bluuebunny/crossref_metadata_2025 huggingface dataset:
Early-Stage NSCLC Patients’ Prognostic Prediction with Multi-information Using Transformer and Graph Neural Network Model
Authors: Lian Jie , Deng Jiajun , Hui Sai Kam , Koohi-Moghadam Mohamad , She Yunlang , Chen Chang , Vardhanabhuti Varut
Published: June 2022

Background

We proposed a population graph with Transformer-generated and clinical features for the purpose of predicting overall survival and recurrence-free survival for patients with early-stage NSCLC and to compare this model with traditional models.

Methods

The study included 1705 patients with lung cancer (stage I and II), and a public dataset for external validation (n=127). We proposed a graph with edges representing non-imaging patient characteristics and nodes representing imaging tumour region characteristics generated by a pretrained Vision Transformer. The model was compared with a TNM model and a ResNet-Graph model. To evaluate the models’ performance, the area under the receiver operator characteristic curve (ROC-AUC) was calculated for both overall survival (OS) and recurrence-free survival (RFS) prediction. The Kaplan–Meier method was used to generate prognostic and survival estimates for low- and high-risk groups, along with net reclassification improvement (NRI), integrated discrimination improvement (IDI), and decision curve analysis (DCA). An additional subanalysis was conducted to examine the relationship between clinical data and imaging features associated with risk prediction.

Results

Our model achieved AUC values of 0·785 (95 % CI:0·716 - 0·855) and 0·695 (95 % CI:0·603 - 0·787) on the testing and external datasets for OS prediction, and 0·726 (95 % CI:0·653 - 0·800) and 0·700 (95 % CI:0·615 - 0·785) for RFS prediction. Additional survival analyses indicated that our model outperformed the present TNM and ResNet-Graph models in terms of net benefit for survival prediction.

Conclusion

Our Transformer-Graph model was effective at predicting survival in patients with early-stage lung cancer, which was constructed using both imaging and non-imaging clinical features. Some high-risk patients were distinguishable by using a similarity score function defined by non-imaging characteristics such as age, gender, histology type, and tumour location, while Transformer-generated features demonstrated additional benefits for patients whose non-imaging characteristics were non-discriminatory for survival outcomes.

Funding

There was no funding source for this study.
Estimating the cumulative impact and zone of influence of anthropogenic features on biodiversity
Authors: Niebuhr Bernardo Brandão , Van Moorter Bram , Stien Audun , Tveraa Torkild , Strand Olav , Langeland Knut , Sandström Per , Alam Moudud , Skarin Anna , Panzacchi Manuela
Published: June 2022

The concept of cumulative impacts is widespread in policy documents, regulations, and ecological studies, but quantification methods are still evolving. Infrastructure development usually takes place in landscapes with preexisting anthropogenic features. Typically, their impact is determined by computing the distance to the nearest feature only, thus ignoring the potential cumulative impacts of multiple features. We propose thecumulative ZOI approachto assess whether and to what extent anthropogenic features lead to cumulative impacts.

The approach estimates both effect size and zone of influence (ZOI) of anthropogenic features and allows for estimation of cumulative effects of multiple features distributed in the landscape. First, we use simulations and an empirical study to understand under which circumstances cumulative impacts arise. Second, we demonstrate the approach by estimating the cumulative impacts of tourist infrastructure in Norway on the habitat of wild reindeer (Rangifer t. tarandus), a nearly-threatened species highly sensitive to anthropogenic disturbance.

Simulations show that analyses based on the nearest feature and our cumulative approach are indistinguishable in two extreme cases: when features are few and scattered and their ZOI is small, and when features are clustered and their ZOI is large. Empirical analyses revealed cumulative impacts of private cabins and tourist resorts on reindeer, extending up to 10 and 20 km, with different decaying functions. Although the impact of an isolated private cabin was negligible, the cumulative impact of ‘cabin villages’ could be much larger than that of a single large tourist resort. Focusing on the nearest feature only underestimates the impact of ‘cabin villages’ on reindeer.

The suggested approach allows us to quantify the magnitude and spatial extent of cumulative impacts of point, linear, and polygon features in a computationally efficient and flexible way and is implemented in theoneimpactR package. The formal framework offers the possibility to avoid widespread underestimations of anthropogenic impacts in ecological and impact assessment studies and can be applied to a wide range of spatial response variables, including habitat selection, population abundance, species richness and diversity, community dynamics, and other ecological processes.
Life cycle exposure to cyhalofop-butyl induced reproductive toxicity toward zebrafish
Authors: Zhu Tao , Wang Siwen , Li Dong
Published: June 2022

Cyhalofop-butyl (CyB) is an herbicide widely used in paddy fields, which may transfer to aquatic ecosystems and cause harm to aquatic organisms. In this study, zebrafish (Danio rerio) were exposed to CyB (0.1, 1 and 10 ug/L) related to the environment throughout its adult life cycle from embryo to sexual maturity. The effects of CyB on zebrafish growth, reproduction and offspring development were studied. It was found that female spawning was inhibited and adult male fertility decreased. In addition, we detected the expression of sex steroid hormones and genes related to hypothalamus-pituitary-gonad-liver (HPGL) axis. After 150days of exposure, the hormone balance of parent zebrafish (F0) was disturbed and the concentrations of 17β-estradiol (E2) and vitellogenin (VTG) in zebrafish were decreased. F1 embryos showed abnormal developmental results, including decreased heart rate, decreased body length, spontaneous motor inhibition, while the developmental abnormalities of F1 embryos were relieved when exposed to CyB-free clear water. The change of sex hormone is regulated by gene expression related to HPGL axis. These results confirmed that long-term exposure to CyB in the environmental concentrations can damage the reproductive capacity of F0 generation zebrafish by disrupting the transcription of genes related to HPGL axis, which may lead to abnormal development of F1. Overall, these data may provide a new understanding of the reproductive toxicity of zebrafish parents and offspring after long-term exposure to CyB.

Highlights

Environmental level of CyB exposure caused gonadal impairment.

CyB exposure suppressed spawning ability of zebrafish.

CyB exposure changed the plasma hormone level of zebrafish and altered HPGL axis in both genders.

Parental CyB exposure led to abnormal development of F1.
An analytical model describing the mechanics of erythrocyte membrane wrapping during active invasion of a plasmodium falciparum merozoite
Authors: Msosa Chimwemwe , Abdalrahman Tamer , Franz Thomas
Published: June 2022

The invasion of a merozoite into an erythrocyte by membrane wrapping is a hallmark of malaria pathogenesis. The invasion involves biomechanical interactions whereby the merozoite exerts actomyosin-based forces to push itself into and through the erythrocyte membrane while concurrently inducing biochemical damage to the erythrocyte membrane. Whereas the biochemical damage process has been investigated, the detailed mechanistic understanding of the invasion mechanics remains limited. Thus, the current study aimed to develop a mathematical model describing the mechanical factors involved in the merozoite invasion into an erythrocyte and explore the invasion mechanics.

A shell theory model was developed comprising constitutive, equilibrium and governing equations of the deformable erythrocyte membrane to predict membrane mechanics during the wrapping of an entire non-deformable ellipsoidal merozoite. Predicted parameters include principal erythrocyte membrane deformations and stresses, wrapping and indentation forces, and indentation work. The numerical investigations considered two limits for the erythrocyte membrane deformation during wrapping (4% and 51% areal strain) and erythrocyte membrane phosphorylation (decrease of membrane elastic modulus from 1 to 0.5 kPa).

For an intact erythrocyte, the maximum indentation force was 1 and 8.5 pN, and the indentation work was 1.92 ×10-18and 1.40 ×10-17J for 4% and 51% areal membrane strain. Phosphorylation damage in the erythrocyte membrane reduced the required indentation work by 50% to 0.97 ×10-18and 0.70 ×10-17J for 4% and 51% areal strain.

The current study demonstrated the developed model’s feasibility to provide new knowledge on the physical mechanisms of the merozoite invasion process that contribute to the invasion efficiency towards the discovery of new invasion-blocking anti-malaria drugs.
Understanding the Dynamics of Fluid-Structure Interaction with an Air Deflected Microfluidic Chip (ADMC)
Authors: ten Pas Chad , Du Ke , Pan Long , Wang Ruo-Qian , Xu Shiyou
Published: June 2022

A deformable microfluidic system and a fluidic dynamic model have been successfully coupled to understand the dynamic fluid-structure interaction in transient flow, designed to understand the dentine hypersensitivity caused by hydrodynamic theory. The Polydimethylsiloxane thin sidewalls of the microfluidic chip are deformed with air pressure ranging from 50 to 500 mbar to move the liquid meniscus in the central liquid channel. The displacement is recorded and compared with our new theoretical model derived from the unsteady Bernoulli equation. We show that our theoretical model can well predict the ending point of the liquid displacement as well as the dynamics process, regardless of the wall thickness. Moreover, an overshooting and oscillation phenomenon is observed by reducing the friction factor by a few orders which could be the key to explain the dentine hypersensitivity caused by the liquid movement in the dentine tubules.
A small H2O-soluble ingredient of royal jelly lower cholesterol levels in liver cells by suppressing squalene epoxidase
Authors: Wang Chi , Jiang Zhen-yu , Wang Jing , Liu Jia-xin , Nian Yuan-yuan , Lixia-Liu  , Dang Tong , Meng Xian-mei
Published: June 2022

Excessive cholesterol in the liver is harmful for our health and may cause many diseases, such as fatty liver disease. Many studies in human and animal models have reported that royal jelly (RJ) can be used to treat atherosclerosis. However, the real mechanisms behind this action is unclear. In this study, we investigated the effectivity of RJ on gene expression of squalene epoxidase (SE) a major enzyme involved in cholesterol biosynthesis in HepG2 cells. We found that the expression of SE was decreased in response to RJ treatment. We also found that the origin of the RJ affected its strength. To find out the active ingredient of RJ in cholesterol suppression, we separated RJ into two parts based on the molecular weights using ultrafiltration membrane. We found that the fraction < 10kDa from RJ had comparable effect on SE expression, especially its water-soluble part. Taken together, we think RJ suppresses cholesterol by decreasing SE gene expression in liver. The active ingredient of RJ in this action is < 10kDa in water-soluble form.
Analysis of the CYP1A2 caffeine metabolism gene in the student population at Lake Superior State University
Authors: Pittsley Rebekka A , Kolomyjec Stephen H
Published: June 2022

85% of Americans drink caffeinated beverages on a daily basis. Each individual responds differently to caffeine depending on age, gender, diet, and ethnicity. Caffeinated beverages cause insomnia in some people, but not in others due to differences in the rate of caffeine metabolism. This study examines the variation in the caffeine metabolism of Lake Superior State University (LSSU) students. My hypothesis was that LSSU student allele frequencies would match those of the general population: 47.5% fast, 41.0% medium, and 11.5% slow caffeine metabolism. 200 LSSU students were sampled via buccal swabs. DNA was successfully isolated from 164 samples. Participants filled out a demographic questionnaire entailing caffeine intake, ethnicity, and sex. The CYP1A2 gene was amplified via standard PCR prior to genotyping by restriction digest and gel electrophoresis. The APAI restriction enzyme was used to determine the genotype of the rs762551 single nucleotide polymorphism (SNP), while the SACI enzyme was used as a positive digestion control. Overall, results showed a total of 42.7% fast, 44.5% medium, and 12.8% slow metabolizers. Of special note is that 24 of the 164 students sampled were of Native American heritage, an important yet underrepresented group in human genomics. This study provides the first reported look at the CYP1A2 variation within this North American subpopulation with metabolism rates being 50% fast, 33.3% medium, and 16.7% slow. The results confirm my initial hypothesis that the variation of caffeine metabolism gene frequencies for the LSSU student population would be representative of published allele frequencies for the general population.
Using 18F-NOS PET Imaging to Measure Pulmonary Inflammation in Electronic and Combustible Cigarette Users: A Pilot Study
Authors: Wetherill Reagan R. , Doot Robert K. , Young Anthony J. , Lee Hsiaoju , Schubert Erin K. , Wiers Corinde E. , Leone Frank T. , Mach Robert H. , Kranzler Henry R. , Dubroff Jacob G.
Published: June 2022

Electronic cigarette (EC) use has increased dramatically, particularly among adolescents and young adults, which, like cigarette use, can cause inflammation of the lungs and increase the risk of lung disease.

Methods

In this preliminary study, we used positron emission tomography with 18F-6-(1/2)(2-fluoro-propyl)-4-methylpyridin-2-amine (18F-NOS) to quantify inflammation of the lungs in vivo in three age- and sex-matched groups: (1) 5 daily EC users, (2) 5 daily cigarette smokers, and (3) 5 never smoke/vape controls.

Results

EC users showed greater 18F-NOS non-displaceable binding potential (BPND) than cigarette smokers (p = 0.03) and never smoke/vape controls (p = 0.01); whereas BPND in cigarette smokers did not differ from controls (p > 0.1). 18F-NOS lung tissue delivery (K1) and iNOS distribution volume (VT) did not significantly differ between groups. Although there were no group differences in the concentration of the peripheral inflammatory markers TNF-α, IL-6 or IL-8, 18F-NOS BPND significantly correlated with the proinflammatory cytokine TNF-α (r = 0.87, p = 0.05) in EC users. Additionally, when EC users and cigarette smokers were pooled together, vaping episodes/cigarettes per day correlated with IL-6 levels (r = 0.86, p = 0.006).

Conclusion

To our knowledge, this is the first PET imaging study to compare lung inflammation between EC and cigarette users in vivo. We found preliminary evidence EC users had greater pulmonary inflammation than cigarette smokers and never smoke/vape controls, with a positive association between pulmonary and peripheral measures of inflammation.
eccDNA purification, full-length sequencing, and genomic mapping
Authors: Wang Yuangao , Wang Meng , Zhang Yi
Published: June 2022

Extrachromosomal circular DNA (eccDNA) has been discovered for more than half a century1. However, its biogenesis and function have just begun to be elucidated. One hurdle that prevented our understanding of eccDNA is the difficulty in obtaining pure eccDNA from cells. The current eccDNA purification methods mainly rely on exonuclease digestion after alkaline lysis. Due to its low abundance and heterogeneity in size, the current eccDNA purification methods are not efficient in obtaining pure eccDNA. Here, we describe a new 3-step eccDNA purification (3SEP) procedure by adding a new step that allows circular, but not linear, DNA that escaped from exonuclease digestion, bound to silica beads in solution A. Our method allows eccDNA purification with high purity and reproducibility. Additionally, we developed a full-length sequencing and genomic mapping method by combining rolling cycle amplification (RCA) with Nanopore sequencing, through which the consensus sequence of multiple tandem copies of eccDNA contained within the debranched RCA product is derived and mapped to its genomic origin. Collectively, our protocol will facilitate eccDNA identification, characterization, and has the potential for diagnostic and clinic applications.
A pangenome analysis pipeline (PSVCP) provides insights into rice functional gene identification
Authors: Wang Jian , Yang Wu , Zhang Shaohong , Hu Haifei , Yuan Yuxuan , Dong Jingfang , Chen Luo , Ma Yamei , Yang Tifeng , Zhou Lian , Chen Jiansong , Liu Bin , Li Chengdao , Edwards David , Zhao Junliang
Published: June 2022

Background

A pangenome aims to capture the complete genetic diversity within a species and reduce bias in genetic analysis inherent in using a single reference genome. However, the current linear format of most plant pangenomes limits the presentation of position information for novel sequences. Graph pangenomes have been developed to overcome this limitation. However, there is a lack of bioinformatics analysis tools for graph format genomes.

Results

To overcome this problem, we have developed a novel pangenome construction strategy and a downstream pangenome analysis pipeline that captures position information while maintaining a linearized layout. We applied this strategy to construct a high-quality rice pangenome using 12 representative rice genomes and analyze an international rice panel with 413 diverse accessions using the pangenome reference. Our results provide insights into rice population structure and genomic diversity. Applying the pangenome for PAV-based GWAS analysis can identify causal structural variations for rice grain weight and plant height, while SNP-based GWAS can only identify approximate genomic locations. Additionally, a new locus (qPH8-1) was found to be associated with plant height on chromosome 8 that could not be detected using the SNP-based GWAS.

Conclusions

Our results demonstrate that the pangenome constructed by our pipeline combined with PAV-based GWAS can provide additional power for genomic and genetic analysis. The pangenome constructed in this study and associated genome sequence data provide valuable genomic resources for future rice crop improvement.
Label-free, fast, 2-photon volume imaging of the structural organization of peripheral neurons and glia in the enteric ganglia
Authors: Hazart Doriane , Delhomme Brigitte , Oheim Martin , Ricard Clément
Published: June 2022

The enteric nervous system (ENS), sometimes considered as a ‘second brain’ due to its large autonomy from central circuits is made of interconnected plexuses organized in a mesh-like network lining the gastrointestinal tract. Originally described as a leading actor of the regulation of digestion, bowel advance and intestinal secretion, its implication in various neuropathologies has recently been demonstrated. However, with few exceptions, its morphology and functions have been studied on thin sections of the intestinal wall or in dissected explants. Due to its intricate morphology, precious information on its three-dimensional (3-D) architecture and connectivity is often lost. In this context, we have developed a fast, label-free 3-D imaging method of the ENS, based on intrinsic signals of the tissue. We adapted a fast tissue-clearing protocol based on a high refractive-index aqueous solution, and then characterized the autofluorescence signals arising from the various cellular and sub-cellular components of the ENS. Immunofluorescence and spectral recordings complete this characterization. Finally, we demonstrate the fast acquisition of detailed 3-D image stacks of unlabeled mouse intestine, across the whole intestinal wall and including both the myenteric and submucosal enteric nervous plexuses using a new spinning-disk two-photon microscope. The combination of fast clearing (less than 15min for 73 % transparency), autofluorescence imaging and rapid volumetric imaging (less than a minute for the acquisition of s z-stack of 100 planes (150*150 µm) at 300-nm spatial resolution) paves the way for new applications in fundamental and clinical research.
Statistical Population Reconstruction of Moose (Alces alces) in Northeastern Minnesota using Integrated Population Models
Authors: Severud William J. , Berg Sergey S. , Ernst Connor A. , DelGiudice Glenn D. , Moore Seth A. , Windels Steve K. , Moen Ron A. , Isaac Edmund J. , Wolf Tiffany M.
Published: June 2022

Given recent and abrupt declines in the abundance of moose (Alces alces) throughout parts of Minnesota, accurately estimating statewide population trends and demographic parameters is a high priority for their continued management and conservation. Statistical population reconstruction using integrated population models provides a flexible framework for combining information from multiple studies across the state to produce robust estimates of population abundance, recruitment, and survival. We used this framework to combine aerial survey data and survival data from telemetry studies to recreate trends and demographics of moose in northeastern Minnesota, USA, from 2005 to 2020. Statistical population reconstruction confirmed the sharp decline in abundance from an estimated 7,841 (90% CI = 6,702–8,933) in 2009 to 3,386 (90% CI = 2,681–4,243) animals in 2013, but also indicated that abundance has remained relatively stable since then, except for a slight decline to 3,163 (90% CI = 2,403– 3,718) in 2020. Subsequent stochastic projection of the population from 2021 to 2030 suggests that this modest decline will continue for the next ten years. Both annual adult survival and per-capita recruitment (number of calves that survived to 1 year per adult female alive during the previous year) decreased substantially in years 2005 and 2019, from 0.902 (SE = 0.043) to 0.689 (SE = 0.061) and from 0.386 (SE = 0.030) to 0.303 (SE = 0.051), respectively. Sensitivity analysis revealed that moose abundance was more sensitive to fluctuations in adult survival than recruitment, leading us to conclude that the steep decline in 2013 was driven primarily by decreasing adult survival. Our analysis demonstrates the potential utility of using statistical population reconstruction to monitor moose population trends and to identify population declines more quickly. Future studies should focus on providing better estimates of per-capita recruitment, using pregnancy rates and calf survival, which can then be incorporated into reconstruction models to help improve estimates of population change through time.
Fatty acid binding protein 1 and fatty acid synthetase overexpression have differential effects on collagen III and cross-linking in Zongdihua pig tissues
Authors: Yang Rong , Zhou Di , Yan Zhihong , Zhao Zhonghai , Wang Yan , Li Jun , Ren Liqun , Xie Lingling , Wang Xin
Published: June 2022

The purpose of this study was to determine whether FABP1 and FAS regulate expression of collagen and its crosslinking via lysyl oxidase in Zongdihua pigs. We wished to identify processes affecting meat quality using molecular genetics to provide a basis for breeding improvement of these animals. We measured expression levels of FABP1 and related genes using qRT-PCR in longissimus dorsi muscle and subcutaneous adipose tissues. Primary adipocytes from fat tissues were isolated and FABP1 and FAS were overexpressed from recombinant plasmids. Our sequence analysis of the cloned genes indicated that FABP1 gene encodes a hydrophobic protein of 128 amino acids and contained 12 predicted phosphorylation sites and no transmembrane region. FAS encodes 333 amino acid hydrophobic protein containing with 26 phosphorylation sites and 0 transmembrane regions. The basal levels of FABP1 and FAS in pig tissues expression were 3 −3.5-fold higher in subcutaneous fat compared with muscle (P < 0.01). Recombinant expression plasmids were successfully transfected into the cloned preadipocytes and (a) overexpression of FAS resulted in significantly increased expression of COL3A1 gene (P < 0.05) and significantly inhibited lysyl oxidase LOX expression (P < 0.01); (b) overexpression of FABP1 significantly increased COL3A1 expression (P < 0.01) and significantly inhibited LOX expression (P < 0.05) and significantly reduced lysyl oxidase activity (P < 0.01). Therefore, enhancing FABP1 expression increases collagen accumulation and this preliminarily suggests that FAS and FABP1 can serve as fat-related candidate genes providing a theoretical basis for the study of fat deposition in Zongdihua pigs.
Sampling strategies and pre-pandemic surveillance gaps for bat coronaviruses
Authors: Cohen Lily E. , Fagre Anna C. , Chen Binqi , Carlson Colin J. , Becker Daniel J.
Published: June 2022

The emergence of SARS-CoV-2, and the challenge of pinpointing its ecological and evolutionary context, has highlighted the importance of evidence-based strategies for monitoring viral dynamics in bat reservoir hosts. Here, we compiled the results of 93,877 samples collected from bats across 111 studies between 1996 and 2018, and used these to develop an unprecedented open database, with over 2,400 estimates of coronavirus infection prevalence or seroprevalence at the finest methodological, spatiotemporal, and phylogenetic level of detail possible from public records. These data revealed a high degree of heterogeneity in viral prevalence, reflecting both real spatiotemporal variation in viral dynamics and the effect of variation in sampling design. Phylogenetically controlled meta-analysis revealed that the most significant determinant of successful viral detection was repeat sampling (i.e., returning to the same site multiple times); however, fewer than one in five studies longitudinally collected and reported data. Viral detection was also more successful in some seasons and from certain tissues, but was not improved by the use of euthanasia, indicating that viral detection may not be improved by terminal sampling. Finally, we found that prior to the pandemic, sampling effort was highly concentrated in ways that reflected concerns about zoonotic risk, leaving several broad geographic regions (e.g., South Asia, Latin America and the Caribbean, and most of Sub-Saharan Africa) and bat subfamilies (e.g., Stenodermatinae and Pteropodinae) measurably undersampled. These gaps constitute a notable vulnerability for global health security and will likely be a future barrier to contextualizing the origin of novel zoonotic coronaviruses.
Duodenal alpha-Synuclein pathology and enteric gliosis in advanced Parkinson’s Disease patients
Authors: Emmi Aron , Sandre Michele , Russo Francesco Paolo , Tombesi Giulia , Garrì Federica , Campagnolo Marta , Carecchio Miryam , Biundo Roberta , Spolverato Gaya , Macchi Veronica , Savarino Edoardo , Farinati Fabio , Parchi Piero , Porzionato Andrea , Bubacco Luigi , De Caro Raffaele , Kovacs Gabor G , Antonini Angelo
Published: June 2022

Background

The role of the gut-brain axis has been recently highlighted as a major contributor to Parkinson’s Disease (PD) physiopathology, with numerous studies investigating bidirectional transmission of pathological protein aggregates, such as α-Synuclein (αSyn), in the context of neurodegenerative disease. However, little and often conflictual evidence is available from human studies due to patient heterogeneity, sampling variability, and the employment of antibodies with affinity for different αSyn epitopes.

Objectives

We aimed to investigate the enteric nervous system (ENS) in PD by characterizing αSyn alterations and glial responses in duodenum biopsies of PD patients by employing topography-specific sampling and conformation-specific αSyn antibodies.

Methods

18 Patients with symptomatic PD who underwent Duodopa Percutaneous Endoscopic Gastrostomy and Jejunal Tube (PEG-J) procedure, as well as 18 age- and -sex-matched Healthy Control subjects undergoing routine diagnostic endoscopy, were included in the study. A mean of 4 duodenal wall biopsies were sampled from each patient. Immunohistochemistry was performed for anti-aggregated αSyn (5G4) and GFAP antibodies. Morphometrical-semi-quantitative analysis was performed to characterize αSyn-5G4+ and GFAP+ density and size.

Results

Elevated immunoreactivity for aggregated α-Syn was identified in all biopsies of PD patients compared to controls. αSyn-5G4+ colocalized with neuronal marker β-III-tubulin. Evaluation of enteric glia cells revealed an increased size and density when compared with controls, suggesting reactive gliosis.

Conclusions

Duodenal biopsy may represent a feasible and reliable tool for characterizing PD pathology in the GI tract and discerning patients from controls. Future studies are required to confirm these findings in a prodromal or early PD phase.
Targeting H3K4 methylation as a novel therapeutic strategy against tumor infiltration and nuclear changes of acute lymphoblastic leukemia cells
Authors: González-Novo Raquel , de Lope-Planelles Ana , González-Murillo África , Madrazo Elena , Acitores David , de Lacoba Mario García , Ramírez Manuel , Redondo-Muñoz Javier
Published: June 2022

Acute lymphoblastic leukemia (ALL) is the most common pediatric cancer, and the infiltration of leukemic cells is critical for disease progression and relapse. In spite of the canonical functions of histone methylation in gene regulation, differentiation, and DNA homeostasis; its contribution to the nuclear deformability of migrating leukemic cells remains unclear. Here, we showed that 3D conditions promoted a fast upregulation of H3K4 methylation, bound to transcriptional changes in ALL cells. Furthermore, we demonstrated that targeting WDR5 (a core subunit involved in H3K4 methylation) impaired the invasion of leukemia cells in vitro, and their tissue infiltration in an immunodeficient mouse model. WDR5 expression correlated with other cell receptors involved in leukemia dissemination in clinical samples from ALL patients. Interestingly, blocking WDR5 did not reduce the chemotactic response of leukemia cells, suggesting a different mechanism by which H3K4 methylation might operate at both nuclear and functional level to control ALL cell invasiveness in 3D conditions. We applied biochemical and biophysical approaches to determine that H3K4 methylation induced by 3D conditions was dependent on MLCK activity, and regulated the chromatin compaction and the mechanical nuclear response of leukemia cells in 3D conditions. Collectively, our data revealed that confined conditions provide novel molecular and biophysical mechanisms used by leukemia cells to disseminate, suggesting H3K4 methylation and nuclear mechanical pathways as promising therapeutic targets against ALL infiltration.

Highlights

3D conditions induce H3K4 methylation and transcriptional changes in ALL cells.

Targeting WDR5 and H3K4 methylation blocks ALL cell invasion in vitro 3D conditions and leukemia dissemination in vivo.

WDR5 expression correlates with other cell receptors related to leukemia migration in clinical samples from patients with ALL.

H3K4 methylation induced by 3D conditions is dependent of MLCK activity and regulates cell movement through 3D environments.

Leukemia cells in 3D conditions alter their chromatin compaction and the biomechanical deformability of their nuclei.
Generative Adversarial Networks Can Create High Quality Artificial Prostate Cancer Magnetic Resonance Images
Authors: Xu Isaac R. L. , Van Booven Derek J , Goberdhan Sankalp , Breto Adrian L. , Alhusseini Mohammad , Algohary Ahmad , Stoyanova Radka , Punnen Sanoj , Mahne Anton , Arora Himanshu
Published: June 2022

Purpose

Recent integration of open-source data to machine learning models, especially in the medical field, has opened new doors to study disease progression and/or regression. However, the limitation of using medical data for machine learning approaches is the specificity of data to a particular medical condition. In this context, most recent technologies like generative adversarial networks (GAN) could be used to generate high quality synthetic data that preserves the clinical variability.

Materials and Methods

In this study, we used 139 T2-weighted prostate magnetic resonant images (MRI) from various sources as training data for Single Natural Image GAN (SinGAN), to make a generative model. A deep learning semantic segmentation pipeline trained the model to segment the prostate boundary on 2D MRI slices. Synthetic images with a high-level segmentation boundary of the prostate were filtered and used in the quality control assessment by participating scientists with varying degree of experience (more than 10 years, 1 year, or no experience) to work with MRI images.

Results

The most experienced participating group correctly identified conventional vs synthetic images with 67% accuracy, the group with 1 year of experience correctly identified the images with 58% accuracy, and group with no prior experience reached 50% accuracy. Nearly half (47%) of the synthetic images were mistakenly evaluated as conventional images. Interestingly, a blinded quality assessment by a board-certified radiologist to differentiate conventional and synthetic images was not significantly different in context of the mean quality of synthetic and conventional images.

Conclusions

This study shows promise that high quality synthetic images from MRI can be generated using GAN. Such an AI model may contribute significantly to various clinical applications which involves supervised machine learning approaches.
Active and passive mechanics for rough terrain traversal in centipedes
Authors: Diaz Kelimar , Erickson Eva , Chong Baxi , Soto Daniel , Goldman Daniel I.
Published: June 2022

Centipedes coordinate body and limb flexion to generate propulsion. On flat solid surfaces, the limb-stepping patterns can be characterized according to the direction in which limbaggregates propagate, opposite to (retrograde) or with the direction of motion (direct). It is unknown how limb and body dynamics are modified in terrain with terradynamic complexity more representative of their natural heterogeneous environments. Here, we investigated how centipedes that use retrograde and direct limp-stepping patterns,S. polymorphaandS. sexspinosus, respectively, coordinate their body and limbs to navigate laboratory environments which present footstep challenges and terrain rugosity. We recorded the kinematics and measured the locomotive performance of these animals traversing two rough terrains with randomly distributed step heights and compared the kinematics to those on a flat frictional surface.S. polymorphaexhibited similar body and limb dynamics across all terrains and a decrease in speed with increased terrain roughness. Unexpectedly, when placed in a rough terrain,S. sexspinosuschanged the limb-stepping pattern from direct to retrograde. Further, for both species, traversal of rough terrains was facilitated by hypothesized passive mechanics: upon horizontal collision of a limb with a block, the limb passively bent and later continued the stepping pattern. While centipedes have many degrees of freedom. our results suggest these animals negotiate limb-substrate interactions and navigate complex terrains, by offloading complex control and leveraging the innate flexibility of their limbs.
X-ray third-order nonlinear diffraction in the asymmetric reflection geometry
Authors: Balyan Minas K.
Published: June 2022

X-ray third-order nonlinear asymmetrical diffraction has three independent parameters: the asymmetry angle, the incident wave intensity and the deviation from the exact Bragg orientation. In contrast to the linear case, in the nonlinear case the total reflection region does not exist for all intensity values and asymmetry angles. Theoretical consideration leads to analytical conditions of the total reflection region, and the analysis can be carried out by a graphical method. An exact solution in the total reflection region is found. The numerical solutions of the third-order nonlinear diffraction allow one to find the reflection curves for a fixed asymmetry angle or for a fixed intensity. For very large or very small asymmetry factors the third-order nonlinear effects can be observed for beams with very low intensities.
Factors influencing intentions to use library social media marketing accounts: taking the example of WeChat
Authors: Xin Chen , Yingxi Liu
Published: June 2022

Purpose

This study aims to explore the factors influencing intentions to use library social media marketing accounts from users’ perspectives to help libraries use social media to provide targeted information services to users to meet their information needs.

Design/methodology/approach

This study is based on the technology acceptance model and theory of planned behaviour and uses WeChat as an example to build the model of factors influencing intentions to use library social media marketing accounts. It takes college students as the research object, performing empirical research through questionnaire surveys and structural equation modeling.

Findings

The results show that attitude, subjective norm and perceived behaviour control have a significant positive impact on library social media marketing – attitude exerts the most significant effect while the impact of perceived usefulness is nonsignificant. Notably, attitude completely mediates perceived usefulness and use intention, while perceived usefulness partially mediates perceived ease of use and attitude. However, birthplace plays a negative moderating role between attitudes and use intention.

Originality/value

This study integrates the theory of planned behaviour and technology acceptance model, discusses the factors influencing intentions to use library social media marketing accounts from the users’ perspectives and proposes strategies and methods for the optimization of library social media marketing. The study helps enhance the effects of library social media marketing by improving the comprehension of current circumstances and influencing factors relevant to this issue.
Energy efficiency compliance towards benchmarking for intermittent use religious buildings
Authors: Abd Rahman Nurul Asra , Kamaruzzaman Syahrul Nizam , Akashah Farid Wajdi , Amran Alyaa Anati
Published: June 2022

Purpose

The purpose of this study is to assess the level of energy efficiency (EE) practices and worshippers’ comfort experience towards energy consumption of a selected energy retrofitted mosque. This study identifies whether the work was done on ad hoc or planned basis and to gauge the success level of the retrofit work.

Design/methodology/approach

Mixed method was used in this study. A selected mosques with a capacity of more than 1,000 worshippers under the Class A of classification places of assembly with operating hour ranging from 45 to 65 h and the penarafan hijau jabatan kerja raya (pHJKR) rating tool as a benchmarking for EE assessment is used. A total of 45 respondents were involved in this study to obtain their perception on comfort experience in mosque. Meanwhile, energy audit and walk-through surveys were conducted to obtain data on energy consumption. To identify whether the work was done on ad hoc or planned basis and to gauge the success level of the retrofit work, pHJKR rating tool and efficiency standard MS1525:2019 are used for benchmarking in keeping with sustainability guidelines.

Findings

The results of this study indicated that the EE score achieved by the mosque is good while there are still rooms for improvement to increase the higher score to the pHJKR’s EE benchmarking tool.

Research limitations/implications

EE is one of the most important agenda under sustainable development initiatives. Part of the initial government strategy is to encourage the use public buildings in demonstrating initiatives for sustainable development to justify high capital resources investment. Mosque buildings have huge potential for this purpose because as religious public buildings for the majority Muslim community, their operations are fully funded from public funds. Selection of mosques is also driven by its unique intermittent energy consumption pattern, while early mosques adopted natural ventilation, modern mosques are often designed with mechanical ventilation (air conditioning).

Practical implications

An encouragement on government initiative towards sustainable development can be escalating by producing exemplary building for intermittent use pattern categories by mosque as a model.

Social implications

Sustainable development especially in EE becomes normal practices and energy and impact towards environment possibly be saved.

Originality/value

Sustainable development especially in EE becomes normal practices and energy and impact towards environment possibly be saved. This research is based on supportive national agenda by assessing EE measure for development of energy management in intermittent use buildings (mosque).
Corporate governance and diversity management: evidence from a disclosure perspective
Authors: Shohaieb Doaa , Elmarzouky Mahmoud , Albitar Khaldoon
Published: June 2022

Purpose

Using textual analysis, this paper aims to measure diversity management disclosure; it also explore the relationship between corporate governance and diversity management disclosure.

Design/methodology/approach

The study is based on a sample of the UK FTSE all-share non-financial organisations over the period from 2013 to 2019. We used a computer-aided textual analysis, and we used a bag of words to score the sample annual reports.

Findings

The results show that the mean of the diversity management disclosure level is very low. Also, there is a positive relationship between the board size, women on board and board independence and the level of diversity management disclosure. The relationship is higher with more board members, women on board and more independent directors, aligning with previous literature.

Practical implications

The implications of this research affect stakeholders and organisations which reflects the importance of communicating diversity practices and researchers by facilitating measuring objectively firms’ diversity management practices that have not been applied previously in the field of diversity.

Originality/value

With different incidents taking place around the globe, such as the incident of George Floyd and the increased attention to diversity, organisations are under increasing social and political pressure to reflect on their diversity management practices. Previous literature has examined firms’ diversity practises from different perspectives, but to the best of the authors’ knowledge, this is the first paper to measure diversity management disclosure.
What lies behind entrepreneurial intentions? Exploring nascent entrepreneurs’ early belief systems
Authors: Laukkanen Mauri
Published: June 2022

Purpose

Studies of entrepreneurial intentions (EIs) have become increasingly common, informed usually by Ajzen’s (1991) theory of planned behaviour (TPB). Although the TPB postulates that beliefs determine EIs, the contents of the beliefs have not been properly studied, leaving EIs’ cognitive underpinnings and cognitive approaches to influencing EIs unclear. To clarify the TPB/EI-belief nexus, the study examines the conceptual background of entrepreneurial cognitions and elicits the beliefs of a group of nascent micro entrepreneurs (NMEs) to compare them with their TPB attitudes and EIs, facilitating assessing their mutual consistency as implied by the TBP.

Design/methodology/approach

The respondents are entrepreneurial novice clients of a micro business advisory organisation. Their TPB attitudes and EIs were measured using standard TPB/EI methods. Comparative causal mapping (CCM) combined with semi-structured interviewing was used to reveal the NMEs’ typical belief systems, presented as aggregated cause maps.

Findings

The NMEs have uniform, relatively detailed belief systems about entrepreneurship and micro business. The belief systems are consistent with theory- and context-based expectations and logically aligned with the NMEs’ expressed TPB attitudes and EIs. CCM provides an accessible method for studying contents of entrepreneurial cognitions.

Research limitations/implications

It was not possible to study “entrepreneurship-negative” respondents or the intensity or origins of some specific beliefs.

Practical implications

Diagnosing and better understanding beliefs can benefit entrepreneurship education and development, in general or connected with TPB/EI studies.

Originality/value

The study reveals entrepreneurial belief systems systematically, evidently not done before generally or in terms of “everyday” micro entrepreneurship or TPB. It clarifies and supports the TPB notion that beliefs underpin actors’ attitudes and intentions.
Voices from the frontline: a review of EMS first responders' experience of COVID-19 in Ireland
Authors: Brown Gavin David , Largey Ann , McMullan Caroline , O'Shea Gráinne , Reilly Niamh
Published: June 2022

Purpose

This study explored the experiences of Irish emergency medical services (EMS) first responders during the first nationwide restrictions to curb the spread of COVID-19.

Design/methodology/approach

A systematic literature review (SLR) of research into healthcare workers' and first responders' experiences during the COVID-19 and 2003 SARS pandemics was performed. The SLR informed the content of an online questionnaire distributed via the Irish Pre-Hospital Emergency Care Council to 2,092 first responders on its live register. Data analysis used both descriptive and content analysis.

Findings

EMS first responders faced many challenges including PPE quality, training on its use, issues with decontamination facilities, and organisational effectiveness. Emotional challenges included the anxiety experienced, the impact on families, and ethical dilemmas confronted related to patient care. Positive findings also emerged, such as first responders' dedication to working through the pandemic, collegiality, and the community goodwill displayed.

Originality/value

While investigations of the impact of the COVID-19 pandemic on healthcare workers have been undertaken globally, studies focussing exclusively on the experiences of EMS first responders have been rare. This study addressed this knowledge gap, providing an insight into the challenges and successes experienced by first responders and identifying opportunities for learning that can be applied to future public health emergencies.