bluuebunny/crossref_metadata_2025 huggingface dataset:
VEGF dose controls the coupling of angiogenesis and osteogenesis in engineered bone
Authors: Grosso Andrea , Lunger Alexander , Burger Maximilian G. , Briquez Priscilla S. , Mai Francesca , Hubbell Jeffrey A. , Schaefer Dirk J. , Banfi Andrea , Di Maggio Nunzia
Published: March 2023

Vascular endothelial growth factor-A (VEGF) physiologically regulates both angiogenesis and osteogenesis, but its application in bone tissue engineering led to contradictory outcomes. A poorly understood aspect is how VEGF dose impacts the coordination between these two processes. Taking advantage of a unique and highly tunable platform, here we dissected the effects of VEGF dose over a 1,000-fold range in the context of tissue-engineered osteogenic grafts. We found that osteo-angiogenic coupling is exquisitely dependent on VEGF dose and that only a tightly defined dose range could stimulate both vascular invasion and osteogenic commitment of progenitors, with significant improvement in bone formation. Further, VEGF dose regulated Notch1 activation and the induction of a specific pro-osteogenic endothelial phenotype, independently of the promotion of vascular invasion. Therefore, in a therapeutic perspective, fine-tuning of VEGF dose in the signaling microenvironment is key to ensure physiological coupling of accelerated vascular invasion and improved bone formation.
Sex differences in brainstem structure volumes in patients with schizophrenia
Authors: Aoyama Shintaro , Okuda Hiroto , Furuzawa Natsu , Yoneda Hirokage , Fujikane Daisuke , Takai Kentaro , Kuramitsu Ayumi , Muto Yukimasa , Sugiyama Shunsuke , Shioiri Toshiki , Ohi Kazutaka
Published: March 2023

Patients with schizophrenia (SZ) display moderate reductions in brainstem volumes, including the midbrain, pons, superior cerebellar peduncle, and medulla oblongata. Here, we investigated alterations in brainstem volumes between SZ patients and healthy controls (HCs) stratified by sex. T1-weighted MRI brain scans were processed with FreeSurfer v6.0 in 156 SZ patients (61 males/95 females) and 205 HCs (133/72). Of the brainstem structures, pons volumes were significantly reduced, particularly in male SZ patients. The decreased pons volumes were correlated with lower levels of education but not duration of illness in male patients. These findings suggest that the reduction in pons volume in male patients might be occurred before or around the onset of the disorder.
Systems serology-based comparison of antibody effector functions induced by adjuvanted vaccines to guide vaccine design
Authors: Loos Carolin , Coccia Margherita , Didierlaurent Arnaud M. , Essaghir Ahmed , Fallon Jonathan K. , Lauffenburger Douglas , Luedemann Corinne , Michell Ashlin , van der Most Robbert , Zhu Alex Lee , Alter Galit , Burny Wivine
Published: March 2023

The mechanisms by which antibodies confer protection vary across vaccines, ranging from simple neutralization to functions requiring innate immune recruitment via Fc-dependent mechanisms. The role of adjuvants in shaping the maturation of antibody-effector functions remains under investigated. Using systems serology, we compared adjuvants in licensed vaccines (AS01B/AS01E/AS03/AS04/Alum) combined with a model antigen. Antigen-naive adults received two adjuvanted immunizations followed by late revaccination with fractional-dosed non-adjuvanted antigen (NCT00805389). A dichotomy in response quantities/qualities emerged post-dose 2 between AS01B/AS01E/AS03 and AS04/Alum, based on four features related to immunoglobulin titers or Fc-effector functions. AS01B/E and AS03 induced similar robust responses that were boosted upon revaccination, suggesting that memory B-cell programming by the adjuvanted vaccinations dictated responses post non-adjuvanted boost. AS04 and Alum induced weaker responses, that were dissimilar with enhanced functionalities for AS04. Distinct adjuvant classes can be leveraged to tune antibody-effector functions, where selective vaccine formulation using adjuvants with different immunological properties may direct antigen-specific antibody functions.
Hepatitis C virus E1 and modified E2 delivered from an mRNA vaccine induces protective immunity
Authors: Patra Tapas , Meyer Keith , Haga Yuki , Reagan Erin K. , Weissman Drew , Ray Ranjit
Published: March 2023

Hepatitis C virus (HCV) is characterized by a high number of chronic cases due to an impairment of protective innate and adaptive immune responses. Here, we examined the contribution of the individual ectodomains of E1, E2, or a modified E2 with reduced CD81 binding and an inserted N-linked glycosylation site in combination as vaccine antigen mRNA-lipid nanoparticles (LNPs). The induction of a protective immune response to surrogate recombinant vaccinia virus (VV) expressing homologous HCV glycoprotein(s) challenge infection in a BALB/c mouse model was observed. Vaccination with a mRNA-LNP expressing soluble E1 (sE1) significantly reduced vv/HCV titer in the mouse ovary. However, the addition of sE2 mRNA-LNP for immunization impaired the efficacy of the sE1 construct. Further analysis showed that Th1 related cytokine responses to the sE1 mRNA-LNP were significantly altered in the presence of sE2 following co-immunization. Evaluation of immunogenicity revealed that the use of modified sE2F442NYT nucleoside mRNA-LNP vaccine results in an improved cellular immune response, IgG2a isotype switching, enhanced total IgG, and an increase in the neutralizing antibody response against HCV pseudotype virus. HCV cross genotype specific reactivity to peptides representing conserved E2 specific linear epitopes were enhanced in modified E2 vaccinated animal sera. In the absence of a suitable immunocompetent small animal model for HCV infection, protection from surrogate HCV vaccinia challenge infection model was observed in the immunized mice as compared to sE1 alone or an unmodified sE2 mRNA-LNP vaccine. Inclusion of sE1 with modified sE2F442NYT as mRNA-LNP vaccine candidate appeared to be beneficial for protection.
Halloysite nanotubes for regulating thermodynamics and kinetics of polysulfone/poly (ethylene-co-vinyl alcohol) membranes with enhanced permeability
Authors: Kadanyo Sania , Matindi Christine N. , Gumbi Nozipho N. , Dlamini Derrick S. , Hu Yunxia , Cui Zhenyu , He Benqiao , Mamba Bhekie B. , Li Jianxin
Published: March 2023

Controlling membrane morphology is crucial to improving the mechanical strength (MS) and hydrophilicity of porous membranes. Here we report on the fabrication of mixed matrix membranes (MMMs) free of macrovoids via non-solvent-induced phase separation (NIPS). Hydrophilic Halloysite nanotubes (HNTs) and poly (ethylene-co-vinyl alcohol) (EVOH) were mixed with Hydrophobic polysulfone (PSF) in the presence of polyethylene glycol (PEG) to fabricate MMMs. The results showed the formation of PSF/EVOH-MMMs with a spongy structure when the content of HNTs varied from 0.06- 0.12 wt.%, owing to the formation of strong hydrogen bonds between PSF, EVOH, PEG, and HNTs, confirmed by molecular dynamics (MD) simulations. The MS of MMMs with 0.12 wt.% HNTs was increased 2.2-fold (up to 6.22 MPa), while the contact angle (CA) was lowest at 47.42 ± 1.9°. In addition, the water permeability increased by a factor of 1.7 up to 419 L m−2 h−1 bar−1. The rejection rates of MMMs (M12) for oil and BSA were >90% and >95%, respectively. While the MMMs had > 90% flux recovery for both oil and BSA. We predict that this study will provide a method for controlling dope thermodynamics, formation dynamics, and morphology of MMMs while maintaining promising properties for improved separation performance.
Metal oxide single-component light-powered micromotors for photocatalytic degradation of nitroaromatic pollutants
Authors: Peng Xia , Urso Mario , Pumera Martin
Published: March 2023

Mass transfer is a key parameter in heterogeneous reactions. Micro/nanomachines, a promising technology for environmental applications, significantly enhance the performance of conventional purification treatments because of the active motion ability and thus enhanced diffusion (superdiffusion) of these photocatalysts, which in turn leads to dramatically improved mass transfer and higher degradation capability compared to stationary microparticles. However, the design of micromotors generally involves noble metals, for instance, Au and Pt, to achieve an effective autonomous motion. Considering the expensive fabrication cost and complicated steps, we present Pt-free single-component light-powered WO3 micromotors capable of enhanced diffusion and effective degradation of nitroaromatic compounds in water. These microswimmers, synthesized by a hydrothermal method, which is highly scalable at low cost, followed by calcination, exhibit fuel-free light-driven motion due to asymmetric light irradiation. Picric acid (PA) and 4-nitrophenol (4-NP) were selected as representative nitroaromatic contaminants and photocatalytically decomposed by WO3 micromotors thanks to the close contact with the micromotors promoted by their self-propulsion. This work provides a low-cost, sustainable, scalable method for enhancing mass transfer by creating moving catalysts with broad application potential for water cleanup.
A multi-organoid platform identifies CIART as a key factor for SARS-CoV-2 infection
Authors: Tang Xuming , Xue Dongxiang , Zhang Tuo , Nilsson-Payant Benjamin E. , Carrau Lucia , Duan Xiaohua , Gordillo Miriam , Tan Adrian Y. , Qiu Yunping , Xiang Jenny , Schwartz Robert E. , tenOever Benjamin R. , Evans Todd , Chen Shuibing
Published: March 2023

COVID-19 is a systemic disease involving multiple organs. We previously established a platform to derive organoids and cells from human pluripotent stem cells to model SARS-CoV-2 infection and perform drug screens1,2. This provided insight into cellular tropism and the host response, yet the molecular mechanisms regulating SARS-CoV-2 infection remain poorly defined. Here we systematically examined changes in transcript profiles caused by SARS-CoV-2 infection at different multiplicities of infection for lung airway organoids, lung alveolar organoids and cardiomyocytes, and identified several genes that are generally implicated in controlling SARS-CoV-2 infection, including CIART, the circadian-associated repressor of transcription. Lung airway organoids, lung alveolar organoids and cardiomyocytes derived from isogenic CIART−/− human pluripotent stem cells were significantly resistant to SARS-CoV-2 infection, independently of viral entry. Single-cell RNA-sequencing analysis further validated the decreased levels of SARS-CoV-2 infection in ciliated-like cells of lung airway organoids. CUT&RUN, ATAC-seq and RNA-sequencing analyses showed that CIART controls SARS-CoV-2 infection at least in part through the regulation of NR4A1, a gene also identified from the multi-organoid analysis. Finally, transcriptional profiling and pharmacological inhibition led to the discovery that the Retinoid X Receptor pathway regulates SARS-CoV-2 infection downstream of CIART and NR4A1. The multi-organoid platform identified the role of circadian-clock regulation in SARS-CoV-2 infection, which provides potential therapeutic targets for protection against COVID-19 across organ systems.
STING signalling is terminated through ESCRT-dependent microautophagy of vesicles originating from recycling endosomes
Authors: Kuchitsu Yoshihiko , Mukai Kojiro , Uematsu Rei , Takaada Yuki , Shinojima Ayumi , Shindo Ruri , Shoji Tsumugi , Hamano Shiori , Ogawa Emari , Sato Ryota , Miyake Kensuke , Kato Akihisa , Kawaguchi Yasushi , Nishitani-Isa Masahiko , Izawa Kazushi , Nishikomori Ryuta , Yasumi Takahiro , Suzuki Takehiro , Dohmae Naoshi , Uemura Takefumi , Barber Glen N. , Arai Hiroyuki , Waguri Satoshi , Taguchi Tomohiko
Published: March 2023

Stimulator of interferon genes (STING) is essential for the type I interferon response against a variety of DNA pathogens. Upon emergence of cytosolic DNA, STING translocates from the endoplasmic reticulum to the Golgi where STING activates the downstream kinase TBK1, then to lysosome through recycling endosomes (REs) for its degradation. Although the molecular machinery of STING activation is extensively studied and defined, the one underlying STING degradation and inactivation has not yet been fully elucidated. Here we show that STING is degraded by the endosomal sorting complexes required for transport (ESCRT)-driven microautophagy. Airyscan super-resolution microscopy and correlative light/electron microscopy suggest that STING-positive vesicles of an RE origin are directly encapsulated into Lamp1-positive compartments. Screening of mammalian Vps genes, the yeast homologues of which regulate Golgi-to-vacuole transport, shows that ESCRT proteins are essential for the STING encapsulation into Lamp1-positive compartments. Knockdown of Tsg101 and Vps4, components of ESCRT, results in the accumulation of STING vesicles in the cytosol, leading to the sustained type I interferon response. Knockdown of Tsg101 in human primary T cells leads to an increase the expression of interferon-stimulated genes. STING undergoes K63-linked ubiquitination at lysine 288 during its transit through the Golgi/REs, and this ubiquitination is required for STING degradation. Our results reveal a molecular mechanism that prevents hyperactivation of innate immune signalling, which operates at REs.
Structural resolution of a small organic molecule by serial X-ray free-electron laser and electron crystallography
Authors: Takaba Kiyofumi , Maki-Yonekura Saori , Inoue Ichiro , Tono Kensuke , Hamaguchi Tasuku , Kawakami Keisuke , Naitow Hisashi , Ishikawa Tetsuya , Yabashi Makina , Yonekura Koji
Published: March 2023

Structure analysis of small crystals is important in areas ranging from synthetic organic chemistry to pharmaceutical and material sciences, as many compounds do not yield large crystals. Here we present the detailed characterization of the structure of an organic molecule, rhodamine-6G, determined at a resolution of 0.82 Å by an X-ray free-electron laser (XFEL). Direct comparison of this structure with that obtained by electron crystallography from the same sample batch of microcrystals shows that both methods can accurately distinguish the position of some of the hydrogen atoms, depending on the type of chemical bond in which they are involved. Variations in the distances measured by XFEL and electron diffraction reflect the expected differences in X-ray and electron scatterings. The reliability for atomic coordinates was found to be better with XFEL, but the electron beam showed a higher sensitivity to charges.
Bipotent transitional liver progenitor cells contribute to liver regeneration
Authors: Pu Wenjuan , Zhu Huan , Zhang Mingjun , Pikiolek Monika , Ercan Caner , Li Jie , Huang Xiuzhen , Han Ximeng , Zhang Zhenqian , Lv Zan , Li Yan , Liu Kuo , He Lingjuan , Liu Xiuxiu , Heim Markus H. , Terracciano Luigi M. , Tchorz Jan S. , Zhou Bin
Published: March 2023

Following severe liver injury, when hepatocyte-mediated regeneration is impaired, biliary epithelial cells (BECs) can transdifferentiate into functional hepatocytes. However, the subset of BECs with such facultative tissue stem cell potential, as well as the mechanisms enabling transdifferentiation, remains elusive. Here we identify a transitional liver progenitor cell (TLPC), which originates from BECs and differentiates into hepatocytes during regeneration from severe liver injury. By applying a dual genetic lineage tracing approach, we specifically labeled TLPCs and found that they are bipotent, as they either differentiate into hepatocytes or re-adopt BEC fate. Mechanistically, Notch and Wnt/β-catenin signaling orchestrate BEC-to-TLPC and TLPC-to-hepatocyte conversions, respectively. Together, our study provides functional and mechanistic insights into transdifferentiation-assisted liver regeneration.
Loss of H3K9 trimethylation alters chromosome compaction and transcription factor retention during mitosis
Authors: Djeghloul Dounia , Dimond Andrew , Cheriyamkunnel Sherry , Kramer Holger , Patel Bhavik , Brown Karen , Montoya Alex , Whilding Chad , Wang Yi-Fang , Futschik Matthias E. , Veland Nicolas , Montavon Thomas , Jenuwein Thomas , Merkenschlager Matthias , Fisher Amanda G.
Published: March 2023

Recent studies have shown that repressive chromatin machinery, including DNA methyltransferases and polycomb repressor complexes, binds to chromosomes throughout mitosis and their depletion results in increased chromosome size. In the present study, we show that enzymes that catalyze H3K9 methylation, such as Suv39h1, Suv39h2, G9a and Glp, are also retained on mitotic chromosomes. Surprisingly, however, mutants lacking histone 3 lysine 9 trimethylation (H3K9me3) have unusually small and compact mitotic chromosomes associated with increased histone H3 phospho Ser10 (H3S10ph) and H3K27me3 levels. Chromosome size and centromere compaction in these mutants were rescued by providing exogenous first protein lysine methyltransferase Suv39h1 or inhibiting Ezh2 activity. Quantitative proteomic comparisons of native mitotic chromosomes isolated from wild-type versus Suv39h1/Suv39h2 double-null mouse embryonic stem cells revealed that H3K9me3 was essential for the efficient retention of bookmarking factors such as Esrrb. These results highlight an unexpected role for repressive heterochromatin domains in preserving transcription factor binding through mitosis and underscore the importance of H3K9me3 for sustaining chromosome architecture and epigenetic memory during cell division.
Comprehensive exploration of graphically defined reaction spaces
Authors: Zhao Qiyuan , Vaddadi Sai Mahit , Woulfe Michael , Ogunfowora Lawal A. , Garimella Sanjay S. , Isayev Olexandr , Savoie Brett M.
Published: March 2023

Existing reaction transition state (TS) databases are comparatively small and lack chemical diversity. Here, this data gap has been addressed using the concept of a graphically-defined model reaction to comprehensively characterize a reaction space associated with C, H, O, and N containing molecules with up to 10 heavy (non-hydrogen) atoms. The resulting dataset is composed of 176,992 organic reactions possessing at least one validated TS, activation energy, heat of reaction, reactant and product geometries, frequencies, and atom-mapping. For 33,032 reactions, more than one TS was discovered by conformational sampling, allowing conformational errors in TS prediction to be assessed. Data is supplied at the GFN2-xTB and B3LYP-D3/TZVP levels of theory. A subset of reactions were recalculated at the CCSD(T)-F12/cc-pVDZ-F12 and ωB97X-D2/def2-TZVP levels to establish relative errors. The resulting collection of reactions and properties are called the Reaction Graph Depth 1 (RGD1) dataset. RGD1 represents the largest and most chemically diverse TS dataset published to date and should find immediate use in developing novel machine learning models for predicting reaction properties.
A dataset of rodent cerebrovasculature from in vivo multiphoton fluorescence microscopy imaging
Authors: Poon Charissa , Teikari Petteri , Rachmadi Muhammad Febrian , Skibbe Henrik , Hynynen Kullervo
Published: March 2023

We present MiniVess, the first annotated dataset of rodent cerebrovasculature, acquired using two-photon fluorescence microscopy. MiniVess consists of 70 3D image volumes with segmented ground truths. Segmentations were created using traditional image processing operations, a U-Net, and manual proofreading. Code for image preprocessing steps and the U-Net are provided. Supervised machine learning methods have been widely used for automated image processing of biomedical images. While much emphasis has been placed on the development of new network architectures and loss functions, there has been an increased emphasis on the need for publicly available annotated, or segmented, datasets. Annotated datasets are necessary during model training and validation. In particular, datasets that are collected from different labs are necessary to test the generalizability of models. We hope this dataset will be helpful in testing the reliability of machine learning tools for analyzing biomedical images.
Improved chromosomal-level genome assembly and re-annotation of leopard coral grouper
Authors: Han Wentao , Wu Shaoxuan , Ding Hui , Wang Mingyi , Wang Mengya , Bao Zhenmin , Wang Bo , Hu Jingjie
Published: March 2023

Plectropomus leopardus, as known as leopard coral grouper, is a valuable marine fish that has gradually been bred artificially. To promote future conservation, molecular breeding, and comparative studies, we generated an improved high-quality chromosomal-level genome assembly of leopard coral grouper using Nanopore long-reads, Illumina short reads, and the Hi-C sequencing data. The draft genome is 849.74 Mb with 45 contigs and N50 of 35.59 Mb. Finally, a total of 846.49 Mb corresponding to 99.6% of the contig sequences was anchored to 24 pseudo-chromosomes using Hi-C technology. A final set of 25,965 genes is annotated after manual curation of the predicted gene models, and BUSCO analysis yielded a completeness score of 99.5%. This study significantly improves the utility of the grouper genome and provided a reference for the study of molecular breeding, genomics and biology in this species.
Individualized precision targeting of dorsal attention and default mode networks with rTMS in traumatic brain injury-associated depression
Authors: Siddiqi Shan H. , Kandala Sridhar , Hacker Carl D. , Trapp Nicholas T. , Leuthardt Eric C. , Carter Alexandre R. , Brody David L.
Published: March 2023

At the group level, antidepressant efficacy of rTMS targets is inversely related to their normative connectivity with subgenual anterior cingulate cortex (sgACC). Individualized connectivity may yield better targets, particularly in patients with neuropsychiatric disorders who may have aberrant connectivity. However, sgACC connectivity shows poor test–retest reliability at the individual level. Individualized resting-state network mapping (RSNM) can reliably map inter-individual variability in brain network organization. Thus, we sought to identify individualized RSNM-based rTMS targets that reliably target the sgACC connectivity profile. We used RSNM to identify network-based rTMS targets in 10 healthy controls and 13 individuals with traumatic brain injury-associated depression (TBI-D). These “RSNM targets” were compared with consensus structural targets and targets based on individualized anti-correlation with a group-mean-derived sgACC region (“sgACC-derived targets”). The TBI-D cohort was also randomized to receive active (n = 9) or sham (n = 4) rTMS to RSNM targets with 20 daily sessions of sequential high-frequency left-sided stimulation and low-frequency right-sided stimulation. We found that the group-mean sgACC connectivity profile was reliably estimated by individualized correlation with default mode network (DMN) and anti-correlation with dorsal attention network (DAN). Individualized RSNM targets were thus identified based on DAN anti-correlation and DMN correlation. These RSNM targets showed greater test–retest reliability than sgACC-derived targets. Counterintuitively, anti-correlation with the group-mean sgACC connectivity profile was also stronger and more reliable for RSNM-derived targets than for sgACC-derived targets. Improvement in depression after RSNM-targeted rTMS was predicted by target anti-correlation with the portions of sgACC. Active treatment also led to increased connectivity within and between the stimulation sites, the sgACC, and the DMN. Overall, these results suggest that RSNM may enable reliable individualized rTMS targeting, although further research is needed to determine whether this personalized approach can improve clinical outcomes.
Effects of UV-B radiation on epiphytic bacterial communities on male and female Sargassum thunbergii
Authors: Wang Jing , Yang Zhibo , Lu Peiyao , Sun Yan , Xue Song , Tang Xuexi , Xiao Hui
Published: March 2023

The effects of increased UV-B radiation on macroalgae have been widely studied, but knowledge concerning the response of communities of algal epiphytic bacteria to increased UV-B radiation and differences between male and female algae is still lacking. Via 16S rDNA high-throughput sequencing technology, changes in the epiphytic bacterial communities on male and female S. thunbergii under increased UV-B radiation were studied in the lab. Under different UV-B radiation intensities, although the α diversity and community composition of epiphytic bacteria changed little, the β diversity indicated that the community structure of bacteria on S. thunbergii was obviously clustered, and the relative abundance of dominant bacteria and indicator species changed considerably. There were unique bacteria in each experimental group, and the bacteria whose abundance obviously changed were members of groups related to environmental resistance or adaptability. The variation in the abundance of epiphytic bacteria was different in male and female S. thunbergii, and the bacteria whose abundance greatly changed were mainly related to algal growth and metabolism. The abundance of genes with predicted functions related to metabolism, genetic information processing, environmental adaptation and infectious diseases changed with increased UV-B radiation, and those variations differed between epiphytic bacteria on male and female S. thunbergii. This study found that the algal epiphytic bacteria were influenced by the increase in UV-B radiation and underwent certain adaptations through adjustments to community structure and function, and this response was also affected by the sex of the macroalgae. These results are expected to serve as experimental basis and provide reference for further understanding of the response of algae epiphytic bacteria to enhanced UV-B radiation caused by the thinning of the ozone layer and the resulting changes in the relationship between algae and bacteria, which may change the community of the marine ecosystem and affect important marine ecological process.
The effect of intravenous unit-dose tranexamic acid on visible and hidden blood loss in posterior lumbar interbody fusion: a randomized clinical trial
Authors: Hao Shenshen , Li Hongke , Liu Shuai , Meng Saike , Zhang Xiaopeng , Wang Linfei , Yang Hongjie , Zhang Liyan , Dong Shengli
Published: March 2023

There are few reports of intravenous unit-dose tranexamic acid (TXA) on the relationship between visible blood loss (VBL) and hidden blood loss (HBL) in posterior lumbar interbody fusion (PLIF). Therefore, the objective of this randomized, prospective, double-blind, single center study was to investigate the effect of intravenous unit-dose TXA on VBL and HBL in patients who underwent PLIF. Among 100 patients, 11 were excluded due to failue to comply with the study, 1 was excluded due to non-conpliance with the study, and 88 were eligible for inclusion in the study. 46 patients who treated with PLIF received unit-dose of TXA (1 g/100 mL) intravenously 15 min before skin incision after general anesthesia (observation group) and 42 patients were given 100 mL of normal saline (control group). The operation time, intraoperative blood loss, postoperative drainage, VBL, HBL, blood transfusion rate, and adverse events were recorded in the two groups. Besides, activated partial prothrombin time (APTT), prothrombin time (PT), thrombin time (TT), fibrinogen (FIB), platelets (PLT), red blood cells (RBC), hemoglobin (HB), hematocrit (HCT), C-reactive protein (CRP), erythrocyte sedimentation rate (ESR) on the 1st postoperative day; and RBC, HB, HCT, CRP, ESR on the 4th postoperative day were recorded. All 88 patients successfully completed the operation, the incision healed well, and there was no deep vein thrombosis of the lower extremity after operation. The intraoperative blood loss, postoperative drainage, VBL, HBL, and blood transfusion rate in the observation group were lower than those in the control group, and the differences were statistically significant (p < 0.05). There was no significant difference in operation time between the two groups (p > 0.05). There was no significant difference in postoperative APTT, PT, TT, FIB, PLT, RBC, HB, HCT, CRP and ESR between the two groups (p > 0.05). Intravenous unit-dose TXA is safe and feasible in PLIF, and it can effectively reduce perioperative VBL and HBL.
Research on SPDTRS-PNN based intelligent assistant diagnosis for breast cancer
Authors: Kong Xixi , Zhou Mengran , Bian Kai , Lai Wenhao , Hu Feng , Dai Rongying , Yan Jingjing
Published: March 2023

Breast cancer is the second dangerous cancer in the world. Breast cancer data often contains more redundant information. Redundant information makes the breast cancer auxiliary diagnosis less accurate and time consuming. Dimension reduction algorithm combined with machine learning can solve these problems well. This paper proposes the single parameter decision theoretic rough set (SPDTRS) combined with the probability neural network (PNN) model for breast cancer diagnosis. We find that when the parameter value of SPDTRS is 2.5 and the SPREAD value is 0.75, the number of 30 attributes of the original breast cancer data dropped to 12, the accuracy of the SPDTRS-PNN model training set is 99.25%, the accuracy of the test set is 97.04%, and the test time is 0.093 s. The experimental results show that the SPDTRS-PNN model can improve the ac-curacy of breast cancer recognition, reduce the time required for diagnosis.
Physical and mental health impact of the COVID-19 pandemic at first year in a Spanish adult cohort
Authors: Castellvi Obiols Pere , Miranda-Mendizabal Andrea , Recoder Silvia , Calbo Sebastian Ester , Casajuana-Closas Marc , Leiva David , Manolov Rumen , Matilla-Santander Nuria , Lloveras-Bernat Isaac , Forero Carlos G.
Published: March 2023

The COVID-19 pandemic and the political and health measures have profoundly affected the health of our populations. However, very few studies have been published assessing its impact using a prospective cohort. The aim of this study is to describe the impact on physical and mental health due to the COVID-19 pandemic in the general population in Spain, and according to COVID-19 clinical status, during the first year of the pandemic. A longitudinal cohort study with two online surveys were performed on a representative sample of the adult Spanish population before (N = 2005, October/November 2019) and during the pandemic (N = 1357, November/December 2020). We assessed disability using the World Health Organisation Disability Assessment Schedule (WHODAS), major depressive episode (MDE) and suicidal thoughts and behaviours (STB), using an adapted version of the Composite International Diagnostic Interview (CIDI 3.0); generalised anxiety disorder (GAD) using the GAD-7 scale; post-traumatic stress disorder (PTSD) symptoms using the PTSD checklist for DSM-5 (PCL-5). For physical health, there was a statistically significant loss of weight (mean/SD) (T0, 73.22/15.56 vs. T1, 71.21/11.94), less use of tobacco (T0, 11.4% vs. T1, 9.0%) and decreased disability (mean/SD) (T0, 21.52/9.22 vs. T1, 19.03/7.32). For mental health, there was a significant increase in MDE (T0, 6.5% vs. T1, 8.8%) and in the prevalence of GAD (T0, 13.7% vs. T1, 17.7%). The prevalence of STB (T0, 15.1% vs. T1, 7.1%) significantly decreased. Individuals who declared they had been diagnosed with COVID-19 (3.6%) showed a worsening in physical health and an increase in mental health problems and PTSD symptoms. Although suicide risk during the first year of the pandemic was significantly less, many suicide risk factors increased: such as the incidence and persistence of MDE and GAD, the presence of PTSD symptoms in those diagnosed with COVID-19, and a worsening in self-assessed health status. We expect an increase in STB in the population in the long-term. Future research should gather information about the long-term impact of the pandemic.
High temperature performance of wire-arc additive manufactured Inconel 718
Authors: James William Sean , Ganguly Supriyo , Pardal Goncalo
Published: March 2023

In developing a wire-arc directed energy deposition process for superalloys used in high-speed flight environments, Inconel 718 was deposited using a plasma arc process and tested for its high temperature performance. The deposited material was tested in both the as deposited condition and after an age-hardening industry standard heat-treatment for this alloy. Results showed a reduced performance in both deposited conditions, with heat-treated material significantly outperforming as deposited material up to 538 °C. The difference in performance was less significant from 760 to 1000 °C, owing to an in-test aging process which increased the performance of the as deposited material. The microstructure of deposited material showed significant cracking throughout the alloy and formation of secondary phases throughout the matrix, with significantly more precipitation after heat-treating.
A simplified model to estimate nonlinear turbulent transport by linear dynamics in plasma turbulence
Authors: Nakayama Tomonari , Nakata Motoki , Honda Mitsuru , Narita Emi , Nunami Masanori , Matsuoka Seikichi
Published: March 2023

A simplified model to estimate nonlinear turbulent transport only by linear calculations is proposed, where the turbulent heat diffusivity in tokamak ion temperature gradient(ITG) driven turbulence is reproduced for a wide parameter range including near- and far-marginal ITG stability. The optimal nonlinear functional relation(NFR) between the turbulent diffusivity, the turbulence intensity $$\mathcal{T}$$
T
, and the zonal-flow intensity $$\mathcal{Z}$$
Z
is determined by means of mathematical optimization methods. Then, an extended modeling for $$\mathcal{T}$$
T
and $$\mathcal{Z}$$
Z
to incorporate the turbulence suppression effects and the temperature gradient dependence is carried out. The simplified transport model is expressed as a modified nonlinear function composed of the linear growth rate and the linear zonal-flow decay time. Good accuracy and wide applicability of the model are demonstrated, where the regression error of $$\sigma _{\textrm{model}} = 0.157$$

σ
model

=
0.157

indicates improvement by a factor of about 1/4 in comparison to that in the previous works.
Based on network pharmacology and bioinformatics to analyze the mechanism of action of Astragalus membranaceus in the treatment of vitiligo and COVID-19
Authors: Wang Yaojun , Ding Ming , Chi Jiaoni , Wang Tao , Zhang Yue , Li Zhimin , Li Qiang
Published: March 2023

Coronavirus disease 2019 (COVID-19) is spreading rapidly around the world. However, the treatment of vitiligo combined with COVID-19 has not been reported. Astragalus membranaceus (AM) has a therapeutic effect on patients with vitiligo and COVID-19. This study aims to discover its possible therapeutic mechanisms and provide potential drug targets. Using the Chinese Medicine System Pharmacological Database (TCMSP), GEO database and Genecards websites and other databases, AM target, vitiligo disease target, and COVID-19 related gene set were established. Then find the crossover genes by taking the intersection. Then use GO, KEGG enrichment analysis, and PPI network to discover its underlying mechanism. Finally, by importing drugs, active ingredients, crossover genes, and enriched signal pathways into Cytoscape software, a “drug-active ingredient-target signal pathway-” network is constructed. TCMSP screened and obtained 33 active ingredients including baicalein (MOL002714), NEOBAICALEIN (MOL002934), Skullcapflavone II (MOL002927), and wogonin (MOL000173), which acted on 448 potential targets. 1166 differentially expressed genes for vitiligo were screened by GEO. CIVID-19 related genes were screened by Genecards. Then by taking the intersection, a total of 10 crossover genes (PTGS2, CDK1, STAT1, BCL2L1, SCARB1, HIF1A, NAE1, PLA2G4A, HSP90AA1, and HSP90B1) were obtained. KEGG analysis found that it was mainly enriched in signaling pathways such as IL-17 signaling pathway, Th17 cell differentiation, Necroptosis, NOD-like receptor signaling pathway. Five core targets (PTGS2, STAT1, BCL2L1, HIF1A, and HSP90AA1) were obtained by analyzing the PPI network. The network of "active ingredients-crossover genes" was constructed by Cytoscape, and the 5 main active ingredients acting on the 5 core crossover genes acacetin, wogonin, baicalein, bis2S)-2-ethylhexyl) benzene-1,2-dicarboxylate and 5,2′-Dihydroxy-6,7,8-trimethoxyflavone. The core crossover genes obtained by PPI and the core crossover genes obtained by the "active ingredient-crossover gene" network are intersected to obtain the three most important core genes (PTGS2, STAT1, HSP90AA1). AM may act on PTGS2, STAT1, HSP90AA1, etc. through active components such as acacetin, wogonin, baicalein, bis2S)-2-ethylhexyl) benzene-1,2-dicarboxylate and 5,2′-Dihydroxy-6,7,8-trimethoxyflavone to activate IL-17 signaling pathway, Th17 cell differentiation, Necroptosis, NOD-like receptor signaling pathway, Kaposi sarcoma-associated herpesvirus infection, and VEGF signaling pathway and other signaling pathways to achieve the effect of treating vitiligo and COVID-19.
Risk factors for Baerveldt glaucoma drainage implantation for uveitic glaucoma
Authors: Manako Kiyofumi , Takahashi Eri , Saruwatari Junji , Matsumura Tomoyo , Kojima Sachi , Inoue Toshihiro
Published: March 2023

Uveitic glaucoma (UG) is sometimes intractable, including intricate interaction between intraocular pressure (IOP) elevation associated with inflammation and side effects of steroids. Based on the Tube Versus Trabeculectomy study in refractory glaucoma results in 2012, tube shunt surgeries have been performed for UG, but few reports have focused on UG. We retrospectively examined the surgical efficacy, complications, and risk factors in 62 eyes with UG that underwent Baerveldt glaucoma drainage device (BGD) implantation at Kumamoto University. The IOPs significantly dropped, and the mean number of glaucoma medications was reduced by more than two. Kaplan‒Meier survival curves were presented under 2 conditions: an IOP reduction of 20% and 6 ≤ IOP ≤ 18 mmHg (criterion A) or 6 ≤ IOP ≤ 15 mmHg (criterion B). In criterion A, the median survival times (MST) were 124 days (complete) and 997 days (qualified). In criterion B, the MST was 129 days (complete) and 867 days (qualified). The Cox hazard proportional model found that the hazard ratio was 0.170 for a history of cataract surgery (95% CI 0.0303–0.950) and 8.669 for systemic immunosuppressive therapy (95% CI 1.810–41.51). BGD implantation is effective for treating UG, but the presence of systemic treatment and the lens status should be considered.
Process optimization and kinetic study of biodegradation of dimethyl phthalate by KS2, a novel strain of Micrococcus sp.
Authors: Patil Sangram Shamrao , Jena Hara Mohan
Published: March 2023

The present study elucidates identification and characterization of dimethyl phthalate (DMP) degrading novel bacterial strain, Micrococcus sp. KS2, isolated from soil contaminated with municipal wastewater. Statistical designs were exercised to achieve optimum values of process parameters for DMP degradation by Micrococcus sp. KS2. The screening of the ten important parameters was performed by applying Plackett–Burman design, and it delivered three significant factors (pH, temperature, and DMP concentration). Further, response surface methodology involving central composite design (CCD) was implemented to examine mutual interactions among variables and achieve their optimal response. The predicted response indicated that maximum DMP degradation (99.67%) could be attained at pH 7.05, temperature 31.5 °C and DMP 289.19 mg/l. The strain KS2 was capable of degrading up to 1250 mg/l of DMP in batch mode and it was observed that oxygen was limiting factor in the DMP degradation. Kinetic modeling of DMP biodegradation indicated that Haldane model fitted well with the experimental data. During DMP degradation, monomethyl phthalate (MMP) and phthalic acid (PA) were identified as degradation metabolites. This study provides insight into DMP biodegradation process and proposes that Micrococcus sp. KS2 is a potential bacterial candidate to treat effluent containing DMP.
An automatic entropy method to efficiently mask histology whole-slide images
Authors: Song Yipei , Cisternino Francesco , Mekke Joost M. , de Borst Gert J. , de Kleijn Dominique P. V. , Pasterkamp Gerard , Vink Aryan , Glastonbury Craig A. , van der Laan Sander W. , Miller Clint L.
Published: March 2023

Tissue segmentation of histology whole-slide images (WSI) remains a critical task in automated digital pathology workflows for both accurate disease diagnosis and deep phenotyping for research purposes. This is especially challenging when the tissue structure of biospecimens is relatively porous and heterogeneous, such as for atherosclerotic plaques. In this study, we developed a unique approach called ‘EntropyMasker’ based on image entropy to tackle the fore- and background segmentation (masking) task in histology WSI. We evaluated our method on 97 high-resolution WSI of human carotid atherosclerotic plaques in the Athero-Express Biobank Study, constituting hematoxylin and eosin and 8 other staining types. Using multiple benchmarking metrics, we compared our method with four widely used segmentation methods: Otsu’s method, Adaptive mean, Adaptive Gaussian and slideMask and observed that our method had the highest sensitivity and Jaccard similarity index. We envision EntropyMasker to fill an important gap in WSI preprocessing, machine learning image analysis pipelines, and enable disease phenotyping beyond the field of atherosclerosis.
Genetic diversity between local landraces and current breeding lines of pepper in China
Authors: Guo Guangjun , Pan Baogui , Yi Xixi , Khan Abid , Zhu Xuemei , Ge Wei , Liu Jinbing , Diao Weiping , Wang Shubin
Published: March 2023

Based on 22 qualitative traits, 13 quantitative traits, and 27 molecular markers (26 SSR and 1 InDel), in the current study we compared the diversity and population structure of 94 local landraces and 85 current breeding lines of pepper in China. The results showed that the Shannon Diversity indices of 9 qualitative traits and 8 quantitative traits in current breeding lines were greater than those of landraces, of which 11 were fruit organ-related traits. Compared with current breeding lines, the mean values of Gene Diversity index and Polymorphism Information content of local landraces were higher by 0.08 and 0.09, respectively. Population structure and phylogenetic tree analysis showed that the 179 germplasm resources could be divided into two taxa, dominated by local landraces and current breeding lines, respectively. The above results indicated that the diversity of quantitative traits of current breeding lines were higher than that of local landraces, especially traits related to fruit organs, but the genetic diversity based on molecular markers was lower than that of local landraces. Therefore, in the future breeding process, we should not only focus on the selection of target traits, but also strengthen the background selection based on molecular markers. Moreover, the genetic information of other domesticated species and wild species will be transferred to the breeding lines through interspecific crosses to expand the genetic background of the breeding material.
Deduction of the operable design space of RP-HPLC technique for the simultaneous estimation of metformin, pioglitazone, and glimepiride
Authors: Marie Aya A. , Hammad Sherin F. , Salim Mohamed M. , Elkhodary Mahmoud M. , Kamal Amira H.
Published: March 2023

A reversed-phase RP-HPLC method was developed for the simultaneous determination of metformin hydrochloride (MET), pioglitazone (PIO), and glimepiride (GLM) in their combined dosage forms and spiked human plasma. Quality risk management principles for determining the critical method parameters (CMPs) and fractional factorial design were made to screen CMPs and subsequently, the Box–Behnken design was employed. The analytical Quality by Design (AQbD) paradigm was used to establish the method operable design region (MODR) for the developed method depended on understanding the quality target product profile (QTPP), analytical target profile (ATP), and risk assessment for different factors that affect the method performance to develop an accurate, precise, cost-effective, and environmentally benign method. The separation was carried out using a mobile phase composed of methanol: 0.05 M potassium dihydrogen phosphate buffer pH 3.7 with 0.05% TEA (78:22, v/v). The flow rate was 1.2 mL/min. DAD detector was set at 227 nm. Linagliptin (LIN) was used as an internal standard. The proposed method was validated according to The International Council for Harmonization of Technical Requirements for Pharmaceuticals for Human Use (ICH). The assay results obtained by using the developed method were statistically compared to those obtained by the reported HPLC method, and a satisfying agreement was observed.
Exact Gaussian processes for massive datasets via non-stationary sparsity-discovering kernels
Authors: Noack Marcus M. , Krishnan Harinarayan , Risser Mark D. , Reyes Kristofer G.
Published: March 2023

A Gaussian Process (GP) is a prominent mathematical framework for stochastic function approximation in science and engineering applications. Its success is largely attributed to the GP’s analytical tractability, robustness, and natural inclusion of uncertainty quantification. Unfortunately, the use of exact GPs is prohibitively expensive for large datasets due to their unfavorable numerical complexity of$$O(N^3)$$O(N3)in computation and$$O(N^2)$$O(N2)in storage. All existing methods addressing this issue utilize some form of approximation—usually considering subsets of the full dataset or finding representative pseudo-points that render the covariance matrix well-structured and sparse. These approximate methods can lead to inaccuracies in function approximations and often limit the user’s flexibility in designing expressive kernels. Instead of inducing sparsity via data-point geometry and structure, we propose to take advantage of naturally-occurring sparsity by allowing the kernel to discover—instead of induce—sparse structure. The premise of this paper is that the data sets and physical processes modeled by GPs often exhibit natural or implicit sparsities, but commonly-used kernels do not allow us to exploit such sparsity. The core concept of exact, and at the same time sparse GPs relies on kernel definitions that provide enough flexibility to learn and encode not only non-zero but also zero covariances. This principle of ultra-flexible, compactly-supported, and non-stationary kernels, combined with HPC and constrained optimization, lets us scale exact GPs well beyond 5 million data points.