bluuebunny/crossref_metadata_2025 huggingface dataset:
Marketing financial services in Africa: exploring the heterogeneous middle-class consumer across nine countries
Authors: Chikweche Tendai , Lappeman James , Egan Paul
Published: September 2022

Our paper investigates how the heterogeneous structure of the middle class in sub-Saharan Africa influences its consumption of financial services, identifying drivers for their selection of these services. Implications for marketing practice are outlined. This research is an across-country city-based exploratory study in ten cities where structured questionnaires were used in interviews to obtain information from respondents over a period of 2 years. Our findings identify the importance of the financial realities of the three middle-class groups of the Accomplished, Comfortable and Vulnerable on their consumption of financial services and answer the question of what drives demand for these services. The three groups have varied spending and saving habits, perceptions of financial services and financial aspirations. We identify six key drivers for selecting services, namely availability, accessibility, affordability, status, security and trust. Technology is a key mediating variable of the marketing mix considerations. Marketing practice implications indicated a need for marketers to recognise the importance of the heterogeneity of the middle class and its influence on segmentation strategies. Opportunities for new approaches to new product development and marketing communication strategies that leverage the heterogeneity of the middle class are outlined. Marketers should also consider the varied influence of the drivers for the choice of financial services among the three groups. Our findings reinforce the need and potential that exist for financial services providers to improve the financial inclusion of previously marginalised consumers.
A hybrid Cartesian-meshless method for the simulation of thermal flows with complex immersed objects
Authors: Huang Tao , Zhao Haibo , Chen Hao , Yao Yang , Yu Peng
Published: September 2022

In this study, a hybrid Cartesian-meshless method is first extended to deal with the thermal flows with complex immersed objects. The temperature and flow fields are governed by energy conservation equations and Navier–Stokes equations with the Boussinesq approximation, respectively. The governing equations are solved by a conventional finite difference scheme on a Cartesian grid and generalized finite difference (GFD) with singular value decomposition (SVD) approximation on meshless nodes, with second-order accuracy. The present thermal SVD–GFD method is applied to simulate the following seven numerical examples over a wide range of governing parameters, including that with the high Prandtl number: (1) forced convection around a circular cylinder; (2) mixed convection around a stationary circular cylinder in a lid-driven cavity; (3) mixed convection involving a moving boundary in a cavity with two rotating circular cylinders; (4) sedimentation of a cold circular particle in a long channel; (5) freely falling of a sphere in viscous fluid with thermal buoyancy; (6) sedimentation of a torus with thermal convection; and (7) flow over a heated circular cylinder. The excellent agreement between the published data and the present numerical results demonstrate the good capability of the thermal SVD–GFD method to simulate the thermal flows with complex immersed objects, especially those involving fluid–structure interaction and the high Prandtl number.
The bimodal instability of thermal convection in a tall vertical annulus
Authors: Wang Chih-Chi , Chen Falin
Published: September 2022

We pursue a three-dimensional linear stability analysis to investigate the convective stability in a cylindrical annulus imposed with a horizontal temperature gradient. The investigation focuses on the stability of both axisymmetric and asymmetric modes in a wide range of Prandtl number Pr and the radii ratio η between the inner to outer cylinders. Results show that, for the axisymmetric mode, the stability strongly depends on the Prandtl number. For 0≤Pr≤1.4, the instability sets in as the shear mode that the instability enhances as η increases while it is virtually independent of Pr. The critical Grashof number can be approximated by Grc(η)≈103×4η−0.68+3. For 1.5≤Pr≤12.5, the buoyant mode appears and competes with the shear mode to predominate the stability under various Pr and η, namely, the bimodal instability occurs. The transition between the two modes occurs at the specific radii ratio η1=0.21Pr0.727−0.31. For Pr≥12.6, the shear mode vanishes and the buoyant mode prevails. The asymmetric modes are less prevailing than the axisymmetric mode for small Prandtl numbers, except that the mode of an azimuthal wavenumber equal to 1 becomes dominant in two small regions of η. When the Prandtl number is large, the axisymmetric mode predominates over the asymmetric mode except when η is very small. Otherwise, the asymmetric mode of a larger azimuthal wavenumber is less prevailing.
Review of coating and curing processes: Evaluation in automotive
industry
Authors: Pendar Mohammad-Reza , Rodrigues Frederico , Páscoa José Carlos , Lima Rui
Published: September 2022

The paint shop plant, as the largest energy consumer in the automotive manufacturing process, requires special attention to optimize energy efficiency and thermal management, reduce environmental impact and diminish the total costs to improve marketability. The current review covers the description of the automotive paint shop, recognition of the paint film layers, characterization of the paint spray applicators, evolution of their technology's advancement, explanation of the coating processes development, and investigation of the curing ovens thermal procedure in an automotive production stage. After systematically recalling pioneering studies dealing with the coating techniques and opening strategies, this paper focuses on reviewing recent findings conducted with improved modern methods in this subject area for higher sustainability and efficiency. Critical performance factors in developing surface durability, corrosion protectivity, paint material consumption, and environmental pollution are discussed. Focus is brought to the electrostatic spray-painting procedure flow physics understanding, particularly the complicated three-dimensional behaviors of paint droplets formation, distribution, control, and deposition on the body in constructed spray plums. Then, the baking and drying process of the produced film layer in the curing oven is precisely reviewed. The review additionally aids in the identification of knowledge gaps in the literature that should be addressed in future research.
Large-scale circulations in a shear-free convective turbulence: Mean-field simulations
Authors: Orian G. , Asulin A. , Tkachenko E. , Kleeorin N. , Levy A. , Rogachevskii I.
Published: September 2022

It has been previously shown [Elperin et al., “Formation of large-scale semi-organized structures in turbulent convection,” Phys. Rev. E 66, 066305 (2002)] that a non-rotating turbulent convection with nonuniform large-scale flows contributes to the turbulent heat flux. As a result, the turbulent heat flux depends explicitly not only on the gradients of the large-scale temperature, but also on the gradients of the large-scale velocity. This is because the nonuniform large-scale flows produce anisotropic velocity fluctuations, which modify the turbulent heat flux. This effect causes an excitation of a convective-wind instability and formation of large-scale semi-organized coherent structures (large-scale convective cells). In the present study, we perform mean-field numerical simulations of shear-free convection, which take into account the modification of the turbulent heat flux by nonuniform large-scale flows. We use periodic boundary conditions in horizontal direction as well as stress-free or no-slip boundary conditions in vertical direction. We show that the redistribution of the turbulent heat flux by the nonuniform large-scale motions in turbulent convection plays a crucial role in the formation of the large-scale semi-organized coherent structures. In particular, this effect results in a strong reduction of the critical effective Rayleigh number (based on the eddy viscosity and turbulent temperature diffusivity) required for the formation of the large-scale convective cells. We demonstrate that the convective-wind instability is excited when the scale separation ratio between the height of the convective layer and the integral turbulence scale is large. The level of the mean kinetic energy at saturation increases with the scale separation ratio. We also show that inside the large-scale convective cells, there are local regions with the positive vertical gradient of the potential temperature, which implies that these regions are stably stratified.
A modified Cercignani–Lampis model with independent momentum and thermal accommodation coefficients for gas molecules scattering on surfaces
Authors: Deng Junchao , Zhang Jun , Liang Tengfei , Zhao Jin , Li Zhihui , Wen Dongsheng
Published: September 2022

To accurately predict the aerodynamic forces and heating of hypersonic vehicles, an elaborate gas–surface interaction (GSI) model is essential to describe the rarefied gas effect at the interface. By far, the Cercignani–Lampis (CL) model is the most sophisticated GSI model, but it has not been systematically examined under hypersonic conditions where the gas flow possesses large velocity and temperature differences relative to the boundary surface. In this work, the accuracy of the CL model is first assessed by comparing with molecular dynamics simulation results under a variety of conditions of temperature and velocity differences, surface temperature, and surface roughness. It is found that the tangential scattering kernel of CL model is perfect only when the surface is smooth and the gas kinetic energy is close to the surface kinetic energy. To accurately capture the momentum and temperature of the reflected gas molecules, a modified CL model with independent momentum and thermal accommodation coefficients is developed. A hybrid diffusive and modified CL model is further proposed to account for the adsorption phenomenon. With these modifications, the new GSI model can accurately describe the scattering of gas molecules in a wider range of hypersonic rarefied gas flows.
Phase field simulation on grain growth with particles located on grain boundaries
Authors: Zhu Nanyang , Sun Chaoyang , Feng Yinghao , Li Xintong
Published: September 2022

The grain size is a key characteristic to strongly affect the mechanical properties and performance, and the presence of additional phases plays an important role in affecting the microstructure evolution. In this work, a phase field model was adopted for immobile second-phase particles distributed at grain boundaries and analysed its pinning effect on polycrystalline grain growth. According to the size and distribution characteristics of second-phase particles in extruded AZ80 magnesium alloy, the effects of the particle morphology, particle size and volume fraction on the grain growth were investigated. The results showed that small-sized rod high-dispersion particles exhibit a stronger pinning effect on grain boundary migration. In addition, the generalised Zener relation of R lim = 2.49 r sp/ f sp−0.322 was obtained for the particles located at grain boundaries.
Performance Information Use in a Purpose-Oriented Network: A Relational Perspective
Authors: Nakashima Manabu
Published: September 2022

Performance information use is an essential component of performance management, which is an important tool to manage purpose-oriented networks (PONs). Conceptualizing performance information use in PONs as network members’ presentation, discussion, and interpretation of performance information during their interactions and communication, this study explores its drivers. Extant studies on performance information use in PONs point out an association between its use and the relationships among network members, but they lack specificity regarding the association. This study focuses on and theorizes that association, relying on network theory (especially the embeddedness approach) and resource dependence theory. Network analysis techniques (Multiple Regression Quadratic Assignment Procedure and Exponential Random Graph Modeling) are applied to investigate the theory empirically, using a pair (dyad) of network members as the unit of analysis. The data were collected from 21 members in a health and human services network serving children and youth with serious emotional disturbance in a US county. Two types of performance information were used in the PON: internally and externally produced information. Despite differences in the breadth and decision-making relevance of using information from these two sources, network analyses identify three relational characteristics consistently associated with the dyads’ use of internal and external performance information: (1) frequency of communication; (2) centrality of position; and (3) extent of mutual dependency. These findings suggest that network members are likely to use performance information in relationships where the benefits of developing a shared understanding of network performance outweigh the costs of using it.
Density distribution function of a self-gravitating isothermal turbulent fluid in the context of molecular cloud ensembles – III. Virial analysis
Authors: Donkov S , Stefanov I Zh , Veltchev T V , Klessen R S
Published: September 2022

In this work, we apply virial analysis to the model of self-gravitating turbulent cloud ensembles introduced by Donkov & Stefanov in two previous papers, clarifying some aspects of turbulence and extending the model to account not only for supersonic flows but for trans- and subsonic ones as well. Making use of the Eulerian virial theorem at an arbitrary scale, far from the cloud core, we derive an equation for the density profile and solve it in approximate way. The result confirms the solution ϱ(ℓ) = ℓ−2 found in the previous papers. This solution corresponds to three possible configurations for the energy balance. For trans- or subsonic flows, we obtain a balance between the gravitational and thermal energy (Case 1) or between the gravitational, turbulent, and thermal energies (Case 2) while for supersonic flows, the possible balance is between the gravitational and turbulent energy (Case 3). In Cases 1 and 2, the energy of the fluid element can be negative or zero; thus the solution is dynamically stable and shall be long lived. In Case 3, the energy of the fluid element is positive or zero, i.e. the solution is unstable or at best marginally bound. At scales near the core, one cannot neglect the second derivative of the moment of inertia of the gas, which prevents derivation of an analytic equation for the density profile. However, we obtain that gas near the core is not virialized and its state is marginally bound since the energy of the fluid element vanishes.
Ultrasound Guidance Combined with C-Arm Fluoroscopy in Selective Semilunar Ganglion Radiofrequency Thermocoagulation Through the Foramen Ovale for Trigeminal Neuralgia: A Randomized Controlled Trial
Authors: Liang Hui , Guo Yuna , Chen Guoqing , Zhao Xiaojing , Dou Zhi , Sun Fenglong , Yu Dejun , Lin Zengmao , Zhang Feng , Liu Xiufen , Wu Baishan , Ni Jiaxiang
Published: September 2022

Objective

To explore the clinical value of ultrasound guidance combined with C-arm guidance during selective semilunar ganglion radiofrequency thermocoagulation via the foramen ovale for trigeminal neuralgia.

Methods

This study enrolled 48 patients diagnosed with trigeminal neuralgia between January 2021 and December 2021 in the Department of Pain Management at Xuanwu Hospital. Patients were randomly and equally divided into a C-arm–only group and an ultrasound-combined-with–C-arm (ultrasound+C-arm) group, according to a random number table. After exclusions, 42 patients were analyzed. Of these, 21 patients underwent selective semilunar ganglion radiofrequency thermocoagulation via the foramen ovale guided by the C-arm alone, whereas 21 patients underwent the same procedure guided by ultrasound combined with C-arm. The number of punctures, the amount of time elapsed until the target area of the semilunar ganglion was punctured, the cumulative dose of radiation exposure, and puncture-related complications were recorded during the operation. Numerical rating scale scores and radiofrequency thermocoagulation–related complications were evaluated preoperatively and at 1 day, 3 days, 7 days, 1 month, and 3 months after surgery.

Results

The number of punctures, the amount of time elapsed until the target area of the semilunar ganglion was punctured, and the cumulative dose of radiation exposure were all lower in the ultrasound+C-arm group than in the C-arm–only group (all P < 0.05). No significant differences were found in numerical rating scale scores and radiofrequency thermocoagulation–related complications between the two groups (P > 0.05). No puncture-related complications occurred in either of the groups.

Conclusion

Ultrasound guidance combined with C-arm guidance could be safely used for puncturing the semilunar ganglion via the foramen ovale, with more efficiency and less radiation exposure than C-arm guidance alone.
Sociolinguistic Variation, Speech Acts, and Discursive Injustice
Authors: Nowak Ethan
Published: September 2022

Despite its status at the heart of a closely related field, philosophers have so far mostly overlooked a phenomenon sociolinguists call ‘social meaning’. My aim in this paper will be to show that by properly acknowledging the significance of social meanings, we can identify an important new set of forms that discursive injustice takes. I begin by surveying some data from variationist sociolinguistics that reveal how subtle differences in the way a particular content is expressed allow us to perform importantly different illocutionary actions, actions we use to do things like constructing a public persona and building a rapport with an audience. The social importance of these activities and the pervasiveness of our engagement in them means that the ethical stakes involved are high—substantial injustices may result if speakers from different social groups are differently empowered with regard to the illocutionary possibilities made available to them by variation.
Persistent consumer response to a nationwide food safety recall in urban India
Authors: Law Cherry , Cornelsen Laura
Published: September 2022

Little is known about consumer response to food safety recalls in low- and middle- income countries. Using an event-study framework, this paper examines the immediate and long-term changes in noodle purchases after the nationwide removal of Maggi instant noodles from the market in India in 2015. We show that this recall had a negative impact on the purchases of Maggi noodles among urban households for at least two years. This provides evidence of the huge costs of recalls on food producers that can be leveraged by policymakers to promote food safety. We also find strong evidence for a positive spillover effect to non-Maggi noodles that is more persistent among households with more regular purchasing habits of Maggi noodles. This indicates that consumers with more persistent habits of buying a recalled product are less likely to stigmatize alike food products under different brands. Our results are robust to alternative assumptions of pre-trends in purchases and placebo tests.
A Suture Fixation Technique for Tibial Spine Avulsion Injuries
Authors: Tayne Samantha , Tran Tram , Vij Neeraj , Vaughn Jeffrey , Treme Gehron , Menzer Heather
Published: September 2022

Introduction:

Tibial spine fractures typically occur in skeletally immature patients between 8 and 14 years of age. Surgical treatment is generally pursued for displaced fractures that cannot be reduced with closed manipulation. Recent biomechanical evidence favors suture fixation over screw fixation. Current suture-only techniques largely revolve around double-crossed suture configuration and lack a description regarding a form of secondary fixation. The purpose of this manuscript is to describe 2 additions to the existing suture-only techniques for pediatric tibial spine avulsion injuries.

Materials and Methods (Surgical Technique):

Our technique involves a U-pattern and an X-pattern suture configuration for the primary fixation. Secondary fixation is achieved with an extra-articular knotless anchor.

Results:

This technical write-up describes a suture fixation technique for pediatric tibial spine injuries.

Discussion:

There has been a shift in the literature toward suture fixation over screw fixation in cartilaginous and comminuted tibial spine avulsion injuries. In this article, we describe an arthroscopic suture fixation technique. The proposed benefits include better anatomic reduction of the fracture and improved force dissipation. Suture fixation is not without complications, namely residual laxity, which can be minimized through the use of a self-tension/continuous compression suture.
Comprehensive analysis identifies as a critical prognostic prediction gene in breast cancer
Authors: Hu Ting , Wang Xu , Xia Yun , Wu Lu , Ma Yuxi , Zhou Rui , Zhao Yanxia
Published: September 2022

Background:

Aurora kinases (AURKs) family plays a vital role not only in cell division but also in tumorigenesis. However, there are still rare systematic analyses of the diverse expression patterns and prognostic value of the AURKs family in breast cancer (BC). Systematic bioinformatics analysis was conducted to explore the biological role, prognostic value, and immunologic function of AURKs family in BC.

Methods:

The expression, prognostic value, and clinical functions of AURKs family in BC were evaluated with several bioinformatics web portals: ONCOMINE Gene Expression Profiling Interactive Analysis, Kaplan–Meier plotter, cBioPortal, Metascape, GeneMANIA, and LinkedOmics; and the result was verified using human tissues.

Results:

The expression of AURKA and AURKB were upregulated in BC in subgroup analyses based on tumor stage (all P 
< 0.05). BC patients with high AURKA and AURKB expression had a worse overall survival, relapse-free survival, and distant metastasis-free survival (all P 
< 0.05). Verification experiment revealed that AURKA and AURKB were upregulated in BC (P < 0.05). AURKA and AURKB were specifically associated with several tumor-associated kinases (polo-like kinase 1 and cyclin-dependent kinase 1), miRNAs (miR-507 and miR-381), and E2F transcription factor 1. Moreover, AURKA and AURKB were correlated with immune cell infiltration. Functional enrichment analysis revealed that AURKA and AURKB were involved in the cell cycle signaling pathway, platinum drug resistance signaling pathway, ErbB signaling pathway, Hippo signaling pathway, and nucleotide-binding and oligomerization domain-like receptor signaling pathway.

Conclusions:

Aurora kinases AURKA and AURKB could be employed as novel prognostic biomarkers or promising therapeutic targets for BC.
Improving on polygenic scores across complex traits using select and shrink with summary statistics
Authors: Tyrer J.P , Peng P. , DeVries A.A , Gayther S.A , Jones M.R , Pharoah P.D
Published: September 2022

Structured Abstract

Motivation

As precision medicine advances, polygenic scores (PGS) have become increasingly important for clinical risk assessment. Many methods have been developed to create polygenic models with increased accuracy for risk prediction. Our select and shrink with summary statistics (S4) PGS method extends a previous method (polygenic risk score – continuous shrinkage (PRS-CS)) by using a continuous shrinkage prior on effect sizes with a selection strategy for including SNPs to create the best performing model.

Results

The S4 method provides overall improved PGS accuracy for UK Biobank participants when compared to LDpred2 and PRS-CS across a variety of phenotypes with differing genetic architectures. Additionally, the S4 method has higher estimated PGS accuracy over LDpred2 in Finnish and Japanese populations. Thus, the S4 method represents an improvement in overall PGS accuracy across multiple phenotypes and increases the transferability of PGS across ancestries.

Availability and Implementation

The S4 program is freely available at https://github.com/jpt34/S4_programs.

Supplementary information

Supplementary data [will be] available at Bioinformatics online.
Addressing the ‘coin flip model’ and the role of ‘process of care’ variables in the analysis of TREWS
Authors: Adams Roy , Henry Katharine E , Saria Suchi
Published: September 2022

Across two recent papers, Henry et al. (Nature Medicine, 2022) and Adams et al. (Nature Medicine, 2022) evaluated a deployed machine learning-based early warning system for sepsis, the Targeted Real-time Early Warning System (TREWS) for sepsis, finding that provider interactions with the tool were associated with reduced time to antibiotics and improved patient outcomes. In a subsequent commentary, Nemati et al. (medRxiv, 2022) assert that “the findings of Adams et al. are likely to be severely biased due to the failure to adjust for ‘processes of care’-related confounding factors.” In this response to Nemati et al., we argue that this conclusion is based on unrealistic assumptions about provider behavior that do not match the data reported in Adams et al. We further show that adjusting for ‘process of care’-related variables does not change the conclusions of Adams et al.
Long-Term Subcortical Electrophysiological Recordings Link Heightened Interhemispheric Subthalamic Beta Synchrony to Progression of Bradykinesia in Parkinson’s Disease
Authors: Wilkins Kevin B. , Kehnemouyi Yasmine M. , Petrucci Matthew N. , Anderson Ross W. , Parker Jordan E. , Trager Megan H. , Neuville Raumin S. , Koop Mandy M. , Velisar Anca , Blumenfeld Zack , Quinn Emma J. , Bronte-Stewart Helen M.
Published: September 2022

Bradykinesia is the major cardinal motor sign of Parkinson’s disease (PD), but its neural underpinnings are unclear. Although impairment in PD has been linked to heightened synchrony within the beta band (13-30 Hz) in the subthalamic nucleus (STN), bradykinesia appears to be the manifestation of a network-level dysfunction including the basal ganglia, motor cortex, and possibly cerebellum. The goal of this study was to examine whether changes in bradykinesia over time following long-term STN deep brain stimulation (DBS) are linked to local STN beta dynamics or a wider bilateral network dysfunction. Twenty-one individuals with Parkinson’s disease chronically implanted with sensing neurostimulators (Activa® PC+S, Medtronic, PLC) in the STN participated in a longitudinal ‘washout’ therapy study every three to six months for an average of three years. At each visit, participants were withdrawn from medication (12/24/48 hours) and had DBS turned off (>60 minutes) prior to completing a repetitive wrist-flexion extension task, a validated quantitative assessment of bradykinesia. Synchronized local field potentials and kinematic data were recorded. Local STN beta dynamics were investigated via STN beta power and burst duration, while interhemispheric beta synchrony was assessed with STN beta coherence. Higher beta power and interhemispheric STN beta coherence, but not burst duration, were significantly associated with worse bradykinesia. Bradykinesia was found to worsen off therapy over time. Interhemispheric STN beta coherence also increased over time, whereas beta power and burst duration remained stable. The observed percent change in bradykinesia was related to the percent change in interhemispheric beta coherence, with greater increases in synchrony associated with further worsening of bradykinesia. Together, these findings implicate interhemispheric beta synchrony as a neural correlate of the progression of bradykinesia following chronic STN DBS. This could imply the existence of a pathological bilateral network contributing to bradykinesia in PD.
Analysis of a Large Patient-Level Dataset to Predict Outcome of Treatment for Drug-Resistant Tuberculosis
Authors: Wang Qinlu , Gu Jingwen , Gabrielian Andrei , Rosenfeld Gabriel , Quiñones Mariam , Hurt Darrell E. , Rosenthal Alex
Published: September 2022

BACKGROUND

Drug-resistant (DR) tuberculosis treatment is challenging and frequently leads to poor outcomes. An international collaboration, the National Institute of Allergy and Infectious Diseases (NIAID) TB Portals develops, maintains, and supports a multi-national database of tuberculosis cases, with an emphasis on drug-resistant tuberculosis. Patient records include clinical, radiological, genomic, and socioeconomic features. Establishing factors associated with unsuccessful treatment may help optimize treatment for the most challenging infections.

METHODS

Association analysis and machine learning algorithms were applied to identify important factors associated with treatment outcome and predict the outcome for three patient cohorts, selected by drug resistance level representing 1575 patients in total. The predicted probabilities of poor treatment outcome from models were calibrated as a risk score ranging from 0 to 100 corresponding to confidence level of the model for treatment outcome.

RESULTS

The features most associated with treatment success in all cohorts were body mass index (BMI), onset age, employment, education, smear-negative microscopy, and percent of abnormal volume in X-ray images, confirming previously reported findings, and identifying novel factors such as pathogen genomic markers.

CONCLUSIONS

The identified features might help in establishing high-risk patients at the time of admission for tuberculosis treatment. This study integrates clinical, radiological, and pathogen genomics into a patient risk model, a way of determining risk through the application of machine learning on real-world data.
An enhanced method for calculating trends in infections caused by pathogens transmitted commonly through food
Authors: Weller Daniel L. , Ray Logan C. , Payne Daniel C. , Griffin Patricia M. , Hoekstra Robert M. , Rose Erica Billig , Bruce Beau B.
Published: September 2022

This brief methods paper is being published concomitantly with “Preliminary Incidence and Trends of Infections Caused by Pathogens Transmitted Commonly Through Food— Foodborne Diseases Active Surveillance Network, 10 U.S. Sites, 2016–2021” in Morbidity and Mortality Weekly Reports (MMWR). That article describes the application of the new model described here to analyze trends and evaluate progress towards the prevention of infection from enteric pathogens in the United States.
Interplay between Chronic Kidney disease, Hypertension, and Stroke: Insights from a Multivariable Mendelian Randomization Analysis
Authors: Kelly Dearbhla M. , Georgakis Marios K. , Franceschini Nora , Blacker Deborah , Viswanathan Anand , Anderson Christopher D.
Published: September 2022

Background and Objectives

Chronic kidney disease (CKD) increases the risk of stroke, but the extent through which this association is mediated by hypertension is unknown. We leveraged large-scale genetic data to explore causal relationships between CKD, hypertension and cerebrovascular disease phenotypes.

Methods

We used data from genome-wide association studies (GWAS) of European ancestry to identify genetic proxies for kidney function (CKD diagnosis, estimated glomerular filtration rate [eGFR], and urinary albumin-to-creatinine ratio [UACR]), systolic blood pressure (SBP), and cerebrovascular disease (ischaemic stroke and its subtypes, and intracerebral haemorrhage [ICH). We then conducted univariable, multivariable and mediation Mendelian randomization (MR) analyses to investigate the effect of kidney function on stroke risk and the proportion of this effect mediated through hypertension.

Results

Univariable Mendelian randomization revealed associations between genetically determined lower eGFR and risk of all stroke (OR per 1-log decrement in eGFR, 1.77; 95% CI, 1.31-2.40; p<0.001), ischaemic stroke (OR, 1.81; 95% CI, 1.31-2.51; p<0.001), and most strongly with large artery stroke (LAS) (OR, 3.00; 95% CI, 1.33-6.75; p=0.008). These associations remained significant in the multivariable MR analysis, controlling for SBP (OR, 1.98; 95% CI, 1.39-2.82; p<0.001 for AS; OR, 2.16; 95% CI, 1.48-3.17; p<0.001 for IS; OR, 4.35; 95% CI, 1.84-10.27; p=0.001 for LAS). with only a small proportion of the total effects mediated by SBP (10.5%, 6.6% and 7.8%, respectively). Total, direct and indirect effect estimates were similar across a number of sensitivity analyses.

Discussion

Our results demonstrate an independent causal effect of impaired kidney function, as assessed by decreased eGFR, on stroke risk, particularly LAS, even when controlled for SBP. Targeted prevention of kidney disease could lower atherosclerotic stroke risk independent of hypertension.
Associations of habitual fish oil use with risk of SARS-CoV-2 infection and COVID-19-related outcomes in UK: national population based cohort study
Authors: Ma Yuying , Zhang Lijun , Zeng Ruijie , Luo Dongling , Jiang Rui , Wu Huihuan , Zhuo Zewei , Yang Qi , Li Jingwei , Leung Felix W , Wang Jinghua , Sha Weihong , Chen Hao
Published: September 2022

Objectives

To prospectively investigate the associations of habitual fish oil use with Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, hospital admission, or mortality with Corona Virus Disease-19 (COVID-19) in a large-scale cohort.

Design

Prospective population-based cohort study.

Setting

UK Biobank.

Participants

A total of 110 440 participants aged 37 -73 years who completed a questionnaire on supplement use, which included fish oil at baseline were enrolled between 2006 and 2010 and followed up until 2022.

Main exposure

All participants filled out questionnaires about the habitual use of supplements, including fish oil.

Main outcome measures

SARS-CoV-2 infection, COVID-19 hospital admission and COVID-19 mortality.

Results

At baseline, 29 424 (26.6%) of the 110 440 participants reported habitual use of fish oil supplements. The multivariable adjusted hazard ratios for habitual users of fish oil versus non-users were 0.95 (0.93 to 0.98) for SARS-CoV-2 infection among participants with follow-up time less than 12.1 years but no significant associations were observed for participants with follow-up time more than 12.1 years. For COVID-19-related outcomes, the hazard ratios were 0.79 (95% confidence interval 0.71 to 0.88) for COVID-19 hospital admission and 0.72 (0.60 to 0.87) for COVID-19 mortality. For COVID-19-related outcomes, the association seemed to be stronger among those with longstanding illness. The Cox proportional hazard analysis after propensity-score matching yielded consistent results.

Conclusions

Habitual fish oil supplement is associated with a lower risk of hospital admission and mortality with COVID-19, but not associated with SARS-CoV-2 infection in the population with more than 12.1 years of follow-up.
Multi-PGS enhances polygenic prediction: weighting 937 polygenic scores
Authors: Albiñana Clara , Zhu Zhihong , Schork Andrew J. , Ingason Andrés , Aschard Hugues , Brikell Isabell , Bulik Cynthia M. , Petersen Liselotte V. , Agerbo Esben , Grove Jakob , Nordentoft Merete , Hougaard David M. , Werge Thomas , Børglum Anders D. , Mortensen Preben Bo , McGrath John J. , Neale Benjamin M. , Privé Florian , Vilhjálmsson Bjarni J.
Published: September 2022

The predictive performance of polygenic scores (PGS) is largely dependent on the number of samples available to train the PGS. Increasing the sample size for a specific phenotype is expensive and takes time, but this sample size can be effectively increased by using genetically correlated phenotypes. We propose a framework to generate multi-PGS from thousands of publicly available genome-wide association studies (GWAS) with no need to individually select the most relevant ones. In this study, the multi-PGS framework increased prediction accuracy over single PGS for all included psychiatric disorders and other available outcomes, with prediction R2 increases of up to 9-fold for attention-deficit/hyperactivity disorder (ADHD) compared to a single PGS. We also generate multi-PGS for phenotypes without an existing GWAS and for case-case predictions, with up to 15-fold increases in prediction accuracy. We benchmark the multi-PGS framework against other methods and highlight its potential application to new emerging biobanks.
Epi-Clock: A sensitive platform to help understand pathogenic disease outbreaks and facilitate the response to future outbreaks of concern
Authors: Ji Cong , Shao Junbin (Jack)
Published: September 2022

The lack of virus fossilization precludes any references or ancestors for inferring evolutionary processes, and viruses have no cell structure, metabolism, or space to reproduce outside host cells. Most mutations yielding high pathogenicity become removed from the population, but adaptive mutations could be epidemically transmitted and fixed in the population. Therefore, determining how viruses originated, how they diverged and how an infectious disease was transmitted are serious challenges. To predict potential epidemic outbreaks, we tested our strategy, Epi-Clock, which applies the ZHU algorithm on different SARS-CoV-2 datasets before outbreaks to search for real significant mutational accumulation patterns correlated with the outbreak events. We imagine that specific amino acid substitutions are triggers for outbreaks. Surprisingly, some inter-species genetic distances ofCoronaviridaewere shorter than the intra-species distances, which may represent the intermediate states of different species or subspecies in the evolutionary history ofCoronaviridae. The insertions and deletions of whole genome sequences between different hosts were separately associated with new functions or turning points, clearly indicating their important roles in the host transmission and shifts ofCoronaviridae. Furthermore, we believe that non-nucleosomal DNA may play dominant roles in the divergence of different lineages of SARS-CoV-2 in different regions of the world because of the lack of nucleosome protection. We suggest that strong selective variation among different lineages of SARS-CoV-2 is required to produce strong codon usage bias, significantly appear in B.1.640.2 and B.1.617.2 (Delta). Interestingly, we found that an increasing number of other types of substitutions, such as those resulting from the hitchhiking effect, have accumulated, especially in the pre-breakout phase, even though some previous substitutions were replaced by other dominant genotypes. From most validations, we could accurately predict the potential pre-phase of outbreaks with a median interval of 5 days before. Using our pipeline, users may review updated information on the websitehttps://bioinfo.liferiver.com.cnwith easy registration.
A modeling-based approach to optimize COVID-19 vaccine dosing schedules for improved protection
Authors: Dogra Prashant , Schiavone Carmine , Wang Zhihui , Ruiz-Ramírez Javier , Caserta Sergio , Staquicini Daniela I. , Markosian Christopher , Wang Jin , Sostman H. Dirk , Pasqualini Renata , Arap Wadih , Cristini Vittorio
Published: September 2022

While the development of different vaccines has slowed the dissemination of SARS-CoV-2, the occurrence of breakthrough infections continues to fuel the pandemic. As a strategy to secure at least partial protection, with a single dose of a given COVID-19 vaccine to maximum possible fraction of the population,delayedadministration of subsequent doses (or boosters) has been implemented in many countries. However, waning immunity and emergence of new variants of SARS-CoV-2 suggest that such measures may jeopardize the attainment of herd immunity due to intermittent lapses in protection. Optimizing vaccine dosing schedules could thus make the difference between periodic occurrence of breakthrough infections or effective control of the pandemic. To this end, we have developed a mechanistic mathematical model of adaptive immune response to vaccines and demonstrated its applicability to COVID-19 mRNA vaccines as a proof-of-concept for future outbreaks. The model was thoroughly calibrated against multiple clinical datasets involving immune response to SARS-CoV-2 infection and mRNA vaccines in healthy and immunocompromised subjects (cancer patients undergoing therapy); the model showed robust clinical validation by accurately predicting neutralizing antibody kinetics, a correlate of vaccine-induced protection, in response to multiple doses of mRNA vaccines. Importantly, we estimated population vulnerability to breakthrough infections and predicted tailored vaccination dosing schedules to maximize protection and thus minimize breakthrough infections, based on the immune status of a sub-population. We have identified a critical waiting window for cancer patients (or, immunocompromised subjects) to allow recovery of the immune system (particularly CD4+ T-cells) for effective differentiation of B-cells to produce neutralizing antibodies and thus achieve optimal vaccine efficacy against variants of concern, especially between the first and second doses. Also, we have obtained optimized dosing schedules for subsequent doses in healthy and immunocompromised subjects, which vary from the CDC-recommended schedules, to minimize breakthrough infections. The developed modeling tool is based on generalized adaptive immune response to antigens and can thus be leveraged to guide vaccine dosing schedules during future outbreaks.
Myalgic Encephalomyelitis/Chronic Fatigue Syndrome and fibromyalgia are indistinguishable by their cerebrospinal fluid proteomes
Authors: Schutzer Steven E. , Liu Tao , Tsai Chia-Feng , Petyuk Vladislav A. , Schepmoes Athena A. , Wang Yi-Ting , Weitz Karl K. , Bergquist Jonas , Smith Richard D. , Natelson Benjamin H
Published: September 2022

Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) and fibromyalgia have overlapping neurologic symptoms particularly disabling fatigue. This has given rise to the question whether they are distinct central nervous system (CNS) entities or is one an extension of the other. To investigate this, we used unbiased quantitative mass spectrometry-based proteomics to examine the most proximal fluid to the brain, cerebrospinal fluid (CSF). This was to ascertain if the proteome profile of one was the same or different from the other. We examined two separate groups of ME/CFS, one with (n=15) and one without (n=15) fibromyalgia. We quantified a total of 2,083 proteins using immunoaffinity depletion, tandem mass tag isobaric labeling and offline two-dimensional liquid chromatography coupled to tandem mass spectrometry, including 1,789 that were quantified in all the CSF samples. ANOVA analysis did not yield any proteins with an adjusted p-value < 0.05. This supports the notion that ME/CFS and fibromyalgia as currently defined are not distinct entities.
Deficiency of the Heterogeneous Nuclear Ribonucleoprotein U locus leads to delayed hindbrain neurogenesis
Authors: Mastropasqua Francesca , Oksanen Marika , Soldini Cristina , Alatar Shemim , Arora Abishek , Ballarino Roberto , Molinari Maya , Agostini Federico , Poulet Axel , Watts Michelle , Rabkina Ielyzaveta , Becker Martin , Li Danyang , Anderlid Britt-Marie , Isaksson Johan , Remnelius Karl Lundin , Moslem Mohsen , Jacob Yannick , Falk Anna , Crosetto Nicola , Bienko Magda , Santini Emanuela , Borgkvist Anders , Bölte Sven , Tammimies Kristiina
Published: September 2022

Genetic variants affectingHeterogeneous Nuclear Ribonucleoprotein U (HNRNPU)have been identified in several neurodevelopmental disorders (NDDs). HNRNPU is widely expressed in the human brain and shows the highest postnatal expression in the cerebellum. Recent studies have investigated the role ofHNRNPUin cerebral cortical development, but the effects ofHNRNPUdeficiency on cerebellar development remain unknown. Here, we describe the molecular and cellular outcomes ofHNRNPUlocus deficiency duringin vitroneural differentiation of patient-derived and isogenic neuroepithelial stem cells with a hindbrain profile. We demonstrate thatHNRNPUdeficiency leads to chromatin remodeling of A/B compartments, and transcriptional rewiring, partly by impacting exon inclusion during mRNA processing. Genomic regions affected by the chromatin restructuring and host genes of exon usage differences show a strong enrichment for genes implicated in epilepsies, intellectual disability, and autism. Lastly, we show that at the cellular level.HNRNPUdownregulation leads to altered neurogenesis and an increased fraction of neural progenitors in the maturing neuronal population. We conclude that,HNRNPUlocus is involved in delayed commitment of neural progenitors to neuronal maturation in cell types with hindbrain profile.
Quantitative bioactivity signatures of dietary supplements and natural products
Authors: Yasgar Adam , Bougie Danielle , Eastman Richard T. , Huang Ruili , Itkin Misha , Kouznetsova Jennifer , Lynch Caitlin , McKnight Crystal , Miller Mitch , Ngan Deborah K. , Peryea Tyler , Shah Pranav , Shinn Paul , Xia Menghang , Zakharov Alexey V. , Simeonov Anton
Published: September 2022

Dietary Supplements and Natural Products have minor oversight of their safety and efficacy. We assembled a collection of Dietary Supplements and Natural Products (DSNP) as well as Traditional Chinese Medicinal (TCM) Plant extracts, which were screened against an in vitro panel of assays, including a liver cytochrome p450 enzyme panel, CAR/PXR signaling pathways, and P-gp transporter assays, to assess their activity. This pipeline facilitated the interrogation of Natural Product-Drug Interaction (NaPDI) through prominent metabolizing pathways. In addition, we compared the activity profiles of the DSNP/TCM substances with those of an approved drug collection. Many of the approved drugs have well-annotated mechanisms of action (MOA) while the MOAs for most of the DSNP and TCM samples remain unknown. Based on the premise that compounds with similar activity profiles tend to share similar targets or MOA, we clustered the library activity profiles to identify overlap with the NCATS Pharmaceutical Collection to predict the MOAs of the DSNP/TCM substances. Overall, we highlight four significant bioactivity profiles (measured by p-values) as examples of this prediction. These results can be used as a starting point for further exploration on the toxicity potential and clinical relevance of these substances.