfields. Finally, the novelty and impact advantages seen with mixed-gender teams persist when considering numerous controls and potential related features, including fixed effects for the individual researchers, team structures, and network positioning, suggesting that a team’s gender balance is an underrecognized yet powerful correlate of novel and impactful scientific discoveries.
Cross-talk between IL-6 trans-signaling and AIM2 inflammasome/IL-1β axes bridge innate immunity and epithelial apoptosis to promote emphysema
Authors: Ruwanpura Saleela M. , McLeod Louise , Dousha Lovisa F. , Seow Huei J. , West Alison C. , West Alice J. , Weng Teresa , Alanazi Mohammad , MacDonald Martin , King Paul T. , Bardin Philip G. , Gabay Cem , Klinman Dennis M. , Bozinovski Steven , Vlahos Ross , Anderson Gary P. , Rose-John Stefan , Saad Mohamed I. , Jenkins Brendan J.
Published: August 2022

Pulmonary emphysema is associated with dysregulated innate immune responses that promote chronic pulmonary inflammation and alveolar apoptosis, culminating in lung destruction. However, the molecular regulators of innate immunity that promote emphysema are ill-defined. Here, we investigated whether innate immune inflammasome complexes, comprising the adaptor ASC, Caspase-1 and specific pattern recognition receptors (PRRs), promote the pathogenesis of emphysema. In the lungs of emphysematous patients, as well as spontaneous
gp130
F/F
and cigarette smoke (CS)-induced mouse models of emphysema, the expression (messenger RNA and protein) and activation of ASC, Caspase-1, and the inflammasome-associated PRR and DNA sensor AIM2 were up-regulated. AIM2 up-regulation in emphysema coincided with the biased production of the mature downstream inflammasome effector cytokine IL-1β but not IL-18. These observations were supported by the genetic blockade of ASC, AIM2, and the IL-1 receptor and therapy with AIM2 antagonistic suppressor oligonucleotides, which ameliorated emphysema in
gp130
F/F
mice by preventing elevated alveolar cell apoptosis. The functional requirement for AIM2 in driving apoptosis in the lung epithelium was independent of its expression in hematopoietic-derived immune cells and the recruitment of infiltrating immune cells in the lung. Genetic and inhibitor-based blockade of AIM2 also protected CS-exposed mice from pulmonary alveolar cell apoptosis. Intriguingly, IL-6 trans-signaling via the soluble IL-6 receptor, facilitated by elevated levels of IL-6, acted upstream of the AIM2 inflammasome to augment AIM2 expression in emphysema. Collectively, we reveal cross-talk between the AIM2 inflammasome/IL-1β and IL-6 trans-signaling axes for potential exploitation as a therapeutic strategy for emphysema.
Sulfur radical formation from the tropospheric irradiation of aqueous sulfate aerosols
Authors: Cope James D. , Bates Kelvin H. , Tran Lillian N. , Abellar Karizza A. , Nguyen Tran B.
Published: August 2022

The sulfate anion radical (SO4•–) is known to be formed in the autoxidation chain of sulfur dioxide and from minor reactions when sulfate or bisulfate ions are activated by OH radicals, NO3radicals, or iron. Here, we report a source of SO4•–, from the irradiation of the liquid water of sulfate-containing organic aerosol particles under natural sunlight and laboratory UV radiation. Irradiation of aqueous sulfate mixed with a variety of atmospherically relevant organic compounds degrades the organics well within the typical lifetime of aerosols in the atmosphere. Products of the SO4•–+ organic reaction include surface-active organosulfates and small organic acids, alongside other products. Scavenging and deoxygenated experiments indicate that SO4•–radicals, instead of OH, drive the reaction. Ion substitution experiments confirm that sulfate ions are necessary for organic reactivity, while the cation identity is of low importance. The reaction proceeds at pH 1–6, implicating both bisulfate and sulfate in the formation of photoinduced SO4•–. Certain aromatic species may further accelerate the reaction through synergy. This reaction may impact our understanding of atmospheric sulfur reactions, aerosol properties, and organic aerosol lifetimes when inserted into aqueous chemistry model mechanisms.
The pathway for coenzyme M biosynthesis in bacteria
Authors: Wu Hsin-Hua , Pun Michael D. , Wise Courtney E. , Streit Bennett R. , Mus Florence , Berim Anna , Kincannon William M. , Islam Abdullah , Partovi Sarah E. , Gang David R. , DuBois Jennifer L. , Lubner Carolyn E. , Berkman Clifford E. , Lange B. Markus , Peters John W.
Published: August 2022

Mercaptoethane sulfonate or coenzyme M (CoM) is the smallest known organic cofactor and is most commonly associated with the methane-forming step in all methanogenic archaea but is also associated with the anaerobic oxidation of methane to CO
2
in anaerobic methanotrophic archaea and the oxidation of short-chain alkanes in
Syntrophoarchaeum
species. It has also been found in a small number of bacteria capable of the metabolism of small organics. Although many of the steps for CoM biosynthesis in methanogenic archaea have been elucidated, a complete pathway for the biosynthesis of CoM in archaea or bacteria has not been reported. Here, we present the complete CoM biosynthesis pathway in bacteria, revealing distinct chemical steps relative to CoM biosynthesis in methanogenic archaea. The existence of different pathways represents a profound instance of convergent evolution. The five-step pathway involves the addition of sulfite, the elimination of phosphate, decarboxylation, thiolation, and the reduction to affect the sequential conversion of phosphoenolpyruvate to CoM. The salient features of the pathway demonstrate reactivities for members of large aspartase/fumarase and pyridoxal 5′-phosphate–dependent enzyme families.
Thiomorpholino oligonucleotides as a robust class of next generation platforms for alternate mRNA splicing
Authors: Le Bao T. , Paul Sibasish , Jastrzebska Katarzyna , Langer Heera , Caruthers Marvin H. , Veedu Rakesh N.
Published: August 2022

Recent advances in drug development have seen numerous successful clinical translations using synthetic antisense oligonucleotides (ASOs). However, major obstacles, such as challenging large-scale production, toxicity, localization of oligonucleotides in specific cellular compartments or tissues, and the high cost of treatment, need to be addressed. Thiomorpholino oligonucleotides (TMOs) are a recently developed novel nucleic acid analog that may potentially address these issues. TMOs are composed of a morpholino nucleoside joined by thiophosphoramidate internucleotide linkages. Unlike phosphorodiamidate morpholino oligomers (PMOs) that are currently used in various splice-switching ASO drugs, TMOs can be synthesized using solid-phase oligonucleotide synthesis methodologies. In this study, we synthesized various TMOs and evaluated their efficacy to induce exon skipping in a Duchenne muscular dystrophy (DMD) in vitro model using
H2K mdx
mouse myotubes. Our experiments demonstrated that TMOs can efficiently internalize and induce excellent exon 23 skipping potency compared with a conventional PMO control and other widely used nucleotide analogs, such as 2′-O-methyl and 2′-O-methoxyethyl ASOs. Notably, TMOs performed well at low concentrations (5–20 nM). Therefore, the dosages can be minimized, which may improve the drug safety profile. Based on the present study, we propose that TMOs represent a new, promising class of nucleic acid analogs for future oligonucleotide therapeutic development.
Matrix Integrable Fourth-Order Nonlinear Schrödinger Equations and Their Exact Soliton Solutions
Authors: Ma Wen-Xiu
Published: August 2022

We construct matrix integrable fourth-order nonlinear Schrödinger equations through reducing the Ablowitz–Kaup–Newell–Segur matrix eigenvalue problems. Based on properties of eigenvalue and adjoint eigenvalue problems, we solve the corresponding reflectionless Riemann–Hilbert problems, where eigenvalues could equal adjoint eigenvalues, and formulate their soliton solutions via those reflectionless Riemann–Hilbert problems. Soliton solutions are computed for three illustrative examples of scalar and two-component integrable fourth-order nonlinear Schrödinger equations.
A study of the sign reversal from a transmission peak to an absorption dip in a V-type system using the D1 and D2 lines of 87Rb in the presence of a buffer gas
Authors: Dey Sekhar , Das Chandan , Bhattacharyya Dipankar , Ray Biswajit
Published: August 2022

In this work, we have investigated the transmission peak and absorption dip in the Doppler broadened V-type system using the D1 and D2 lines of  87Rb atoms in the presence of nitrogen buffer gas. The effects of the probe power variations at a fixed pump power on these resonances are examined both experimentally and theoretically. We have explored the fact that the transmission peak essentially turns into an absorption dip when the probe power is stronger than the pump power. Moreover, the theoretical model of a five-level V-type system is found to be sufficient to support the experimental outcomes when the effect of collision due to the presence of buffer gas is included in the theoretical model. We have also shown the variation of the resonance amplitude and population distribution in the upper level (|5〉) with increasing probe power.
A case study on long-term performance optimization of a geothermal heating system
Authors: Jia Guosheng , Duan Kefeng , Xue Yuze , Ma Zhendi , Wang Jiawei , Tong Zixiang
Published: August 2022

The optimal use of geothermal energy necessitates the performance evaluation and economic analysis of the geothermal heating systems. This work presented a field study of the long-term operating performance of a geothermal heating system in Xixian New Area, China. Nine deep coaxial ground heat exchangers (GHEs) with depths of 2,500 m were adopted for space heating to the residential buildings, with a total heating area and heating load of 136,097.71 m2 and 6,082 kW, respectively. The system’s 30-year running performance at various volumetric flow rates and operating modes was simulated. Through response surface analysis and multi-objective optimization, the levelized cost of energy (LCOE) and payback period were obtained based on the thermal performance analysis. It is concluded that the operating parameters have a significant impact on the system economy. When the daily operating time reduces from 24 hours to 8 hours, the payback period will be lowered from more than 25 years to approximately 11 years. When the volumetric flow rate is 35 m3·h-1, the examined system achieves the lowest LCOE. The minimum values of LCOE are 13.2 $/GJ, 11.6 $/GJ, 9.4 $/GJ, 7.8 $/GJ and 5.6 $/GJ when the system operates 24 hours (continuous operation), 20 hours, 16 hours, 12 hours and 8 hours a day, respectively. With the optimal flow rate, the average heat exchange rate of the single GHE increases from 295 kW to 519 kW after 30 years of operation when the daily operating time is reduced from 20 hours to 8 hours. The proposed method and findings can be used to guide the high-efficiency operation, which is conducive to reducing operating costs of geothermal heating systems.
Study on sustainable defluoridization approaches for rural drinking water treatment in northern China
Authors: Mingru Chen , Xu Guo , Zehan Zhang , Lyu Zhou
Published: August 2022

Groundwater for potable uses containing high fluoride is a worldwide threat to human health. Electrocoagulation is a sustainable approach for decentralized treatment. This study aims to analyse the economic and environmental impacts of electrocoagulation applied at different scale in rural area of northern China by life cycle cost (LCC) and life cycle assessment (LCA) methods. Decentralized treatment for defluoridization in rural Fangshan District, Beijing, where the groundwater quality is typical in northern China, is surveyed as a case study. Three scenarios were evaluated. In scenario 1 (S1) all domestic water is electrocoagulated at community scale without dual water supply system. In scenario 2 (S2) only water for potable uses is electrocoagulated at community scale and raw water and treated water are distributed via dual water pipeline systems. In scenario 3 (S3) water for potable uses is electrocoagulated at household scale. Life cycle assessment is performed with openLCA software and Ecoinvent database. S1 has the highest impacts for eutrophication and global warming. S2 has the lowest impact for toxicity but highest impact for ozone layer depletion. S3 has the lowest impact for global warming and acidification but highest impact for human toxicity. S2 is the costliest while S3 is the most economical. In this case, life cycle cost and global warming impact are the most restricted factors so electrocoagulation at household scale is recommended.
Applying paper material to landscape architecture design: a systematic review and a pioneer experiment (1995 – 2020)
Authors: Lin Jiawei , Song Limin , Ren Dingding
Published: August 2022

With the support of new technology, recyclable paper is capable of being both waterproof and fireproof, and it has been used in architectural design to some extent. However, there are limited studies on the use of paper materials in landscape architecture. The purpose of this study is to investigate the potential of paper materials practice in landscape architecture design from both functional and aesthetic perspectives. The method includes two parts: 1. a systematic review to investigate paper’s properties and capabilities to demonstrate it is qualified as a landscape construction material; 2. Provide a prototype to illustrate how to use paper materials in a practical landscape design. This paper found that the application of paper materials in landscape architecture has the following benefits: low-cost material, easy assemble and removal, build fast, easy transport, recyclable, unique material aesthetic feeling, low technical requirement, educational. Through a systematic review and case studies, this study explored the practical application value of paper materials in landscape architecture, and provided a feasible idea and direction for the landscape architecture industry to practice the concept of sustainable development.
Synthesis and characterization of green-functionalized graphene nanofluids as an enhanced working fluid in heat transfer applications
Authors: Rahman U.Z.A. , Teng K. H. , Yeap S. P. , Kazi S. N.
Published: August 2022

Energy crisis is one of the major concerns that requires significant attention around the world. An access to reliable, sustainable, and affordable energy will not be attractive if the safety of human and environmental is neglected. Hence, the advancement of energy harvesting method is expected not to be just efficient, but also clean, safe, and environmental-friendly. In this research work, synthesis, and characterization of a green-based functionalized graphene nanofluids is presented. Clove extract was prepared and functionalized on the graphene nanoplatelets (GNP) using apple cider vinegar, followed by dispersion in distilled water to produce clove with apple cider vinegar functionalized graphene (clove+ACV GNP) nanofluids at 0.1 wt.% concentration. Characterization of the clove+ACV GNP nanofluids was carried out using Fourier Transform Infrared Spectroscopy (FTIR) and Scanning Electron Microscopy (SEM) to examine the successfulness of the synthesis and functionalization, while the thermal conductivity was determined using KD2 Pro Thermal Properties Analyzer. The covalent bonds shown in the FTIR spectrum, and the morphological structure from the SEM images have indicated that the synthesis and functionalization of clove+ACV GNP have been successfully carried out. As for the thermal conductivity, 0.1 wt.% of clove+ACV GNP nanofluids have shown up to 24.4% enhancement when compared with distilled water, 3.9% enhancement when compared to clove-functionalized GNP at the same concentration, and up to 6.8% when compared with conventional GNP nanofluids. These findings have given a preliminary insight that this safe, non-toxic- clove+ACV functionalized graphene nanofluids is a promising alternative to the conventional, toxic- nanofluids as an enhanced and effective working fluid in heat transfer applications.
Comparing Anxiety and Depression in Information Technology Workers with Others in Employment: A UK Biobank Cohort Study
Authors: Lalloo Drushca , Lewsey Jim , Katikireddi Srinivasa Vittal , Macdonald Ewan B , Campbell Desmond , Demou Evangelia
Published: August 2022

Objectives

Despite reported psychological hazards of information technology (IT) work, studies of diagnosed mental health conditions in IT workers are lacking. We investigated self-reported mental health outcomes and incident anxiety/depression in IT workers compared to others in employment in a large population-based cohort.

Methods

We evaluated self-reported mental health outcomes in the UK Biobank cohort and incident diagnosed anxiety/depression through health record linkage. We used logistic regression and Cox models to compare the risks of prevalent and incident anxiety/depression among IT workers with all other employed participants. Furthermore, we compared outcomes within IT worker subgroups, and between these subgroups and other similar occupations within their major Standard Occupational Classification (SOC) group.

Results

Of 112 399 participants analyzed, 4093 (3.6%) were IT workers. At baseline, IT workers had a reduced odds (OR = 0.66, 95%CI: 0.52–0.85) of anxiety/depression symptoms and were less likely (OR = 0.87, 95%CI: 0.83–0.91) to have ever attended their GP for anxiety/depression, compared to all other employed participants, after adjustment for confounders. The IT technician subgroup were more likely (OR = 1.22, 95%CI: 1.07–1.40) to have previously seen their GP or a psychiatrist (OR = 1.31, 95%CI: 1.06–1.62) for anxiety/depression than their SOC counterparts. IT workers had lower incident anxiety/depression (HR = 0.84, 95%CI 0.77–0.93) compared to all other employed participants, after adjustment for confounders.

Conclusions

Our findings from this, the first longitudinal study of IT worker mental health, set the benchmark in our understanding of the mental health of this growing workforce and identification of high-risk groups. This will have important implications for targeting mental health workplace interventions.
SEMgraph: an R package for causal network inference of high-throughput data with structural equation models
Authors: Grassi Mario , Palluzzi Fernando , Tarantino Barbara
Published: August 2022

Motivation

With the advent of high-throughput sequencing in molecular biology and medicine, the need for scalable statistical solutions for modeling complex biological systems has become of critical importance. The increasing number of platforms and possible experimental scenarios raised the problem of integrating large amounts of new heterogeneous data and current knowledge, to test novel hypotheses and improve our comprehension of physiological processes and diseases.

Results

Combining network analysis and causal inference within the framework of structural equation modeling (SEM), we developed the R package SEMgraph. It provides a fully automated toolkit, managing complex biological systems as multivariate networks, ensuring robustness and reproducibility through data-driven evaluation of model architecture and perturbation, which is readily interpretable in terms of causal effects among system components.

Availability and implementation

SEMgraph package is available at https://cran.r-project.org/web/packages/SEMgraph.

Supplementary information

Supplementary data are available at Bioinformatics online.
Aclust2.0: a revamped unsupervised R tool for Infinium methylation beadchips data analyses
Authors: Oluwayiose Oladele A , Wu Haotian , Gao Feng , Baccarelli Andrea A , Sofer Tamar , Pilsner J Richard
Published: August 2022

Motivation

A wide range of computational packages has been developed for regional DNA methylation analyses of Illumina’s Infinium array data. Aclust, one of the first unsupervised algorithms, was originally designed to analyze regional methylation of Infinium’s 27K and 450K arrays by clustering neighboring methylation sites prior to downstream analyses. However, Aclust relied on outdated packages that rendered it largely non-operational especially with the newer Infinium EPIC and mouse arrays.

Results

We have created Aclust2.0, a streamlined pipeline that involves five steps for the analyses of human (450K and EPIC) and mouse array data. Aclust2.0 provides a user-friendly pipeline and versatile for regional DNA methylation analyses for molecular epidemiological and mouse studies.

Availability and implementation

Aclust2.0 is freely available on Github (https://github.com/OluwayioseOA/Alcust2.0.git).
DeepToA: an ensemble deep-learning approach to predicting the theater of activity of a microbiome
Authors: Zeng Wenhuan , Gautam Anupam , Huson Daniel H
Published: August 2022

Motivation

Metagenomics is the study of microbiomes using DNA sequencing. A microbiome consists of an assemblage of microbes that is associated with a ‘theater of activity’ (ToA). An important question is, to what degree does the taxonomic and functional content of the former depend on the (details of the) latter? Here, we investigate a related technical question: Given a taxonomic and/or functional profile estimated from metagenomic sequencing data, how to predict the associated ToA? We present a deep-learning approach to this question. We use both taxonomic and functional profiles as input. We apply node2vec to embed hierarchical taxonomic profiles into numerical vectors. We then perform dimension reduction using clustering, to address the sparseness of the taxonomic data and thus make the problem more amenable to deep-learning algorithms. Functional features are combined with textual descriptions of protein families or domains. We present an ensemble deep-learning framework DeepToA for predicting the ToA of amicrobial community, based on taxonomic and functional profiles. We use SHAP (SHapley Additive exPlanations) values to determine which taxonomic and functional features are important for the prediction.

Results

Based on 7560 metagenomic profiles downloaded from MGnify, classified into 10 different theaters of activity, we demonstrate that DeepToA has an accuracy of 98.30%. We show that adding textual information to functional features increases the accuracy.

Availability and implementation

Our approach is available at http://ab.inf.uni-tuebingen.de/software/deeptoa.

Supplementary information

Supplementary data are available at Bioinformatics online.
scFeatures: multi-view representations of single-cell and spatial data for disease outcome prediction
Authors: Cao Yue , Lin Yingxin , Patrick Ellis , Yang Pengyi , Yang Jean Yee Hwa
Published: August 2022

Motivation

With the recent surge of large-cohort scale single cell research, it is of critical importance that analytical methods can fully utilize the comprehensive characterization of cellular systems that single cell technologies produce to provide insights into samples from individuals. Currently, there is little consensus on the best ways to compress information from the complex data structures of these technologies to summary statistics that represent each sample (e.g. individuals).

Results

Here, we present scFeatures, an approach that creates interpretable cellular and molecular representations of single-cell and spatial data at the sample level. We demonstrate that summarizing a broad collection of features at the sample level is both important for understanding underlying disease mechanisms in different experimental studies and for accurately classifying disease status of individuals.

Availability and implementation

scFeatures is publicly available as an R package at https://github.com/SydneyBioX/scFeatures. All data used in this study are publicly available with accession ID reported in the Section 2.

Supplementary information

Supplementary data are available at Bioinformatics online.
Demographic trends in the incidence of malignant appendiceal tumours in England between 1995 and 2016: Population-based analysis
Authors: Orchard Philippa , Preece Ryan , Thomas Michael G , Dixon Steven W , Wong Newton A C S , Chambers Adam C , Messenger David E
Published: August 2022

Aims

Recent data suggest that the incidence of malignant appendiceal tumours is increasing. This study aimed to determine temporal trends in the incidence of malignant appendiceal tumours within England and a possible influence by demographic factors.

Methods

All incident cases of appendiceal tumours in patients aged 20 years and above were identified from the National Cancer Registration and Analysis Service database between 1995 and 2016 using ICD-9/10 codes. Cancers were categorized according to histology. Joinpoint regression analysis was used to investigate changes in age-standardized incidence rates by age, sex, histological subtype and index of multiple deprivation quintiles, based on socioeconomic domains (income, employment, education, health, crime, barriers to housing and services and living environment). Average annual per cent changes (AAPCs) were estimated by performing Monte-Carlo permutation analysis.

Results

A total of 7333 tumours were diagnosed and 7056 patients were analysed, comprising 3850 (54.6 per cent) neuroendocrine tumours (NETs), 1892 (26.8 per cent) mucinous adenocarcinomas and 1314 (18.6 per cent) adenocarcinoma (not otherwise specified). The overall incidence of appendiceal tumours increased from 0.3 per 100 000 to 1.6 per 100 000 over the study interval. Incidence rate increases of comparable magnitude were observed across all age groups, but the AAPC was highest among patients aged 20–29 years (15.6 per cent, 95 per cent c.i 12.7–18.6 per cent) and 30–39 years (14.2 per cent, 12.2–16.2 per cent) and lowest among those aged 70–79 years (6.8 per cent, 5.7–8.0 per cent). Similar incidence rate increases were reported across all socioeconomic deprivation quintiles and in both sexes. Analysis by grade of NET showed that grade 1 tumours accounted for 63 per cent between 2010 and 2013, compared with 2 per cent between 2000 and 2003.

Conclusions

The incidence rate of malignant appendiceal tumours has increased significantly since 1995 and is mainly attributed to an increase in NETs. The increased diagnosis of low-grade NETs may in part be due to changes in pathological classification systems.
Rescue of lysosomal function as therapeutic strategy for SPG15 hereditary spastic paraplegia
Authors: Vantaggiato Chiara , Orso Genny , Guarato Giulia , Brivio Francesca , Napoli Barbara , Panzeri Elena , Masotti Simona , Santorelli Filippo Maria , Lamprou Maria , Gumeni Sentiljana , Clementi Emilio , Bassi Maria Teresa
Published: August 2022

SPG15 is a hereditary spastic paraplegia subtype caused by mutations in Spastizin, a protein encoded by the ZFYVE26 gene. Spastizin is involved in autophagosome maturation and autophagic lysosome reformation and SPG15-related mutations lead to autophagic lysosome reformation defects with lysosome enlargement, free lysosome depletion and autophagosome accumulation. Symptomatic and rehabilitative treatments are the only therapy currently available for patients. Here, we targeted autophagy and lysosomes in SPG15 patient-derived cells by using a library of autophagy-modulating compounds. We identified a rose of compounds affecting intracellular calcium levels, the calcium-calpain pathway or lysosomal functions, which reduced autophagosome accumulation. The six most effective compounds were tested in vivo in a new SPG15 loss of function Drosophila model that mimicked the reported SPG15 phenotype, with autophagosome accumulation, enlarged lysosomes, reduced free lysosomes, autophagic lysosome reformation defects and locomotor deficit. These compounds, namely verapamil, Bay K8644, 2′,5′-dideoxyadenosine, trehalose, Small-Molecule Enhancer of Rapamycin 28 and trifluoperazine, improved lysosome biogenesis and function in vivo, demonstrating that lysosomes are a key pharmacological target to rescue SPG15 phenotype. Among the others, the Small-Molecule Enhancer of Rapamycin 28 was the most effective, rescuing both autophagic lysosome reformation defects and locomotor deficit, and could be considered as a potential therapeutic compound for this hereditary spastic paraplegia subtype.
DJ-1 is an essential downstream mediator in PINK1/parkin-dependent mitophagy
Authors: Imberechts Dorien , Kinnart Inge , Wauters Fieke , Terbeek Joanne , Manders Liselot , Wierda Keimpe , Eggermont Kristel , Madeiro Rodrigo Furtado , Sue Carolyn , Verfaillie Catherine , Vandenberghe Wim
Published: August 2022

Loss-of-function mutations in the PRKN, PINK1 and PARK7 genes (encoding parkin, PINK1 and DJ-1, respectively) cause autosomal recessive forms of Parkinson’s disease. PINK1 and parkin jointly mediate selective autophagy of damaged mitochondria (mitophagy), but the mechanisms by which loss of DJ-1 induces Parkinson’s disease are not well understood. Here, we investigated PINK1/parkin-mediated mitophagy in cultured human fibroblasts and induced pluripotent stem cell-derived neurons with homozygous PARK7 mutations. We found that DJ-1 is essential for PINK1/parkin-mediated mitophagy. Loss of DJ-1 did not interfere with PINK1 or parkin activation after mitochondrial depolarization but blocked mitophagy further downstream by inhibiting recruitment of the selective autophagy receptor optineurin to depolarized mitochondria. By contrast, starvation-induced, non-selective autophagy was not affected by loss of DJ-1. In wild-type fibroblasts and induced pluripotent stem cell-derived dopaminergic neurons, endogenous DJ-1 translocated to depolarized mitochondria in close proximity to optineurin. DJ-1 translocation to depolarized mitochondria was dependent on PINK1 and parkin and did not require oxidation of cysteine residue 106 of DJ-1. Overexpression of DJ-1 did not rescue the mitophagy defect of PINK1- or parkin-deficient cells. These findings position DJ-1 downstream of PINK1 and parkin in the same pathway and suggest that disruption of PINK1/parkin/DJ-1-mediated mitophagy is a common pathogenic mechanism in autosomal recessive Parkinson’s disease.
GFPT1 promotes the proliferation of cervical cancer via regulating the ubiquitination and degradation of PTEN
Authors: Li Dailing , Guan Mingmei , Cao Xiaofei , Zha Zhi Qiang , Zhang Peiling , Xiang Hong , Zhou Yun , Peng Qian , Xu Zhixiang , Lu Lin , Liu Guolong
Published: August 2022

Cervical cancer demonstrates the fourth incidence and death rate in females worldwide. Glutamine--fructose-6-phosphate transaminase 1 (GFPT1), the first rate-limited enzyme of the hexosamine biosynthesis pathway, has been reported to promote the progression of cancers. However, the prognostic value and roles of GFPT1 in cervical cancer are largely unknown. Transcription expression data for cervical cancer were downloaded from public databases. GFPT1 overexpressed and knockdown cell lines were constructed. Colony formation assays, Edu assays and 3-(4,5-dimethylthiazole-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assays were used to measure the proliferation capabilities of cervical cancer cells. Western blot, Immunofluorescence and co-immunoprecipitation assays were performed to verify the interaction between GFPT1and Phosphatase and tensin homolog (PTEN). Animal assays were applied to verify the results in vivo. GFPT1 expression was higher in cervical cancer cell lines. The proliferation capabilities of cervical cancer cells were suppressed in GFPT1 knockdown cells and GFPT1 inhibitor L-DON treated cells. And overexpression of GFPT1 promoted cell proliferation. PTEN was up-regulated in GFPT1 knockdown cells and downregulated in GFPT1 overexpression cells. Immunofluorescence and co-immunoprecipitation results showed that GFPT1 was co-localized and interacted with PTEN. GFPT1 promoted the ubiquitination and degradation of PTEN. Silence of PTEN offsets the growth inhibition of cervical cancer caused by GFPT1 knockdown. Animal assays showed that GFPT1 promoted the proliferation of cervical cancer in vivo. Our study revealed that GFPT1 could promote the progression of cervical cancer by regulating PTEN expression. Our study highlights the GFPT1-PTEN regulation as a potential therapy target for cervical cancer. .
Persistence of Severe Acute Respiratory Syndrome Coronavirus 2 Omicron Variant in Children and Utility of Rapid Antigen Testing as an Indicator of Culturable Virus
Authors: Lohse Zoe M , Shapiro Jerne J , Lednicky John A , Cash Melanie N , Jun Inyoung , Mavian Carla N , Tagliamonte Massimiliano S , Saleem Cyrus , Yang Yang , Nelson Eric J , Salemi Marco , Ryan Kathleen A , Morris J Glenn
Published: August 2022

We screened 65 longitudinally collected nasal swab samples from 31 children aged 0–16 years who were positive for severe acute respiratory syndrome coronavirus 2 Omicron BA.1. By day 7 after onset of symptoms, 48% of children remained positive by rapid antigen test. In a sample subset, we found 100% correlation between antigen test results and virus culture.
Physiological Differences Between Seasonal Dimorphs of Agonoscena pistaciae (Hemiptera: Aphalaridae) Elicit Distinct Host Plant Responses, Informing Novel Pest Management Insights
Authors: Homayoonzadeh Mohammad , Michaud J P , Esmaeily Mojtaba , Talebi Khalil , Allahyari Hossein , Wright Denis J
Published: August 2022

We examined differences in the physiology and life history between dimorphs of the common pistachio psyllid, Agonoscena pistaciae (Burckhardt and Lauterer) (Hemiptera: Aphalaridae), and how they differ in elicitating host plant production of key metabolites and volatile compounds involved in the recruitment of herbivores and natural enemies. Summer morphs had higher activities of glutathione S-transferase, carboxylesterase, acetylcholinesterase, and cytochrome P450 monooxygenase, superoxide dismutase, catalase, peroxidase, phenoloxidase, and a higher total protein content compared to winter morphs, whereas the latter had higher amounts of lipid, carbohydrate, and glycogen. Winter morphs were heavier, with a higher chitin content and longer preoviposition period, but greater fecundity and longevity than summer morphs. A lower LC50 to thiamethoxam for winter morphs resulted in higher mortality following exposure to the recommended rate of this insecticide in a greenhouse trial. Feeding by winter morphs elicited more strongly the release of volatile compounds known to be attractive to other herbivores, whereas feeding by summer morphs elicited more strongly the release of volatiles implicated in the attraction of natural enemies. Feeding by psyllids increased the concentrations of nitrogenous compounds, carbohydrates, vitamins, and amino acids in plants, the winter morph eliciting larger changes and more improved host plant quality. We conclude that winter morphs are more vulnerable targets for chemical control in early spring, whereas management of summer morphs could rely more on conservation biological control.
Critical Care Cardiology Trials Network (CCCTN): a cohort profile
Authors: Metkus Thomas S , Baird-Zars Vivian M , Alfonso Carlos E , Alviar Carlos L , Barnett Christopher F , Barsness Gregory W , Berg David D , Bertic Mia , Bohula Erin A , Burke James , Burstein Barry , Chaudhry Sunit-Preet , Cooper Howard A , Daniels Lori B , Fordyce Christopher B , Ghafghazi Shahab , Goldfarb Michael , Katz Jason N , Keeley Ellen C , Keller Norma M , Kenigsberg Benjamin , Kontos Michael C , Kwon Younghoon , Lawler Patrick R , Leibner Evan , Liu Shuangbo , Menon Venu , Miller P Elliott , Newby L Kristin , O'Brien Connor G , Papolos Alexander I , Pierce Matthew J , Prasad Rajnish , Pisani Barbara , Potter Brian J , Roswell Robert O , Sinha Shashank S , Shah Kevin S , Smith Timothy D , Snell R Jeffrey , So Derek , Solomon Michael A , Ternus Bradley W , Teuteberg Jeffrey J , van Diepen Sean , Zakaria Sammy , Morrow David A
Published: August 2022

Aims

The aims of the Critical Care Cardiology Trials Network (CCCTN) are to develop a registry to investigate the epidemiology of cardiac critical illness and to establish a multicentre research network to conduct randomised clinical trials (RCTs) in patients with cardiac critical illness.

Methods and results

The CCCTN was founded in 2017 with 16 centres and has grown to a research network of over 40 academic and clinical centres in the United States and Canada. Each centre enters data for consecutive cardiac intensive care unit (CICU) admissions for at least 2 months of each calendar year. More than 20 000 unique CICU admissions are now included in the CCCTN Registry. To date, scientific observations from the CCCTN Registry include description of variations in care, the epidemiology and outcomes of all CICU patients, as well as subsets of patients with specific disease states, such as shock, heart failure, renal dysfunction, and respiratory failure. The CCCTN has also characterised utilization patterns, including use of mechanical circulatory support in response to changes in the heart transplantation allocation system, and the use and impact of multidisciplinary shock teams. Over years of multicentre collaboration, the CCCTN has established a robust research network to facilitate multicentre registry-based randomised trials in patients with cardiac critical illness.

Conclusion

The CCCTN is a large, prospective registry dedicated to describing processes-of-care and expanding clinical knowledge in cardiac critical illness. The CCCTN will serve as an investigational platform from which to conduct randomised controlled trials in this important patient population.
Pulmonary artery banding as adjunct therapy for ventricular recovery after anomalous left coronary artery from the pulmonary artery repair: a case report
Authors: Mets Gilles , Bové Thierry , François Katrien , Panzer Joseph
Published: August 2022

Anomalous left coronary artery from the pulmonary artery is a rare congenital coronary anomaly commonly associated with severe but reversible left ventricular dysfunction. We present an anomalous left coronary artery from the pulmonary artery case of persisting left ventricular failure with inability to wean off the ventilator and inotropes after successful coronary reimplantation, in whom pulmonary artery banding enhanced myocardial recovery.
Reoperative aortic valve replacement after bio-Bentall using a double sewing ring technique
Authors: Ikeno Yuki , Motoki Tatsuo , Kurushima Atsushi , Fukumura Yoshiaki
Published: August 2022

We report an 89-year-old haemodialysis patient with a structural valve deterioration following a Bentall–de Bono operation with a tissue valve using the double sewing ring technique. The bioprosthesis was extracted easily, and the aortic valve replacement was performed without any complications in a high-risk patient. This procedure may be feasible given the prospects of reoperation.