bluuebunny/crossref_metadata_2025 huggingface dataset:
Controlled acceleration of GeV electron beams in an all-optical plasma waveguide
Authors: Oubrerie Kosta , Leblanc Adrien , Kononenko Olena , Lahaye Ronan , Andriyash Igor A. , Gautier Julien , Goddet Jean-Philippe , Martelli Lorenzo , Tafzi Amar , Ta Phuoc Kim , Smartsev Slava , Thaury Cédric
Published: June 2022

Laser-plasma accelerators (LPAs) produce electric fields of the order of 100 GV m−1, more than 1000 times larger than those produced by radio-frequency accelerators. These uniquely strong fields make LPAs a promising path to generate electron beams beyond the TeV, an important goal in high-energy physics. Yet, large electric fields are of little benefit if they are not maintained over a long distance. It is therefore of the utmost importance to guide the ultra-intense laser pulse that drives the accelerator. Reaching very high energies is equally useless if the properties of the electron beam change completely from shot to shot, due to the intrinsic lack of stability of the injection process. State-of-the-art laser-plasma accelerators can already address guiding and control challenges separately by tweaking the plasma structures. However, the production of beams that are simultaneously high quality and high energy has yet to be demonstrated. This paper presents a novel experiment, coupling laser-plasma waveguides and controlled injection techniques, facilitating the reliable and efficient acceleration of high-quality electron beams up to 1.1 GeV, from a 50 TW-class laser.
Up and down the spectrum: upconversion nanocrystal and semiconductor material fused into a single nanocomposite
Authors: Gorris Hans H. , Farka Zdeněk
Published: June 2022

A nanocomposite consisting of a cubic EuSe semiconductor material grown on a hexagonal upconversion nanoparticle has overcome the crystal lattice mismatch that typically prevents the epitaxial growth of such heterogeneous nanocrystals. Eu3+ at the interface layer shows its characteristic red emission band both under UV excitation light due to energy transfer from the semiconductor and under NIR excitation light due to energy transfer after photon-upconversion. Data storage and security applications are suggested for this new nanocomposite.
Application of positron emission tomography in psychiatry—methodological developments and future directions
Authors: Cervenka Simon , Frick Andreas , Bodén Robert , Lubberink Mark
Published: June 2022

Mental disorders represent an increasing source of disability and high costs for societies globally. Molecular imaging techniques such as positron emission tomography (PET) represent powerful tools with the potential to advance knowledge regarding disease mechanisms, allowing the development of new treatment approaches. Thus far, most PET research on pathophysiology in psychiatric disorders has focused on the monoaminergic neurotransmission systems, and although a series of discoveries have been made, the results have not led to any material changes in clinical practice. We outline areas of methodological development that can address some of the important obstacles to fruitful progress. First, we point towards new radioligands and targets that can lead to the identification of processes upstream, or parallel to disturbances in monoaminergic systems. Second, we describe the development of new methods of PET data quantification and PET systems that may facilitate research in psychiatric populations. Third, we review the application of multimodal imaging that can link molecular imaging data to other aspects of brain function, thus deepening our understanding of disease processes. Fourth, we highlight the need to develop imaging study protocols to include longitudinal and interventional paradigms, as well as frameworks to assess dimensional symptoms such that the field can move beyond cross-sectional studies within current diagnostic boundaries. Particular effort should be paid to include also the most severely ill patients. Finally, we discuss the importance of harmonizing data collection and promoting data sharing to reach the desired sample sizes needed to fully capture the phenotype of psychiatric conditions.
Reconsidering the role of patriarchy in upholding female genital modifications: analysis of contemporary and pre-industrial societies
Authors: Gruenbaum Ellen , Earp Brian D. , Shweder Richard A.
Published: June 2022

According to the World Health Organization (WHO), customary female genital modification practices common in parts of Africa, South and Southeast Asia, and the Middle East are inherently patriarchal: they reflect deep-rooted inequality between the sexes characterized by male dominance and constitute an extreme form of discrimination against women. However, scholars have noted that while many societies have genital modification rites only for boys, with no equivalent rite for girls, the inverse does not hold. Rather, almost all societies that practice ritual female genital modification also practice ritual male genital modification, often for comparable reasons on children of similar ages, with the female rites led by women and the male rites led by men. In contrast, then, to the situation for boys in various cultures, girls are not singled out for genital modification on account of their sex or gender; nor do the social meanings of the female rites necessarily reflect a lower status. In some cases, the women’s rite serves to promote female within-sex bonding and network building—as the men’s rite typically does for males—thereby counterbalancing gendered asymmetries in political power and weakening male dominance in certain spheres. In such cases, and to that extent, the female rites can be described as counter-patriarchal. Selective efforts to discourage female genital modifications may thus inadvertently undermine women-centered communal networks while leaving male bonding rites intact. Scholars and activists should not rely on misleading generalizations from the WHO about the relationship between genital cutting and the social positioning of women as compared to men. To illustrate the complexity of this relationship, we compare patterns of practice across contemporary societies while also highlighting anthropological data regarding pre-industrial societies. Regarding the latter, we find no association between the presence of a female initiation rite and a key aspect of patriarchy as it is classically understood, namely, social endorsement of a gendered double-standard regarding premarital sexual activity. We situate this finding within the broader literature and discuss potential implications.
Cas9-induced large deletions and small indels are controlled in a convergent fashion
Authors: Kosicki Michael , Allen Felicity , Steward Frances , Tomberg Kärt , Pan Yangyang , Bradley Allan
Published: June 2022

Repair of Cas9-induced double-stranded breaks results primarily in formation of small insertions and deletions (indels), but can also cause potentially harmful large deletions. While mechanisms leading to the creation of small indels are relatively well understood, very little is known about the origins of large deletions. Using a library of clonal NGS-validated mouse embryonic stem cells deficient for 32 DNA repair genes, we have shown that large deletion frequency increases in cells impaired for non-homologous end joining and decreases in cells deficient for the central resection gene Nbn and the microhomology-mediated end joining gene Polq. Across deficient clones, increase in large deletion frequency was closely correlated with the increase in the extent of microhomology and the size of small indels, implying a continuity of repair processes across different genomic scales. Furthermore, by targeting diverse genomic sites, we identified examples of repair processes that were highly locus-specific, discovering a role for exonuclease Trex1. Finally, we present evidence that indel sizes increase with the overall efficiency of Cas9 mutagenesis. These findings may have impact on both basic research and clinical use of CRISPR-Cas9, in particular in conjunction with repair pathway modulation.
An index of access to essential infrastructure to identify where physical distancing is impossible
Authors: Günther Isabel , Harttgen Kenneth , Seiler Johannes , Utzinger Jürg
Published: June 2022

To identify areas at highest risk of infectious disease transmission in Africa, we develop a physical distancing index (PDI) based on the share of households without access to private toilets, water, space, transportation, and communication technology and weight it with population density. Our results highlight that in addition to improving health systems, countries across Africa, especially in the western part of Africa, need to address the lack of essential domestic infrastructure. Missing infrastructure prevents societies from limiting the spread of communicable diseases by undermining the effectiveness of governmental regulations on physical distancing. We also provide high-resolution risk maps that show which regions are most limited in protecting themselves. We find considerable spatial heterogeneity of the PDI within countries and show that it is highly correlated with detected COVID-19 cases. Governments could pay specific attention to these areas to target limited resources more precisely to prevent disease transmission.
Automated detection and segmentation of non-small cell lung cancer computed tomography images
Authors: Primakov Sergey P. , Ibrahim Abdalla , van Timmeren Janita E. , Wu Guangyao , Keek Simon A. , Beuque Manon , Granzier Renée W. Y. , Lavrova Elizaveta , Scrivener Madeleine , Sanduleanu Sebastian , Kayan Esma , Halilaj Iva , Lenaers Anouk , Wu Jianlin , Monshouwer René , Geets Xavier , Gietema Hester A. , Hendriks Lizza E. L. , Morin Olivier , Jochems Arthur , Woodruff Henry C. , Lambin Philippe
Published: June 2022

Detection and segmentation of abnormalities on medical images is highly important for patient management including diagnosis, radiotherapy, response evaluation, as well as for quantitative image research. We present a fully automated pipeline for the detection and volumetric segmentation of non-small cell lung cancer (NSCLC) developed and validated on 1328 thoracic CT scans from 8 institutions. Along with quantitative performance detailed by image slice thickness, tumor size, image interpretation difficulty, and tumor location, we report an in-silico prospective clinical trial, where we show that the proposed method is faster and more reproducible compared to the experts. Moreover, we demonstrate that on average, radiologists & radiation oncologists preferred automatic segmentations in 56% of the cases. Additionally, we evaluate the prognostic power of the automatic contours by applying RECIST criteria and measuring the tumor volumes. Segmentations by our method stratified patients into low and high survival groups with higher significance compared to those methods based on manual contours.
Tropical volcanism enhanced the East Asian summer monsoon during the last millennium
Authors: Liu Fei , Gao Chaochao , Chai Jing , Robock Alan , Wang Bin , Li Jinbao , Zhang Xu , Huang Gang , Dong Wenjie
Published: June 2022

Extreme East Asian summer monsoon (EASM) rainfall frequently induces floods that threaten millions of people, and has been generally attributed to internal climate variability. In contrast to the hydrological weakening theory of volcanic eruptions, here we present convergent empirical and modeling evidence for significant intensification of EASM rainfall in response to strong tropical volcanic eruptions. Our multi-proxy analyses show a significantly increased EASM in the first summer after tropical eruptions from 1470 AD to the present, and the more frequent occurrence of El Niños in the first boreal winter after eruptions is necessary for the enhanced EASM. Model simulation ensembles show that a volcano-induced El Niño and the associated stronger than non-volcanic El Niño warm pool air-sea interaction intensify EASM precipitation, overwhelming volcanic-induced moisture deficiency. This work sheds light on the intertwined relationship between external forcing and internal climate variability and potential flood disasters resulting from tropical volcanic eruptions.
A longitudinal multi-scanner multimodal human neuroimaging dataset
Authors: Hawco Colin , Dickie Erin W. , Herman Gabrielle , Turner Jessica A. , Argyelan Miklos , Malhotra Anil K. , Buchanan Robert W. , Voineskos Aristotle N.
Published: June 2022

Human neuroimaging has led to an overwhelming amount of research into brain function in healthy and clinical populations. However, a better appreciation of the limitations of small sample studies has led to an increased number of multi-site, multi-scanner protocols to understand human brain function. As part of a multi-site project examining social cognition in schizophrenia, a group of “travelling human phantoms” had structural T1, diffusion, and resting-state functional MRIs obtained annually at each of three sites. Scan protocols were carefully harmonized across sites prior to the study. Due to scanner upgrades at each site (all sites acquired PRISMA MRIs during the study) and one participant being replaced, the end result was 30 MRI scans across 4 people, 6 MRIs, and 4 years. This dataset includes multiple neuroimaging modalities and repeated scans across six MRIs. It can be used to evaluate differences across scanners, consistency of pipeline outputs, or test multi-scanner harmonization approaches.
Enhancing the REMBRANDT MRI collection with expert segmentation labels and quantitative radiomic features
Authors: Sayah Anousheh , Bencheqroun Camelia , Bhuvaneshwar Krithika , Belouali Anas , Bakas Spyridon , Sako Chiharu , Davatzikos Christos , Alaoui Adil , Madhavan Subha , Gusev Yuriy
Published: June 2022

Malignancy of the brain and CNS is unfortunately a common diagnosis. A large subset of these lesions tends to be high grade tumors which portend poor prognoses and low survival rates, and are estimated to be the tenth leading cause of death worldwide. The complex nature of the brain tissue environment in which these lesions arise offers a rich opportunity for translational research. Magnetic Resonance Imaging (MRI) can provide a comprehensive view of the abnormal regions in the brain, therefore, its applications in the translational brain cancer research is considered essential for the diagnosis and monitoring of disease. Recent years has seen rapid growth in the field of radiogenomics, especially in cancer, and scientists have been able to successfully integrate the quantitative data extracted from medical images (also known as radiomics) with genomics to answer new and clinically relevant questions. In this paper, we took raw MRI scans from the REMBRANDT data collection from public domain, and performed volumetric segmentation to identify subregions of the brain. Radiomic features were then extracted to represent the MRIs in a quantitative yet summarized format. This resulting dataset now enables further biomedical and integrative data analysis, and is being made public via the NeuroImaging Tools & Resources Collaboratory (NITRC) repository (https://www.nitrc.org/projects/rembrandt_brain/).
Genotypic and tissue-specific variation of Populus nigra transcriptome profiles in response to drought
Authors: Eckert Christian , Wildhagen Henning , Paulo Maria João , Scalabrin Simone , Ballauff Johannes , Schnabel Sabine K. , Vendramin Vera , Keurentjes Joost J. B. , Bogeat-Triboulot Marie-Béatrice , Taylor Gail , Polle Andrea
Published: June 2022

Climate change is one of the most important challenges for mankind in the far and near future. In this regard, sustainable production of woody crops on marginal land with low water availability is a major challenge to tackle. This dataset is part of an experiment, in which we exposed three genetically differentiated genotypes of Populus nigra originating from contrasting natural habitats to gradually increasing moderate drought. RNA sequencing was performed on fine roots, developing xylem and leaves of those three genotypes under control and moderate drought conditions in order to get a comprehensive dataset on the transcriptional changes at the whole plant level under water limiting conditions. This dataset has already provided insight in the transcriptional control of saccharification potential of the three Populus genotypes under drought conditions and we suggest that our data will be valuable for further in-depth analysis regarding candidate gene identification or, on a bigger scale, for meta-transcriptome analysis.
Rough backs: taxonomic value of epicuticular sculpturing in the genus Milnesium Doyère, 1840 (Tardigrada: Apochela)
Authors: Morek Witold , Wałach Karol , Michalczyk Łukasz
Published: June 2022

The phylum Tardigrada comprises ~ 1400 described species that inhabit a wide range of ecosystems throughout the globe. Tardigrades are generally considered taxonomically challenging due to a strongly limited number of taxonomically informative morphological traits and microscopic size. Of all tardigrade groups, the taxonomy of Milnesium Doyère, 1840 is particularly difficult because in comparison with most other eutardigrades, the genus lacks the taxonomically informative egg shell ornamentation and/or placoids in the muscle pharynx. Therefore, any new morphological traits that could be used in species delineation and identification are priceless. In this contribution, we review and evaluate taxonomic value of the dorsal cuticle morphology. Specifically, by means of experimental taxonomy, we demonstrate the first extreme case of ontogenetic variability in dorsal epicuticle sculpturing using a new species from Portugal, Milnesium decorumsp. nov. Furthermore, we verify the existence of dorsal gibbosities in Milnesium reticulatum Pilato, Binda, Lisi, 2002, the only species of the genus allegedly exhibiting these structures. Finally, we provide a diagnostic key to the Milnesium granulatum morphogroup.
A multicentre cross-sectional survey study on acute wound classification in the emergency department and its interobserver variability
Authors: van Gennip Lisanne , Haverkamp Frederike J. C. , Sir Özcan , Tan Edward C. T. H.
Published: June 2022

Annually, a vast number of patients visits the emergency department for acute wounds. Many wound classification systems exist, but often these were not originally designed for acute wounds. This study aimed to assess the most frequently used classifications for acute wounds in the Netherlands and the interobserver variability of the Gustilo Anderson wound classification (GAWC) and Red Cross wound classification (RCWC) in acute wounds. This multicentre cross-sectional survey study employed an online oral questionnaire. We contacted emergency physicians from eleven hospitals in the south-eastern part of the Netherlands and identified the currently applied classifications. Participants classified ten fictitious wounds by applying the GAWC and RCWC. Afterwards, they rated the user-friendliness of these classifications. We examined the interobserver variability of both classifications using a Fleiss’ kappa analysis, with a subdivision in RCWC grades and types representing wound severity and injured tissue structures. The study included twenty emergency physicians from eight hospitals. Fifty percent of the participants reported using a classification for acute wounds, mostly the GAWC. The interobserver variability of the GAWC (κ = 0.46; 95% CI 0.44–0.49) and RCWC grades (κ = 0.56; 95% CI 0.53–0.59) was moderate, and it was good for the RCWC types (κ = 0.69; 95% CI 0.66–0.73). Participants considered both classifications helpful for acute wound assessment when the emergency physician was less experienced, despite a moderate user-friendliness. The GAWC was only of additional value in wounds with fractures, whereas the RCWC’s additional value in acute wound assessment was independent of the presence of a fracture. Emergency physicians are reserved to use a classification for acute wound assessment. The interobserver variability of the GAWC and RCWC in acute wounds is promising, and both classifications are easy to apply. However, their user-friendliness is moderate. It is recommended to apply the GAWC to acute wounds with underlying fractures and the RCWC to major traumatic injuries. Awareness should be raised of existing wound classifications, specifically among less experienced healthcare professionals.
Radiomics-based machine learning models to distinguish between metastatic and healthy bone using lesion-center-based geometric regions of interest
Authors: Naseri Hossein , Skamene Sonia , Tolba Marwan , Faye Mame Daro , Ramia Paul , Khriguian Julia , Patrick Haley , Andrade Hernandez Aixa X. , David Marc , Kildea John
Published: June 2022

Radiomics-based machine learning classifiers have shown potential for detecting bone metastases (BM) and for evaluating BM response to radiotherapy (RT). However, current radiomics models require large datasets of images with expert-segmented 3D regions of interest (ROIs). Full ROI segmentation is time consuming and oncologists often outline just RT treatment fields in clinical practice. This presents a challenge for real-world radiomics research. As such, a method that simplifies BM identification but does not compromise the power of radiomics is needed. The objective of this study was to investigate the feasibility of radiomics models for BM detection using lesion-center-based geometric ROIs. The planning-CT images of 170 patients with non-metastatic lung cancer and 189 patients with spinal BM were used. The point locations of 631 BM and 674 healthy bone (HB) regions were identified by experts. ROIs with various geometric shapes were centered and automatically delineated on the identified locations, and 107 radiomics features were extracted. Various feature selection methods and machine learning classifiers were evaluated. Our point-based radiomics pipeline was successful in differentiating BM from HB. Lesion-center-based segmentation approach greatly simplifies the process of preparing images for use in radiomics studies and avoids the bottleneck of full ROI segmentation.
Youth with Down syndrome display widespread increased functional connectivity during rest
Authors: Csumitta Kelsey D. , Gotts Stephen J. , Clasen Liv S. , Martin Alex , Raitano Lee Nancy
Published: June 2022

Studies of resting-state functional connectivity in young people with Down syndrome (DS) have yielded conflicting results. Some studies have found increased connectivity while others have found a mix of increased and decreased connectivity. No studies have examined whole-brain connectivity at the voxel level in youth with DS during an eyes-open resting-state design. Additionally, no studies have examined the relationship between connectivity and network selectivity in youth with DS. Thus, the current study sought to fill this gap in the literature. Nineteen youth with DS (Mage = 16.5; range 7–23; 13 F) and 33 typically developing (TD) youth (Mage = 17.5; range 6–24; 18 F), matched on age and sex, completed a 5.25-min eyes-open resting-state fMRI scan. Whole-brain functional connectivity (average Pearson correlation of each voxel with every other voxel) was calculated for each individual and compared between groups. Network selectivity was then calculated and correlated with functional connectivity for the DS group. Results revealed that whole-brain functional connectivity was significantly higher in youth with DS compared to TD controls in widespread regions throughout the brain. Additionally, participants with DS had significantly reduced network selectivity compared to TD peers, and selectivity was significantly related to connectivity in all participants. Exploratory behavioral analyses revealed that regions showing increased connectivity in DS predicted Verbal IQ, suggesting differences in connectivity may be related to verbal abilities. These results indicate that network organization is disrupted in youth with DS such that disparate networks are overly connected and less selective, suggesting a potential target for clinical interventions.
Monitoring and imaging pH in biofilms utilizing a fluorescent polymeric nanosensor
Authors: Kromer Charlotte , Schwibbert Karin , Gadicherla Ashish K. , Thiele Dorothea , Nirmalananthan-Budau Nithiya , Laux Peter , Resch-Genger Ute , Luch Andreas , Tschiche Harald R.
Published: June 2022

Biofilms are ubiquitous in nature and in the man-made environment. Given their harmful effects on human health, an in-depth understanding of biofilms and the monitoring of their formation and growth are important. Particularly relevant for many metabolic processes and survival strategies of biofilms is their extracellular pH. However, most conventional techniques are not suited for minimally invasive pH measurements of living biofilms. Here, a fluorescent nanosensor is presented for ratiometric measurements of pH in biofilms in the range of pH 4.5–9.5 using confocal laser scanning microscopy. The nanosensor consists of biocompatible polystyrene nanoparticles loaded with pH-inert dye Nile Red and is surface functionalized with a pH-responsive fluorescein dye. Its performance was validated by fluorometrically monitoring the time-dependent changes in pH in E. coli biofilms after glucose inoculation at 37 °C and 4 °C. This revealed a temperature-dependent decrease in pH over a 4-h period caused by the acidifying glucose metabolism of E. coli. These studies demonstrate the applicability of this nanosensor to characterize the chemical microenvironment in biofilms with fluorescence methods.
Identification of neuropeptides and neuropeptide receptor genes in Phauda flammans (Walker)
Authors: Wu Hai-Pan , Wang Xiao-Yun , Hu Jin , Su Ran-Ran , Lu Wen , Zheng Xia-Lin
Published: June 2022

Neuropeptides and neuropeptide receptors are crucial regulators to insect physiological processes. The 21.0 Gb bases were obtained from Illumina sequencing of two libraries representing the female and male heads of Phauda flammans (Walker) (Lepidoptera: Phaudidae), which is a diurnal defoliator of ficus plants and usually outbreaks in the south and south-east Asia, to identify differentially expressed genes, neuropeptides and neuropeptide receptor whose tissue expressions were also evaluated. In total, 99,386 unigenes were obtained, in which 156 up-regulated and 61 down-regulated genes were detected. Fifteen neuropeptides (i.e., F1b, Ast, NP1, IMF, Y, BbA1, CAP2b, NPLP1, SIF, CCH2, NP28, NP3, PDP3, ARF2 and SNPF) and 66 neuropeptide receptor genes (e.g., A2-1, FRL2, A32-1, A32-2, FRL3, etc.) were identified and well-clustered with other lepidopteron. This is the first sequencing, identification neuropeptides and neuropeptide receptor genes from P. flammans which provides valuable information regarding the molecular basis of P. flammans.
Identification of metastatic primary cutaneous squamous cell carcinoma utilizing artificial intelligence analysis of whole slide images
Authors: Knuutila Jaakko S. , Riihilä Pilvi , Karlsson Antti , Tukiainen Mikko , Talve Lauri , Nissinen Liisa , Kähäri Veli-Matti
Published: June 2022

Cutaneous squamous cell carcinoma (cSCC) harbors metastatic potential and causes mortality. However, clinical assessment of metastasis risk is challenging. We approached this challenge by harnessing artificial intelligence (AI) algorithm to identify metastatic primary cSCCs. Residual neural network-architectures were trained with cross-validation to identify metastatic tumors on clinician annotated, hematoxylin and eosin-stained whole slide images representing primary non-metastatic and metastatic cSCCs (n = 104). Metastatic primary tumors were divided into two subgroups, which metastasize rapidly (≤ 180 days) (n = 22) or slowly (> 180 days) (n = 23) after primary tumor detection. Final model was able to predict whether primary tumor was non-metastatic or rapidly metastatic with slide-level area under the receiver operating characteristic curve (AUROC) of 0.747. Furthermore, risk factor (RF) model including prediction by AI, Clark’s level and tumor diameter provided higher AUROC (0.917) than other RF models and predicted high 5-year disease specific survival (DSS) for patients with cSCC with 0 or 1 RFs (100% and 95.7%) and poor DSS for patients with cSCCs with 2 or 3 RFs (41.7% and 40.0%). These results indicate, that AI recognizes unknown morphological features associated with metastasis and may provide added value to clinical assessment of metastasis risk and prognosis of primary cSCC.
Phytochemical profiling and anti-fibrotic activities of Plumbago indica L. and Plumbago auriculata Lam. in thioacetamide-induced liver fibrosis in rats
Authors: Selim Nabil Mohamed , Melk Mina Michael , Melek Farouk Rasmy , Saleh Dalia Osama , Sobeh Mansour , El-Hawary Seham S.
Published: June 2022

This study aimed at investigating the chemical composition and the hepatoprotective activities of Plumbago indica L. and P. auriculata Lam. LC–MS/MS analyses for the hydroalcoholic extracts of the aerial parts of the two Plumbago species allowed the tentative identification of thirty and twenty-five compounds from P. indica and P. auriculata, respectively. The biochemical and histopathological alterations associated with thioacetamide (TAA)-induced liver fibrosis in rats were evaluated in vivo where rats received the two extracts at three different dose levels (100, 200 and 400 mg/kg p.o, daily) for 15 consecutive days with induction of hepatotoxicity by TAA (200 mg/kg/day, i.p.) at 14th and 15th days. Results of the present study showed a significant restoration in liver function biomarkers viz. alanine transaminase (ALT), aspartate transaminase (AST), gamma glutamyl transferase and total bilirubin. The liver homogenates exhibited increased levels of antioxidant biomarkers: reduced glutathione (GSH) and catalase (CAT), accompanied with decline in malondialdehyde (MDA). Furthermore, treated groups exhibited a significant suppression in liver inflammatory cytokines: tumor necrosis factor-α (TNF-α) and interlukin-6 (IL-6), and fibrotic biomarker: alpha smooth muscle relaxant. Histopathological examination of the liver showed normality of hepatocytes. Noteworthy, P. indica extract showed better hepatoprotective activity than P. auriculata, particularly at 200 mg/kg. To sum up, all these results indicated the hepatoprotective properties of both extracts, as well as their antifibrotic effect was evidenced by reduction in hepatic collagen deposition. However, additional experiments are required to isolate their individual secondary metabolites, assess the toxicity of the extracts and explore the involved mechanism of action.
Gut mucosa dissociation protocols influence cell type proportions and single-cell gene expression levels
Authors: Uniken Venema Werna T. C. , Ramírez-Sánchez Aarón D. , Bigaeva Emilia , Withoff Sebo , Jonkers Iris , McIntyre Rebecca E. , Ghouraba Mennatallah , Raine Tim , Weersma Rinse K. , Franke Lude , Festen Eleonora A. M. , van der Wijst Monique G. P.
Published: June 2022

Single-cell RNA sequencing (scRNA-seq) has revolutionized the study of the cellular landscape of organs. Most single-cell protocols require fresh material, which limits sample size per experiment, and consequently, introduces batch effects. This is especially true for samples acquired through complex medical procedures, such as intestinal mucosal biopsies. Moreover, the tissue dissociation procedure required for obtaining single cells is a major source of noise; different dissociation procedures applied to different compartments of the tissue induce artificial gene expression differences between cell subsets. To overcome these challenges, we have developed a one-step dissociation protocol and demonstrated its use on cryopreserved gut mucosal biopsies. Using flow cytometry and scRNA-seq analysis, we compared this one-step dissociation protocol with the current gold standard, two-step collagenase digestion, and an adaptation of a recently published alternative, three-step cold-active Bacillus licheniformus protease digestion. Both cell viability and cell type composition were comparable between the one-step and two-step collagenase dissociation, with the former being more time-efficient. The cold protease digestion resulted in equal cell viability, but better preserves the epithelial cell types. Consequently, to analyze the rarer cell types, such as glial cells, larger total biopsy cell numbers are required as input material. The multi-step protocols affected cell types spanning multiple compartments differently. In summary, we show that cryopreserved gut mucosal biopsies can be used to overcome the logistical challenges and batch effects in large scRNA-seq studies. Furthermore, we demonstrate that using cryopreserved biopsies digested using a one-step collagenase protocol enables large-scale scRNA-seq, FACS, organoid generation and intraepithelial lymphocyte expansion.
Temporal perceptual learning distinguishes between empty and filled intervals
Authors: Li Luhe , Yotsumoto Yuko , Hayashi Masamichi J.
Published: June 2022

Temporal perceptual learning (TPL) refers to improved temporal performance as a result of training with sub-second intervals. Most studies on TPL have focused on empty intervals (i.e. intervals marked by two brief stimuli); however, scholars have suggested that filled intervals (i.e. intervals presented as continuous sensory inputs) might have different underlying mechanisms. Therefore, the current study aimed to test whether empty and filled intervals yield similar TPL performance and whether such learning effects could transfer mutually. To this end, we trained two groups of participants with empty and filled intervals of 200 ms for four days, respectively. We found that the empty-interval group clearly improved their timing performances after training, and such an effect transferred to filled intervals of 200 ms. By contrast, the filled-interval group had neither learning nor transfer effect. Our results further shed light on the distinct mechanisms between empty and filled intervals in time perception while simultaneously replicating the classical findings on TPL involving empty intervals.
Investigation of complex nonlinear dynamic behaviors observed in a simplified driveline system with multistage clutch dampers
Authors: Yoon Jong-Yun , Kim Byeongil
Published: June 2022

The results of the harmonic balance method (HBM) for a nonlinear system generally show nonlinear response curves with primary, super-, and sub-harmonic resonances. In addition, the stability conditions can be examined by employing Hill’s method. However, it is difficult to understand the practical dynamic behaviors with only their stability conditions, especially with respect to unstable regimes. Thus, the main goal of this study is to suggest mathematical and numerical approaches to determine the complex dynamic behaviors regarding the bifurcation characteristics. To analyze the bifurcation phenomena, the HBM is first implemented utilizing Hill’s method where various local unstable areas are found. Second, the bifurcation points are determined by tracking the stability variational locations on the arc-length continuation scheme. Then, their points are defined for various bifurcation types. Finally, the real parts of the eigenvalues are analyzed to examine the practical dynamic behaviors, specifically in the unstable regimes, which reflect the relevance of various bifurcation types on the real part of eigenvalues. The methods employed in this study successfully explain the basic ways to examine the bifurcation phenomena when the HBM is implemented. Thus, this study suggests fundamental method to understand the bifurcation phenomena using only the HBM with Hill’s method.
Application of mathematical statistics to shale gas-bearing property evaluation and main controlling factor analysis
Authors: Li Min , Pang Xiongqi , Xiong Liang , Hu Tao , Chen Di , Zhao Zhen , Hui Shasha
Published: June 2022

Gas-bearing property evaluation and main controlling factor analysis have remained a concern in shale gas research. The application of principal component analysis, an important mathematical statistical method, in gas-bearing property evaluation and main controlling factor analysis of the Longmaxi shale in the Weirong area, Sichuan Basin, was examined. The Longmaxi shale exhibits high heterogeneity, manifested in the organic matter abundance, mineral composition, and pore structure. Seven geological factors, including the temperature, pressure, TOC content, clay content, brittle mineral content, pore volume, and specific surface area (SSA), were selected in principal component analysis. Four principal components with geological significance, such as mineral composition, formation condition, pore structure, and organic matter abundance, were extracted through principal component analysis, and further constituted a comprehensive factor. Shale gas-bearing properties were evaluated according to the score of the comprehensive factor. The Longmaxi shale could be identified as exhibiting good, medium, and poor gas-bearing properties based on the comprehensive factor scores of these samples. According to each geological factor’s contribution to the comprehensive factor, combined with geological analysis, it could be considered that gas-bearing properties are primarily controlled by pore volume, SSA, and clay content, followed by TOC content, brittle mineral content, temperature and pressure.
Early childhood circumstances and educational wellbeing inequality among tribal and non-tribal children in India: evidence from a panel study
Authors: Rashmi Rashmi , Paul Ronak
Published: June 2022

Despite efforts towards bridging the education gap between tribal (Scheduled Tribe) and non-tribal (Non-Scheduled Tribe) children, contrasting poor-quality education questioned the tribal children’s educational wellbeing in India. Early childhood circumstances render a remarkable impact on the educational wellbeing of children in later years. This study examined the influence of early childhood circumstances (child, household and community characteristics) during 2005 on the educational wellbeing inequality (among India’s tribal and non-tribal children) during 2012 using the India Human Development Survey panel dataset of 8611 children. The Educational wellbeing score was obtained from reading, mathematical and writing test scores using Principal Component Factor Analysis. We performed the Blinder-Oaxaca decomposition of the educational wellbeing inequality among India’s tribal and non-tribal children. The ST children’s average educational wellbeing score (−0.41) was much lower than the Non-ST children (0.04). Findings from the Blinder-Oaxaca decomposition show that the household economic condition in children’s early ages contributed to 24% of educational wellbeing inequality among tribal and non-tribal children. Further, the education status of males and female adults and the sanitation condition of families considerably impacted educational wellbeing. The present study concludes that caste antagonism has not reduced with time. The missing focus on the minority groups resulted in a deteriorated educational wellbeing.
Heart age estimated using explainable advanced electrocardiography
Authors: Lindow Thomas , Palencia-Lamela Israel , Schlegel Todd T. , Ugander Martin
Published: June 2022

Electrocardiographic (ECG) Heart Age conveying cardiovascular risk has been estimated by both Bayesian and artificial intelligence approaches. We hypothesised that explainable measures from the 10-s 12-lead ECG could successfully predict Bayesian 5-min ECG Heart Age. Advanced analysis was performed on ECGs from healthy subjects and patients with cardiovascular risk or proven heart disease. Regression models were used to predict patients’ Bayesian 5-min ECG Heart Ages from their standard, resting 10-s 12-lead ECGs. The difference between 5-min and 10-s ECG Heart Ages were analyzed, as were the differences between 10-s ECG Heart Age and the chronological age (the Heart Age Gap). In total, 2,771 subjects were included (n = 1682 healthy volunteers, n = 305 with cardiovascular risk factors, n = 784 with cardiovascular disease). Overall, 10-s Heart Age showed strong agreement with the 5-min Heart Age (R2 = 0.94, p < 0.001, mean ± SD bias 0.0 ± 5.1 years). The Heart Age Gap was 0.0 ± 5.7 years in healthy individuals, 7.4 ± 7.3 years in subjects with cardiovascular risk factors (p < 0.001), and 14.3 ± 9.2 years in patients with cardiovascular disease (p < 0.001). Heart Age can be accurately estimated from a 10-s 12-lead ECG in a transparent and explainable fashion based on known ECG measures, without deep neural network-type artificial intelligence techniques. The Heart Age Gap increases markedly with cardiovascular risk and disease.
A clinical study of peripherally inserted central catheter-related venous thromboembolism in patients with hematological malignancies
Authors: Yue Jing , Zhang Ya , Xu Fang , Mi Ai , Zhou Qiaolin , Chen Bin , Shi Lin
Published: June 2022

This study aimed to explore the risk factors of peripherally inserted central catheter (PICC)-related venous thromboembolism (CRT) in patients with hematological malignancies and the predictive ability of the thrombotic risk assessment models (RAMs). The clinical data of the 117 eligible patients with hematological neoplasms at Mianyang Central Hospital with PICC from May 2018 to May 2020 were analyzed in this retrospective study. Thrombosis risk scores were calculated in patients with image-confirmed PICC-related thromboembolism. CRT occurred in 19 cases. Compared to the CRT-free group, the CRT group was older and showed higher body mass index (BMI), leukocyte count level, and the prevalence of diabetes mellitus. Multivariable logistic regression analysis showed that BMI (P = 0.03) was a significant risk factor for CRT. The area under the receiver operating characteristic curve for the Caprini scale (P = 0.01) was higher than that of the modified Wells scale (P = 0.94), the revised Geneva scale (P = 0.83), Padua scale (P = 0.59), and Michigan scale (P = 0.80). The sensitivity and specificity for the Caprini scale, Padua scale, modified Wells scale, the revised Geneva scale, and Michigan risk score were 63.3%/73.7%, 100%/0.00%, 95.9%/5.3%, 31.6%/73.7%, and 1.0%/99.0%, respectively. Caprini RAM had a better predictive ability for CRT in patients with hematological malignancies. Michigan risk score may not be better than Caprini RAM in this population.
Abdominal adipose tissue and liver fat imaging in very low birth weight adults born preterm: birth cohort with sibling-controls
Authors: Kuula Juho , Lundbom Jesper , Hakkarainen Antti , Hovi Petteri , Hauta-alus Helena , Kaseva Nina , Sandboge Samuel , Björkqvist Johan , Eriksson Johan , Pietiläinen Kirsi H. , Lundbom Nina , Kajantie Eero
Published: June 2022

Preterm birth at very low birth weight (VLBW, < 1500 g) is associated with an accumulation of cardiovascular and metabolic risk factors from childhood at least to middle age. Small-scale studies suggest that this could partly be explained by increased visceral or ectopic fat. We performed magnetic resonance imaging on 78 adults born preterm at VLBW in Finland between 1978 and 1990 and 72 term same-sex siblings as controls, with a mean age of 29 years. We collected T1-weighted images from the abdomen, and magnetic resonance spectra from the liver, subcutaneous abdominal adipose tissue, and tibia. The adipose tissue volumes of VLBW adults did not differ from their term siblings when adjusting for age, sex, and maternal and perinatal factors. The mean differences were as follows: subcutaneous − 0.48% (95% CI − 14.8%, 16.3%), visceral 7.96% (95% CI − 10.4%, 30.1%), and total abdominal fat quantity 1.05% (95% CI − 13.7%, 18.4%). Hepatic triglyceride content was also similar. VLBW individuals displayed less unsaturation in subcutaneous adipose tissue (− 4.74%, 95% CI − 9.2%, − 0.1%) but not in tibial bone marrow (1.68%, 95% CI − 1.86%, 5.35%). VLBW adults displayed similar adipose tissue volumes and hepatic triglyceride content as their term siblings. Previously reported differences could thus partly be due to genetic or environmental characteristics shared between siblings. The VLBW group displayed less unsaturation in subcutaneous abdominal adipose tissue, suggesting differences in its metabolic activity and energy storage.
Air pollution exposure disparities in US public housing developments
Authors: Chakraborty Jayajit , Collins Timothy W. , Grineski Sara E. , Aun Jacob J.
Published: June 2022

Fine particulate matter 2.5 microns or less in diameter (PM2.5) is widely recognized to be a major public health concern. While ethnic/racial minority and lower socioeconomic status individuals in the US experience higher PM2.5 exposure, previous research on social disparities in PM2.5 exposure has not examined residents of federally-assisted public housing developments (PHDs). Here we present the first national-scale analysis of the relationship between outdoor PM2.5 exposure and PHD residency in the US, as well as exposure disparities within the population of households residing in PHDs. We integrated data on average annual PM2.5 concentrations (2011–2015) with US Department of Housing and Urban Development data on PHDs (2015), and socio-demographic information from the 2011–2015 American Community Survey. Results from multivariable generalized estimating equations indicated that PHD locations, units, and residents are significantly overrepresented in neighborhoods with greater PM2.5 exposure, after accounting for clustering, urbanization, and other socio-demographic factors. Additionally, significantly higher percentages of Black, Hispanic, disabled, and extremely low-income households reside in PHDs with greater PM2.5 exposure. Findings represent an important starting point for future research and emphasize the urgent need to identify gaps in environmental, public health, and housing policies that contribute to disproportionate air pollution exposures among PHD residents.
Artificial intelligence for distinguishment of hammering sound in total hip arthroplasty
Authors: Homma Yasuhiro , Ito Shun , Zhuang Xu , Baba Tomonori , Fujibayashi Kazutoshi , Kaneko Kazuo , Nishiyama Yu , Ishijima Muneaki
Published: June 2022

Recent studies have focused on hammering sound analysis during insertion of the cementless stem to decrease complications in total hip arthroplasty. However, the nature of the hammering sound is complex to analyse and varies widely owing to numerous possible variables. Therefore, we performed a preliminary feasibility study that aimed to clarify the accuracy of a prediction model using a machine learning algorithm to identify the final rasping hammering sound recorded during surgery. The hammering sound data of 29 primary THA without complication were assessed. The following definitions were adopted. Undersized rasping: all undersized stem rasping before the rasping of the final stem size, Final size rasping: rasping of the final stem size, Positive example: hammering sound during final size rasping, Negative example A: hammering sound during minimum size stem rasping, Negative example B: hammering sound during all undersized rasping. Three datasets for binary classification were set. Finally, binary classification was analysed in six models for the three datasets. The median values of the ROC-AUC in models A–F among each dataset were dataset a: 0.79, 0.76, 0.83, 0.90, 0.91, and 0.90, dataset B: 0.61, 0.53, 0.67, 0.69, 0.71, and 0.72, dataset C: 0.60, 0.48, 0.57, 0.63, 0.67, and 0.63, respectively. Our study demonstrated that artificial intelligence using machine learning was able to distinguish the final rasping hammering sound from the previous hammering sound with a relatively high degree of accuracy. Future studies are warranted to establish a prediction model using hammering sound analysis with machine learning to prevent complications in THA.