bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mesenchymal stromal cell-derived septoclasts resorb cartilage during developmental ossification and fracture healing
Authors: Sivaraj Kishor K. , Majev Paul-Georg , Jeong Hyun-Woo , Dharmalingam Backialakshmi , Zeuschner Dagmar , Schröder Silke , Bixel M. Gabriele , Timmen Melanie , Stange Richard , Adams Ralf H. 
Published: January 2022

AbstractDevelopmental osteogenesis, physiological bone remodelling and fracture healing require removal of matrix and cellular debris. Osteoclasts generated by the fusion of circulating monocytes degrade bone, whereas the identity of the cells responsible for cartilage resorption is a long-standing and controversial question. Here we show that matrix degradation and chondrocyte phagocytosis are mediated by fatty acid binding protein 5-expressing cells representing septoclasts, which have a mesenchymal origin and are not derived from haematopoietic cells. The Notch ligand Delta-like 4, provided by endothelial cells, is necessary for septoclast specification and developmental bone growth. Consistent with the termination of growth, septoclasts disappear in adult and ageing bone, but re-emerge in association with growing vessels during fracture healing. We propose that cartilage degradation is mediated by rare, specialized cells distinct from osteoclasts. Our findings have implications for fracture healing, which is frequently impaired in aging humans.
Decisive role of water and protein dynamics in residence time of p38α MAP kinase inhibitors
Authors: Pantsar Tatu , Kaiser Philipp D. , Kudolo Mark , Forster Michael , Rothbauer Ulrich , Laufer Stefan A. 
Published: January 2022

AbstractTarget residence time plays a crucial role in the pharmacological activity of small molecule inhibitors. Little is known, however, about the underlying causes of inhibitor residence time at the molecular level, which complicates drug optimization processes. Here, we employ all-atom molecular dynamics simulations (~400 μs in total) to gain insight into the binding modes of two structurally similar p38α MAPK inhibitors (type I and type I½) with short and long residence times that otherwise show nearly identical inhibitory activities in the low nanomolar IC50range. Our results highlight the importance of protein conformational stability and solvent exposure, buried surface area of the ligand and binding site resolvation energy for residence time. These findings are further confirmed by simulations with a structurally diverse short residence time inhibitor SB203580. In summary, our data provide guidance in compound design when aiming for inhibitors with improved target residence time.
Multiphase flow detection with photonic crystals and deep learning
Authors: Feng Lang , Natu Stefan , Som de Cerff Edmonds Victoria , Valenza John J. 
Published: January 2022

AbstractMultiphase flows are ubiquitous in industrial settings. It is often necessary to characterize these fluid mixtures in support of process optimization. Unfortunately, existing commercial technologies often fail to provide frequent, accurate, and cost-efficient data necessary to enable process optimization. Here we show a new physics-based concept and testing with lab and field prototypes leveraging photonic crystals for real-time characterization of multiphase flows. In particular, low power (~1 mW) microwave transmission through photonic crystals filled with fluid mixtures may be interrogated by deep learning analysis techniques to provide a fast and accurate characterization of phase fraction and flow morphology. Moreover when these flow characteristics are known, the flow rate is accurately inferred from the differential pressure necessary for the flow to pass through the photonic crystal. This insight provides a basis to develop a unique class of inexpensive, accurate, and convenient techniques to characterize multiphase flows.
Memory B cell repertoire from triple vaccinees against diverse SARS-CoV-2 variants
Authors: Wang Kang , Jia Zijing , Bao Linilin , Wang Lei , Cao Lei , Chi Hang , Hu Yaling , Li Qianqian , Zhou Yunjiao , Jiang Yinan , Zhu Qianhui , Deng Yongqiang , Liu Pan , Wang Nan , Wang Lin , Liu Min , Li Yurong , Zhu Boling , Fan Kaiyue , Fu Wangjun , Yang Peng , Pei Xinran , Cui Zhen , Qin Lili , Ge Pingju , Wu Jiajing , Liu Shuo , Chen Yiding , Huang Weijin , Wang Qiao , Qin Cheng-Feng , Wang Youchun , Qin Chuan , Wang Xiangxi 
Published: January 2022

AbstractOmicron (B.1.1.529), the most heavily mutated SARS-CoV-2 variant so far, is highly resistant to neutralizing antibodies, raising concerns about the effectiveness of antibody therapies and vaccines1,2. Here we examined whether sera from individuals who received two or three doses of inactivated SARS-CoV-2 vaccine could neutralize authentic Omicron. The seroconversion rates of neutralizing antibodies were 3.3% (2 out of 60) and 95% (57 out of 60) for individuals who had received 2 and 3 doses of vaccine, respectively. For recipients of three vaccine doses, the geometric mean neutralization antibody titre for Omicron was 16.5-fold lower than for the ancestral virus (254). We isolated 323 human monoclonal antibodies derived from memory B cells in triple vaccinees, half of which recognized the receptor-binding domain, and showed that a subset (24 out of 163) potently neutralized all SARS-CoV-2 variants of concern, including Omicron. Therapeutic treatments with representative broadly neutralizing monoclonal antibodies were highly protective against infection of mice with SARS-CoV-2 Beta (B.1.351) and Omicron. Atomic structures of the Omicron spike protein in complex with three classes of antibodies that were active against all five variants of concern defined the binding and neutralizing determinants and revealed a key antibody escape site, G446S, that confers greater resistance to a class of antibodies that bind on the right shoulder of the receptor-binding domain by altering local conformation at the binding interface. Our results rationalize the use of three-dose immunization regimens and suggest that the fundamental epitopes revealed by these broadly ultrapotent antibodies are rational targets for a universal sarbecovirus vaccine.
Hypoxia-induced HIF1α activation regulates small extracellular vesicle release in human embryonic kidney cells
Authors: Muñiz-García Ana , Romero Montserrat , Falcόn-Perez Juan Manuel , Murray Patricia , Zorzano Antonio , Mora Silvia 
Published: January 2022

AbstractExtracellular vesicles (EVs) are membrane enclosures released by eukaryotic cells that carry bioactive molecules and serve to modulate biological responses in recipient cells. Both increased EV release and altered EV composition are associated with the development and progression of many pathologies including cancer. Hypoxia, a feature of rapidly growing solid tumours, increases the release of EVs. However, the molecular mechanisms remain unknown. The hypoxia inducible factors (HIFs) are transcription factors that act as major regulators of the cellular adaptations to hypoxia. Here, we investigated the requirement of HIF pathway activation for EV release in Human Embryonic Kidney Cells (HEK293). Time course experiments showed that EV release increased concomitantly with sustained HIF1α and HIF2α activation following the onset of hypoxia. shRNA mediated knock-down of HIF1α but not HIF2α abrogated the effect of hypoxia on EV release, suggesting HIF1α is involved in this process. However, stabilization of HIF proteins in normoxic conditions through: (i) heterologous expression of oxygen insensitive HIF1α or HIF2α mutants in normoxic cells or (ii) chemical inhibition of the prolyl hydroxylase 2 (PHD2) repressor protein, did not increase EV release, suggesting HIF activation alone is not sufficient for this process. Our findings suggest HIF1α plays an important role in the regulation of EV release during hypoxia in HEK293 cells, however other hypoxia triggered mechanisms likely contribute as stabilization of HIF1α alone in normoxia is not sufficient for EV release.
Representing living architecture through skeleton reconstruction from point clouds
Authors: Middleton Wilfrid , Shu Qiguan , Ludwig Ferdinand 
Published: January 2022

AbstractLiving architecture, changing in structure with annual growth, requires precise, regular characterisation. However, its geometric irregularity and topological complexity make documentation using traditional methods difficult and presents challenges in creating useful models for mechanical and physiological analyses. Two kinds of living architecture are examined: historic living root bridges grown in Meghalaya, India, and contemporary ‘Baubotanik’ structures designed and grown in Germany. These structures exhibit common features, in particular network-like structures of varying complexity that result from inosculations between shoots or roots. As an answer to this modelling challenge, we present the first extensive documentation of living architecture using photogrammetry and a subsequent skeleton extraction workflow that solves two problems related to the anastomoses and varying nearby elements specific to living architecture. Photogrammetry was used as a low cost method, supplying detailed point clouds of the structures’ visible surfaces. A workflow based on voxel-thinning (using deletion templates and adjusted p-simplicity criteria) provides efficient, accurate skeletons. A volume reconstruction method is derived from the thinning process. The workflow is assessed on seven characteristics beneficial in representing living architecture in comparison with alternative skeleton extraction methods. The resulting models are ready for use in analytical tools, necessary for functional, responsible design.
Radiation dose enhancement using gold nanoparticles with a diamond linear accelerator target: a multiple cell type analysis
Authors: Piccolo Olivia , Lincoln John D. , Melong Nicole , Orr Benno C. , Fernandez Nicholas R. , Borsavage Jennifer , Berman Jason N. , Robar James , Ha Michael N. 
Published: January 2022

AbstractRadiotherapy (RT) is an effective cancer treatment modality, but standard RT often causes collateral damage to nearby healthy tissues. To increase therapeutic ratio, radiosensitization via gold nanoparticles (GNPs) has been shown to be effective. One challenge is that megavoltage beams generated by clinical linear accelerators are poor initiators of the photoelectric effect. Previous computer models predicted that a diamond target beam (DTB) will yield 400% more low-energy photons, increasing the probability of interacting with GNPs to enhance the radiation dose by 7.7-fold in the GNP vicinity. After testing DTB radiation coupled with GNPs in multiple cell types, we demonstrate decreased head-and-neck cancer (HNC) cell viability in vitro and enhanced cell-killing in zebrafish xenografts compared to standard RT. HNC cell lines also displayed increased double-stranded DNA breaks with DTB irradiation in the presence of GNPs. This study presents preclinical responses to GNP-enhanced radiotherapy with the novel DTB, providing the first functional data to support the theoretical evidence for radiosensitization via GNPs in this context, and highlighting the potential of this approach to optimize the efficacy of RT in anatomically difficult-to-treat tumors.
Imaging through diffuse media using multi-mode vortex beams and deep learning
Authors: Balasubramaniam Ganesh M. , Biton Netanel , Arnon Shlomi 
Published: January 2022

AbstractOptical imaging through diffuse media is a challenging issue and has attracted applications in many fields such as biomedical imaging, non-destructive testing, and computer-assisted surgery. However, light interaction with diffuse media leads to multiple scattering of the photons in the angular and spatial domain, severely degrading the image reconstruction process. In this article, a novel method to image through diffuse media using multiple modes of vortex beams and a new deep learning network named “LGDiffNet” is derived. A proof-of-concept numerical simulation is conducted using this method, and the results are experimentally verified. In this technique, the multiple modes of Gaussian and Laguerre-Gaussian beams illuminate the displayed digits dataset number, and the beams are then propagated through the diffuser before being captured on the beam profiler. Furthermore, we investigated whether imaging through diffuse media using multiple modes of vortex beams instead of Gaussian beams improves the imaging system's imaging capability and enhances the network's reconstruction ability. Our results show that illuminating the diffuser using vortex beams and employing the “LGDiffNet” network provides enhanced image reconstruction compared to existing modalities. When employing vortex beams for image reconstruction, the best NPCC is − 0.9850. However, when using Gaussian beams for imaging acquisition, the best NPCC is − 0.9837. An enhancement of 0.62 dB, in terms of PSNR, is achieved using this method when a highly scattering diffuser of grit 220 and width 2 mm (7.11 times the mean free path) is used. No additional optimizations or reference beams were used in the imaging system, revealing the robustness of the “LGDiffNet” network and the adaptability of the imaging system for practical applications in medical imaging.
Effect of the substrate on the electrical transport and fluctuation processes in NbRe and NbReN ultrathin films for superconducting electronics applications
Authors: Barone C. , Cirillo C. , Carapella G. , Granata V. , Santoro D. , Attanasio C. , Pagano S. 
Published: January 2022

AbstractNbRe-based superconducting thin films recently received relevant interest in the field of low-temperature electronics. However, for these materials the electrical conduction mechanisms, in particular in the normal state, still need to be investigated in more detail. Here, NbRe and NbReN films of different thicknesses have been deposited on two different substrates, namely monocrystalline Si and $$\text {SiO}_2$$

SiO
2

buffered Si. The films were characterized by DC electrical transport measurements. Moreover, a connection with the charge carriers fluctuation processes has been made by analyzing the electrical noise generated in the normal state region. Despite the films morphology seems not to be affected by the substrate used, a lower noise level has been found for the ones grown on $$\text {SiO}_2$$

SiO
2

, in particular for NbReN. From this study it emerges that both NbRe and NbReN ultrathin films are of very good quality, as far as the low-temperature electrical noise and conduction are concerned, with noise levels competitive with NbN. These results may further support the proposal of using these materials in a nanowire form in the field of superconducting electronics.
Contribution of obesity and cardiometabolic risk factors in developing cardiovascular disease: a population-based cohort study
Authors: Bakhtiyari Mahmood , Kazemian Elham , Kabir Kourosh , Hadaegh Farzad , Aghajanian Sepehr , Mardi Parham , Ghahfarokhi Nooshin Taherzadeh , Ghanbari Ali , Mansournia Mohammad Ali , Azizi Freidoun 
Published: January 2022

AbstractThis study aims to assess the effects of central and general adiposity on development of cardiovascular diseases (CVDs) mediated by cardiometabolic risk factors and to analyze their degree of dependency for mediating their effects. To this end, data from the the Tehran Lipid and Glucose Study cohort with 6280 participants were included in this study. The hazard ratios were calculated using a 2-stage regression model in the context of a survival model. Systolic blood pressure (BP), total serum cholesterol, and fasting plasma glucose were designated as mediators. Assessing the interactions revealed that BP was the most important mediator for general ( (HRNIE: 1.11, 95% CI 1.17–1.24) and central obesity (CO) (HRNIE: 1.11, 95% CI 1.07–1.15) with 60% and 36% proportion of the effects mediated in the total population, respectively. The proportion of mediated risk for all three metabolic risk factors was 46% (95% CI 31–75%) for overweight, 66% (45–100%) for general obesity and 52% (39–87%) for central obesity. BP was the most important mediator for overweight and central obesity in men, comprising 29% and 36% of the risk, respectively. The proportion of the risk mediated through all three metabolic risk factors in women was 23% (95% CI 13–50%) for overweight, 36% (21–64%) for general obesity and 52% (39–87%) for central obesity. Based on the results of this study, cardiometabolic mediators have conciliated more than 60% of the adverse effects of high BMI on CVDs in men. Controlling the metabolic risk factors in women does not efficiently contribute to decreasing CVDs as effectively.
Identify potential prognostic indicators and tumor-infiltrating immune cells in pancreatic adenocarcinoma
Authors: Shi Ting , Gao Ge 
Published: January 2022

Abstract
Background: Pancreatic adenocarcinoma (PAAD) is a kind of highly malignant tumor and lacks early diagnosis method and effective treatment. Tumor microenvironment (TME) is of great importance for the occurrence and development of PAAD. Thus, a comprehensive overview of genes and tumor-infiltrating immune cells (TICs) related to TME dynamic changes conduce to develop novel therapeutic targets and prognostic indicators.
Methods: We used MAlignant Tumors using Expression data (ESTIMATE) algorithm to analyze the transcriptome RNA-seq data of 182 PAAD cases on The Cancer Genome Atlas (TCGA) platform. Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), protein–protein interaction (PPI) network, COX regression analysis and gene set enrichment analysis (GSEA) were carried out to get the hub genes related to the prognosis of PAAD patients. These core genes were validated in GEPIA. CXCL10 expression as a poor prognostic indicator was validated in GEO database. Finally, CIBERSORT algorithm was applied to understand the status of TICs.
Results: A total of 715 up-regulated differential expression genes (DEGs) and 57 down-regulated DEGs were found simultaneously in stromal and immune groups. These DEGs were mainly enriched in immune recognition, activation and response processes. CD4, CXCL12, CXCL10, CCL5 and CXCL9 were the top five core genes. Then, the validation of these genes showed that CD4, CXCL10, CXCL5, CXCL9 were up-regulated in PAAD. Among the core genes, CXCL10 had a negative correlation with the survival time of PAAD patients. CD8+ T cells, CD4+ T cells memory activated, macrophages M1 had positive correlation of CXCL10 expression, whereas regulatory T cells (Tregs), macrophages M0 and B cells memory had negative correlation.
Conclusion: We generated a series of genes related to TME with prognostic implications and TICs in PAAD, which have the potential to be novel immunotherapy targets and prognostic markers. The data showed that CXCL10 was favorable as a poor prognostic indicator in PAAD patients.
Anxiety and Depression Symptoms in Children and Adolescents Who Stutter: A Systematic Review and Meta-Analysis
Authors: Bernard Ria , Hofslundsengen Hilde , Frazier Norbury Courtenay 
Published: January 2022

Purpose:The purpose of this study was to investigate whether there are elevated symptoms of anxiety or depression in children and adolescents (aged 2–18 years) who stutter, and to identify potential moderators of increased symptom severity.Method:We conducted a preregistered systematic review of databases and gray literature; 13 articles met criteria for inclusion. A meta-analysis using robust variance estimation was conducted with 11 cohort studies comparing symptoms of anxiety in children and adolescents who do and do not stutter. Twenty-six effect sizes from 11 studies contributed to the summary effect size for anxiety symptoms (851 participants). Meta-analysis of depression outcomes was not possible due to the small number of studies.Results:The summary effect size indicates that children and adolescents who stutter present with increased anxiety symptoms (g= 0.42) compared with nonstuttering peers. There were insufficient studies to robustly analyze depression symptoms, and qualitative review is provided. No significant between-groups differences were reported in any of the depression studies.Conclusions:Preliminary evidence indicates elevated symptoms of anxiety in some children and adolescents who stutter relative to peers. There was a tendency toward higher depression scores in this population, although reported between-groups differences did not reach statistical significance. These findings require replication in larger, preferably longitudinal studies that consider factors that may moderate risk. Nevertheless, our findings highlight a need for careful monitoring of mental health and well-being in young people who stutter.Supplemental Materials:http://osf.io/5m6zv
The strong influence of management factors on coccidian infections in smallholder pig farms and the first molecular identification ofCystoisospora suisin Myanmar
Authors: Bawm Saw , Chel Hla Myet , Khaing Yadanar , Hmoon Myint Myint , Thein Su Su , Win Shwe Yee , Soe Nyein Chan , Thaw Yu Nandi , Hayashi Naoki , Win Mar Mar , Htun Lat Lat , Nonaka Nariaki , Katakura Ken , Nakao Ryo 
Published: January 2022

A cross-sectional study was conducted to investigate coccidian infection and associated factors in smallholder pigs, and to identifyCystoisosporaoocysts by PCR. A total of 500 pig faecal samples from 330 smallholder farms were collected in Nay Pyi Taw, Myanmar. The faecal flotation method was used to identifyEimeriaandCystoisosporaspecies, and oocyst counts per gram (OPG) of faeces were recorded. Oocysts were differentiated after sporulation. Oocyst DNA was subjected to ITS1-targetedCystoisospora-specific PCR. The overall coccidian oocyst detection rate by microscopic was 89.0% (445/500). Among the studied samples, 74.0% (370/500) and 70.6% (353/500), were found to be positive withEimeriaspp. andCystoisospora suisoocysts, respectively. The sequences ofC. suisdetected were 100% identical to those ofC. suisreported from Japan, and had 99.5% resemblance to sequences from Australia and China. Weaner pigs showed the significantly highest (p < 0.05) OPG when compared to other age groups. The highest intensity of coccidian infection (p < 0.05) was found in pigs fed local feed, pigs raised on earthen floors and pigs under poor hygienic conditions. Factors such as age, breed, feed type, and housing floors were found to be significantly associated with coccidian infection (p < 0.05). Age, as well as management factors including floor type, feed type, and hygiene practices on the farm, had a strong influence on the occurrence of coccidian infection in pigs. This is the first study in Myanmar on coccidian infection in pigs and molecular detection ofC. suis.