bluuebunny/crossref_metadata_2025 huggingface dataset:
Assessment of predictive probability models for effective mechanical design feature reuse
Authors: Vasantha Gokula , Purves David , Quigley John , Corney Jonathan , Sherlock Andrew , Randika Geevin
Published: May 2022

This research envisages an automated system to inform engineers when opportunities occur to use existing features or configurations during the development of new products. Such a system could be termed a "predictive CAD system" because it would be able to suggest feature choices that follow patterns established in existing products. The predictive CAD literature largely focuses on predicting components for assemblies using 3D solid models. In contrast, this research work focuses on feature-based predictive CAD system using B-rep models. This paper investigates the performance of predictive models that could enable the creation of such an intelligent CAD system by assessing three different methods to support inference: sequential, machine learning, or probabilistic methods using N-Grams, Neural Networks (NNs), and Bayesian Networks (BNs) as representative of these methods. After defining the functional properties that characterize a predictive design system, a generic development methodology is presented. The methodology is used to carry out a systematic assessment of the relative performance of three methods each used to predict the diameter value of the next hole and boss feature type being added during the design of a hydraulic valve body. Evaluating predictive performance providing five recommendations (

$k = 5$

) for hole or boss features as a new design was developed, recall@k increased from around 30% to 50% and precision@k from around 50% to 70% as one to three features were added. The results indicate that the BN and NN models perform better than those using N-Grams. The practical impact of this contribution is assessed using a prototype (implemented as an extension to a commercial CAD system) by engineers whose comments defined an agenda for ongoing research in this area.
Genetische Grundlagen der ADHS – ein Update
Authors: Hohmann Sarah , Häge Alexander , Millenet Sabina , Banaschewski Tobias
Published: May 2022

Zusammenfassung. Die Forschungsanstrengungen der letzten Jahre haben ergeben, dass genetische Risiken eine gewichtige Rolle in der Ätiologie der einfachen Aktivitäts- und Aufmerksamkeitsstörung (auch Aufmerksamkeitsdefizit-/Hyperaktivitätsstörung oder ADHS genannt) spielen. Ausgehend von den Ergebnissen von Familien- bzw. Zwillingsuntersuchungen, über die Ergebnisse von Kopplungs- und Assoziationsuntersuchungen bis hin zu den neueren Befunden von genomweiten Assoziationsstudien und der Suche nach seltenen Varianten oder epigenetischen Veränderungen möchten wir im Rahmen dieser Übersichtsarbeit exemplarisch den derzeitigen Stand der Kenntnisse im Zusammenhang mit den genetischen Grundlagen der ADHS zusammenfassen. Auch soll hier auf die Befunde zur Pleiotropie vor allem im Hinblick auf die bei ADHS häufig auftretenden psychiatrischen Komorbiditäten eingegangen werden.
TRIM47 is a novel endothelial activation factor that aggravates lipopolysaccharide-induced acute lung injury in mice via K63-linked ubiquitination of TRAF2
Authors: Qian Yisong , Wang Ziwei , Lin Hongru , Lei Tianhua , Zhou Zhou , Huang Weilu , Wu Xuehan , Zuo Li , Wu Jie , Liu Yu , Wang Ling-Fang , Guan Xiao-Hui , Deng Ke-Yu , Fu Mingui , Xin Hong-Bo
Published: May 2022

Endothelial activation plays an essential role in the pathogenesis of sepsis-induced acute lung injury, however, the detailed regulatory mechanisms remain largely unknown. Here, we reported that TRIM47, an E3 ubiquitin ligase of the tripartite motif-containing protein family, was highly expressed in vascular endothelial cells. TRIM47-deficient mice were effectively resistant to lipopolysaccharide (LPS)-induced acute lung injury and death by attenuating pulmonary inflammation. TRIM47 was upregulated during TNFα-induced endothelial activation in vitro. Knockdown of TRIM47 in endothelial cells inhibited the transcription of multiple pro-inflammatory cytokines, reduced monocyte adhesion and the expression of adhesion molecules, and suppressed the secretion of IL-1β and IL-6 in endothelial cells. By contrast, overexpression of TRIM47 promoted inflammatory response and monocyte adhesion upon TNFα stimulation. In addition, TRIM47 was able to activate the NF-κB and MAPK signaling pathways during endothelial activation. Furthermore, our experiments revealed that TRIM47 resulted in endothelial activation by promoting the K63-linked ubiquitination of TRAF2, a key component of the TNFα signaling pathway. Taken together, our studies demonstrated that TRIM47 as a novel activator of endothelial cells, promoted LPS-induced pulmonary inflammation and acute lung injury through potentiating the K63-linked ubiquitination of TRAF2, which in turn activates NF-κB and MAPK signaling pathways to trigger an inflammatory response in endothelial cells.
Identification of beneficial and detrimental bacteria impacting sorghum responses to drought using multi-scale and multi-system microbiome comparisons
Authors: Qi Mingsheng , Berry Jeffrey C , Veley Kira W , O’Connor Lily , Finkel Omri M , Salas-González Isai , Kuhs Molly , Jupe Julietta , Holcomb Emily , Glavina del Rio Tijana , Creech Cody , Liu Peng , Tringe Susannah G , Dangl Jeffery L , Schachtman Daniel P , Bart Rebecca S
Published: May 2022

Drought is a major abiotic stress limiting agricultural productivity. Previous field-level experiments have demonstrated that drought decreases microbiome diversity in the root and rhizosphere. How these changes ultimately affect plant health remains elusive. Toward this end, we combined reductionist, transitional and ecological approaches, applied to the staple cereal crop sorghum to identify key root-associated microbes that robustly affect drought-stressed plant phenotypes. Fifty-three Arabidopsis-associated bacteria were applied to sorghum seeds and their effect on root growth was monitored. Two Arthrobacter strains caused root growth inhibition (RGI) in Arabidopsis and sorghum. In the context of synthetic communities, Variovorax strains were able to protect plants from Arthrobacter-caused RGI. As a transitional system, high-throughput phenotyping was used to test the synthetic communities. During drought stress, plants colonized by Arthrobacter had reduced growth and leaf water content. Plants colonized by both Arthrobacter and Variovorax performed as well or better than control plants. In parallel, we performed a field trial wherein sorghum was evaluated across drought conditions. By incorporating data on soil properties into the microbiome analysis, we accounted for experimental noise with a novel method and were able to observe the negative correlation between the abundance of Arthrobacter and plant growth. Having validated this approach, we cross-referenced datasets from the high-throughput phenotyping and field experiments and report a list of bacteria with high confidence that positively associated with plant growth under drought stress. In conclusion, a three-tiered experimental system successfully spanned the lab-to-field gap and identified beneficial and deleterious bacterial strains for sorghum under drought.
Multi-omics signatures of alcohol use disorder in the dorsal and ventral striatum
Authors: Zillich Lea , Poisel Eric , Frank Josef , Foo Jerome C. , Friske Marion M. , Streit Fabian , Sirignano Lea , Heilmann-Heimbach Stefanie , Heimbach André , Hoffmann Per , Degenhardt Franziska , Hansson Anita C. , Bakalkin Georgy , Nöthen Markus M. , Rietschel Marcella , Spanagel Rainer , Witt Stephanie H.
Published: May 2022

Alcohol Use Disorder (AUD) is a major contributor to global mortality and morbidity. Postmortem human brain tissue enables the investigation of molecular mechanisms of AUD in the neurocircuitry of addiction. We aimed to identify differentially expressed (DE) genes in the ventral and dorsal striatum between individuals with AUD and controls, and to integrate the results with findings from genome- and epigenome-wide association studies (GWAS/EWAS) to identify functionally relevant molecular mechanisms of AUD. DNA-methylation and gene expression (RNA-seq) data was generated from postmortem brain samples of 48 individuals with AUD and 51 controls from the ventral striatum (VS) and the dorsal striatal regions caudate nucleus (CN) and putamen (PUT). We identified DE genes using DESeq2, performed gene-set enrichment analysis (GSEA), and tested enrichment of DE genes in results of GWASs using MAGMA. Weighted correlation network analysis (WGCNA) was performed for DNA-methylation and gene expression data and gene overlap was tested. Differential gene expression was observed in the dorsal (FDR < 0.05), but not the ventral striatum of AUD cases. In the VS, DE genes at FDR < 0.25 were overrepresented in a recent GWAS of problematic alcohol use. TheARHGEF15gene was upregulated in all three brain regions. GSEA in CN and VS pointed towards cell-structure associated GO-terms and in PUT towards immune pathways. The WGCNA modules most strongly associated with AUD showed strong enrichment for immune response and inflammation pathways. Our integrated analysis of multi-omics data sets provides further evidence for the importance of immune- and inflammation-related processes in AUD.
The roles of osteoprotegerin in cancer, far beyond a bone player
Authors: Wang Yufei , Liu Yiyang , Huang Zhao , Chen Xiaoping , Zhang Bixiang
Published: May 2022

Osteoprotegerin (OPG), also known as tumor necrosis factor receptor superfamily member 11B (TNFRSF11B), is a member of the tumor necrosis factor (TNF) receptor superfamily. Characterized by its ability to bind to receptor activator of nuclear factor kappa B ligand (RANKL), OPG is critically involved in bone remodeling. Emerging evidence implies that OPG is far beyond a bone-specific modulator, and is involved in multiple physiological and pathological processes, such as immunoregulation, vascular function, and fibrosis. Notably, numerous preclinical and clinical studies have been conducted to assess the participation of OPG in tumorigenesis and cancer development. Mechanistic studies have demonstrated that OPG is involved in multiple hallmarks of cancer, including tumor survival, epithelial to mesenchymal transition (EMT), neo-angiogenesis, invasion, and metastasis. In this review, we systematically summarize the basis and advances of OPG from its molecular structure to translational applications. In addition to its role in bone homeostasis, the physiological and pathological impacts of OPG on human health and its function in cancer progression are reviewed, providing a comprehensive understanding of OPG. We aim to draw more attention to OPG in the field of cancer, and to propose it as a promising diagnostic or prognostic biomarker as well as potential therapeutic target for cancer.
BMP9 reduces age-related bone loss in mice by inhibiting osteoblast senescence through Smad1-Stat1-P21 axis
Authors: Xu Jing-zun , Zhou Yan-man , Zhang Lin-lin , Chen Xiao-jing , Yang Yu-ying , Zhang Deng , Zhu Ke-cheng , Kong Xiao-ke , Sun Li-hao , Tao Bei , Zhao Hong-yan , Liu Jian-min
Published: May 2022

Age-related osteoporosis is characterized by the accumulation of senescent osteoblastic cells in bone microenvironment and significantly reduced osteogenic differentiation. Clearing of the senescent cells is helpful to improve bone formation in aged mice. Bone morphogenetic protein 9 (BMP9), a multifunctional protein produced and secreted by liver, was reported to improve osteoporosis caused by estrogen withdrawal. However, the mechanism of BMP9 has not been fully elucidated, and its effect on senile osteoporosis has not been reported. This study reveals that BMP9 significantly increases bone mass and improves bone biomechanical properties in aged mice. Furthermore, BMP9 reduces expression of senescent genes in bone microenvironment, accompanied by decreased senescence-associated secretory phenotypes (SASPs) such as Ccl5, Mmp9, Hmgb1, Nfkb1, and Vcam1. In vitro, Bmp9 treatment inhibits osteoblast senescence through activating Smad1, which suppresses the transcriptional activity of Stat1, thereby inhibits P21 expression and SASPs production. Furthermore, inhibiting the Smad1 signal in vivo can reverse the inhibitory effect of BMP9 on Stat1 and downstream senescent genes, which eliminates the protection of BMP9 on age-related osteoporosis. These findings highlight the critical role of BMP9 on reducing age-related bone loss by inhibiting osteoblast senescence through Smad1-Stat1-P21 axis.
Therapeutic response in the HAWK and HARRIER trials using deep learning in retinal fluid volume and compartment analysis
Authors: Schmidt-Erfurth Ursula , Mulyukov Zufar , Gerendas Bianca S. , Reiter Gregor S. , Lorand Daniel , Weissgerber Georges , Bogunović Hrvoje
Published: May 2022

Objectives

To assess the therapeutic response to brolucizumab and aflibercept by deep learning/OCT-based analysis of macular fluid volumes in neovascular age-related macular degeneration.

Methods

In this post-hoc analysis of two phase III, randomised, multi-centre studies (HAWK/HARRIER), 1078 and 739 treatment-naive eyes receiving brolucizumab or aflibercept according to protocol-specified criteria in HAWK and HARRIER, respectively, were included. Macular fluid on 41,840 OCT scans was localised and quantified using a validated deep learning-based algorithm. Volumes of intraretinal fluid (IRF), subretinal fluid (SRF), pigment epithelial detachment (PED) for all central macular areas (1, 3 and 6 mm) in nanolitres (nL) and best corrected visual acuity (BCVA) change in ETDRS letters were associated using mixed models for repeated measures.

Results

Baseline IRF volumes decreased by >92% following the first intravitreal injection and consistently remained low during follow-up. Baseline SRF volumes decreased by >74% following the first injection, while PED volume resolved by 68–79% of its baseline volume. Resolution of SRF and PED was dependent on the substance and regimen used. Larger residual post-loading IRF, SRF and PED volumes were all independently associated with progressive vision loss during maintenance, where the differences in mean BCVA change between high and low fluid volume subgroups for IRF, SRF and PED were 3.4 letters (p < 0.0001), 1.7 letters (p < 0.001) and 2.5 letters (p < 0.0001), respectively.

Conclusions

Deep-learning methods allow an accurate assessment of substance and regimen efficacy. Irrespectively, all fluid compartments were found to be important markers of disease activity and were relevant for visual outcomes.
Calcium bursts allow rapid reorganization of EFhD2/Swip-1 cross-linked actin networks in epithelial wound closure
Authors: Lehne Franziska , Pokrant Thomas , Parbin Sabnam , Salinas Gabriela , Großhans Jörg , Rust Katja , Faix Jan , Bogdan Sven
Published: May 2022

Changes in cell morphology require the dynamic remodeling of the actin cytoskeleton. Calcium fluxes have been suggested as an important signal to rapidly relay information to the actin cytoskeleton, but the underlying mechanisms remain poorly understood. Here, we identify the EF-hand domain containing protein EFhD2/Swip-1 as a conserved lamellipodial protein strongly upregulated in Drosophila macrophages at the onset of metamorphosis when macrophage behavior shifts from quiescent to migratory state. Loss- and gain-of-function analysis confirm a critical function of EFhD2/Swip-1 in lamellipodial cell migration in fly and mouse melanoma cells. Contrary to previous assumptions, TIRF-analyses unambiguously demonstrate that EFhD2/Swip-1 proteins efficiently cross-link actin filaments in a calcium-dependent manner. Using a single-cell wounding model, we show that EFhD2/Swip-1 promotes wound closure in a calcium-dependent manner. Mechanistically, our data suggest that transient calcium bursts reduce EFhD2/Swip-1 cross-linking activity and thereby promote rapid reorganization of existing actin networks to drive epithelial wound closure.
Dandelion pappus morphing is actuated by radially patterned material swelling
Authors: Seale Madeleine , Kiss Annamaria , Bovio Simone , Viola Ignazio Maria , Mastropaolo Enrico , Boudaoud Arezki , Nakayama Naomi
Published: May 2022

Plants generate motion by absorbing and releasing water. Many Asteraceae plants, such as the dandelion, have a hairy pappus that can close depending on moisture levels to modify dispersal. Here we demonstrate the relationship between structure and function of the underlying hygroscopic actuator. By investigating the structure and properties of the actuator cell walls, we identify the mechanism by which the dandelion pappus closes. We developed a structural computational model that can capture observed pappus closing and used it to explore the critical design features. We find that the actuator relies on the radial arrangement of vascular bundles and surrounding tissues around a central cavity. This allows heterogeneous swelling in a radially symmetric manner to co-ordinate movements of the hairs attached at the upper flank. This actuator is a derivative of bilayer structures, which is radial and can synchronise the movement of a planar or lateral attachment. The simple, material-based mechanism presents a promising biomimetic potential in robotics and functional materials.
A FoxA2+ long-term stem cell population is necessary for growth plate cartilage regeneration after injury
Authors: Muruganandan Shanmugam , Pierce Rachel , Teguh Dian Astari , Perez Rocio Fuente , Bell Nicole , Nguyen Brandon , Hohl Katherine , Snyder Brian D. , Grinstaff Mark W. , Alberico Hannah , Woods Dori , Kong Yiwei , Sima Corneliu , Bhagat Sanket , Ho Kailing , Rosen Vicki , Gamer Laura , Ionescu Andreia M.
Published: May 2022

Longitudinal bone growth, achieved through endochondral ossification, is accomplished by a cartilaginous structure, the physis or growth plate, comprised of morphologically distinct zones related to chondrocyte function: resting, proliferating and hypertrophic zones. The resting zone is a stem cell-rich region that gives rise to the growth plate, and exhibits regenerative capabilities in response to injury. We discovered a FoxA2+group of long-term skeletal stem cells, situated at the top of resting zone, adjacent the secondary ossification center, distinct from the previously characterized PTHrP+ stem cells. Compared to PTHrP+ cells, FoxA2+ cells exhibit higher clonogenicity and longevity. FoxA2+ cells exhibit dual osteo-chondro-progenitor activity during early postnatal development (P0-P28) and chondrogenic potential beyond P28. When the growth plate is injured, FoxA2+ cells expand in response to trauma, and produce physeal cartilage for growth plate tissue regeneration.
Structure of the Arabidopsis guard cell anion channel SLAC1 suggests activation mechanism by phosphorylation
Authors: Li Yawen , Ding Yinan , Qu Lili , Li Xinru , Lai Qinxuan , Zhao Pingxia , Gao Yongxiang , Xiang Chengbin , Cang Chunlei , Liu Xin , Sun Linfeng
Published: May 2022

Stomata play a critical role in the regulation of gas exchange and photosynthesis in plants. Stomatal closure participates in multiple stress responses, and is regulated by a complex network including abscisic acid (ABA) signaling and ion-flux-induced turgor changes. The slow-type anion channel SLAC1 has been identified to be a central controller of stomatal closure and phosphoactivated by several kinases. Here, we report the structure of SLAC1 in Arabidopsis thaliana (AtSLAC1) in an inactivated, closed state. The cytosolic amino (N)-terminus and carboxyl (C)-terminus of AtSLAC1 are partially resolved and form a plug-like structure which packs against the transmembrane domain (TMD). Breaking the interactions between the cytosolic plug and transmembrane domain triggers channel activation. An inhibition-release model is proposed for SLAC1 activation by phosphorylation that the cytosolic plug dissociates from the transmembrane domain upon phosphorylation, and induces conformational changes to open the pore. These findings facilitate our understanding of the regulation of SLAC1 activity and stomatal aperture in plants.
Comprehensive characterization of pre- and post-treatment samples of breast cancer reveal potential mechanisms of chemotherapy resistance
Authors: Hoogstraat Marlous , Lips Esther H. , Mayayo-Peralta Isabel , Mulder Lennart , Kristel Petra , van der Heijden Ingrid , Annunziato Stefano , van Seijen Maartje , Nederlof Petra M. , Sonke Gabe S. , Zwart Wilbert , Wesseling Jelle , Wessels Lodewyk F. A.
Published: May 2022

When locally advanced breast cancer is treated with neoadjuvant chemotherapy, the recurrence risk is significantly higher if no complete pathologic response is achieved. Identification of the underlying resistance mechanisms is essential to select treatments with maximal efficacy and minimal toxicity. Here we employed gene expression profiles derived from 317 HER2-negative treatment-naïve breast cancer biopsies of patients who underwent neoadjuvant chemotherapy, deep whole exome, and RNA-sequencing profiles of 22 matched pre- and post-treatment tumors, and treatment outcome data to identify biomarkers of response and resistance mechanisms. Molecular profiling of treatment-naïve breast cancer samples revealed that expression levels of proliferation, immune response, and extracellular matrix (ECM) organization combined predict response to chemotherapy. Triple negative patients with high proliferation, high immune response and low ECM expression had a significantly better treatment response and survival benefit (HR 0.29, 95% CI 0.10–0.85;p = 0.02), while in ER+ patients the opposite was seen (HR 4.73, 95% CI 1.51–14.8;p = 0.008). The characterization of paired pre-and post-treatment samples revealed that aberrations of known cancer genes were either only present in the pre-treatment sample (CDKN1B) or in the post-treatment sample (TP53, APC, CTNNB1). Proliferation-associated genes were frequently down-regulated in post-treatment ER+ tumors, but not in triple negative tumors. Genes involved in ECM were upregulated in the majority of post-chemotherapy samples. Genomic and transcriptomic differences between pre- and post-chemotherapy samples are common and may reveal potential mechanisms of therapy resistance. Our results show a wide range of distinct, but related mechanisms, with a prominent role for proliferation- and ECM-related genes.
High-throughput discovery of fluoride-ion conductors via a decoupled, dynamic, and iterative (DDI) framework
Authors: Sundberg Jack D. , Druffel Daniel L. , McRae Lauren M. , Lanetti Matthew G. , Pawlik Jacob T. , Warren Scott C.
Published: May 2022

Fluoride–ion batteries are a promising alternative to lithium–ion batteries with higher theoretical capacities and working voltages, but they have experienced limited success due to the poor ionic conductivities of known electrolytes and electrodes. Here, we report a high-throughput computational screening of 9747 fluoride-containing materials in search of fluoride-ion conductors. Via a combination of empirical, lightweight DFT, and nudged elastic band (NEB) calculations, we identified >10 crystal systems with high fluoride mobility. We applied a search strategy where calculations are performed in any order (decoupled), computational resources are reassigned based on need (dynamic), and predictive models are repeatedly updated (iterative). Unlike hierarchical searches, our decoupled, dynamic, and iterative framework (DDI) began by calculating high-quality barrier heights for fluoride-ion mobility in a large and diverse group of materials. This high-quality dataset provided a benchmark against which a rapid calculation method could be refined. This accurate method was then used to measure the barrier heights for 6797 fluoride–ion pathways. The final dataset has allowed us to discover many fascinating, high-performance conductors and to derive the design rules that govern their performance. These materials will accelerate experimental research into fluoride–ion batteries, while the design rules will provide an improved foundation for understanding ionic conduction.
The rubber hand illusion in microgravity and water immersion
Authors: Bruno V. , Sarasso P. , Fossataro C. , Ronga I. , Neppi-Modona M. , Garbarini F.
Published: May 2022

Our body has evolved in terrestrial gravity and altered gravitational conditions may affect the sense of body ownership (SBO). By means of the rubber hand illusion (RHI), we investigated the SBO during water immersion and parabolic flights, where unconventional gravity is experienced. Our results show that unconventional gravity conditions remodulate the relative weights of visual, proprioceptive, and vestibular inputs favoring vision, thus inducing an increased RHI susceptibility.
The stress-vulnerability model on the path to schizophrenia: Interaction between BDNF methylation and schizotypy on the resting-state brain network
Authors: Park Hye Yoon , Bang Minji , Seo Eunchong , Koo Se Jun , Lee Eun , Lee Seung-Koo , An Suk Kyoon
Published: May 2022

The interplay between schizophrenia liability and environmental influences has been considered to be responsible for the development of schizophrenia. Recent neuroimaging studies have linked aberrant functional connectivity (FC) between the default-mode network (DMN) and the frontoparietal network (FPN) in the resting-state to the underlying neural mechanism of schizophrenia. By using schizotypy as the proxy for genetic-based liability to schizophrenia and methylation of brain-derived neurotrophic factor (BDNF) to represent environmental exposure, this study investigated the impact of the interaction between vulnerability and the environment on the neurobiological substrates of schizophrenia. Participants in this study included 101 healthy adults (HC) and 46 individuals with ultra-high risk for psychosis (UHR). All participants were tested at resting-state by functional magnetic resonance imaging, and group-independent component analysis was used to identify the DMN and the FPN. The Perceptual Aberration Scale (PAS) was used to evaluate the schizotypy level. The methylation status of BDNF was measured by pyrosequencing. For moderation analysis, the final sample consisted of 83 HC and 32 UHR individuals. UHR individuals showed reduced DMN-FPN network FC compared to healthy controls. PAS scores significantly moderated the relationship between the percentage of BDNF methylation and DMN-FPN network FC. The strength of the positive relationship between BDNF methylation and the network FC was reduced when the schizotypy level increased. These findings support the moderating role of schizotypy on the neurobiological mechanism of schizophrenia in conjunction with epigenetic changes.
Omicron infection enhances Delta antibody immunity in vaccinated persons
Authors: Khan Khadija , Karim Farina , Cele Sandile , Reedoy Kajal , San James Emmanuel , Lustig Gila , Tegally Houriiyah , Rosenberg Yuval , Bernstein Mallory , Jule Zesuliwe , Ganga Yashica , Ngcobo Nokuthula , Mazibuko Matilda , Mthabela Ntombifuthi , Mhlane Zoey , Mbatha Nikiwe , Miya Yoliswa , Giandhari Jennifer , Ramphal Yajna , Naidoo Taryn , Sivro Aida , Samsunder Natasha , Kharsany Ayesha B. M. , Amoako Daniel , Bhiman Jinal N. , Manickchund Nithendra , Abdool Karim Quarraisha , Magula Nombulelo , Abdool Karim Salim S. , Gray Glenda , Hanekom Willem , von Gottberg Anne ,   COMMIT-KZN Team, Harrichandparsad Rohen , Herbst Kobus , Jeena Prakash , Khoza Thandeka , Kløverpris Henrik , Leslie Alasdair , Madansein Rajhmun , Marakalala Mohlopheni , Moshabela Mosa , Naidoo Kogie , Ndhlovu Zaza , Ndung’u Thumbi , Nyamande Kennedy , Patel Vinod , Smit Theresa , Steyn Adrie , Wong Emily , Milo Ron , Gosnell Bernadett I. , Lessells Richard J. , Moore Penny L. , de Oliveira Tulio , Moosa Mahomed-Yunus S. , Sigal Alex
Published: May 2022

The extent to which Omicron infection1–9, with or without previous vaccination, elicits protection against the previously dominant Delta (B.1.617.2) variant is unclear. Here we measured the neutralization capacity against variants of severe acute respiratory syndrome coronavirus 2 in 39 individuals in South Africa infected with the Omicron sublineage BA.1 starting at a median of 6 (interquartile range 3–9) days post symptom onset and continuing until last follow-up sample available, a median of 23 (interquartile range 19–27) days post symptoms to allow BA.1-elicited neutralizing immunity time to develop. Fifteen participants were vaccinated with Pfizer's BNT162b2 or Johnson & Johnson's Ad26.CoV2.S and had BA.1 breakthrough infections, and 24 were unvaccinated. BA.1 neutralization increased from a geometric mean 50% focus reduction neutralization test titre of 42 at enrolment to 575 at the last follow-up time point (13.6-fold) in vaccinated participants and from 46 to 272 (6.0-fold) in unvaccinated participants. Delta virus neutralization also increased, from 192 to 1,091 (5.7-fold) in vaccinated participants and from 28 to 91 (3.0-fold) in unvaccinated participants. At the last time point, unvaccinated individuals infected with BA.1 had low absolute levels of neutralization for the non-BA.1 viruses and 2.2-fold lower BA.1 neutralization, 12.0-fold lower Delta neutralization, 9.6-fold lower Beta variant neutralization, 17.9-fold lower ancestral virus neutralization and 4.8-fold lower Omicron sublineage BA.2 neutralization relative to vaccinated individuals infected with BA.1. These results indicate that hybrid immunity formed by vaccination and Omicron BA.1 infection should be protective against Delta and other variants. By contrast, infection with Omicron BA.1 alone offers limited cross-protection despite moderate enhancement.
Multispectral pattern recognition measures change in drusen area in age-related macular degeneration with high congruency to expert graders
Authors: Nam Judy , Ly Angelica , Kalloniatis Michael , Nivison-Smith Lisa
Published: May 2022

Drusen are a hallmark lesion of age-related macular degeneration (AMD) and changes in their area and/or volume are strongly associated with disease progression. Assessment of longitudinal change in drusen size in clinical practice however is limited to a single commercial tool or manual inspection by clinicians. In this study we analysed change in drusen area in 33 eyes with intermediate AMD across two separate visits using a novel technique known as multispectral pattern recognition for en face retinal images from various imaging modalities (infrared (815 nm), fundus autofluorescence (488 nm) and green (532 nm) scanning laser ophthalmoscopy). We found 91% (30/33 eyes) agreement in the direction of drusen change for multispectral pattern recognition relative to expert graders who graded eyes as having drusen progression, regression or being stable. Multispectral pattern recognition showed 100% sensitivity (22/22 eyes) and 73% specificity (8/11 eyes). In comparison, we found only 70% (23/33 eyes) agreement in the direction of drusen change with a commercially available change analysis software, the Cirrus Advanced RPE Analysis relative to expert graders, with a sensitivity 64% (14/22 eyes) and specificity of 82% (9/11 eyes). Total drusen area or amount of change between visits had no significant effect on agreement. This suggests multispectral pattern recognition can quantify longitudinal change in drusen area from multimodal imaging with greater congruency to expert graders than a commercially available platform based on a single imaging modality. Considering the association of drusen area and disease progression, this method could aid clinical assessment and monitoring of AMD.
The association between anion gap and in-hospital mortality of post-cardiac arrest patients: a retrospective study
Authors: Chen Jun , Dai Chuxing , Yang Yang , Wang Yimin , Zeng Rui , Li Bo , Liu Qiang
Published: May 2022

We aimed to determine the association between anion gap and in-hospital mortality in post-cardiac arrest (CA) patients. Extracted the data of patients diagnosed with CA from MIMIC-IV database. Generalized additive model (GAM), Cox regression and Kaplan–Meier survival analysis were used to demonstrate the association between AG levels and in-hospital mortality. ROC curve analysis for assessing the discrimination of AG for predicting in-hospital mortality. Totally, 1724 eligible subjects were included in our study finally. 936 patients (551 males and 385 females) died in hospital, with the prevalence of in-hospital mortality was 54.3%. The result of the Kaplan–Meier analysis showed that the higher value of AG had significant lower survival possibility during the hospitalization compared with the lower-value of AG patients. In the crude Cox regression model, high-level of AG subjects was associated with significant higher HR compared with low-level of AG subjects. After adjusted the vital signs data, laboratory data, and treatment, high-level of AG (group Q3 and group Q4) were also associated with increased risk of in-hospital mortality compared with low-level of AG group, 1.52 (95% Cl 1.17–1.85; P < 0.001), 1.64 (95% Cl 1.21–2.08; P < 0.001), respectively. The ROC curve indicated that AG has acceptable discrimination for predicting in-hospital mortality. The AUC value was found to be 0.671 (95% CI 0.646–0.698). Higher AG levels was associated with poor prognosis in post-CA patients. AG is a predictor for predicting in-hospital mortality of CA, and could help refine risk stratification.
Optimization of IL-1RA structure to achieve a smaller protein with a higher affinity to its receptor
Authors: Nouri Barkestani Mahsa , Naserian Sina , Khoddam Fatemeh , Shamdani Sara , Bambai Bijan
Published: May 2022

Interleukine-1 family cytokines are key orchestrators of innate and adaptive immunity. In particular, up-regulation of IL-1R1 via its agonistic ligands consisting of IL-1β and IL-1α is implicated in a variety of human diseases, such as rheumatoid arthritis, psoriasis, type I diabetes, amyotrophic lateral sclerosis, and dry-eye disease. Until now, there are no small-molecule inhibitors of the IL-1R1 with increased antagonistic potency to be used for the treatment of peripheral inflammation. The objective of this study was to engineer a low-molecular-weight version of IL-1RA with increased affinity and enhanced antagonistic activity for potential therapeutic use. To develop a smaller protein–ligand with a better affinity to IL-1R, we used bioinformatics studies and in silico simulations to anticipate non-binding areas on IL-1RA. In this study, we have identified a 41aa (F57-F98) non-binding site of IL-1RA. Overall RMSF of the Truncated complex (1.5 nm) was lower than the Native complex (2 nm), which could prove higher stability of the Truncated complex. The free binding energy of the T-IL-1RA (− 1087.037 kJ/mol) was significantly lower than the IL-1RA (− 836.819 kJ/mol) which could demonstrate a higher binding affinity of the truncated ligand with its receptor as a result of new important interactions. These findings have demonstrated a higher binding affinity of the T-IL-1RA with its receptor than the native protein. These results should: have an impact on the development of new treatments that block IL-1 signaling, although more research is needed in vitro and in vivo.
Eye movement analysis of children’s attention for midline diastema
Authors: Cho Vanessa Y. , Hsiao Janet H. , Chan Antoni B. , Ngo Hien C. , King Nigel M. , Anthonappa Robert P.
Published: May 2022

No previous studies have investigated eye-movement patterns to show children’s information processing while viewing clinical images. Therefore, this study aimed to explore children and their educators’ perception of a midline diastema by applying eye-movement analysis using the hidden Markov models (EMHMM). A total of 155 children between 2.5 and 5.5 years of age and their educators (n = 34) viewed pictures with and without a midline diastema while Tobii Pro Nano eye-tracker followed their eye movements. Fixation data were analysed using data-driven, and fixed regions of interest (ROIs) approaches with EMHMM. Two different eye-movement patterns were identified: explorative pattern (76%), where the children’s ROIs were predominantly around the nose and mouth, and focused pattern (26%), where children’s ROIs were precise, locating on the teeth with and without a diastema, and fixations transited among the ROIs with similar frequencies. Females had a significantly higher eye-movement preference for without diastema image than males. Comparisons between the different age groups showed a statistically significant difference for overall entropies. The 3.6–4.5y age groups exhibited higher entropies, indicating lower eye-movement consistency. In addition, children and their educators exhibited two specific eye-movement patterns. Children in the explorative pattern saw the midline diastema more often while their educators focussed on the image without diastema. Thus, EMHMMs are valuable in analysing eye-movement patterns in children and adults.
The effects of modest drinking on life expectancy and mortality risks: a population-based cohort study
Authors: Liu Yen-Tze , Lee June Han , Tsai Min Kuang , Wei James Cheng-Chung , Wen Chi-Pang
Published: May 2022

Modest drinking has been repeatedly discussed in scientific papers as protective against certain diseases, such as cardiovascular diseases, but in most cases, alcohol worsens health conditions, especially when consumed at high risk levels. The complexity of the risk relationship between alcohol and health conditions has confused clinicians as to whether it should be recommended. The study aims to balance the risks and benefits of modest drinking. This retrospective cohort study of 430,016 adults recruited from a standard health-screening program since 1994, with 11,031 deaths identified as of 2008. Drinking distinguished “modest drinker” (no more than one drink a day) from “regular drinker”. Mortality risks including all-cause mortality and diseases-specific mortality with hazard ratio (HR) were calculated by adjusting for 15 confounders. Life table was used for life expectancy. Risk predictors were subjected to Cox proportional hazards regression analysis to identify significant predictors in multivariate models and life expectancy analysis. Nearly one out of 4 males (23%) was a modest drinker, who gained 0.94 year (95% CI 0.65–1.23 year) in life over non-drinker and had 8% reduction in adjusted all-cause mortality (HR 0.92, 95% CI 0.86–0.97). In contrast, regular drinkers had 43% increase in overall mortality (HR 1.43, CI 1.35–1.52) and shortened life by 6.9 years (95% CI 6.6–7.1 years). As most drinkers also smoked, 59% in modest and 75% in regular, the combined effect shortened life by 2.0 years (95% CI 1.6–2.4 years) in modest drinker and 10.3 years (95% CI 9.8–10.7 years) in regular drinker. Cancer were increased in modest drinkers for oral (HR 2.35, CI 1.38–4.01) and esophageal (HR 3.83, CI 1.90–7.73) cancer. The gain of one year by modest drinkers was erased by a two to fourfold increase in oral and esophageal cancer and that drinking beyond modest amount led to a large loss of life expectancy. Given that drinkers are prone to cross the line of drinking, clinicians should balance the risks and benefits of drinking, as well as the understanding of whether the patient is at risk for addiction.
Migraine abortive treatment in children and adolescents in Israel
Authors: Genizi Jacob , Lahoud Dana , Cohen Rony
Published: May 2022

Migraine headaches in children may cause attacks that require abortive treatment. This study evaluated the incidence and efficacy of medications used for relieving migraine headache attacks in the pediatric population in Israel. Children 6–18 years of age who were diagnosed in our pediatric neurology clinic as having migraine headaches were enrolled into the study. Children and their parents recorded the children response to abortive treatment during consecutive migraine attacks. Fifty children, with 116 migraine attacks, were included in the study (30 females; mean age 12; range 6–18). Forty-seven (94%) reported on abortive treatment on the first migraine attack, 43 (86%) on a second migraine attack and 26 (52%) on a third migraine attack. During the first recorded migraine attack, 41 children (87.5%) reported taking only one type of medication for each headache episode, mainly ibuprofen or acetaminophen; less than a quarter used dipyrone (metamizol). Overall the improvement rate after two hours was 65.4% ± 27 for ibuprofen, 59.8 ± 35.3 for acetaminophen and 50.9 ± 27.4 for dipyrone without statistical difference. However, in the first recorded headache episode, males had a significantly better response to acetaminophen, compared to ibuprofen (95% ± 28 vs 75 ± 20). In conclusion, Children with migraine in Israel mainly use a single medication for each headache episode. Ibuprofen is the most commonly used abortive treatment; however, acetaminophen was associated with a better response among some of our patients.
Preparation of bioplastic consisting of salmon milt DNA
Authors: Yamada Masanori , Kawamura Midori , Yamada Tetsuya
Published: May 2022

The microplastic that pollutes the ocean is a serious problem around the world. The bioplastic consisting of biopolymers which is degraded in nature, is one of the strategies to solve this problem. Although the bioplastics consisting of protein, polysaccharide, polylactic acid, etc., have been reported, which consist of DNA, one of the most important materials in the genetic process, have not been reported to the best of our knowledge. In addition, a large amount of DNA-containing materials, such as salmon milts, is discarded as industrial waste around the world. Therefore, we demonstrated the preparation of a bioplastic consisting of salmon milt DNA. The DNA plastic was prepared by the immersion of a DNA pellet in a formaldehyde (HCHO) solution and heating. As a result, the water-stable DNA plastics were obtained at the HCHO concentration of 20% or more. Particularly, the DNA plastic with a 25% HCHO treatment showed water-insoluble, thermally stable, and highly mechanical properties. These are due to the formation of a three-dimensional network via the crosslinking reaction between the DNA chains. In addition, since DNA in plastic possesses the double-stranded structure, these plastics effectively accumulated the DNA intercalator, such as ethidium bromide. Furthermore, the DNA plastics indicated a biodegradable property in a nuclease-containing aqueous solution and the biodegradable stability was able to be controlled by the HCHO concentration. Therefore, salmon milt DNA has shown the potential to be a biodegradable plastic.
Taphonomic history and trophic interactions of an ammonoid fauna from the Upper Triassic Polzberg palaeobiota
Authors: Lukeneder Alexander , Lukeneder Petra
Published: May 2022

The taphonomic mechanisms of a mono- to pauci-specific ammonoid fauna comprising 3565 specimens from the lower Carnian Polzberg Konservat-Lagerstätte near Lunz am See (Northern Calcareous Alps, Lower Austria) is described. The fossiliferous layers were deposited during the Julian 2 Ib (Austrotrachyceras austriacum Zone, Austrotrachyceras minor biohorizon). The deposits comprise abundant nektic ammonoids of the trachyceratid genus Austrotrachyceras. The bivalve Halobia, dominant among the invertebrates, is followed in abundance by the ammonoids Austrotrachyceras and Paratrachyceras, the coleoid Phragmoteuthis and frequent vertebrate actinopterygian fish. The monotonous ammonoid assemblage comprises abundant Austrotrachyceras, frequent Paratrachyceras, rare Carnites and Simonyceras. Recently collected ammonoids were sampled bed-by-bed and compared to extensive historical collections from the same localities. Bromalites (coprolites and regurgitalites) produced by large durophagous fish comprise ammonoid and fish masses and accompany the ammonoid-dominated Polzberg palaeobiota. The ammonoid fauna here presents a window into the nektic cephalopod world of the Upper Triassic assemblage and palaeoenvironment during the deposition of the fossiliferous layers. The frequent occurrence of the vertically oriented (external side horizontal to bedding plane) ammonoid shell fragments hint at a deposition after lethal fish or coleoid attacks. The Polzberg ammonoids were deposited under calm and dysoxic conditions in fine-laminated marlstones and shales of the lower Carnian Polzberg Sub-Basin within the Polzberg Konservat-Lagerstätte.
Dynamic penetration behaviors of single/multi-layer graphene using nanoprojectile under hypervelocity impact
Authors: Sun Weifu , Zhang Tao , Jiang Jun , Chen Pengwan
Published: May 2022

Single/multilayer graphene holds great promise in withstanding impact/penetration as ideal protective material. In this work, dynamic penetration behaviors of graphene has been explored using molecular dynamics simulations. The crashworthiness performance of graphene is contingent upon the number of layers and impact velocity. The variables including residual velocity and kinetic energy loss under different layers or different impact velocities have been monitored during the hypervelocity impact. Results show that there exists deviation from the continuum Recht–Ipson and Rosenberg–Dekel models, but these models tend to hold to reasonably predict the ballistic limit velocity of graphene with increasing layers. Besides, fractal theory has been introduced here and proven valid to quantitatively describe the fracture morphology. Furthermore, Forrestal–Warren rigid body model II still can well estimate the depth of penetration of multilayer graphene under a certain range of velocity impact. Finally, one modified model has been proposed to correlate the specific penetration energy with the number of layer and impact velocity.
The effects of dietary proline, β-alanine, and γ-aminobutyric acid (GABA) on the nest construction behavior in the Oriental hornet (Vespa orientalis)
Authors: Bouchebti Sofia , Bodner Levona , Bergman Maya , Magory Cohen Tali , Levin Eran
Published: May 2022

Adult wasps primary food resource is larval saliva. This liquid secretion consists mainly of amino acids and carbohydrates processed from the prey brought to the colony by the foragers. However, adults also regularly consume floral nectar. The nectar's most abundant proteinogenic amino acid is proline, and the two most abundant non-proteinogenic amino acids are β-alanine and GABA. These three amino acids are also common in larval saliva. Here, we study the effect of these dietary amino acids on the physiology and nest construction behavior of the Oriental hornet. Our results reveal their deleterious effects, especially at high concentrations: β-alanine and GABA consumption reduced the hornets' lifespan and completely inhibited their construction behavior; while proline induced a similar but more moderate effect. At low concentrations, these amino acids had no effect on hornet survival but did slow down the nest construction process. Using carbon isotopically labeled amino acids, we show that, unlike proline, β-alanine is stored in most body tissues (brain, muscles, and fat body), suggesting that it is rapidly metabolized after consumption. Our findings demonstrate how a single amino acid can impact the fitness of a nectarivore insect.