bluuebunny/crossref_metadata_2025_split huggingface dataset:
Increase in gut permeability and oxidized ldl is associated with post-acute sequelae of SARS-CoV-2
Authors: Mouchati Christian , Durieux Jared C. , Zisis Sokratis N. , Labbato Danielle , Rodgers Michael A. , Ailstock Kate , Reinert Brian L. , Funderburg Nicholas T. , McComsey Grace A. 
Published: May 2023

BackgroundPost-acute sequelae of SARS-CoV-2 (PASC) is marked by persistent or newly developing symptoms beyond 4 weeks of infection. Investigating gut integrity, oxidized lipids and inflammatory markers is important for understanding PASC pathogenesis.MethodsA cross-sectional study including COVID+ with PASC, COVID+ without PASC, and COVID-negative (COVID-) participants. We measured plasma markers by enzyme-linked immunosorbent assay to assess intestinal permeability (ZONULIN), microbial translocation (lipopolysaccharide-binding protein or LBP), systemic inflammation (high-sensitivity C-reactive protein or hs-CRP), and oxidized low-density lipoprotein (Ox-LDL).Results415 participants were enrolled in this study; 37.83% (n=157) had prior COVID diagnosis and among COVID+, 54% (n=85) had PASC. The median zonulin among COVID- was 3.37 (IQR: 2.13, 4.91) mg/mL, 3.43 (IQR: 1.65, 5.25) mg/mL among COVID+ no PASC, and highest [4.76 (IQR: 3.2, 7.35) mg/mL] among COVID+ PASC+ (p&lt;.0001). The median ox-LDL among COVID- was 47.02 (IQR: 35.52, 62.77) U/L, 57.24 (IQR: 40.7, 75.37) U/L among COVID+ No PASC, and the highest [76.75 (IQR: 59.95, 103.28) U/L] among COVID+ PASC+ (p&lt;.0001). COVID+ PASC+ was positively associated with zonulin (p=0.0002) and ox-LDL (p&lt;.0001), and COVID- was negatively associated with ox-LDL (p=0.01), compared to COVID+ No PASC. Every unit increase in zonulin was associated with 44% higher predicted odds of having PASC [aOR: 1.44 (95%CI: 1.1, 1.9)] and every one-unit increase in ox-LDL was associated with more than four-fold increased odds of having PASC [aOR: 2.44 (95%CI: 1.67, 3.55)].ConclusionsPASC is associated with increased gut permeability and oxidized lipids. Further studies are needed to clarify whether these relationships are causal which could lead to targeted therapeutics.
The offshore renewables industry may be better served by new bespoke design guidelines than by automatic adoption of recommended practices developed for oil and gas infrastructure: A recommendation illustrated by subsea cable design
Authors: Griffiths Terry , Draper Scott , Cheng Liang , An Hongwei , Schläppy Marie-Lise , Fogliani Antonino , White David , Noble Stuart , Coles Daniel , Johnson Fraser , Thurstan Bryan , Teng Yunfei 
Published: May 2023

IntroductionThere is an emerging need for the offshore renewable industry to have their own bespoke design guidelines because the associated projects and offshore facilities differ in fundamental ways to oil and gas facilities. Offshore renewable energy (ORE) facilities have already surpassed the numbers of installed facilities in the oil and gas industry by an order of magnitude and demand is forecast to continue growing exponentially. In addition ORE facilities often have different response characteristics and limit states or failure modes as well as profoundly different risk and consequence profiles given they are generally uncrewed and do not contain explosive hydrocarbon fluids which might be released into the environment. Therefore, the purpose of this paper is to advocate for licensing bodies and regulators (such as the various national PEL 114 committees) to challenge the process of automatic adoption of oil and gas design processes, while pushing for offshore renewables to be treated differently, when appropriate, with more relevant and applicable guidance.MethodsTo support this argument we present new bespoke design guidance developed for subsea cables based on specific modes of cable behaviour, which often differ from pipelines. We also show worked examples from recent project experience. The results from on-bottom stability analyses of a set of cables are compared between conventional oil and gas guidance following DNV-RP-F109 versus the stability using cable-optimised approaches.ResultsThe outcomes from the ‘conventional’ oil and gas results are not simply biased compared to cable-optimised design methods, with a trend of being either conservative or unconservative. Instead, the results of the two methods are very poorly correlated. This shows that the oil and gas approach isn't simply biased when applied to cables, but is instead unreliable because it doesn't capture the underlying failure conditions. These analytical comparisons are supported by field observation - the ocean doesn't lie, and makes short work of any anthropogenic structures which are designed with inadequate appreciation of the real world conditions.DiscussionTo support the rapid growth of ORE, we should therefore actively pursue opportunities to rewrite the design rules and standards, so that they better support the specific requirements of ORE infrastructure, rather than legacy oil and gas structures. With more appropriate design practices, we can accelerate the roll out of ORE to meet net zero, and mitigate the climate crisis.
Region-specific deep learning models for accurate segmentation of rectal structures on post-chemoradiation T2w MRI: a multi-institutional, multi-reader study
Authors: DeSilvio Thomas , Antunes Jacob T. , Bera Kaustav , Chirra Prathyush , Le Hoa , Liska David , Stein Sharon L. , Marderstein Eric , Hall William , Paspulati Rajmohan , Gollamudi Jayakrishna , Purysko Andrei S. , Viswanath Satish E. 
Published: May 2023

IntroductionFor locally advanced rectal cancers, in vivo radiological evaluation of tumor extent and regression after neoadjuvant therapy involves implicit visual identification of rectal structures on magnetic resonance imaging (MRI). Additionally, newer image-based, computational approaches (e.g., radiomics) require more detailed and precise annotations of regions such as the outer rectal wall, lumen, and perirectal fat. Manual annotations of these regions, however, are highly laborious and time-consuming as well as subject to inter-reader variability due to tissue boundaries being obscured by treatment-related changes (e.g., fibrosis, edema).MethodsThis study presents the application of U-Net deep learning models that have been uniquely developed with region-specific context to automatically segment each of the outer rectal wall, lumen, and perirectal fat regions on post-treatment, T2-weighted MRI scans.ResultsIn multi-institutional evaluation, region-specific U-Nets (wall Dice = 0.920, lumen Dice = 0.895) were found to perform comparably to multiple readers (wall inter-reader Dice = 0.946, lumen inter-reader Dice = 0.873). Additionally, when compared to a multi-class U-Net, region-specific U-Nets yielded an average 20% improvement in Dice scores for segmenting each of the wall, lumen, and fat; even when tested on T2-weighted MRI scans that exhibited poorer image quality, or from a different plane, or were accrued from an external institution.DiscussionDeveloping deep learning segmentation models with region-specific context may thus enable highly accurate, detailed annotations for multiple rectal structures on post-chemoradiation T2-weighted MRI scans, which is critical for improving evaluation of tumor extent in vivo and building accurate image-based analytic tools for rectal cancers.
Real-world experience with secukinumab in the entire axial spondyloarthritis spectrum
Authors: Sivera Francisca , Núñez-Monje Victoria , Campos-Fernández Cristina , Balaguer-Trull Isabel , Robustillo-Villarino Montserrat , Aguilar-Zamora Marta , Garijo-Bufort Marta , López-Gómez Juan Miguel , Peña-González Carolina , de la Morena Isabel , Bedoya-Sanchís Diego , Yankova-Komsalova Liliya , Conesa-Mateos Arantxa , Martínez-Cristóbal Anna , Navarro-Blasco Francisco Javier , Senabre-Gallego José Miguel , Alegre-Sancho Juan José 
Published: May 2023

BackgroundSecukinumab is a biologic disease-modifying antirheumatic drug (bDMARD) that has demonstrated efficacy in the treatment of axial spondyloarthritis (axSpA, i.e., ankylosing spondylitis and non-radiographic axSpA) across various clinical trials. However, data of secukinumab in clinical practice is still limited. Here, we aimed to provide real-world data on secukinumab use, effectiveness, and persistence in axSpA.Patients and methodsRetrospective, multicenter study of patients with a diagnosis of axSpA treated with secukinumab at 12 centers up to June 2021 in the Valencian Community (Spain). Information was gathered on BASDAI measurement, pain, patient and physician global assessment (ptGA, phGA) using a 100-mm visual analog scale (VAS), persistence and other secondary variables by treatment line (first, second, and ≥ third) for up to 24 months.Results221 patients were included (69% men; mean age [standard deviation, SD]: 46.7 [12.1] years old). Secukinumab was used as a first-line bDMARD in 38% of patients, as a second-line in 34% and as a ≥ hird-line in 28%. The percentage of patients achieving low disease activity (BASDAI&lt;4) increased from 9% at baseline to 48% at month 6 and was maintained (49%) up to month 24. Improvements in BASDAI were observed across all treatment lines: in naïve patients (month 6: −2.6; month 24: −2.7), in second-line (month 6: −1.9; month 24: −3.1), and in patients on third lines (month 6: −1.3; month 24: −1.7). Reductions in mean pain VAS (−23.3; −31.9), ptGA (−25.1; −31.9) and phGA (−25.1; −31) were also observed at 6 and 24 months. Secukinumab showed an overall 12-months persistence rate of 70% (95% confidence interval [CI]: 63–77%) and a 24-months persistence rate of 58% (95% CI, 51–66%). Patients receiving first-line secukinumab had the highest 24-months persistence rate (p = 0.05).ConclusionSecukinumab improved disease activity in axSpA patients, especially in naive, and second-line patients, which was accompanied by high persistence rates up to 24 months.
Content development and validation for a mobile application designed to train family caregivers in the use of music to support care of people living with dementia
Authors: Thompson Zara , Tamplin Jeanette , Vieira Sousa Tanara , Carrasco Romina , Flynn Libby , Lamb Karen E. , Lampit Amit , Lautenschlager Nicola T. , McMahon Kate , Waycott Jenny , Vogel Adam P. , Woodward-Kron Robyn , Stretton-Smith Phoebe A. , Baker Felicity A. 
Published: May 2023

BackgroundMusic therapy is increasingly recognized as an effective support for people living with dementia. However, with incidences of dementia increasing, and limited availability of music therapists, there is a need for affordable and accessible ways that caregivers can learn to use music-therapy based strategies to support the people they care for. The MATCH project aims to address this by creating a mobile application that can train family caregivers in the use of music to support people living with dementia.MethodsThis study details the development and validation of training material for the MATCH mobile application. Training modules developed based on existing research were assessed by 10 experienced music therapist clinician-researchers, and seven family caregivers who had previously completed personalized training in music therapy strategies via the HOMESIDE project. Participants reviewed the content and scored each training module based on content (music therapists) and face (caregivers) validity scales. Descriptive statistics were used to calculate scores on the scales, while thematic analysis was used to analyze short-answer feedback.ResultsParticipants scored the content as valid and relevant, however, they provided additional suggestions for improvement via short-answer feedback.ConclusionThe content developed for the MATCH application is valid and will be trailed by family caregivers and people living with dementia in a future study.
Altered gut microbiome profile in patients with knee osteoarthritis
Authors: Wang Xi , Wu Yifan , Liu Yanli , Chen Feihong , Chen Sijie , Zhang Feiyu , Li Shujin , Wang Chaowei , Gong Yi , Huang Ruitian , Hu Minhan , Ning Yujie , Zhao Hongmou , Guo Xiong 
Published: May 2023

IntroductionOsteoarthritis (OA) is a kind of chronic, degenerative disorder with unknown causes. In this study, we aimed to improve our understanding of the gut microbiota profile in patients with knee OA.Methods16S rDNA gene sequencing was performed to detect the gut microbiota in fecal samples collected from the patients with OA (n = 32) and normal control (NC, n = 57). Then the metagenomic sequencing was used to identify the genes or functions linked with gut microbial changes at the species level in the fecal samples from patients with OA and NC groups.ResultsThe Proteobacteria was identified as dominant bacteria in OA group. We identified 81 genera resulted significantly different in abundance between OA and NC. The abundance of Agathobacter, Ruminococcus, Roseburia, Subdoligranulum, and Lactobacillus showed significant decrease in the OA compared to the NC. The abundance of genera Prevotella_7, Clostridium, Flavonifractor and Klebsiella were increasing in the OA group, and the families Lactobacillaceae, Christensenellaceae, Clostridiaceae_1 and Acidaminococcaceae were increasing in the NC. The metagenomic sequencing showed that the abundance of Bacteroides stercoris, Bacteroides vulgatus and Bacteroides uniformis at the species level were significantly decreasing in the OA, and the abundance of Escherichia coli, Klebsiella pneumoniae, Shigella flexneri and Streptococcus salivarius were significantly increased in OA.DiscussionThe results of our study interpret a comprehensive profile of the gut microbiota in patients with knee OA and offer the evidence that the cartilage-gut-microbiome axis could play a crucial role in underlying the mechanisms and pathogenesis of OA.
RpoZ regulates 2,4-DAPG production and quorum sensing system in Pseudomonas fluorescens 2P24
Authors: Wei Yarui , Dong Baozhu , Wu Xiaogang , Zhao Mingmin , Wang Dong , Li Na , Zhang Qian , Zhang Liqun , Zhou Hongyou 
Published: May 2023

IntroductionPseudomonas fluorescens 2P24 was isolated from soil of natural decay associated with wheat take-all and it can effectively control soil-borne diseases caused by a variety of plant pathogens. 2,4-diacetylphloroglucinol (2,4-DAPG), is produced by P. fluorescens 2P24 and plays an important role in the prevention and control of plant diseases. To understand the resistant mechanism, in this study, we conducted experiments to explore the regulation role of rpoZ in the synthesis of the antibiotic 2,4-DAPG and regulation of QS system.MethodsA random mini-Tn5 mutagenesis procedure was used to screen regulators for phlA transcription in stain PM901, which containing a phlA∷lacZ transcriptional fusion reporter plasmid. We identified 12 insertion mutants could significantly change phlA gene expression. By analyzing the amino acid sequences of the interrupted gene, we obtained a mutant strain Aa4-29 destroyed the rpoZ gene, which encodes the omiga subunit. We constructed the plasmid of rpoZ mutant (pBBR-△rpoZ) transformed into competent cells of P. fluorescens 2P24 by electro-transformation assay. The strains of P. fluorescens 2P24/pBBR, 2P24-△rpoZ/pBBR, 2P24-△rpoZ/pBBR-rpoZ were used to evaluate the regulation role of rpoZ in 2,4-DAPG production and quorum sensing system.ResultsAccording to β-galactosidase activity, we found that rpoZ positively regulated the expression of phlA (a synthesis gene of 2,4-DAPG) and PcoI (a synthesis gene of PcoI/PcoR QS signal system) at the transcriptional level. The production of 2,4-DAPG antibiotic and signal molecule AHL was influenced by rpoZ. Further, rpoZ was involved in regulating rsmA expression. RpoZ also has a certain regulatory effect on rpoS transcription, but no effect on the transcription of phlF, emhABC and emhR. According to the biocontrol assay, P. fluorescens 2P24 strains with rpoZ showed obvious antagonism ability against the Rhizoctonia solani in cotton, while the mutant strain of rpoZ lost the biocontrol effect. RpoZ had a significant effect on the swimming and biofilm formation in P. fluorescens 2P24.ConclusionOur data showed that rpoZ was an important regulator of QS system, 2,4-DAPG in P. fluorescens 2P24. This may imply that P. fluorescens 2P24 has evolved different regulatory features to adapt to different environmental threats.
L-leucine increases the sensitivity of drug-resistant Salmonella to sarafloxacin by stimulating central carbon metabolism and increasing intracellular reactive oxygen species level
Authors: Yang Heng , Zhou Yanhong , Luo Qiong , Zhu Chunyang , Fang Binghu 
Published: May 2023

IntroductionThe overuse of antibiotics has made public health and safety face a serious cisis. It is urgent to develop new clinical treatment methods to combat drug resistant bacteria to alleviate the health crisis. The efficiency of antibiotics is closely related to the metabolic state of bacteria. However, studies on fluoroquinolone resistant Salmonella are relatively rare.MethodsCICC21484 were passaged in medium with and without sarafloxacin and obtain sarafloxacin- susceptible Salmonella Typhimurium (SAR-S) and sarafloxacin resistant Salmonella Typhimurium (SAR-R), respectively. Non-targeted metabolomics was used to analyze the metabolic difference between SAR-S and SAR-R. Then we verified that exogenous L-leucine promoted the killing effect of sarafloxacin in vitro, and measured the intracellular ATP, NADH and reactive oxygen species levels of bacteria. Gene expression was determined using Real Time quantitative PCR.ResultsWe confirmed that exogenous L-leucine increased the killing effect of sarafloxacin on SAR-R and other clinically resistant Salmonella serotypes. Exogenous L-leucine stimulated the metabolic state of bacteria, especially the TCA cycle, which increased the working efficiency of the electron transfer chain and increased the intracellular NADH, ATP concentration, and reactive oxygen species level. Our results suggest that when the metabolism of drug-resistant bacteria is reprogrammed, the bactericidal effect of antibiotics improves.DiscussionThis study further enhances research in the anti-drug resistance field at the metabolic level and provides theoretical support for solving the current problem of sarafloxacin drug resistance, a unique fluoroquinolone drug for animals and indicating the potential of L-leucine as a new antibiotic adjuvant.
Docking guided phase display to develop fusion protein with novel scFv and alkaline phosphatase for one-step ELISA salbutamol detection
Authors: Hu Shuai , Yang Guangbo , Chen Zhou , Li Qiuye , Liu Bin , Liu Ming , Zhang Dawei , Chang Shan , Kong Ren 
Published: May 2023

IntroductionSalbutamol (SAL) is a β2 adrenergic receptor agonist which has potential hazardous effects for human health. It is very important to establish a sensitive and convenient method to monitor SAL.MethodsHere we introduce a method to combine the information from docking and site specific phage display, with the aim to obtain scFv with high affinity to SAL. First, single chain variable fragment (scFv) antibodies against SAL were generated through phage display. By using molecular docking approach, the complex structure of SAL with antibody was predicted and indicated that H3 and L3 contribute to the binding. Then new libraries were created by randomization specific residues located on H3 and L3 according to the docking results.Results and discussionAnti-SAL scFv antibodies with high efficiency were finally identified. In addition, the selected scFv was fused with alkaline phosphatase and expressed in E coli to develop a rapid and low-cost one step ELISA to detect SAL.
Emerging field: O-GlcNAcylation in ferroptosis
Authors: Zhang Hongshuo , Zhang Juan , Dong Haojie , Kong Ying , Guan Youfei 
Published: May 2023

In 2012, researchers proposed a non-apoptotic, iron-dependent form of cell death caused by lipid peroxidation called ferroptosis. During the past decade, a comprehensive understanding of ferroptosis has emerged. Ferroptosis is closely associated with the tumor microenvironment, cancer, immunity, aging, and tissue damage. Its mechanism is precisely regulated at the epigenetic, transcriptional, and post-translational levels. O-GlcNAc modification (O-GlcNAcylation) is one of the post-translational modifications of proteins. Cells can modulate cell survival in response to stress stimuli, including apoptosis, necrosis, and autophagy, through adaptive regulation by O-GlcNAcylation. However, the function and mechanism of these modifications in regulating ferroptosis are only beginning to be understood. Here, we review the relevant literature within the last 5 years and present the current understanding of the regulatory function of O-GlcNAcylation in ferroptosis and the potential mechanisms that may be involved, including antioxidant defense system-controlled reactive oxygen species biology, iron metabolism, and membrane lipid peroxidation metabolism. In addition to these three areas of ferroptosis research, we examine how changes in the morphology and function of subcellular organelles (e.g., mitochondria and endoplasmic reticulum) involved in O-GlcNAcylation may trigger and amplify ferroptosis. We have dissected the role of O-GlcNAcylation in regulating ferroptosis and hope that our introduction will provide a general framework for those interested in this field.
Lipoprotein(a) and stroke: a two-sample Mendelian randomization study
Authors: Huang Yi , Zhang Ruijie , Han Liyuan , Wu Yiwen , Deng Xinpeng , Xu Tianqi , Wu Yuefei , Gao Xiang , Zhou Chenhui , Sun Jie 
Published: May 2023

BackgroundTo evaluate the causal relationship between lipoprotein(a) Lp(a) and stroke risk.MethodAdopting two grand scale genome-wide association study (GWAS) databases, the instrumental variables were selected on the basis that the genetic loci met the criteria of being independent of each other and closely related to Lp(a). Summary-level data for outcomes, ischemic stroke and its subtypes were acquired from the UK Biobank and MEGASTROKE consortium databases. Two-sample MR analyses were achieved using inverse variance-weighted (IVW) meta-analysis (primary analysis), weighted median analysis, and the MR Egger regression method. Multivariable-adjusted Cox regression models were also used for observational analysis.ResultGenetically predicted Lp(a) was marginally related with higher odds of total stroke (odds ratio (OR) [95% confidence intervals (CI)]: 1.003 [1.001–1.006], p = 0.010), ischemic stroke (OR [95% CI]: 1.004[1.001–1.007], p = 0.004), and large-artery atherosclerotic stroke (OR [95% CI]: 1.012 [1.004–1.019], p = 0.002) when the IVW estimator was used on the MEGASTROKE data. The associations of Lp(a) with stroke and ischemic stroke were also remarkable in the primary analysis using the UK Biobank data. Higher Lp(a) levels were also related with increased total stroke and ischemic stroke risk in the observational research data in the UK Biobank database.ConclusionGenetically predicted higher Lp(a) perhaps rise the risk of total stroke, ischemic stroke, and large-artery atherosclerotic stroke.