bluuebunny/crossref_metadata_2025_split huggingface dataset:
Interim analysis from a phase 2 randomized trial of EuCorVac-19: a recombinant protein SARS-CoV-2 RBD nanoliposome vaccine
Authors: Lovell Jonathan F. , Baik Yeong Ok , Choi Seuk Keun , Lee Chankyu , Lee Jeong-Yoon , Miura Kazutoyo , Huang Wei-Chiao , Park Young-Shin , Woo Sun-Je , Seo Sang Hwan , Kim Jae-Ouk , Song Manki , Kim Chung-Jong , Choi Jae-Ki , Kim Jieun , Choo Eun Ju , Choi Jung-Hyun 
Published: November 2022

Abstract
Background
Numerous vaccine strategies are being advanced to control SARS-CoV-2, the cause of the COVID-19 pandemic. EuCorVac-19 (ECV19) is a recombinant protein nanoparticle vaccine that displays the SARS-CoV-2 receptor-binding domain (RBD) on immunogenic nanoliposomes.

Methods
Initial study of a phase 2 randomized, observer-blind, placebo-controlled trial to assess the immunogenicity, safety, and tolerance of ECV19 was carried out between July and October 2021. Two hundred twenty-nine participants were enrolled at 5 hospital sites in South Korea. Healthy adults aged 19–75 without prior known exposure to COVID-19 were vaccinated intramuscularly on day 0 and day 21. Of the participants who received two vaccine doses according to protocol, 100 received high-dose ECV19 (20 μg RBD), 96 received low-dose ECV19 (10 μg RBD), and 27 received placebo. Local and systemic adverse events were monitored. Serum was assessed on days 0, 21, and 42 for immunogenicity analysis by ELISA and neutralizing antibody response by focus reduction neutralization test (FRNT).

Results
Low-grade injection site tenderness and pain were observed in most participants. Solicited systemic adverse events were less frequent, and mostly involved low-grade fatigue/malaise, myalgia, and headache. No clinical laboratory abnormalities were observed. Adverse events did not increase with the second injection and no serious adverse events were solicited by ECV19. On day 42, Spike IgG geometric mean ELISA titers were 0.8, 211, and 590 Spike binding antibody units (BAU/mL) for placebo, low-dose and high-dose ECV19, respectively (p < 0.001 between groups). Neutralizing antibodies levels of the low-dose and high-dose ECV19 groups had FRNT50 geometric mean values of 129 and 316, respectively. Boosting responses and dose responses were observed. Antibodies against the RBD correlated with antibodies against the Spike and with virus neutralization.

Conclusions
ECV19 was generally well-tolerated and induced antibodies in a dose-dependent manner that neutralized SARS-CoV-2. The unique liposome display approach of ECV19, which lacks any immunogenic protein components besides the antigen itself, coupled with the lack of increased adverse events during boosting suggest the vaccine platform may be amenable to multiple boosting regimes in the future. Taken together, these findings motivate further investigation of ECV19 in larger scale clinical testing that is underway.

Trial registration
The trial was registered at ClinicalTrials.gov as # NCT04783311.
The developmental miR-17–92 cluster and the Sfmbt2 miRNA cluster cannot rescue the abnormal embryonic development generated using obstructive epididymal environment-producing sperm in C57BL/6 J mice
Authors: Wu Xunwei , He Xiaomei , Liu Qian , Li Honggang 
Published: November 2022

Abstract
Background
Sperm, during epididymal transit, acquires microRNAs(miRNAs), which are crucial for embryonic development. However, whether sperm miRNAs influenced by an obstructive epididymal environment affect embryonic development remains unknown.

Method
The sham operation and vasectomy were performed in C57BL/6 J mice to create the control group (CON) and the obstructive epididymal environment group(OEE) group, respectively. The morphology of the testis and epididymis was observed using hematoxylin and eosin staining (HE staining) to establish the OEE mice model. The sperm quality test, intracytoplasmic sperm injection (ICSI), and epididymosomes fusion were employed to observe the effect of the obstructive epididymal environment on sperm and resultant embryonic development. The alteration of the sperm small RNA (sRNA) profile was analyzed by sRNA sequencing. RT-qPCR and DNA methylation were applied to observe the effect of obstructive epididymis on the expression of sperm miRNAs. The miRNAs microinjection was used to explore the impacts of sperm miRNAs on embryonic development.

Results
We confirmed postoperative 8-week mice as the OEE mice model by examining the morphology of the testis and epididymis. In the OEE group, we observed that sperm quality degraded and the development potential of embryos was reduced, which can be saved by the normal epididymal environment. The sperm sRNA sequencing revealed that the expression of the developmental miR-17–92 cluster and the Sfmbt2 miRNA cluster was downregulated in the OEE group. The expression of these two miRNA clusters in epididymis was also downregulated and regulated by DNA methylation. However, the downregulation of either the miR-17–92 cluster or the Sfmbt2 miRNA cluster in normal zygotes did not impair embryonic development.

Conclusion
The obstructive epididymal environment influences sperm quality and resultant embryonic development, as well as the abundance of the developmental miR-17–92 cluster and the Sfmbt2 miRNA cluster in sperm, but these miRNA clusters are not the cause of abnormal embryonic development. It implies that epididymis is important in early embryonic development and may play a potential role in sperm epigenome.
Atrial fibrillation and anticoagulation are associated with hospitalisations in patients with end-stage kidney disease on haemodialysis: a prospective population-based cohort study
Authors: Steiner Daniel , Schmaldienst Sabine , Lorenz Matthias , Klauser-Braun Renate , Pabinger Ingrid , Ay Cihan , Säemann Marcus , Königsbrügge Oliver 
Published: November 2022

Abstract
Background
Patients with end-stage kidney disease on haemodialysis suffer from frequent complications requiring hospitalisation. Atrial fibrillation is a burdensome comorbidity amongst patients on haemodialysis. We aimed to assess frequency, reasons, and duration of hospitalisations in haemodialysis patients and their association with atrial fibrillation and anticoagulation.

Methods
Prevalent patients with end-stage kidney disease on haemodialysis were recruited into a prospective cohort study and observed for a median observation time of 3.4 years. Hospitalisations were recorded from discharge letters, medical records, and patient interviews. The association of atrial fibrillation, anticoagulation, and time-in-therapeutic range of vitamin K antagonist treatment with hospitalisations was analysed using negative binomial regression.

Results
Out of 625 patients, 238 (38.1%) had atrial fibrillation. Median number of hospitalisations per patient was 3.0 (1.0–5.0). Incidence rate of hospitalisation was 1.7 per patient-year in all and 1.9 in atrial fibrillation patients, median duration per hospitalisation was 7.9 (4.8–12.9) and 8.8 (5.7–13.3) days, respectively. Most frequent reasons for hospitalisation were vascular access complication/intervention (11.7%) and infection/fever (11.4%), while bleeding events comprised 6.0% of all hospitalisations. Atrial fibrillation patients had 27% higher risk of hospitalisation than patients without atrial fibrillation (incidence rate ratio [IRR] 1.27, 95% confidence interval [CI] 1.10–1.47). In atrial fibrillation patients, anticoagulation (enoxaparin or phenprocoumon, 41.6% of AF patients) was associated with increased risk of all-cause (IRR 1.38, 95%CI 1.14–1.69) and bleeding-related hospitalisation (IRR 1.96, 95%CI 1.06–3.63). There was no association between anticoagulation and stroke-related hospitalisation. In atrial fibrillation patients on phenprocoumon, increasing time-in-therapeutic range was associated with decreased risk of all-cause (IRR 0.35, 95%CI 0.14–0.87), but not bleeding-related hospitalisation (IRR 0.13, 95%CI 0.01–1.38).

Conclusion
In haemodialysis patients, presence of atrial fibrillation and, among those with atrial fibrillation, anticoagulation were associated with higher risk of all-cause hospitalisation, including bleeding-related hospitalisation in the latter. Increasing time-in-therapeutic range in patients on vitamin K antagonist treatment was associated with decreased risk of all-cause, but not bleeding-related hospitalisation.
Volumetric imaging and morphometric analysis of breast tumor angiogenesis using a new contrast-free ultrasound technique: a feasibility study
Authors: Gu Juanjuan , Ternifi Redouane , Sabeti Soroosh , Larson Nicholas B. , Carter Jodi M. , Fazzio Robert T. , Fatemi Mostafa , Alizad Azra 
Published: November 2022

Abstract
Background
There is a strong correlation between the morphological features of new tumor vessels and malignancy. However, angiogenic heterogeneity necessitates 3D microvascular data of tumor microvessels for more reliable quantification. To provide more accurate information regarding vessel morphological features and improve breast lesion characterization, we introduced a quantitative 3D high-definition microvasculature imaging (q3D-HDMI) as a new easily applicable and robust tool to morphologically characterize microvasculature networks in breast tumors using a contrast-free ultrasound-based imaging approach.

Methods
In this prospective study, from January 2020 through December 2021, a newly developed q3D-HDMI technique was evaluated on participants with ultrasound-identified suspicious breast lesions recommended for core needle biopsy. The morphological features of breast tumor microvessels were extracted from the q3D-HDMI. Leave-one-out cross-validation (LOOCV) was applied to test the combined diagnostic performance of multiple morphological parameters of breast tumor microvessels. Receiver operating characteristic (ROC) curves were used to evaluate the prediction performance of the generated pooled model.

Results
Ninety-three participants (mean age 52 ± 17 years, 91 women) with 93 breast lesions were studied. The area under the ROC curve (AUC) generated with q3D-HDMI was 95.8% (95% CI 0.901–1.000), yielding a sensitivity of 91.7% and a specificity of 98.2%, that was significantly higher than the AUC generated with the q2D-HDMI (p = 0.02). When compared to q2D-HDMI, the tumor microvessel morphological parameters obtained from q3D-HDMI provides distinctive information that increases accuracy in differentiating breast tumors.

Conclusions
The proposed quantitative volumetric imaging technique augments conventional breast ultrasound evaluation by increasing specificity in differentiating malignant from benign breast masses.
SIEVE: joint inference of single-nucleotide variants and cell phylogeny from single-cell DNA sequencing data
Authors: Kang Senbai , Borgsmüller Nico , Valecha Monica , Kuipers Jack , Alves Joao M. , Prado-López Sonia , Chantada Débora , Beerenwinkel Niko , Posada David , Szczurek Ewa 
Published: November 2022

AbstractWe present SIEVE, a statistical method for the joint inference of somatic variants and cell phylogeny under the finite-sites assumption from single-cell DNA sequencing. SIEVE leverages raw read counts for all nucleotides and corrects the acquisition bias of branch lengths. In our simulations, SIEVE outperforms other methods in phylogenetic reconstruction and variant calling accuracy, especially in the inference of homozygous variants. Applying SIEVE to three datasets, one for triple-negative breast (TNBC), and two for colorectal cancer (CRC), we find that double mutant genotypes are rare in CRC but unexpectedly frequent in the TNBC samples.
MoDLE: high-performance stochastic modeling of DNA loop extrusion interactions
Authors: Rossini Roberto , Kumar Vipin , Mathelier Anthony , Rognes Torbjørn , Paulsen Jonas 
Published: November 2022

AbstractDNA loop extrusion emerges as a key process establishing genome structure and function. We introduce MoDLE, a computational tool for fast, stochastic modeling of molecular contacts from DNA loop extrusion capable of simulating realistic contact patterns genome wide in a few minutes. MoDLE accurately simulates contact maps in concordance with existing molecular dynamics approaches and with Micro-C data and does so orders of magnitude faster than existing approaches. MoDLE runs efficiently on machines ranging from laptops to high performance computing clusters and opens up for exploratory and predictive modeling of 3D genome structure in a wide range of settings.
Isolation and production optimization of a novel milk-clotting enzyme Bacillus velezensis DB219
Authors: Zhang Yao , Hu Jiayun , Liu Xiaofeng , Jiang Chunmin , Sun Juan , Song Xinjie , Wu Yuanfeng 
Published: November 2022

AbstractThe milk-clotting enzyme (MCE) is a crucial ingredient in cheese manufacture. Due to the limits of traditional MCE, finding viable substitute is a pressing issue. This study aims to isolate and identify a wild strain with high milk-clotting activity (MCA) and low proteolytic activity (PA) and optimize the fermentation conditions for MCE production. A strain of Bacillus velezensis DB219 with high MCA/PA value (9.2) was isolated from dairy soil (Wuchang, Heilongjiang, China) and identified through 16S rRNA from 40 strains. The optimal wheat bran, carbon, nitrogen, inoculum size, volume and initial pH were 60 g/L, soluble starch 12.5 g/L, corn steep liquor 3 g/L, 5%, 40 mL and 6.15, respectively for improving DB219 MCE production through single factor experiment. The wheat bran concentration, corn steep liquor concentration and volume were the most critical factor and their changed range was determined through Plackett–Burman design and the steepest ascent/descent experiments. The response surface analysis experiment of three factors and three levels was conducted by Box–Behnken design. The theoretical optimal fermentation conditions for DB219 MCE were as follows: wheat bran concentration 60.14 g/L, soluble starch 12.5 g/L, corn steep liquor 3 g/L, inoculum size 5%, volume 40.08 mL and initial pH 6.15. DB219 MCE achieved the maximal MCA (3164.84 SU/mL) that was 101.9% of the predicted value (3104.49 SU/mL) and 4.3-fold higher than the control.
Identification and characterization of drought-induced long noncoding RNAs (DRILs) in rice
Authors: Oh Nuri , Seo Jun Sung , Chung Pil Joong , Lee Jimin , Seo Jang-Kyun , Kang Jin-Ho , Cho Hye Sun , Jung Choonkyun 
Published: November 2022

AbstractLong noncoding RNAs (lncRNAs) act as transcriptional regulators in plants and animals. To date, they have been reported to regulate various biological processes, such as phosphate homeostasis, grain yield, and fertility in rice (Oryza sativa L.). However, the lncRNAs involved in abiotic stress responses remain poorly identified in rice. In this study, we analyzed the expression profiles of lncRNAs using public rice transcriptome datasets derived from abiotic stress-treated samples. We found that the expression of thousands of rice lncRNAs was significantly altered in the shoot and root tissues under different abiotic stresses (drought, high salinity, low temperature, and abscisic acid). We selected six novel drought-induced lncRNAs (DRILs, specifically DRIL1 to DRIL6) for further study. Real-time polymerase chain reaction analysis revealed the differential expression patterns of these DRILs under various stress conditions. The expression of abiotic stress-responsive genes was upregulated in the protoplasts by transiently overexpressed DRIL1 and DRIL4. Therefore, DRILs may be involved in the transcriptional regulation of abiotic stress-responsive genes in rice.
Somatic copy number variant load in neurons of healthy controls and Alzheimer’s disease patients
Authors: Turan Zeliha Gözde , Richter Vincent , Bochmann Jana , Parvizi Poorya , Yapar Etka , Işıldak Ulas , Waterholter Sarah-Kristin , Leclere-Turbant Sabrina , Son Çağdaş Devrim , Duyckaerts Charles , Yet İdil , Arendt Thomas , Somel Mehmet , Ueberham Uwe 
Published: November 2022

AbstractThe possible role of somatic copy number variations (CNVs) in Alzheimer’s disease (AD) aetiology has been controversial. Although cytogenetic studies suggested increased CNV loads in AD brains, a recent single-cell whole-genome sequencing (scWGS) experiment, studying frontal cortex brain samples, found no such evidence. Here we readdressed this issue using low-coverage scWGS on pyramidal neurons dissected via both laser capture microdissection (LCM) and fluorescence activated cell sorting (FACS) across five brain regions: entorhinal cortex, temporal cortex, hippocampal CA1, hippocampal CA3, and the cerebellum. Among reliably detected somatic CNVs identified in 1301 cells obtained from the brains of 13 AD patients and 7 healthy controls, deletions were more frequent compared to duplications. Interestingly, we observed slightly higher frequencies of CNV events in cells from AD compared to similar numbers of cells from controls (4.1% vs. 1.4%, or 0.9% vs. 0.7%, using different filtering approaches), although the differences were not statistically significant. On the technical aspects, we observed that LCM-isolated cells show higher within-cell read depth variation compared to cells isolated with FACS. To reduce within-cell read depth variation, we proposed a principal component analysis-based denoising approach that significantly improves signal-to-noise ratios. Lastly, we showed that LCM-isolated neurons in AD harbour slightly more read depth variability than neurons of controls, which might be related to the reported hyperploid profiles of some AD-affected neurons.
Evaluation of a skills-based peer-led art therapy online-group for people with emotion dysregulation
Authors: Jewell Mahlie , Bailey Rachel C , Curran Renae L , Grenyer Brin F.S. 
Published: November 2022

Abstract
Objective
We developed and piloted a novel art-based online skills program led by a peer mental health professional with lived experience of complex mental health, including Borderline Personality Disorder (BPD). Key challenges of living with BPD and emotion dysregulation were addressed through artmaking informed by a dialectical framework and skills, to evaluate acceptability and efficacy.

Method
A structured, manualised 2-hour weekly arts-based skills program was piloted for people with BPD over 18 weeks. Evaluation included both quantitative and qualitative measures at commencement and completion.

Results
Thirty-eight participants enrolled in the program (89.5% identified she/her pronouns, average age 33.6 years), and 31 completed (82% retention). Multilevel modelling analysis of the primary outcome variable Difficulties in Emotion Regulation Scale (DERS) demonstrated a large improvement over time (effect size Cohen’s d = 1.77). Qualitative thematic analysis found participants had improved capacity to regulate emotions and tolerate distress, improved connection with others, enhanced understanding of the self, and higher hope for living well. We found that artmaking facilitated processes and helped the expression of difficult emotions, symbolise challenging relationships, and facilitate greater self-understanding. Participants reported high levels of satisfaction, and 77.4% reported that the program had increased wellbeing.

Conclusion
This novel artmaking program for emotion dysregulation and BPD was acceptable and potentially effective. Peer facilitation using arts-based skills is a modality of therapy for further investigation.
Decision support system for handling control decisions and decision-maker related to supply chain
Authors: Alahmadi Dimah Hussein , Jamjoom Arwa A. 
Published: November 2022

AbstractBackgroundThe present study presents a knowledge-based DSS framework for supporting the decision-maker and handling control decisions related to supply chains.MethodsTwo binary variables were adopted for denoting at which time point a given task$$i$$istarts and finishes. The scheduling issues are represented through the ontological model and appropriately interpreted using the Java environment. Regarding primary data, digital form of administration using google form platform took precedence over physical administration.ResultsThe findings might not be exact replication of the findings from previous studies that are limited to the influence of information and material flow on the performance of supply chain as there are concerns of what factors constitute information and material flow that need to be identified and considered. However, with the finding of associating factors of information and material flow may need to consider this in managing the flow and the supply chain. Associating factors such as information quality, information visibility, material cost, fund shortage and so on, play a role in information and material flow and the decisions made in an organization.ConclusionsFactors associating with information and material flow need to be considered in decision making as well, as the cost in any of the elements affects the flow and this would impede supply chain performance of the organization.
Efficient 1,3-dihydroxyacetone biosynthesis in Gluconobacter oxydans using metabolic engineering and a fed-batch strategy
Authors: Zeng Weizhu , Shan Xiaoyu , Liu Li , Zhou Jingwen 
Published: November 2022

Abstract1,3-Dihydroxyacetone (DHA) is a commercially important chemical and widely used in cosmetics, pharmaceuticals, and food industries as it prevents excessive water evaporation, and provides anti-ultraviolet radiation protection and antioxidant activity. Currently, the industrial production of DHA is based on a biotechnological synthetic route using Gluconobacter oxydans. However, achieving higher production requires more improvements in the synthetic process. In this study, we compared DHA synthesis levels in five industrial wild-type Gluconobacter strains, after which the G. oxydans WSH-003 strain was selected. Then, 16 dehydrogenase genes, unrelated to DHA synthesis, were individually knocked out, with one strain significantly enhancing DHA production, reaching 89.49 g L−1 and 42.27% higher than the wild-type strain. By optimizing the culture media, including seed culture and fermentation media, DHA production was further enhanced. Finally, using an established fed-batch fermentation system, DHA production reached 198.81 g L−1 in a 5 L bioreactor, with a glycerol conversion rate of 82.84%.
Graphical Abstract
Developing and testing the ExerciseGuide UK website for people with lung cancer: reflections on the added value of patient and public involvement within a doctoral degree
Authors: Curry Jordan , Roberts Helen , Smith Alan , Riley Diane , Pearson Mark , Forbes Cynthia C. 
Published: November 2022

Abstract
Background
Lung cancer has one of the highest incidence and mortality rates worldwide. Physical activity can provide those diagnosed with lung cancer with several physical and psychological benefits. However, the examination of digitally delivered physical activity to those with lung cancer is not as researched as other common cancers. Often, those diagnosed with lung cancer are older adults (65 years or older). Older adults are often wrongly assumed to lack digital skills, interest, and not engage with digital technology regularly. Although individuals are interested, would involving older people in designing of websites and apps result in better engagement?

Main body
In this article, the authors discuss the process of adapting a digital platform with a patient and public involvement group to provide those who have received a lung cancer diagnosis with a tailored physical activity program and health educational modules. We discuss the influence of recurrent patient and public involvement on the study, the patient and public involvement members, and the doctoral researcher.

Conclusion
Working with a patient and public involvement group over several months, especially potential users of a digital intervention, may enhance its relevance, accessibility, and usability. By engaging with patients, family, or caregivers for someone with lung cancer, the doctoral student gained insight into the needs of the study population and what to consider during development. All group members expressed their interest and enjoyment in their involvement, and several are now active members of a wider patient and public involvement network.