bluuebunny/crossref_metadata_2025 huggingface dataset:
Process optimization for the rapid conversion of calcite into hydroxyapatite microspheres for chromatographic applications
Authors: Ashokan Anbuthangam , Kumar T. S. Sampath , Jayaraman Guhan
Published: July 2022

Microsphere hydroxyapatite (HAp) is widely used in various biomedical and chromatographic applications. The work described in this manuscript focuses on a dissolution precipitation method for production of HAp microspheres. This method overcomes certain drawbacks of conventional preparation methods used for HAp preparation, which produce polydisperse particles and are time-consuming and expensive. In the present work, the calcium carbonate (calcite) particles were directly and rapidly converted into HAp microspheres using an inexpensive dissolution precipitation method. The effects of the reaction temperature, time, and mechanical stirring rates were studied, and the reaction parameters were optimized. As confirmed by the XRD studies, the higher reaction temperature and time promote complete HAp conversion, while calcite residues were observed for lower temperatures and times. SEM images show the influence of reaction parameters on the surface microstructure of the microspheres produced. It was observed that the HAp microspheres undergo disintegration at a higher stirring rate. The reaction parameters optimized in this work were ideal for preparing HAp microspheres. The resultant HAp particles were utilized as matrices for chromatographic separation of protein mixtures.
A novel magnetic compression technique for cystostomy in rabbits
Authors: Zhang Miaomiao , Mao Jianqi , Li Yixing , Xu Shuqin , Gai Jingci , Lan Ting , Wang Yirui , Ren Yuxiang , Shi Aihua , Lyu Yi , Yan Xiaopeng
Published: July 2022

Magnetic compression technique (MCT) is a popular new anastomosis method. In this paper, we aimed to explore the feasibility of use of MCT for performing cystotomy in rabbits. The parent magnets and daughter magnets for rabbit cystostomy were designed and manufactured according to the anatomical characteristics of rabbit lower urinary tract. Twelve female New Zealand rabbits were used as animal models. After anesthesia, a daughter magnet was inserted into the bladder through the urethra, and the parent magnet was placed on the body surface projection of the bladder over the abdominal wall. The two magnets automatically attract each other. Postoperatively, the state of magnets was monitored daily, and the time when the magnets fell off was recorded. Cystostomy with MCT was successfully performed in all twelve rabbits. The mean operation time was 4.46 ± 0.75 min. The magnets fell off from the abdominal wall after a mean duration of 10.08 ± 1.62 days, resulting in the formation of bladder fistula. Macroscopic and microscopic examination showed that the fistula was well formed and unobstructed. The junction between bladder and abdominal wall was tight and smooth. We provide preliminary experimental evidence of the safety and feasibility of cystostomy based on MCT.
Value-added fabrication of NiO-doped CuO nanoflakes from waste flexible printed circuit board for advanced photocatalytic application
Authors: Hossain Rumana , Nekouei Rasoul Khayyam , Al Mahmood Abdullah , Sahajwalla Veena
Published: July 2022

The disposal of electronic waste (e-waste) presents a number of environmental problems. However, there are great opportunities to use this problem waste as a source of value-added metals. These metals could be recovered and transformed for use in beneficial applications, such as the manufacture of nanomaterials for the generation of hydrogen through thermodynamic water-splitting. This study used microrecycling techniques to synthesise Nitrogen oxide (NiO) doped copper oxide (CuO) nanoflakes from waste flexible printed circuit boards (FPCBs) using microrecycling techniques. Several precise characterisation and experimental analysis were used to validate the synthesised nanoflakes’ phase purity, surface chemistry, morphology and optical properties. XRD analysis confirmed the nanoflakes produced in the system were predominantly Tenorite, CuO (98.5% ± 4.5) with a dopant of NiO (1.5% ± 0.1). The nanoflakes had a specific surface area of 115.703 m2/g and mesoporous structure with an average pore diameter of 11 nm. HRTEM analysis confirmed that the nanoflakes were not a single structure but assembled from 2D nanorods. The width of the nanorods varied from ∼ 10 to 50 nm, and the length from ∼ 30 to 80 nm. After rapid thermal processing, the photocurrent response of the synthesised material was assessed, revealing a higher photocurrent density (− 1.9 mA/cm2 at 0.6 V vs. reversible hydrogen electrode (RHE) under 1.5G AM). Mott Schottky analysis and electrochemical impedance spectroscopy showed that the synthesised nanomaterial had the potential thermodynamic water-splitting capability. These results were an encouraging indication of the promise of techniques which use e-waste to produce nanomaterials with valuable properties. This has the potential to both decrease problem waste and preserves dwindling natural resources.
Three-dimensional conditional generative adversarial network-based virtual thin-slice technique for the morphological evaluation of the spine
Authors: Nakamoto Atsushi , Hori Masatoshi , Onishi Hiromitsu , Ota Takashi , Fukui Hideyuki , Ogawa Kazuya , Masumoto Jun , Kudo Akira , Kitamura Yoshiro , Kido Shoji , Tomiyama Noriyuki
Published: July 2022

Virtual thin-slice (VTS) technique is a generative adversarial network-based algorithm that can generate virtual 1-mm-thick CT images from images of 3–10-mm thickness. We evaluated the performance of VTS technique for assessment of the spine. VTS was applied to 4-mm-thick CT images of 73 patients, and the visibility of intervertebral spaces was evaluated on the 4-mm-thick and VTS images. The heights of vertebrae measured on sagittal images reconstructed from the 4-mm-thick images and VTS images were compared with those measured on images reconstructed from 1-mm-thick images. Diagnostic performance for the detection of compression fractures was also compared. The intervertebral spaces were significantly more visible on the VTS images than on the 4-mm-thick images (P < 0.001). The absolute value of the measured difference in mean vertebral height between the VTS and 1-mm-thick images was smaller than that between the 4-mm-thick and 1-mm-thick images (P < 0.01–0.54). The diagnostic performance of the VTS images for detecting compression fracture was significantly lower than that of the 4-mm-thick images for one reader (P = 0.02). VTS technique enabled the identification of each vertebral body, and enabled accurate measurement of vertebral height. However, this technique is not suitable for diagnosing compression fractures.
Multisite implementation of a workflow-integrated machine learning system to optimize COVID-19 hospital admission decisions
Authors: Hinson Jeremiah S. , Klein Eili , Smith Aria , Toerper Matthew , Dungarani Trushar , Hager David , Hill Peter , Kelen Gabor , Niforatos Joshua D. , Stephens R. Scott , Strauss Alexandra T. , Levin Scott
Published: July 2022

Demand has outstripped healthcare supply during the coronavirus disease 2019 (COVID-19) pandemic. Emergency departments (EDs) are tasked with distinguishing patients who require hospital resources from those who may be safely discharged to the community. The novelty and high variability of COVID-19 have made these determinations challenging. In this study, we developed, implemented and evaluated an electronic health record (EHR) embedded clinical decision support (CDS) system that leverages machine learning (ML) to estimate short-term risk for clinical deterioration in patients with or under investigation for COVID-19. The system translates model-generated risk for critical care needs within 24 h and inpatient care needs within 72 h into rapidly interpretable COVID-19 Deterioration Risk Levels made viewable within ED clinician workflow. ML models were derived in a retrospective cohort of 21,452 ED patients who visited one of five ED study sites and were prospectively validated in 15,670 ED visits that occurred before (n = 4322) or after (n = 11,348) CDS implementation; model performance and numerous patient-oriented outcomes including in-hospital mortality were measured across study periods. Incidence of critical care needs within 24 h and inpatient care needs within 72 h were 10.7% and 22.5%, respectively and were similar across study periods. ML model performance was excellent under all conditions, with AUC ranging from 0.85 to 0.91 for prediction of critical care needs and 0.80–0.90 for inpatient care needs. Total mortality was unchanged across study periods but was reduced among high-risk patients after CDS implementation.
Identification of a guanine-specific pocket in the protein N of SARS-CoV-2
Authors: Rafael Ciges-Tomas J. , Franco María Luisa , Vilar Marçal
Published: July 2022

The SARS-CoV-2 nucleocapsid protein (N) is responsible for RNA binding. Here we report the crystal structure of the C-terminal domain (NCTD) in open and closed conformations and in complex with guanine triphosphate, GTP. The crystal structure and biochemical studies reveal a specific interaction between the guanine, a nucleotide enriched in the packaging signals regions of coronaviruses, and a highly conserved tryptophan residue (W330). In addition, EMSA assays with SARS-CoV-2 derived RNA hairpin loops from a putative viral packaging sequence showed the preference interaction of the N-CTD to RNA oligonucleotides containing G and the loss of the specificity in the mutant W330A. Here we propose that this interaction may facilitate the viral assembly process. In summary, we have identified a specific guanine-binding pocket in the N protein that may be used to design viral assembly inhibitors.
Deployed measurement-device independent quantum key distribution and Bell-state measurements coexisting with standard internet data and networking equipment
Authors: Berrevoets Remon C. , Middelburg Thomas , Vermeulen Raymond F. L. , Chiesa Luca Della , Broggi Federico , Piciaccia Stefano , Pluis Rene , Umesh Prathwiraj , Marques Jorge F. , Tittel Wolfgang , Slater Joshua A.
Published: July 2022

The forthcoming quantum Internet is poised to allow new applications not possible with the conventional Internet. The ability for both quantum and conventional networking equipment to coexist on the same fiber network would facilitate the deployment and adoption of coming quantum technology. Most quantum networking tasks, like quantum repeaters and the connection of quantum processors, require nodes for multi-qubit quantum measurements (often Bell-State measurements), and their real-world coexistence with the conventional Internet has yet to be shown. Here we field deploy a Measurement-Device Independent Quantum Key Distribution (MDI-QKD) system, containing a Bell-State measurement node, over the same fiber connection as multiple standard Internet Protocol (IP) data networks, between three nearby cities in the Netherlands. We demonstrate over 10 Gb/s classical data communication rates simultaneously with our next-generation QKD system, and estimate 200 GB/s of classical data transmission would be easily achievable without significantly affecting QKD performance. Moreover, as the system ran autonomously for two weeks, this shows an important step towards the coexistence and integration of quantum networking into the existing telecommunication infrastructure.
Climate variability and multi-decadal diatom abundance in the Northeast Atlantic
Authors: Edwards Martin , Beaugrand Gregory , Kléparski Loïck , Hélaouët Pierre , Reid Philip C.
Published: July 2022

Diatoms are important contributors to marine primary production and the ocean carbon cycle. In the North Atlantic and its adjacent seas primary production is driven by diatoms that transfer a significant part of the produced energy to higher trophic levels and carbon to the deep ocean. Anthropogenic warming and climate variability will likely have important consequences for the productivity and spatial dynamics of these eukaryotic phytoplankton. Using multidecadal diatom abundance data (>60 years) for the Northeast Atlantic and the North Sea, we show significant spatial and temporal correlations over these scales between diatoms and climate variability. A general multidecadal trend is established where climate warming is increasing diatom populations in northerly systems but decreasing populations in more southerly systems. We discover major phase shifts in diatom abundance synchronous with multi-decadal trends in Atlantic climate variability that occurred after the mid-1990s.
Role of Sn/ZSM-5 in direct syngas conversion
Authors: Chen Yuxiang , Jiao Feng , Pan Xiulian , Bao Xinhe
Published: July 2022

Sn/ZSM-5 catalyzes direct syngas conversion into ethane with ethane selectivity 84% via an ethylene intermediate.
Coordination/cation exchangeable dual sites intercalated multilayered T3C2Tx MXene for selective and ultrafast removal of thallium(i) from water
Authors: Luo Yu , Weng Zonglin , Lin Yuanfang , Han Bin , Ou Xinwen , Zhou Yang , Jiang Jin
Published: July 2022

By intercalating KOH into multilayered Ti3C2Tx, an efficient adsorbent with coordination/cation exchangeable sites is developed for Tl+ removal. The –OH sites can coordinate Tl+ while the exchange of K+/Tl+ contributes selective and fast adsorption.
High-throughput computational evaluation of lattice thermal conductivity using an optimized Slack model
Authors: Qin Guangzhao , Huang An , Liu Yinqiao , Wang Huimin , Qin Zhenzhen , Jiang Xue , Zhao Jijun , Hu Jianjun , Hu Ming
Published: July 2022

An optimized Slack model is proposed, which can be used for high-throughput computational evaluation of κ for finding materials of ultrahigh or ultralow κ with broad applications.
Cobalt sandwich-stabilized rhodium nanocatalysts for ammonia borane and tetrahydroxydiboron hydrolysis
Authors: Zhao Qiuxia , Espuche Bruno , Kang Naixin , Moya Sergio , Astruc Didier
Published: July 2022

A bulky organocobalt sandwich-supported Rh nanoparticle is an efficient, stable and recyclable nanocatalyst for hydrolysis of both ammonia borane and tetrahydroxydiboron to H2.
Recent endeavours in the development of organo chromo-fluorogenic probes towards the targeted detection of the toxic industrial pollutants Cu2+ and CN−: recognition to implementation in sensory device
Authors: Paul Suparna , Das Riyanka , Banerjee Priyabrata
Published: July 2022

Cu2+ and CN− detection by chromo-fluorogenic probes with insight of photophysical signaling mechanisms has been systematically discussed. Exquisite integration of chemical response with RGB mediated electronic sensing prototype have been summarized.
Robust multi‐model controllers design without impulse in switching times for non‐linear vibrations suppression of sandwich plate
Authors: Zazerani Amir Amini , Faraji Alireza , Mohammadimehr Mahdi
Published: July 2022

Generally multi‐model controllers design has three stages: Decomposition of complicated non‐linear systems into local linear models, designing the local controllers, and composition of them in sub‐regions. In the present paper an algorithm is proposed in which all the three stages are simultaneously done to decrease the number of controllers. Determining a specific threshold based on non‐linear model characteristics is a good criterion for this purpose. The threshold depends on the knowledge of the system features and designing method, and the improper selection of the threshold will increase the number of local models and the complexity of the global controller structure. This non‐convex optimization problem is solved by the genetic algorithm whose cost function is defined by the complementary sensitivity function to guarantee the robust stability and optimal performance of the close loop the system, respectively. Another challenge in designing multi‐model controllers is the transient performance degradation when switching from one local model to another. In the present research, the problem is solved by the system input generated by the online controller error signal and the feedback coefficient of the offline controller. The proposed robust controller in the presence of the uncertainties is evaluated for vibration suppression of a sandwich plate.
Design of current detection LDO regulator with silicon controlled rectifier based electrostatic discharge protection circuit to provide optimized voltage and power for system‐on‐chip applications
Authors: Kwon Sang Wook , Koo Yong Seo
Published: July 2022

Various levels of circuits and systems in the ultra‐low nanometer fabrication process should be considered to implement a system‐on‐chip (SOC) application to reduce power consumption. This letter is intended to propose a current detection structure that supplies and discharges additional current along the load current to provide the optimized voltage and power for SOC applications. The proposed electrostatic discharge (ESD) protection circuit placed on the power line and I/O has improved the reliability by preventing the direct or indirect destruction of the internal integrated circuit (IC) due to ESD. In addition, the proposed low drop out (LDO) regulator for the low‐voltage applications has combined an ESD protection circuit to secure the high reliability of the IC. The proposed LDO regulator is implemented with a 0.18‐μm BCD process and is kept an undershoot voltage of 23 mV and an overshoot voltage of 25 mV for a load current of 200 mA.
General framework for the study of dynamical properties and arrested states of ionic liquids
Authors: Farias-Anguiano Mariana E. , Sánchez-Díaz Luis E. , Cortés-Morales Ernesto C. , Ramírez-González Pedro E.
Published: July 2022

In this work, we present a first-principles theoretical framework for the description of structural and dynamical behaviors of ionic liquids. This framework applies the self-consistent generalized Langevin equation (SCGLE) theory, which predicts the dynamically arrested states of several physical systems, including charge and size asymmetric ionic liquids. In its current form, the SCGLE is a particularly useful framework for predictions of arrested and partially arrested states in both classical and room-temperature molten salts, electrolytic solutions, and superionic conductors. Some illustrative examples of the predictive power of our framework are presented in this work, showing its potential application in design and development of novel conducting materials.
Law of incipient separation for turbulent flows over airfoils as inferred by Reynolds-averaged Navier–Stokes
Authors: Huang Shao-Chi , Aithal Abhiram B. , Ferrante Antonino
Published: July 2022

Lu, Aithal, and Ferrante [“Law of incipient separation over curved ramps as inferred by Reynolds-averaged Navier–Stokes,” AIAA J. 59, 196–214 (2021)] discovered a law that predicts the incipience of flow separation over curved ramps by knowing only a few geometrical parameters of the ramp and the Reynolds number of the flow. In that spirit, we have searched for a similar law for airfoils by performing simulations of incompressible turbulent flows over 32 NACA (National Advisory Committee for Aeronautics) airfoils using Reynolds-averaged Navier–Stokes (RANS) equations. First, we have carried out verification and validation of RANS against the experimental measurements by A. J. Wadcock (“Investigation of low-speed turbulent separated flow around airfoils,” NASA Contractor Report No. 177450, 1987), which show the accuracy of the RANS prediction at small angles of attack when flow separation begins to occur on the upper side of the airfoil. Then, we have investigated the effects of the angle of attack, airfoil thickness, and camber on the incipience of flow separation for the Reynolds number based on airfoil chord Rec∈[1.64×106,6×106]. From the analysis of the RANS results, we have determined a law for predicting the incipience of turbulent flow separation over airfoils that relies only on airfoil's newly defined characteristic slope, thickness, camber, and Rec.
Addressing Methamphetamine Use in Primary Care: Provider Perspectives
Authors: Dunn Julia , Yuan Mina , Ramírez Fernando , Chokron Garneau Hélène , Brown-Johnson Cati , Breland Haley , Antonini Valerie , Larkins Sherry , Rawson Richard , McGovern Mark
Published: July 2022

Introduction

The opioid epidemic has evolved into a combined stimulant epidemic, with escalating stimulant and fentanyl-related overdose deaths. Primary care providers are on the frontlines grappling with patients’ methamphetamine use. Although effective models exist for treating opioid use disorder in primary care, little is known about current clinical practices for methamphetamine use.

Methods

Six semistructured group interviews were conducted with 38 primary care providers. Interviews focused on provider perceptions of patients with methamphetamine use problems and their care. Data were analyzed using inductive and thematic analysis and summarized along the following dimensions: (1) problem identification, (2) clinical management, (3) barriers and facilitators to care, and (4) perceived needs to improve services.

Results

Primary care providers varied in their approach to identifying and treating patient methamphetamine use. Unlike opioid use disorders, providers reported lacking standardized screening measures and evidence-based treatments, particularly medications, to address methamphetamine use. They seek more standardized screening tools, Food and Drug Administration–approved medications, reliable connections to addiction medicine specialists, and more training. Interest in novel behavioral health interventions suitable for primary care settings was also noteworthy.

Conclusions

The findings from this qualitative analysis revealed that primary care providers are using a wide range of tools to screen and treat methamphetamine use, but with little perceived effectiveness. Primary care faces multiple challenges in effectively addressing methamphetamine use among patients singularly or comorbid with opioid use disorders, including the lack of Food and Drug Administration–approved medications, limited patient retention, referral opportunities, funding, and training for methamphetamine use. Focusing on patients’ medical issues using a harm reduction, motivational interviewing approach, and linkage with addiction medicine specialists may be the most reasonable options to support primary care in compassionately and effectively managing patients who use methamphetamines.
ComBat Harmonization: Empirical Bayes versus Fully Bayes Approaches
Authors: Reynolds Maxwell , Chaudhary Tigmanshu , Torbati Mahbaneh Eshaghzadeh , Tudorascu Dana L. , Batmanghelich Kayhan ,   the Alzheimer’s Disease Neuroimaging Initiative
Published: July 2022

Studying small effects or subtle neuroanatomical variation requires large-scale sample size data. As a result, combining neuroimaging data from multiple datasets is necessary. Variation in acquisition protocols, magnetic field strength, scanner build, and many other non-biologically related factors can introduce undesirable bias into studies. Hence, harmonization is required to remove the bias-inducing factors from the data. ComBat is one of the most common methods applied to features from structural images. ComBat models the data using a hierarchical Bayesian model and uses the empirical Bayes approach to infer the distribution of the unknown factors. The empirical Bayes harmonization method is computationally efficient and provides valid point estimates. However, it tends to underestimate uncertainty. This paper investigates a new approach, fully Bayesian ComBat, where Monte Carlo sampling is used for statistical inference. When comparing fully Bayesian and empirical Bayesian ComBat, we found Empirical Bayesian ComBat more effectively removed scanner strength information and was much more computationally efficient. Conversely, fully Bayesian ComBat better preserved biological disease and age-related information while performing more accurate harmonization on traveling subjects. The fully Bayesian approach generates a rich posterior distribution, which is useful for generating simulated imaging features for improving classifier performance in a limited data setting. We show the generative capacity of our model for augmenting and improving the detection of patients with Alzheimer’s disease. Posterior distributions for harmonized imaging measures can also be used for brain-wide uncertainty comparison and more principled downstream statistical analysis. Code for our new fully Bayesian ComBat extension is available athttps://github.com/batmanlab/BayesComBat.
Early-life stress lastingly impacts microglial transcriptome and function under basal and immune-challenged conditions
Authors: Reemst Kitty , Kracht Laura , Kotah Janssen M. , Rahimian Reza , van Irsen Astrid A.S. , Sotomayor Gonzalo Congains , Verboon Laura , Brouwer Nieske , Simard Sophie , Turecki Gustavo , Mechawar Naguib , Kooistra Susanne M. , Eggen Bart J. L. , Korosi Aniko
Published: July 2022

Early-life stress (ELS) leads to increased vulnerability to psychiatric disorders including depression later in life. Neuroinflammatory processes have been implicated in ELS-induced negative health outcomes, but how ELS impacts microglia, the main tissue-resident macrophages of the central nervous system, is unknown. Here, we determined the effects of ELS induced by limited bedding and nesting material during the first week of life (postnatal days [P]2 – 9) on microglial i) morphology; ii) hippocampal gene expression; and iii) synaptosome phagocytic capacity in male pups (P9) and adult (P200) mice. The hippocampus of ELS-exposed adult mice displayed altered proportions of morphological subtypes of microglia, as well as microglial transcriptomic changes related to the tumor necrosis factor response and protein ubiquitination. ELS exposure leads to distinct gene expression profiles during microglial development from P9 to P200 and in response to an LPS challenge at P200. Functionally, synaptosomes from ELS-exposed mice were phagocytosed less by age-matched microglia. At P200, but not P9, ELS microglia showed reduced synaptosome phagocytic capacity when compared to CTRL microglia. Lastly, we confirmed the ELS-induced increased expression of the phagocytosis-related gene GAS6 that we observed in mice, in the dentate gyrus of individuals with a history of child abuse using in situ hybridization. These findings reveal persistent effects of ELS on microglial function and suggest that altered microglial phagocytic capacity is a key contributor to ELS-induced phenotypes.
Tra1 controls the transcriptional landscape of the aging cell
Authors: Bari Khaleda Afrin , Berg Matthew D. , Genereaux Julie , Brandl Christopher J. , Lajoie Patrick
Published: July 2022

Gene expression undergoes considerable changes during the aging process. The mechanisms regulating the transcriptional response to cellular aging remain poorly understood. Here, we employ the budding yeast Saccharomyces cerevisiae to better understand how organisms adapt their transcriptome to promote longevity. Chronological lifespan (CLS) assays in yeast measure the survival of non-dividing cells at stationary phase over time, providing insights into the aging process of post-mitotic cells. Tra1 is an essential component of both the yeast SAGA/SLIK and NuA4 complexes, where it recruits these complexes to acetylate histones at targeted promoters. Importantly, Tra1 regulates the transcriptional response to multiple stresses. To evaluate the role of Tra1 in chronological aging, we took advantage of a previously characterized mutant allele that carries mutations in the TRA1 PI3K domain (tra1Q3). We found that loss of functions associated with tra1Q3 sensitized cells to growth media acidification and shortens lifespan. Transcriptional profiling reveals that genes differentially regulated by Tra1 during the aging process are enriched for components of the response to stress. Notably, expression of catalases (CTA1, CTT1) involved in hydrogen peroxide detoxification decreases in chronologically aged tra1Q3 cells. Consequently, they display increased sensitivity to oxidative stress. tra1Q3 cells are unable to grow on glycerol indicating a defect in mitochondria function. Aged tra1Q3 cells also display reduced expression of peroxisomal genes, exhibit decreased numbers of peroxisomes and cannot grow on media containing oleate. Thus, Tra1 emerges as an important regulator of longevity in yeast via multiple mechanisms.
A maximum-type microbial differential abundance test with application to high-dimensional microbiome data analyses
Authors: Li Zhengbang , Yu Xiaochen , Guo Hongping , Lee TingFang , Hu Jiyuan
Published: July 2022

Abstract

Background

High-throughput metagenomic sequencing technologies have shown prominent advantages over traditional pathogen detection methods, bringing great potential in clinical pathogen diagnosis and treatment of infection diseases. Yet, how to accurately detect the difference of microbiome profiles between treatment or disease conditions remains computationally challenging.

Results

In this study, we propose a novel test for identifying the difference between two high-dimensional microbiome abundance data matrices based on the centred log-ratio transformation of the microbiome compositions. The test p-value can be calculated directly with a closed-form solution from the derived asymptotic null distribution. We also investigate the asymptotic statistical power against sparse alternatives which are typically encountered in microbiome studies. The proposedMaximum-type test isEqual-Covariance-Assumption-Free (MECAF), making it widely applicable to studies that compare microbiome compositions between conditions. Our simulation studies demonstrated that the proposed MECAF test achieves desirable power than competing methods while having the type I error rate well controlled under various scenarios. The usefulness of the proposed test is further illustrated with two real microbiome data analyses. The source code of the proposed method is freely available athttps://github.com/JiyuanHu.

Conclusions

MECAF is a flexible differential abundance test and achieves statistical efficiency in analyzing high-throughput microbiome data. The proposed new method will allow us to efficiently discover shifts of microbiome abundances between disease and treatment conditions, broadening our understanding of the disease and ultimately improving clinical diagnosis and treatment.
R methylCIPHER: A Methylation Clock Investigational Package for Hypothesis-Driven Evaluation & Research
Authors: Thrush Kyra L. , Higgins-Chen Albert T. , Liu Zuyun , Levine Morgan E.
Published: July 2022

Background

Epigenetic clocks are promising tools for the study of aging in humans. The clocks quantify biological aging above and beyond chronological age, demonstrate systematic associations with risk factors that accelerate aging, and predict age-related morbidity and mortality. There is interest in using them as surrogate endpoints in intervention studies. However, the large number of clocks, decentralized publication and explosive popularity in the last decade has made for poor accessibility and standardization. This has hampered the abilities of new researchers to conduct truly hypothesis driven research—whether by not knowing about the best available clocks for a given question, or by systematically testing many or all as they become available.

Results

We report a centralized R package which can be installed and run locally on the user’s machine, and provides a standardized syntax for epigenetic clock calculation. The package includes a set of helper functions to assist with navigating clock literature and selecting clocks for analysis, as well as affording the user with the details of clock calculation. We describe each clock’s resilience to missing CpG information, combined with functionality to assess the need for imputation in the user’s own data. Furthermore, we demonstrate that while CpGs may not be shared among clocks with similar outputs, many clocks have highly correlated outputs.

Conclusions

Due to the previous decentralization of epigenetic clocks, gathering code and performing systematic analysis, particularly in protected datasets, has required significant information gathering effort. Here, we offer an R package with standardized implementation and potential for future growth and clock incorporation to assist with hypothesis driven investigation of aging as measured by epigenetic clocks. We show the potential of this package to drive the user to think globally about signals captured by epigenetic clocks, as well as to properly identify the potential and limitations of each clock in their current research.
Teeth outside the mouth: the evolution and development of shark denticles
Authors: Cooper Rory L. , Nicklin Ella F. , Rasch Liam J. , Fraser Gareth J.
Published: July 2022

Vertebrate skin appendages are incredibly diverse. This diversity, which includes structures such as scales, feathers, and hair, likely evolved from a shared anatomical placode, suggesting broad conservation of the early development of these organs. Some of the earliest known skin appendages are dentine and enamel-rich tooth-like structures, collectively known as odontodes. These appendages evolved over 450 million years ago. Elasmobranchs (sharks, skates, and rays) have retained these ancient skin appendages in the form of both dermal denticles (scales) and oral teeth. Despite our knowledge of denticle function in adult sharks, our understanding of their development and morphogenesis is less advanced. Even though denticles in sharks appear structurally similar to oral teeth, there has been limited data directly comparing the molecular development of these distinct elements. Here, we chart the development of denticles in the embryonic small-spotted catshark (Scyliorhinus canicula) and characterise the expression of conserved genes known to mediate dental development. We find that shark denticle emergence shares a vast gene expression signature with developing teeth. However, denticles have restricted regenerative potential, as they lack asox2+stem cell niche associated with the maintenance of a dental lamina, an essential requirement for continuous tooth replacement. We compare developing denticles to other skin appendages, including both sensory skin appendages and avian feathers. This reveals that denticles are not only tooth-like in structure, but that they also share an ancient developmental gene set that is likely common to all epidermal appendages.
Discrete GPCR-triggered endocytic modes enable β-arrestins to flexibly regulate cell signaling
Authors: Barsi-Rhyne Benjamin , Manglik Aashish , von Zastrow Mark
Published: July 2022

β-arrestins are master regulators of cellular signaling that operate by desensitizing ligand-activated G protein-coupled receptors (GPCRs) at the plasma membrane and promoting their subsequent endocytosis. The endocytic activity of β-arrestins is ligand-dependent, triggered by GPCR binding, and increasingly recognized to have a multitude of downstream signaling and trafficking consequences that are specifically programmed by the bound GPCR. However, only one biochemical ‘mode’ for GPCR-mediated triggering of the endocytic activity is presently known– displacement of the β-arrestin C-terminus (CT) to expose CCP-binding determinants that are masked in the inactive state. Here we revise this view by uncovering a second mode of GPCR-triggered endocytic activity that is independent of the β-arrestin CT and, instead, requires the cytosolic base of the β-arrestin C-lobe (CLB). We further show each of the discrete endocytic modes is triggered in a receptor-specific manner, with GPCRs that bind β-arrestin transiently (‘class A’) primarily triggering the CLB-dependent mode and GPCRs that bind more stably (‘class B’) triggering both the CT and CLB-dependent modes in combination. Moreover, we show that each mode has opposing effects on the net signaling output of receptors– with the CLB-dependent mode promoting rapid signal desensitization and the CT-dependent mode enabling prolonged signaling. Together, these results fundamentally revise understanding of how β-arrestins operate as efficient endocytic adaptors while facilitating diversity and flexibility in the control of cell signaling.
Attitude of reproductive age women towards male involvement in family planning; a community-based cross-sectional study in Nakawa Division, Kampala, Uganda
Authors: Wambete Sarah Namee , Baru Ararso , Serwaa Dorcas , Dzantor Edem Kojo , Poku-Agyemang Evelyn , Kukeba Margaret Wekem , Olayemi Oladapo O.
Published: July 2022

Background

In African countries, men are often the primary decision-makers and that have a significant influence on their spouse’s health and access to health care including family planning (FP) decisions. This study aimed to assess the attitude of women in Nakawa Division, Kampala, Uganda towards male involvement in FP and the associated factors.

Methods

This was a community-based cross-sectional study carried out in Nakawa Division, Kampala, Uganda. A total of 480 women aged 18-49 years were selected as participants for the study using multi-stage sampling. A semi-structured interviewer-administered questionnaire was used to collect information from the participants. The data collected was analyzed using SPSS version 22. Data were described using frequency and percentage while associations were assessed using logistic regression analysis at P<0.05.

Results

A total of 485 participants with mean age of 28.29±6.57 years were involved in this study; 197(41.0%) were aged 26-33 years, 399 (83.1%) were Christians, 240(50.0%) had attained secondary school education and 239(49.8%) of their partners had attained tertiary education. The most utilized contraceptives among the women were injectables 151(32.5%), pills 122(26.2%), condoms 76(16.3%), implants 37(8%) and calendar method 30(6.5%). More, 302/465(62.9%) of the women had adequate partner involvement in their FP and a total of 438/480 (91.3%) of the participants had favorable attitude of women toward male involvement in FP. After adjusting for confounders, participants with an average monthly income of 600,000/= and above were more likely to have favorable attitude towards male involvement in FP (AOR=10.51, 95% CI {1.19−93.25}, p=0.035) compared with those earning 0-100,000/= average monthly income per month. Also, participants with adequate male partner involvement in FP/contraceptive use were more likely to have favorable attitude towards male involvement in FP (AOR=2.78, 95% CI {1.23−6.30, p<0.014)

Conclusion

The study found high favourable attitude of women towards male partner involvement at FP. The average monthly income of participants and male involvement were predictors of favourable attitude towards male involvement in FP. This finding indicates the need for increased sensitization of the men as a means of attaining the broader objective of increasing male partner involvement in FP for better contraceptive use and better birth spacing.
Phosphotungstic acid (PTA) preferentially binds to collagen-rich regions of porcine carotid arteries and human atherosclerotic plaques using 3D micro-computed tomography (CE-μCT)
Authors: Hanly A. , Johnston R. D , Lemass C. , Jose A. , Tornifoglio B. , Lally C.
Published: July 2022

Background and aims

Atherosclerotic plaque rupture in the carotid artery can cause small emboli to travel to cerebral arteries, causing blockages and preventing blood flow leading to stroke. Contrast enhanced micro computed tomography (CEμCT) using a novel stain, phosphotungstic acid (PTA) can provide insights into the microstructure of the vessel wall and atherosclerotic plaque, and hence their likelihood to rupture. Furthermore, it has been suggested that collagen content and orientation can be related to mechanical integrity. This study aims to build on existing literature and establish a robust and reproducible staining and imaging technique to non-destructively quantify the collagen content within arteries and plaques as an alternative to routine histology.

Methods

Porcine carotid arteries and human atherosclerotic plaques were stained with a concentration of 1% PTA staining solution and imaged using MicroCT to establish the in-situ architecture of the tissue and measure collagen content. A histological assessment of the collagen content was also performed from picrosirius red (PSR) staining.

Results

PTA stained arterial samples highlight the reproducibility of the PTA staining and MicroCT imaging technique used with a quantitative analysis showing a positive correlation between the collagen content measured from CEμCT and histology. Furthermore, collagen-rich areas can be clearly visualised in both the vessel wall and atherosclerotic plaque. 3D reconstruction was also performed showing that different layers of the vessel wall and various atherosclerotic plaque components can be differentiated using Hounsfield Unit (HU) values.

Conclusions

The work presented here is unique as it offers a quantitative method of segmenting the vessel wall into its individual components and non-destructively quantifying the collagen content withing these tissues, whilst also delivering a visual representation of the fibrous structure using a single contrast agent.

Graphical Abstract
Scalable large-area mesh-structured microfluidic gradient generator for drug testing applications
Authors: Yadav Shital , Tawade Pratik , Bachal Ketaki , Rakshe Makrand A. , Pundlik Yash , Gandhi Prasanna S. , Majumder Abhijit
Published: July 2022

Microfluidic concentration gradient generators are useful in drug testing. drug screening, and other cellular applications to avoid manual errors, save time, and labor. However, expensive fabrication techniques make such devices prohibitively costly. Here, in the present work, we developed a microfluidic concentration gradient generator (μCGG) using a recently proposed non-conventional photolithography-less method. In this method, ceramic suspension fluid was shaped into a square mesh by controlling Saffman Taylor instability in a Multiport Lifted Hele-Shaw Cell (MLHSC). Using the shaped ceramic structure as template, the microfluidic concentration gradient generator (μCGG) was prepared by soft lithography. The concentration gradient was characterized and effect of the flow rates were studied usingCOMSOL simulations. The simulation result was further validated by creating fluorescein dye (Fluorescein isothiocanate, FITC) gradient in the fabricated μCGG. To demonstrate the use of this device for drug testing, we created various concentrations of an anticancer drug - curcumin - using the device and determined its inhibitory concentration on cervical cancer cell-line HeLa. We found that the IC50 of curcumin for HeLa to be 28.6 ± 6.1 μM which matched well with the conventional muti-well drug testing method (34.9 ± 1.7 μM). This method of μCGG fabrication has multiple advantages over conventional photolithography such as: i) the channel layout and inlet-outlet arrangements can be changed by simply wiping the ceramic fluid before it solidifies, (ii) it is cost effective, (iii) large area patterning is easily achievable, and (iv) the method is scalable. This technique can be utilised to achieve broad range of concentration gradient to be used for various biological and non-biological applications.

Table of Content
Universality of spatial livestock disease transmission patterns
Authors: Boender Gert Jan , Hagenaars Thomas J.
Published: July 2022

The risk of epidemic spread of diseases in livestock poses a threat to animal and often also human health. Important for the assessment of the effect of control measures is a statistical model quantification of between-farm transmission during epidemics. In particular, quantification of the between-farm transmission kernel has proven its importance for a range of different diseases in livestock. In this paper we explore if a comparison of the different transmission kernels yields further insight. Our comparison identifies universal features that connect across the different pathogen-host combinations and thereby provide generic insights.

Comparison of the shape of the spatial transmission kernel suggests that, in absence of animal movement bans, the distance dependence of transmission has a universal shape analogous to Lévy-walk model descriptions of human movement patterns. Also, our analysis suggests that interventions such as movement bans and zoning, through their impact on these movement patterns, change the shape of the kernel in a universal fashion. We discuss how the generic insights obtained can be of practical use for assessing risks of spread and optimizing control measures, in particular when outbreak data is scarce.
Does forest heterogeneity affect mean throughfall for regenerating secondary forests on Borneo?
Authors: Keller Nadine , van Meerveld Ilja , Philipson Christopher David , Asner Gregory P. , Godoong Elia , Tangki Hamzah , Ghazoul Jaboury
Published: July 2022

Tropical landscape regeneration affects hydrological ecosystem functioning by regulating the amount of water that reaches the soil surface and changing soil infiltration rates. This affects the recharge and storage of water in the soil and streamflow responses. Therefore, it is important to assess how the fraction of rainfall that reaches the forest floor changes as secondary forests mature, and how forest structure affects throughfall via changes in storage capacity and evapotranspiration. Therefore, we monitored throughfall for twelve regenerating, logged-over forest plots in Sabah, Malaysian Borneo over a 7-month period and tested if inclusion of measures of forest heterogeneity improved the prediction of throughfall as a fraction of precipitation. On average across all plots, throughfall was 84% of precipitation, but was lower (as low as 74%) in plots with a longer recovery time since logging. There was a significant relationship between throughfall and tree density and basal area, as well as the Shannon Diversity Index and the coefficient of variation of the diameter at breast height, although species and structural diversity measures (Shannon Index and the coefficient of variation) did not improve model performance substantially. The overall best performing model was a linear regression with tree density. There was no relation between LiDAR-derived Top of Canopy (TCH) and mean throughfall, suggesting that this remotely sensed proxy of canopy height is not needed to estimate throughfall and more in-depth analysis of other LiDAR-products such as point clouds may be required. Our results imply that estimating throughfall in this forest type can be reliably achieved using tree density, and that this is not substantially affected by species diversity or structural heterogeneity variables, at least in the context of logged and regenerating forests in Sabah.

Graphical abstract

Forest of a similar size or height can have a different structure. In this study we investigate if diversity also affects the amount of throughfall for plots across a disturbance gradient.