bluuebunny/crossref_metadata_2025 huggingface dataset:
Predicting Future Depressive Episodes from Resting-State fMRI with Generative Embedding
Authors: Galioulline Herman , Frässle Stefan , Harrison Sam , Pereira Inês , Heinzle Jakob , Stephan Klaas Enno
Published: November 2022

After a first episode of major depressive disorder (MDD), there is substantial risk for a long-term remitting-relapsing course. Prevention and early interventions are thus critically important. Various studies have examined the feasibility of detecting at-risk individuals based on out-of-sample predictions about the future occurrence of depression. However, functional magnetic resonance imaging (MRI) has received very little attention for this purpose so far.

Here, we explored the utility of generative models (i.e. different dynamic causal models, DCMs) as well as functional connectivity (FC) for predicting future episodes of depression in never-depressed adults, using a large dataset (N=906) of task-free (“resting state”) fMRI data from the UK Biobank. Connectivity analyses were conducted using timeseries from pre-computed spatially independent components of different dimensionalities. Over a three year period, 50% of participants showed indications of at least one depressive episode, while the other 50% did not. Using nested cross-validation for training and a held-out test set (80/20 split), we systematically examined the combination of 8 connectivity feature sets and 17 classifiers. We found that a generative embedding procedure based on combining regression DCM (rDCM) with a support vector machine (SVM) enabled the best predictions, both on the training set (0.63 accuracy, 0.66 area under the curve, AUC) and the test set (0.62 accuracy, 0.64 AUC; p<0.001). However, on the test set, rDCM was only slightly superior to predictions based on FC (0.59 accuracy, 0.61 AUC). Interpreting model predictions based on SHAP (SHapley Additive exPlanations) values suggested that the most predictive connections were widely distributed and not confined to specific networks. Overall, our analyses suggest (i) ways of improving future fMRI-based generative embedding approaches for the early detection of individuals at-risk for depression and that (ii) achieving accuracies of clinical utility may require combination of fMRI with other data modalities.
Maternal synapsin 1 autoantibodies are associated with neurodevelopmental delay
Authors: Bünger Isabel , Makridis Konstantin L. , Kreye Jakob , Nikolaus Marc , Sedlin Eva , Ullrich Tim , Rasmussen Helle Foverskov , Milovanovic Dragomir , Hoffmann Christian , Tromm Johannes , Höltje Markus , Prüss Harald , Kaindl Angela M.
Published: November 2022

Maternal autoantibodies can be transmitted diaplacentally, with potentially deleterious effects on neurodevelopment. Synapsin 1 (SYN1) is a neuronal protein that is important for synaptic communication and neuronal plasticity. While monoallelic loss of function (LoF) variants in theSYN1gene result in X-linked intellectual disability (ID), learning disabilities, epilepsy, behavioral problems, and macrocephaly, the effect of SYN1 autoantibodies on neurodevelopment remains unclear. We recruited a clinical cohort of 208 mothers and their children with neurologic abnormalities and analyzed the role of maternal SYN1 autoantibodies. We identified seropositivity in 9.6% of mothers, and seropositivity was associated with an increased risk for ID and behavioral problems. Furthermore, children more frequently had epilepsy, macrocephaly, and developmental delay, in line with the SYN1 LoF phenotype. Whether SYN1 autoantibodies have a direct pathogenic effect on neurodevelopment or serve as biomarkers requires functional experiments.
Validation of semi-automatic citation screening software for creating clinical practice guidelines: A protocol for a prospective observational study
Authors: Oami Takehiko , Okada Yohei , Fukuda Tatsuma , Sakuraya Masaaki , Nakada Taka-aki , Shime Nobuaki
Published: November 2022

Background

This study aims to investigate the quality of the literature search and workload saving using the semi-automatic software for citation screening in the development of the Japanese Clinical Practice Guidelines for Management of Sepsis and Septic Shock (J-SSCG).

Methods

We will conduct a prospective study to compare the efficiency of citation screening between the conventional method using Rayyan and semi-automatic citation screening using ASReview. The two independent reviewers will conduct literature searches for clinical questions. During the session, we objectively measure the time to accomplish the citation screening. After the citation screening, we will calculate the sensitivity and specificity from the results of the conventional and semi-automatic procedures. Also, we will compare the accumulated time between the two methods.

Trial registration

This research is submitted with the University hospital medical information network clinical trial registry (UMIN-CTR) [UMIN000049366].

Conflicts of interest

All authors declare no conflicts of interest to have.

Funding

None
Population-wide analysis of laboratory tests to assess seasonal variation and the relevance of temporal reference interval modification
Authors: Muse Victorine P. , Aguayo-Orozco Alejandro , Balaganeshan Sedrah B. , Brunak Søren
Published: November 2022

We identified mortality-, age-, and sex-associated differences in relation to reference intervals (RI) for laboratory tests in population-wide data from nearly two million hospital patients in Denmark and comprising of more than 300 million measurements. A low-parameter mathematical wave-based modification method was developed to adjust for dietary and environment influences during the year. The resulting mathematical fit allowed for improved association rates between re-classified abnormal laboratory tests, patient diagnoses and mortality. The study highlights the need for seasonally modified RIs and presents an approach that has the potential to reduce over- and underdiagnosis, impacting both physician-patient interactions and EHR research as a whole.
Cross-Sectional Study on Philippine National Insurance Data on Malignancy
Authors: Alip S , Castillo C , Ong K. , Castro A J , Gonzales K , Gasa G , Fernandez P , Firaza P , Manalaysay F , Semblante C , Sergio S , Prodigalidad J , Macalalag M , Arcinas R , Roque A
Published: November 2022

Introduction

The purpose of the Urologic Diseases in the Philippines study is three-fold: to assess the burden of urologic disease in the country in prevalence and incidence, to identify orphan populations or underserved areas where urological care is most needed, and to provide an administrative data registry for which clinical data may be anchored on.

Materials & Methods

The data were then requested from the Corporate Planning Unit of PhilHealth, with the following inclusion parameters: all beneficiaries (members and their dependents) with a hospital claim in the years 2011 to 2021 with the following primary or secondary diagnoses e following variables: age, sex, admission date, outpatient/inpatient classification, specific illness code, claim amount, claim status, region and type of facility. Prevalence and incidence data were computed considering a 2-year lookback period. Health claims data is limited by limited clinical information it contains, and the selection bias of patients in frequent contact with the healthcare system.

Results

More than 30,000 health claims were reviewed. Incidence data for 2020, in comparison with the Globocan model is as follows: kidney cancer incidence (Philhealth 371 cases, Globocan model 2211) bladder cancer (Philhealth 261 cases, Globocan model 1,541), prostate cancer incidence (Philhealth 934, Globocan model 7,290), testicular cancer incidence (Philhealth 129, Globocan model 355), and penile cancer incidence (Philhealth 32, Globocan model 114). Other information such as prevalence data, regional and facility-type data are contained in the tables and supplementary material. Disparities in reporting may be due to remediable logistical and reporting issues, RVS and ICD exclusivity, and low service utilization.

Conclusion

Incidence across cancer types follow the trend of global estimates, with prostate cancer being the most prevalent, followed by kidney, bladder, testis, and penile cancers. For future studies, it is imperative that administrative and clinical data linkages are established to form a more holistic picture of the urologic disease burden in the country.
Glomerular spatial transcriptomics of IgA nephropathy according to the presence of mesangial proliferation
Authors: Park Sehoon , Kang Minji , Kim Yong Chul , Kim Dong Ki , Oh Kook-Hwan , Joo Kwon Wook , Kim Yon Su , Kim Hyunje , Moon Kyung Chul , Lee Hajeong
Published: November 2022

Background

Mesangial proliferation is a key pathologic feature of diagnosis and also a risk factor for progression in immunoglobulin A nephropathy (IgAN). We aimed to investigate the gene expression profiles of IgAN glomerulus according to the presence of mesangial proliferation.

Methods

We performed spatial-specific transcriptomic profiling for formalin-fixed-paraffin-embedded kidney biopsy tissues using the GeoMX Digital Spatial Profiler. A total of 3 glomeruli with direct pathologic classification for each case were profiled, including 12 cases (4 M1-IgAN, 4 M0-IgAN, and 4 donor controls). The differentially expressed genes (DEGs) were analyzed between the groups with gene ontology (GO) term annotation.

Results

In the result which successfully enriched glom-specific genes, M1-IgAN were distinctively separated from controls (77 upregulated and 55 downregulated DEGs), while certain DEGs were identified between M1-IgAN and M0-IgAN cases (24 upregulated and 8 downregulated DEGs) or between M0 and controls (1 upregulated and 16 downregulated DEGs). The upregulated DEG that was consistent in M1-IgAN and M0-IgAN cases was TCF21 which is known as early podocyte injury marker while the DEGs uniformly downregulated in IgAN cases included ATF3, EGR1, DUSP1, FOS, JUNB, KLF2, KLF4, NR4A1, RHOB, and ZFP36. Glomeruli from M1-IgAN cases were significantly enriched for cell surface/adhesion molecules and the gene expressions that consist vascular development or extracellular matrix.

Conclusion

We found certain transcriptomic differences according to the histologic changes in IgAN which was present even in the early stage of the disease. Spatial transcriptomic analysis may contribute to dissecting structure-specific pathogenesis and molecular changes in IgAN.

Significance Statement

Immunoglobulin A nephropathy (IgAN) is the most common primary glomerulonephritis with distinct pathologic features of mesangial proliferation with IgA deposition. The authors used spatial transcriptomic analysis to investigate the gene expression profiles from glomeruli with direct pathology annotation. The analysis revealed notable differentially expressed genes in IgAN with and without mesangial proliferation including early podocyte changes, expressions of cell adhesion molecules, alteration in transcription factor pathway, vascular development and extracellular matrix production. The current spatial transcriptomic analysis suggests notable gene expression profiles that may contribute to pathogenesis and progression of IgAN.
Reliability and validity of the hidden hunger assessment scale for Chinese high school students
Authors: Zhang Ning , Wang Minao , Zhang Yuchen , Cao Huake , Yang Yang , Shi Yuhang , Pei Yang , Yang Feixiang , Du Yinan
Published: November 2022

Background

Hidden hunger, also known as insufficient micronutrient intake, is still a severe public health problem, affecting over 2 billion people worldwide. High school students are in an important stage of growth and development. Due to huge academic stress, high school students often lack nutrition knowledge and have unhealthy eating habits, suggesting a higher risk for hidden hunger. However, information on the hidden hunger risk of high school students is limited, and tools for assessing hidden hunger are inadequate.

Objectives

To revise the hidden hunger assessment scale for high school students (HHAS-HSS) in China and assess its reliability and validity.

Methods

Based on the literature review, expert consultation, pre-experiment, and formal survey, a hidden hunger assessment scale was revised for high school students. The formal survey involved 9,336 high school students in 11 of the 16 cities in Anhui Province, China, from 1 September 2020 to 31 December 2020, and 9,038 valid questionnaires were collected and included in the analysis. The item analysis, internal consistency reliability, test-retest reliability, content validity, exploratory factor analysis, and confirmatory factor analysis of the HHAS-HSS were examined.

Results

The HHAS-HSS included a total of 4 dimensions and 12 items: “vegetables and food diversity” (3 items), “fruits and dairy products” (3 items), “micronutrient-dense foods” (4 items), and “health condition and eating habits” (2 items). The results showed a Cronbach’s alpha of 0.758, a split-half reliability of 0.829, and a test-retest reliability of 0.793, indicating good internal consistency. The exploratory factor analysis presented a four-factor model of the HHAS-HSS (KMO=0.820, P<0.001). Using the maximum variance rotation method, 4 factors were obtained, and the cumulative variance explained rate was 57.974%. Confirmatory factor analysis also supported the division of the scale into four dimensions and the above results showed that the construct validity of the scale has reached an acceptable level.

Conclusions

The HHAS-HSS is an effective and convenient tool for the assessment of hidden hunger with good reliability and validity.
FIFA Football Nurse – A task sharing approach in Sports and Exercise Medicine practice in grassroots women’s football in low- and middle- income settings. A study protocol for a parallel randomised controlled trial
Authors: Mkumbuzi Nonhlanhla Sharon , Massey Andrew , Lubega Samuel Kiwanuka , Chisati Enock
Published: November 2022

Football (soccer) is a very popular team sport among African women and girls, with player numbers continuing to rise at all levels of the sport. Whereas the participation in football and associated injuries are on the rise, there are not enough sports and exercise medicine (SEM) personnel to attend to these women football players. While Africa may not currently have enough SEM trained medical doctors and/or physiotherapists, it has relatively higher numbers of other healthcare workers; for example, nurses, who lead healthcare services provision from community to tertiary levels. The objectives of this study will be to develop a task sharing approach to actively recruit and train nurses as pitch side responders in grassroots women’s football in Malawi’s Women’s Football League. This study will be a parallel randomised control trial will recruit 24 teams from the Women’s Football League in Malawi, which will be randomised to either the intervention group or the control group. A cohort of 12 nurses will receive training in basic football medicine; after which they will be attached to a total of 12 women’s football teams (intervention group) during one competitive season. The Football Nurses will be directly report to a physiotherapist or doctor in their district to whom they will refer serious injuries for investigations, or further management. The teams with Football Nurses will be compared to other teams that will not have Football Nurses. We expect to develop a low cost, sustainable and context relevant solution to manage the treatment gap of football injuries/illnesses in underserved communities such as women’s football.

Trial registration number

Pan African Clinical Trial Registry

(PACTR202205481965514).
Frameworks for measuring population health: a scoping review
Authors: Chan Sze Ling , Ho Clement Zhong Hao , Khaing Nang Ei Ei , Ho Ezra , Pong Candelyn , Chua Calida , Li Zongbin , Lim Trudi , Lam Sean Shao Wei , Low Lian Leng , How Choon How
Published: November 2022

Introduction

Many regions in the world are using the population health approach and require a means to measure the health of their population of interest. Population health frameworks provide a theoretical grounding for conceptualization of population health and therefore a logical basis for selection of indicators. The aim of this scoping review was to provide an overview and summary of the characteristics of existing population health frameworks that have been used to conceptualize the measurement of population health.

Methods

We used the Population, Concept and Context (PCC) framework to define eligibility criteria of frameworks. We were interested in frameworks applicable for general populations, that contained components of measurement of health with or without its antecedents and applied at the population level or used a population health approach. Eligible reports of eligible frameworks should include at least domains and subdomains, purpose, or indicators. We searched 5 databases (Pubmed, EMBASE, Web of Science, NYAM Grey Literature Report, and OpenGrey), governmental and organizational sites on Google and websites of selected organizations using keywords from the PCC framework. Characteristics of the frameworks were summarized descriptively and narratively.

Results

Forty-eight frameworks were included. The majority originated from the US (42%), Canada (23%) and Europe (23%). Apart from 1 framework developed for rural populations and 2 for indigenous populations, the rest were for general urban populations. The numbers of domains, subdomains and indicators were highly variable. Health status and social determinants of health were the most common domains across all frameworks. Different frameworks had different priorities and therefore focus on different domains.

Conclusion

Key domains common across frameworks other than health status were social determinants of health, health behaviours and healthcare system performance. The results in this review serve as a useful resource for governments and healthcare organizations for informing their population health measurement efforts.
Determining the toxicity and potential for environmental transport of pyridine using the brown crabCancer pagurus(L.)
Authors: Eastabrook Chloe L. , Maqueda Miguel Morales , Vagg Charlotte , Idomeh Joyce , Nasif-Whitestone Taskeen A. , Lawrence Poppy , Bronowska Agnieszka K. , Bothwell John H. , Sallach Brett J. , Redfern Joe , Caldwell Gary S.
Published: November 2022

1

A series of mass mortalities (wash-ups) of marine life were documented along England’s north east coastline with peaks in September and October 2021, coincident with a programme of intensified maintenance dredging of the River Tees. Decapod crustaceans were the worst affected fauna, with brown crab (Cancer pagurus), European lobster (Homarus gammarus, L.), green shore crab (Carcinus maenas, L.) and velvet swimming crab (Necora puber, L.) populations severely affected. Moribund animals presented with twitching behaviours and paralysis. A potential release of the industrial pollutant pyridine was forwarded as one explanation; however, toxicology data for pyridine in decapods is lacking. In this study, we address this knowledge gap by executing a programme of immersion exposure experiments (pyridine at 2 - 100 mg L-1) usingC. pagurus, measuring toxicity effects at the individual (survival) and cellular levels (cellular, mitochondrial, and lipid peroxidation reactive oxygen species (ROS) formation in the gills, hepatopancreas and claw muscle). Highest mortality rates were seen after 72 hours of exposure, returning an LC50value of 2.75 mg L-1. Exposed crabs presented with patterns of convulsions, limb twitching, paralysis, and death. Crabs exposed to the lowest pyridine dose (2 mg L-1) were noticeably more docile than controls. Concentration was a significant factor influencing mitochondrial ROS formation at low concentrations, with tissue type, time, and their interaction all significant at 100 mg L-1. Computer simulations were used to model the transport of any pyridine released from the dredging work, demonstrating the potential for a pyridine plume to extend from Seaham to the north of the Tees to Whitby and Robin Hood’s Bay to the south. This range corresponds well with the reported wash-ups and subsequent declines in catch rates.
Quantitative analyses of T cell motion in tissue reveals factors driving T cell search in tissues
Authors: Torres David J , Mrass Paulus , Byrum Janie , Gonzales Arrick , Martinez Dominick , Juarez Evelyn , Thompson Emily , Vezys Vaiva , Moses Melanie E , Cannon Judy L.
Published: November 2022

T cells are required to clear infection, moving first in lymph nodes to interact with antigen bearing dendritic cells leading to activation. T cells then move to sites of infection to find and clear infection. T cell motion plays a role in how quickly a T cell finds its target, from initial naïve T cell activation by a dendritic cell to interaction with target cells in infected tissue. To better understand how different tissue environments might affect T cell motility, we compared multiple features of T cell motion including speed, persistence, turning angle, directionality, and confinement of motion from T cells moving in multiple tissues using tracks collected with microscopy from murine tissues. We quantitatively analyzed naïve T cell motility within the lymph node and compared motility parameters with activated CD8 T cells moving within the villi of small intestine and lung under different activation conditions.

Our motility analysis found that while the speeds and the overall displacement of T cells vary within all tissues analyzed, T cells in all tissues tended to persist at the same speed, particularly if the previous speed is very slow (less than 2µm/min) or very fast (greater than 8µm/min) with the exception of T cells in the villi for speeds greater than 10µm/min. Interestingly, we found that turning angles of T cells in the lung show a marked population of T cells turning at close to 180o, while T cells in lymph nodes and villi do not exhibit this “reversing” movement. Additionally, T cells in the lung showed significantly decreased meandering ratios and increased confinement compared to T cells in lymph nodes and villi. The combination of these differences in motility patterns led to a decrease in the total volume scanned by T cells in lung compared to T cells in lymph node and villi. These results suggest that the tissue environment in which T cells move can impact the type of motility and ultimately, the efficiency of T cell search for target cells within specialized tissues such as the lung.
Autotrophic biofilms sustained by deeply-sourced groundwater host diverse CPR bacteria implicated in sulfur and hydrogen metabolism
Authors: Alvarado Luis E. Valentin , Fakra Sirine C. , Probst Alexander J. , Giska Jonathan R. , Jaffe Alexander L. , Oltrogge Luke M. , West-Roberts Jacob , Rowland Joel , Manga Michael , Savage David F. , Greening Chris , Baker Brett J. , Banfield Jillian F.
Published: November 2022

Background

Candidate Phyla Radiation (CPR) bacteria are commonly detected yet enigmatic members of diverse microbial communities. Their host associations, metabolic capabilities, and potential roles in biogeochemical cycles remain under-explored. We studied chemoautotrophically-based biofilms that host diverse CPR bacteria and grow in sulfide-rich springs using bulk geochemical analysis, genome-resolved metagenomics and scanning transmission x-ray microscopy (STXM) at room temperature and 87° K.

Results

CPR-affiliated Gracilibacteria, Absconditabacteria, Saccharibacteria, Peregrinibacteria, Berkelbacteria, Microgenomates, and Parcubacteria are members of two biofilm communities dominated by chemolithotrophic sulfur-oxidizing bacteria includingThiothrixorBeggiatoa. STXM imaging revealed ultra-small cells along the surfaces of filamentous bacteria that we interpret are CPR bacterial episymbionts. STXM and NEXAFS spectroscopy at carbon K and sulfur L2,3edges show protein-encapsulated elemental sulfur spherical granules associated with filamentous bacteria, indicating that they are sulfur-oxidizers, likelyThiothrix. Berkelbacteria and Moranbacteria in the same biofilm sample are predicted to have a novel electron bifurcating group 3b [NiFe]-hydrogenase, putatively a sulfhydrogenase, potentially linked to sulfur metabolism via redox cofactors. This complex could potentially underpin a symbiosis involving Berkelbacteria and/or Moranbacteria and filamentous sulfur-oxidizing bacteria such asThiothrixthat is based on cryptic sulfur cycling. One Doudnabacteria genome encodes adjacent sulfur dioxygenase and rhodanese genes that may convert thiosulfate to sulfite. We find similar conserved genomic architecture associated with CPR bacteria from other sulfur-rich subsurface ecosystems.

Conclusions

Our combined metagenomic, geochemical, spectromicroscopic and structural bioinformatics analyses link some CPR bacteria to sulfur-oxidizing Proteobacteria, likelyThiothrix, and indicate roles for CPR bacteria in sulfur and hydrogen cycling.
Callosal inputs generate side-invariant receptive fields in the barrel cortex
Authors: Montanari Roberto , Alonso-Andrés Alicia , Cabrera-Moreno Jorge , Alegre-Cortés Javier , Reig Ramón
Published: November 2022

Barrel cortex integrates contra- and ipsilateral whiskers’ inputs. While contralateral inputs depend on the thalamocortical innervation, ipsilateral ones are thought to rely on callosal axons. These are more abundant in the barrel cortex region bordering with S2 and containing the row A-whiskers representation, the row lying nearest to the facial midline. Here we ask what role this callosal axonal arrangement plays in ipsilateral tactile signalling. We found that novel object exploration with ipsilateral whiskers confines c-Fos expression within the highly callosal subregion. Targeting this area within vivopatch-clamp recordings revealed neurons with uniquely strong ipsilateral responses dependent on the corpus callosum, as assessed by tetrodotoxin silencing and by optogenetic activation of the contralateral hemisphere. Still, in this area, stimulation of contra- or ipsilateral row A-whiskers evoked an indistinguishable response in some neurons, mostly located in layers 5/6, indicating their involvement in the midline representation of the whiskers’ sensory space.
Genome Report: A blue mussel chromosome-scale genome assembly for aquaculture, marine ecology and evolution
Authors: Regan Tim , Hori Tiago S. , Bean Tim P.
Published: November 2022

The blue mussel,Mytilus edulisis part of theMytilus edulisspecies complex, encompassing at least three putative species:M. edulis, M. galloprovincialisandM. trossulus. These three species occur on both sides of the Atlantic and hybridize in nature, and bothM. edulisandM. galloprovincialisare important aquaculture species. They are also invasive species in many parts of the world. Here, we present a chromosome-level assembly ofMytilus edulis. We used a combination of PacBio sequencing and Dovetail’s Omni-C technology to generate an assembly with 14 long scaffolds containing 94% of the predicted length of theM. edulisgenome (1.6 out of 1.7 Gb). Assembly statistics were total length 1.65 Gb, N50 = 116 Mb, L50 = 7 and, L90 = 13. BUSCO analysis showed 92.55% eukaryote BUSCOs identified. AB-Initioannotation using RNA-seq from mantle, gills, muscle and foot predicted 47,128 genes. These gene models were combined with Isoseq validation resulting in 65,505 gene models and 129,708 isoforms. Using GBS and shotgun sequencing, we also sequenced 3 North American populations ofMytilusto characterize single-nucleotide as well as structural variance. This high-quality genome forM. edulisprovides a platform to develop tools that can be used in breeding, molecular ecology and evolution to address questions of both commercial and environmental perspectives.
In siliconetwork-based screening reveals candidates for endothelial dysfunction therapy
Authors: Pinheiro-de-Sousa Iguaracy , Giudice Girolamo , Fonseca-Alaniz Miriam Helena , Modestia Silvestre Massimo , Mattioli Sarah Viana , Fang Yun , Petsalaki Evangelia , Krieger Jose E.
Published: November 2022

Endothelial dysfunction (ED) is a hallmark of cardiovascular (CV) disorders and influences their progression; however, there are currently no direct therapeutic targets, primarily due to the lack of knowledge regarding ED’s molecular basis. We used a computational approach to identify candidate targets for ED treatment. We constructed an ED disease gene network by combining the integration of epigenomics (ATAC-seq and ChIP-seq-H3K27ac) and transcriptomics data (RNA-seq) from human aorta endothelial cells (HAEC) exposed to surrogates of primary CV risk factors using network propagation. We then usedin silicoperturbation to prioritise genes that could influence the ED network most when removed. This process resulted in identifying 17 key candidates for which chemical inhibitors are available. These are genes associated with ED and atherosclerosis, and drugs that target those genes have not yet been tested for the treatment of CV disorders. The EGLN3 target and its inhibitor displayed significant anti-inflammatory and antioxidant properties in ECs assessed using a high-content screening platform. These findings illustrate the potential ofin silicoknockouts to discover disease-specific candidate targets for drug development or repositioning.
Actinobacillus pleuropneumoniaeencodes multiple phase-variable DNA methyltransferases that comprise distinct phasevarions
Authors: Nahar Nusrat , Tram Greg , Jen Freda E-C , Phillips Zachary N. , Weinert Lucy A. , Bossé Janine T. , Jabbari Jafar S. , Gouil Quentin , Du Mei R. M. , Ritchie Matthew E. , Bowden Rory , Langford Paul R. , Tucker Alexander W. , Jennings Michael P. , Turni Conny , Blackall Patrick J. , Atack John M.
Published: November 2022

ABSTRACT

Actinobacillus pleuropneumoniaeis the cause of porcine pleuropneumonia, a severe respiratory tract infection that is responsible for major economic losses to the swine industry. Many host-adapted bacterial pathogens encode systems known as phasevarions (phase- variable regulons). Phasevarions result from variable expression of cytoplasmic DNA methyltransferases. Variable expression results in genome-wide methylation differences within a bacterial population, leading to altered expression of multiple genes via epigenetic mechanisms. Our examination of a diverse population ofA. pleuropneumoniaestrains determined that Type I and Type III DNA methyltransferases with the hallmarks of phase variation were present in this species. We demonstrate that phase variation is occurring in these methyltransferase, and show associations between particular Type III methyltransferase alleles and serovar. Using Pacific BioSciences Single-Molecule, Real-Time (SMRT) sequencing and Oxford Nanopore sequencing, we demonstrate the presence of the first ever characterised phase-variable, cytosine-specific Type III DNA methyltransferase. Phase variation of distinct Type III DNA methyltransferase variants results in the regulation of distinct phasevarions, and in multiple phenotypic differences relevant to pathobiology. Our characterisation of these newly described phasevarions inA. pleuropneumoniaewill aid in the selection of stably expressed antigens, and direct and inform development of a rationally designed subunit vaccine against this major veterinary pathogen.
Deconvolution of plasma pharmacokinetics from dynamic heart imaging data obtained by SPECT/CT imaging
Authors: Wang Zengtao , Wang Lushan , Ebbini Malik , Curran Geoffry L. , Min Paul H. , Siegel Ronald A. , Lowe Val J. , Kandimalla Karunya K.
Published: November 2022

Plasma pharmacokinetic (PK) data is required as an input function for graphical analysis (e.g., Patlak plot) of single positron emission computed tomography/computed tomography (SPECT/CT) and positron emission tomography/CT (PET/CT) data to evaluate tissue influx rate of radiotracers. Dynamic heart imaging data is often used as a surrogate of plasma PK. However, accumulation of radiolabel (representing both intact and degraded tracer) in the heart tissue may interfere with accurate prediction of plasma PK from the heart data. Therefore, we developed a compartmental model, which involves forcing functions to describe intact and degraded radiolabeled proteins in plasma and their accumulation in heart tissue, to deconvolve plasma PK of125I-amyloid beta 40 (125I-Aβ40) and125I-insulin from their dynamic heart imaging data. The three-compartment model was shown to adequately describe the plasma concentration-time profile of intact/degraded proteins and the heart radioactivity time data obtained from SPECT/CT imaging for both tracers. The model was successfully applied to deconvolve the plasma PK of both tracers from their naïve datasets of dynamic heart imaging. In agreement with our previous observations made by conventional serial plasma sampling, the deconvolved plasma PK of125I-Aβ40and125I-insulin in young mice exhibited lower area under the curve (AUC) than the aged mice. Further, Patlak plot parameters (Ki) extracted using deconvolved plasma PK as input function successfully recapitulated age-dependent blood-to-brain influx kinetics changes for both125I-Aβ40and125I-insulin. Therefore, the compartment model developed in this study provides a novel approach to deconvolve plasma PK of radiotracers from their noninvasive dynamic heart imaging. This method facilitates the application of preclinical SPECT or PET imaging data to characterize distribution kinetics of tracers where simultaneous plasma sampling is not feasible.
Machine learning-based personalized composite score dissects risk and protective factors for cognitive and motor function in elderly
Authors: Schalkamp Ann-Kathrin , Lerche Stefanie , Wurster Isabel , Roeben Benjamin , Zimmermann Milan , Fries Franca , von Thaler Anna-Katharina , Eschweiler Gerhard , Gasser Thomas , Maetzler Walter , Berg Daniela , Brockmann Kathrin , Sinz Fabian H.
Published: November 2022

Most nations worldwide have aging populations. With age, sensory, cognitive and motor abilities decline and the risk for neurodegenerative disorders increases. These multiple impairments influence the quality of life and increase the need for care, thus putting a high burden on society, the economy, and the healthcare system. Therefore, it is important to identify factors that influence healthy aging, in particular ones that are potentially modifiable by each subject through choice of lifestyle. However, large-scale studies that investigate the influence of multiple multi-modal factors on a global description of healthy aging measured by multiple clinical assessments are sparse. Here, we propose a Machine Learning (ML) model that simultaneously predicts multiple cognitive and motor outcome measurements on a personalized level recorded from one learned composite score. This personalized composite score is derived by the model from a large set of multi-modal components from the TREND cohort including genetic, biofluid, clinical, demographic and lifestyle factors. We found that a model based on a single composite score was able to predict cognitive and motor abilities almost as well as a flexible regression model specifically trained for each single clinical score. In contrast to the flexible regression model, our composite score-based model is able to identify factors that globally influence cognitive and motoric abilities as measured by multiple clinical scores. We used the model to identify several risk and protective factors for healthy aging and recover physical exercise as a major, modifiable, protective factor.
Innate immune response to SARS-CoV-2 infection contributes to neuronal damage in human iPSC-derived peripheral neurons
Authors: Passos Vania , Henkel Lisa M. , Wang Jiayi , Zapatero-Belinchón Francisco J. , Möller Rebecca , Sun Guorong , Waltl Inken , Ritter Birgit , Kropp Kai A. , Zhu Shuyong , Deleidi Michela , Kalinke Ulrich , Höglinger Günter , Gerold Gisa , Wegner Florian , Viejo-Borbolla Abel
Published: November 2022

Severe acute respiratory coronavirus 2 (SARS-CoV-2) infection causes neurological disease in some patients suggesting that infection can affect both the peripheral and central nervous system (PNS and CNS, respectively). It is not clear whether the outcome of SARS-CoV-2 infection of PNS and CNS neurons is similar, and which are the key factors that cause neurological disease: SARS-CoV-2 infection or the subsequent immune response. Here, we addressed these questions by infecting human induced-pluripotent stem cell-derived CNS and PNS neurons with the β strain of SARS-CoV-2. Our results show that SARS-CoV-2 infects PNS neurons more efficiently than CNS neurons, despite lower expression levels of angiotensin converting enzyme 2. Infected PNS neurons produced interferon λ1, several interferon stimulated genes and proinflammatory cytokines. They also displayed neurodegenerative-like alterations, as indicated by increased levels of sterile alpha and Toll/interleukin receptor motif-containing protein 1, amyloid precursor protein and α-synuclein and lower levels of nicotinamide mononucleotide adenylyltransferase 2 and β-III-tubulin. Interestingly, blockade of the Janus kinase and signal transducer and activator of transcription pathway by Ruxolitinib did not increase SARS-CoV-2 infection, but reduced neurodegeneration, suggesting that an exacerbated neuronal innate immune response contributes to pathogenesis in the PNS.
Hierarchical Bayesian hedonic regression analysis of Japanese rice wine: is the price right?
Authors: Saito Wakuo , Nakatsuma Teruo
Published: November 2022

Purpose

This paper aims to formulate a hedonic pricing model for Japanese rice wine, sake, via hierarchical Bayesian modeling estimated using an efficient Markov chain Monte Carlo (MCMC) method. Using the estimated model, the authors examine how producing regions, rice breeds and taste characteristics affect sake prices.

Design/methodology/approach

The datasets in the estimation consist of cross-sectional observations of 403 sake brands, which include sake prices, taste indicators, premium categories, rice breeds and regional dummy variables. Data were retrieved from Rakuten, Japan’s largest online shopping site. The authors used the Bayesian estimation of the hedonic pricing model and used an ancillarity–sufficiency interweaving strategy to improve the sampling efficiency of MCMC.

Findings

The estimation results indicate that Japanese consumers value sweeter sake more, and the price of sake reflects the cost of rice preprocessing only for the most-expensive category of sake. No distinctive differences were identified among rice breeds or producing regions in the hedonic pricing model.

Originality/value

To the best of the authors’ knowledge, this study is the first to estimate a hedonic pricing model of sake, despite the rich literature on alcoholic beverages. The findings may contribute new insights into consumer preference and proper pricing for sake breweries and distributors venturing into the e-commerce market.
Case study on barriers to building information modelling implementation in Malaysia
Authors: Munianday Praveena , A. Rahman Rahimi , Esa Muneera
Published: November 2022

Purpose

There is a dearth of studies conducted by local academics on actual building information modelling (BIM) projects to analyse the actual hurdles of BIM adoption. The majority of BIM research focuses on the technology’s general advantages, disadvantages, issues and limitations. In addition, research on actual BIM projects that have integrated BIM throughout the project is necessary to increase the current low number of BIM users in Malaysia. Consequently, the purpose of this study is to examine the challenges BIM adopters experience while implementing BIM in their projects and how they overcome them.

Design/methodology/approach

An in-depth interview session was used to collect data based on a case-study methodology. In Malaysia, three BIM projects were chosen, given the available resources. To evaluate the data in this qualitative study, NVivo was used.

Findings

According to the findings, the most important elements influencing the adoption of new technology and innovation were people and capital. The most significant impediments to BIM adoption are the appraisal of time and finances, as well as the tolerance of changes in approach.

Originality/value

Collaborative training and BIM education have been the most explored solutions for reducing BIM difficulties. As a result, these concerns and solutions should be investigated and implemented to ensure project success and fully use technological innovation.
A practical framework for ranking universities by their competitive advantages: a mixed methods study on foundation universities in Turkey
Authors: Ayhan İrfan , Özdemir Ali
Published: November 2022

Purpose

The purpose of this research is to determine the competitive advantages of higher education institutions (HEIs) and create a new methodology to rank universities according to the competitive advantages.

Design/methodology/approach

The research determines the competitive advantages of HEIs by analysing expert opinions through a semi-structured interview form, matches codes and themes to performance indicators using Saldana's two-cycle coding methods, evaluates content validity through Lawshe and reveals the item weights of the ranking with analytical hierarchy process (AHP). Simple additive weighting (SAW) and Technique for Order of Preference by Similarity (TOPSIS) methods were used for ranking universities.

Findings

Seven dimensions stand out in regard to what should be considered while ranking HEIs: research and publication, education, management, infrastructure, financial resources, human resources and social and economic contribution. Under the 7 dimensions, 69 indicators were determined.

Practical implications

The research provides a scientific reference point where HEIs can compare themselves with other HEIs regarding where they are in the sector, especially in terms of competitive advantages.

Originality/value

Although there are many different ranking methods that rank universities in the national and international literature, almost all these methods are largely based on the outputs of the university such as the number of publications, the number of patents, the number of projects, etc. A framework which ranks universities by considering different aspects of the institution, such as management, human resources and financial resources, has not been developed yet. In this respect, this research aims to fill this gap in the literature.
Ocean bottom seismometer data velocity analysis and Kirchhoff pre‐stack time migration
Authors: Qian Hongfei , Wang Xiangchun , Chen Fengying , Yang Zhu , Chen Xuelei , Zhao Linjing
Published: November 2022

With the increasing maturity of ocean bottom seismometer technology in gas hydrate exploration, more and more researchers apply ocean bottom seismometer exploration technology for offshore oil exploration. However, due to the special observation mode of ocean bottom seismometer, it is impracticable to process ocean bottom seismometer data using traditional data processing methods, such as velocity analysis and pre‐stack time migration. This manuscript proposed a new velocity analysis method for ocean bottom seismometer data, which obtains more accurate root‐mean‐square velocity than the existing method. Then we deduced the Kirchhoff pre‐stack time migration formula for ocean bottom seismometer data. Two models demonstrate the correctness of the velocity analysis and migration methods. Finally, the two methods were applied to the actual ocean bottom seismometer data, and the obtained migration profile is consistent well with the profile of towed streamer data in the nearby area.
Gender differences in the laryngectomee experience
Authors: Gresham Malia S. , Mann Hayley , Ward Gregory M. , Payne Michelle A.
Published: November 2022

Background

Laryngectomy is a pivotal event in patients. lives, with pervasive and far‐reaching effects. Understanding gender differences in these effects may improve care of laryngectomy patients. This paper describes gender differences in the experience after laryngectomy.

Aim

To explore the similarities and differences in the laryngectomee experience based on gender.

Methods & Procedures

Four gender‐matched focus groups were conducted; dialogue was audio recorded, transcribed and studied using interpretative phenomenological analysis (IPA).

Outcomes & Results

A total of 17 laryngectomees, eight female and nine male, age range 41–80 years, participated in focus groups. Laryngectomy represented a turning point in the lives of both genders. Four themes emerged: perception of loss, adjusting to alaryngeal communication, finding a positive outlook and re‐establishing the self. Themes applied to both genders, with subthemes demonstrating similarities and differences between men and women.

Conclusions & Implications

Men and women experienced destabilization after laryngectomy related to perceived losses and shifts in identity. Men described navigating from physical disability toward recovery of function, while women described an emotional journey concerning loss and rediscovery of meaning in their lives. Understanding the laryngectomee experience in better detail, which includes recognizing gender differences and rejecting a one‐size‐fits‐all approach, may facilitate more effective preoperative counselling and post‐operative support from providers.

WHAT THIS PAPER ADDS

What is already known on the subject

Patients who undergo total laryngectomy often struggle with problems with physical, emotional, and social functioning and decreased quality of life. As the literature currently stands, the understanding of the experience of laryngectomees has primarily focused on the perspective of a singular gender. Thus, this is the first qualitative study specifically investigating differences in the laryngectomee experience between men and women.

What this paper adds to existing knowledge

This study finds that women and men both endorse significant mental and physical changes following laryngectomy; however, their perception of their experience differed by gender. Women endorsed alteration to meaningful life and men demonstrated distress related to loss of physical functioning; both genders described laryngectomy as a formative event that helped them rediscover joy and redefine themselves for the better.

What are the potential or actual clinical implications of this work?

Our findings suggest men and women have distinct mental and emotional struggles after laryngectomy despite similar physical changes. This suggests that tailoring care with consideration of these gender differences, including preoperative counselling, post‐operative support and gender‐matched visitors or support groups, may help beneficial in recovery after laryngectomy.