bluuebunny/crossref_metadata_2025_split huggingface dataset:
von Willebrand factor modulates immune complexes and the recall response against factor VIII in a murine hemophilia A model
Authors: Oleshko Olga , Vollack-Hesse Nadine , Tiede Andreas , Hegermann Jan , Curth Ute , Werwitzke Sonja 
Published: September 2023

Abstract
Achieving tolerance toward factor VIII (FVIII) remains an important goal of hemophilia treatment. Up to 40% of patients with severe hemophilia A (HA) develop neutralizing antibodies against FVIII, and the only proven treatment to achieve tolerance is infusion of FVIII over prolonged periods in the context of immune tolerance induction. Here, we addressed the role of von Willebrand factor (VWF) as a modulator of anti-FVIII antibody effector functions and the FVIII-specific recall response in an HA mouse model. Analytical ultracentrifugation was used to demonstrate formation of FVIII-containing immune complexes (FVIII-ICs). VWF did not fully prevent FVIII-IC formation but was rather incorporated into larger macromolecular complexes. VWF prevented binding of FVIII-ICs to complement C1q, most efficiently when it was preincubated with FVIII before the addition of antibodies. It also prevented binding to immobilized Fc-γ receptor and to bone marrow–derived dendritic cells. An in vitro model of the anti-FVIII recall response demonstrated that addition of VWF to FVIII abolished the proliferation of FVIII-specific antibody-secreting cells. After adoptive transfer of sensitized splenocytes into immunocompetent HA mice, the FVIII recall response was diminished by VWF. In summary, these data indicate that VWF modulates the formation and effector functions of FVIII-ICs and attenuates the secondary immune response to FVIII in HA mice.
Runx1-R188Q germ line mutation induces inflammation and predisposition to hematologic malignancies in mice
Authors: Ahmad Mohd Hafiz , Hegde Mahesh , Wong Waihay J. , Mohammadhosseini Mona , Garrett Lisa , Carrascoso Anneliese , Issac Neethu , Ebert Benjamin , Silva Jeffrey C. , Pihan German , Zhu Lihua J. , Wolfe Scot A. , Agarwal Anupriya , Liu P. Paul , Castilla Lucio H. 
Published: September 2023

Abstract
Germ line mutations in the RUNX1 gene cause familial platelet disorder (FPD), an inherited disease associated with lifetime risk to hematopoietic malignancies (HM). Patients with FPD frequently show clonal expansion of premalignant cells preceding HM onset. Despite the extensive studies on the role of RUNX1 in hematopoiesis, its function in the premalignant bone marrow (BM) is not well-understood. Here, we characterized the hematopoietic progenitor compartments using a mouse strain carrying an FPD-associated mutation, Runx1R188Q. Immunophenotypic analysis showed an increase in the number of hematopoietic stem and progenitor cells (HSPCs) in the Runx1R188Q/+ mice. However, the comparison of Sca-1 and CD86 markers suggested that Sca-1 expression may result from systemic inflammation. Cytokine profiling confirmed the dysregulation of interferon-response cytokines in the BM. Furthermore, the expression of CD48, another inflammation-response protein, was also increased in Runx1R188Q/+ HSPCs. The DNA-damage response activity of Runx1R188Q/+ hematopoietic progenitor cells was defective in vitro, suggesting that Runx1R188Q may promote genomic instability. The differentiation of long-term repopulating HSCs was reduced in Runx1R188Q/+ recipient mice. Furthermore, we found that Runx1R188Q/+ HSPCs outcompete their wild-type counterparts in bidirectional repopulation assays, and that the genetic makeup of recipient mice did not significantly affect the clonal dynamics under this setting. Finally, we demonstrate that Runx1R188Q predisposes to HM in cooperation with somatic mutations found in FPDHM, using 3 mouse models. These studies establish a novel murine FPDHM model and demonstrate that germ line Runx1 mutations induce a premalignant phenotype marked by BM inflammation, selective expansion capacity, defective DNA-damage response, and predisposition to HM.
Mechanisms for leaf color changes in Osmanthus fragrans ‘Ziyan Gongzhu’ using physiology, transcriptomics and metabolomics
Authors: Guo Peng , Huang Ziqi , Zhao Wei , Lin Nan , Wang Yihan , Shang Fude 
Published: September 2023

Abstract
Background
Color-leaved O. fragrans is a variety of Osmanthus fragrans, which has both the fragrance of Osmanthus and the color of color-leaved plants. However, the molecular mechanism of color change of color-leaved O. fragrans is not clear. In this study, we analyzed the regulatory mechanism of four different color leaves of ‘Ziyan Gongzhu’ through physiological, transcriptome and metabolome levels.

Results
Firstly, we measured the leaf pigments content and leaf chromatic parameters for correlation analysis, indicating a significant correlation between them. Overall, the content of chlorophyll a + b is low and the content of anthocyanin is high in T1 and T2 leaves, along with low expression of chlorophyll synthesis genes (HEMA, CHLG, and CAO, etc.) and high expression of anthocyanin synthesis genes (F3H, F3’H, DFR and ANS, etc.), resulting purple red and light purple in T1 and T2 leaves, respectively. It was also found that the pigment closely related to the color leaves of ‘Ziyan Gongzhu’ was cyanidin. The content anthocyanins, may be regulated by two putative MYB activators (OfMYB3 and OfMYB4) and two putative MYB repressors (OfMYB1 and OfMYB2). In contrast, the content of chlorophyll a + b is high and the content of anthocyanin is low in T3 and T4 leaves, along with high expression of chlorophyll synthesis genes and low expression of anthocyanin synthesis genes, resulting yellow green and dark green in T3 and T4 leaves, respectively. And abnormal chloroplast development affects chlorophyll content in T1, T2, and T3 leaves. Although the content of carotenoids first dropped in T2 leaves, it then rapidly accumulated in T4 leaves, in sync with the increase in the expression of genes related to carotenoid biosynthesis (ZDS, LHYB, and ZEP, for example). Analysis of photosynthetic, carbohydrate and hormone-related differentially abundant metabolites (DAMs) and DEGs found that they may participate in the regulation of leaf color change of ‘Ziyan Gongzhu’ by affecting pigment synthesis.

Conclusion
Our results pave the way for a comprehensive knowledge of the regulatory processes governing leaf color in ‘Ziyan Gongzhu’ and identify possible genes for application regarding molecular colored-leaf cultivar breeding.
A case report of a brain abscess due to prevotella oris and a review of the literature
Authors: Li Chenlu , Lv Chaonan , Yu Miao , Zhang Yajing , Ling Ling , Yue Wei 
Published: September 2023

Abstract
Background
Brain abscesses caused by Prevotella oris are rarely reported. Here, we described a case of a brain infection caused by Prevotella oris that was detected by metagenomic next-generation sequencing (mNGS).

Case presentation
A 63-year-old man with no medical history reported headache in the right frontotemporal region, fever, and intermittent diplopia. Magnetic resonance imaging (MRI) revealed abnormal signals and enhancement changes in the superior sellar region. mNGS testing showed that cerebrospinal fluid collected from the spine was positive for Prevotella oris. After receiving a combined treatment of antibiotic therapy, the patient recovered well.

Conclusion
We reviewed the relevant literature and summarized the characteristics and prognosis of this type of bacterial infection to provide ideas for clinicians to diagnose and treat this disease.
Predicting sepsis onset in ICU using machine learning models: a systematic review and meta-analysis
Authors: Yang Zhenyu , Cui Xiaoju , Song Zhe 
Published: September 2023

Abstract
Background
Sepsis is a life-threatening condition caused by an abnormal response of the body to infection and imposes a significant health and economic burden worldwide due to its high mortality rate. Early recognition of sepsis is crucial for effective treatment. This study aimed to systematically evaluate the performance of various machine learning models in predicting the onset of sepsis.

Methods
We conducted a comprehensive search of the Cochrane Library, PubMed, Embase, and Web of Science databases, covering studies from database inception to November 14, 2022. We used the PROBAST tool to assess the risk of bias. We calculated the predictive performance for sepsis onset using the C-index and accuracy. We followed the PRISMA guidelines for this study.

Results
We included 23 eligible studies with a total of 4,314,145 patients and 26 different machine learning models. The most frequently used models in the studies were random forest (n = 9), extreme gradient boost (n = 7), and logistic regression (n = 6) models. The random forest (test set n = 9, acc = 0.911) and extreme gradient boost (test set n = 7, acc = 0.957) models were the most accurate based on our analysis of the predictive performance. In terms of the C-index outcome, the random forest (n = 6, acc = 0.79) and extreme gradient boost (n = 7, acc = 0.83) models showed the highest performance.

Conclusion
Machine learning has proven to be an effective tool for predicting sepsis at an early stage. However, to obtain more accurate results, additional machine learning methods are needed. In our research, we discovered that the XGBoost and random forest models exhibited the best predictive performance and were most frequently utilized for predicting the onset of sepsis.

Trial registration
CRD42022384015
Use of immunoinformatics and the simulation approach to identify Helicobacter pylori epitopes to design a multi-epitope subunit vaccine for B- and T-cells
Authors: Chaleshtori Zahra Ahmadzadeh , Rastegari Ali Asghar , Nayeri Hashem , Doosti Abbas 
Published: September 2023

Abstract
Background
Helicobacter pylori cause a variety of gastric malignancies, gastric ulcers, and cause erosive diseases. The extreme nature of the bacterium and the implantation of this bacterium protects it against designing a potent drug against it. Therefore, employing a precise and effective design for a more safe and stable antigenic vaccine against this pathogen can effectively control its associated infections. This study, aimed at improving the design of multiple subunit vaccines against H. pylori, adopts multiple immunoinformatics approaches in combination with other computational approaches.

Results
In this regard, 10 HTL, and 11 CTL epitopes were employed based on appropriate adopted MHC binding scores and c-terminal cut-off scores of 4 main selected proteins (APO, LeoA, IceA1, and IceA2). An adjuvant was added to the N end of the vaccine to achieve higher stability. For validation, immunogenicity and sensitization of physicochemical analyses were performed. The vaccine could be antigenic with significantly strong interactions with TOLK-2, 4, 5, and 9 receptors. The designed vaccine was subjected to Gromacs simulation and immune response prediction modelling that confirmed expression and immune-stimulating response efficiency. Besides, the designed vaccine showed better interactions with TLK-9.

Conclusions
Based on our analyses, although the suggested vaccine could induce a clear response against H. pylori, precise laboratory validation is required to confirm its immunogenicity and safety status.
Temporomandibular joint disc repositioning and occlusal splint for adolescents with skeletal class II malocclusion: a single-center, randomized, open-label trial
Authors: Sun Jiali , Zhu Huimin , Lu Chuan , Zhao Jieyun , Nie Xin , Yang Zhi , He Dongmei 
Published: September 2023

Abstract
Background
Temporomandibular joint (TMJ) disc repositioning through open suturing (OSu) is a new disc repositioning method. Its result for adolescents with condylar resorption and dentofacial deformities combined with and without postoperative occlusal splints (POS) has not been well studied.

Objective
This study was to evaluate and compare the effects of OSu with and without POS in the treatment of TMJ anterior disc displacement without reduction (ADDwoR) in adolescent skeletal Class II malocclusion.

Methods
A total of 60 adolescents with bilateral ADDwoR were enrolled in this study. They were randomly allocated into two groups: OSu with and without POS. Magnetic resonance imaging (MRI) and lateral cephalometric radiographs were used to measure changes in condylar height and the degree of skeletal Class II malocclusion from before operation and at 12 months postoperatively. Changes in these indicators were compared within and between the two groups.

Results
After OSu, both groups exhibited significant improvements in condylar height and occlusion at the end of 12 months follow-up (P < 0.05). The group of OSu with POS had significantly more new bone formation (2.83 ± 0.75 mm vs. 1.42 ± 0.81 mm, P < 0.001) and improvement in dentofacial deformity than the group of OSu only (P < 0.05). The new bone height was significantly correlated with POS (P < 0.001), the changes of SNB (P = 0.018), overjet (P = 0.012), and Wits appraisal (P < 0.001).

Conclusion
These findings indicated that OSu can effectively stimulate condylar regeneration and improve skeletal Class II malocclusion in adolescents with bilateral ADDwoR. The results are better when combined with POS.

Trial registration
This trial was prospectively registered on the chictr.org.cn registry with ID: ChiCTR1900021821 on 11/03/2019
Cervical ulcer caused by group B streptococcus with bacterial vaginosis: a case report
Authors: Chen Yi , Wu Dan 
Published: September 2023

AbstractThe female genital ulcer is a manifestation of many diseases, which may vary depending on the etiology, disease duration, age, and host immunity. A middle-aged (40–50 years) woman had a 4-month history of vaginal bleeding. The results of syphilis, herpes, the cervical cancer, tuberculosis, and fungi or acute cervical inflammation caused by Chlamydia trachomatis and Mycoplasma hominis were negative through the blood test and the biopsy. Cervical discharge culture revealed positive for group B Streptococcus and bacterial vaginosis. The patient was treated with oral antibiotics for 7 days. One month later, repeat colposcopy revealed a smooth cervix and complete ulcer disappearance, while cervical discharge culture retested no group B Streptococcus and bacterial vaginosis. The patient was diagnosed with cervical ulcer. Complete medical history taking and bacterial culture of cervical discharge are important for identifying the etiology of the cervical ulcer and deciding the appropriate treatment for the disease.
Chronic stress and turnover intention of resident physicians after experiencing COVID-19
Authors: Jia Qingwen , Qu Yi , Huo Huisheng , Yin Hongxia , Jiang Meijun , You Dianping 
Published: September 2023

Abstract
Background
Previous studies have explored the stress and turnover intention of healthcare workers, but as important backup talents in the healthcare system, resident physicians have received little attention from researchers, especially after experiencing COVID-19. Therefore, this study aims to evaluate the chronic stress and turnover intention of resident physicians after experiencing COVID-19.

Methods
From June to August 2022, we conducted a questionnaire survey on resident physicians in the Children's Hospital of Hebei Province through the online platform (Wenjuanxing) to evaluate their chronic stress and turnover intention after experiencing COVID-19. For the collected data, we used frequency and percentage to make the statistical description, the Chi-square test to make a univariate analysis on the scores of chronic stress and turnover intention scale, and binary logistic regression analysis to explore the influencing factors of turnover intention.

Results
Out of 143 respondents, we finally received 127 questionnaires, with a response rate of 88.81%. Among 127 respondents, 80.31% of resident physicians experienced varying degrees of chronic stress (mild: 36.22%, moderate: 35.43%, severe: 8.66%), and 74.80% of resident physicians showed varying degrees of turnover intention (mild: 23.62%, moderate: 37.79%, severe: 13.39%). Moreover, age (OR = 0.772, P = 0.042), identity (OR = 8.648, P = 0.021), and chronic stress levels (mild: OR = 6.938, P = 0.003; moderate: OR = 44.049, P < 0.003; severe: OR = 46.141, P = 0.004) can significantly affect turnover intention.

Conclusion
In this study, we reported a relatively high proportion of resident physicians with high chronic stress and high turnover intention after experiencing COVID-19. We suggest that the relevant departments should pay more attention to the resident physicians’ group and formulate corresponding measures to solve the problems faced by the resident physicians and ensure the stability of the health human resources.
Concordance between 8-1-1 HealthLink BC Emergency iDoctor-in-assistance (HEiDi) virtual physician advice and subsequent health service utilization for callers to a nurse-managed provincial health information telephone service
Authors: Duncan Ross , Stewart Kurtis , Scheuermeyer Frank X. , Abu-Laban Riyad B. , Ho Kendall , Lavallee Danielle , Christenson Jim , Wood Nancy , Bryan Stirling , Hedden Lindsay 
Published: September 2023

Abstract
Background
British Columbia 8–1-1 callers who are advised by a nurse to seek urgent medical care can be referred to virtual physicians (VPs) for supplemental assessment and advice. Prior research indicates callers’ subsequent health service use may diverge from VP advice. We sought to 1) estimate concordance between VP advice and subsequent health service use, and 2) identify factors associated with concordance to understand potential drivers of discordant cases.

Methods
We linked relevant provincial administrative databases to obtain inpatient, outpatient, and emergency service use by callers. We developed operational definitions of concordance collaboratively with researcher, patient, VP, and management perspectives. We used Kaplan–Meier curves to describe health service use post-VP consultation and Cox regression to estimate the association of caller factors (rurality, demography, attachment to primary care) and call factors (reason, triage level, time of day) with concordance as hazard ratios.

Results
We analyzed 17,188 calls from November 16, 2020 to April 30, 2021. Callers advised to attend an emergency department (ED) immediately were the most concordant (73%) while concordance was lowest for those advised to seek Family Physician (FP) care either immediately (41%) or within 7 days (47%). Callers unattached to FPs were less likely to schedule an FP visit (hazard ratio = 0.76 [95%CI: 0.68–0.85]). Rural callers were less likely to attend an ED within 48 h when advised to go immediately (0.53 [95%CI:0.46–0.61]) compared to urban callers. Rural callers advised to see an FP, either immediately (1.28 [95%CI:1.01–1.62]) or within 7 days (1.23 [95%CI: 1.11–1.37]), were more likely to do so than urban callers.

Interpretation
Concordance between VP advice and subsequent caller health service use varies substantially by category of advice and caller rurality. Concordance with advice to “Go to ED” is high overall but to access primary care is below 50%, suggesting potential issues with timely access to FP care. Future research from a patient/caller centered perspective may reveal additional barriers and facilitators to concordance.
Understanding the relationship between circulating lipids and risk of chronic kidney disease: a prospective cohort study and large-scale genetic analyses
Authors: Wang Yutong , Zhang Li , Zhang Wenqiang , Tang Mingshuang , Cui Huijie , Wu Xueyao , Zhao Xunying , Chen Lin , Yan Peijing , Yang Chao , Xiao Chenghan , Zou Yanqiu , Liu Yunjie , Zhang Ling , Yang Chunxia , Yao Yuqin , Li Jiayuan , Liu Zhenmi , Jiang Xia , Zhang Ben 
Published: September 2023

Abstract
Background
This study aims to comprehensively investigate the phenotypic and genetic relationships between four common lipids (high-density lipoprotein cholesterol, HDL-C; low-density lipoprotein cholesterol, LDL-C; total cholesterol, TC; and triglycerides, TG), chronic kidney disease (CKD), and estimated glomerular filtration rate (eGFR).

Methods
We first investigated the observational association of lipids (exposures) with CKD (primary outcome) and eGFR (secondary outcome) using data from UK Biobank. We then explored the genetic relationship using summary statistics from the largest genome-wide association study of four lipids (N = 1,320,016), CKD (Ncase = 41,395, Ncontrol = 439,303), and eGFR(N = 567,460).

Results
There were significant phenotypic associations (HDL-C: hazard ratio (HR) = 0.76, 95%CI = 0.60–0.95; TG: HR = 1.08, 95%CI = 1.02–1.13) and global genetic correlations (HDL-C: $${r}_{g}$$

r
g

= − 0.132, P = 1.00 × 10–4; TG: $${r}_{g}$$

r
g

= 0.176; P = 2.66 × 10–5) between HDL-C, TG, and CKD risk. Partitioning the whole genome into 2353 LD-independent regions, twelve significant regions were observed for four lipids and CKD. The shared genetic basis was largely explained by 29 pleiotropic loci and 36 shared gene-tissue pairs. Mendelian randomization revealed an independent causal relationship of genetically predicted HDL-C (odds ratio = 0.91, 95%CI = 0.85–0.98), but not for LDL-C, TC, or TG, with the risk of CKD. Regarding eGFR, a similar pattern of correlation and pleiotropy was observed.

Conclusions
Our work demonstrates a putative causal role of HDL-C in CKD and a significant biological pleiotropy underlying lipids and CKD in populations of European ancestry. Management of low HDL-C levels could potentially benefit in reducing the long-term risk of CKD.

Graphical Abstract
Romosozumab in osteoporosis: yesterday, today and tomorrow
Authors: Wu Dong , Li Lei , Wen Zhun , Wang Guangbin 
Published: September 2023

AbstractOsteoporosis is a systemic bone disease characterized by low bone mass, microarchitectural deterioration, increased bone fragility, and fracture susceptibility. It commonly occurs in older people, especially postmenopausal women. As global ageing increases, osteoporosis has become a global burden. There are a number of medications available for the treatment of osteoporosis, categorized as anabolic and anti-resorptive. Unfortunately, there is no drugs which have dual influence on bone, while all drugs have limitations and adverse events. Some serious adverse events include jaw osteonecrosis and atypical femoral fracture. Recently, a novel medication has appeared that challenges this pattern. Romosozumab is a novel drug monoclonal antibody to sclerostin encoded by the SOST gene. It has been used in Japan since 2019 and has achieved promising results in treating osteoporosis. However, it is also accompanied by some controversy. While it promotes rapid bone growth, it may cause serious adverse events such as cardiovascular diseases. There has been scepticism about the drug since its inception. Therefore, the present review comprehensively covered romosozumab from its inception to its clinical application, from animal studies to human studies, and from safety to cost. We hope to provide a better understanding of romosozumab for its clinical application.
Artificial switches induce the bespoke production of functional compounds in marine microalgae Chlorella by neutralizing CO2
Authors: Gu Jiahua , Xiao Yuan , Wu Mingcan , Wang Aoqi , Cui Xinyu , Xin Yi , Paithoonrangsarid Kalyanee , Lu Yandu 
Published: September 2023

AbstractTo improve the CO2 tolerance of a marine microalga Chlorella sp. of which the production capacity has been demonstrated industrially, a mutant library was created and a strain hct53 was screened. Compared to the parental strain, hct53 shows a high CO2 capture capacity, while starch biosynthesis is compromised, with increases in health beneficial metabolites and antioxidant capacity. Global gene expression and genome-wide mutation distribution revealed that transcript choreography was concomitant with more active CO2 sequestration, an increase in the lipid synthesis, and a decrease in the starch and protein synthesis. These results suggest that artificial trait improvement via mutagenesis, couple with multiomics analysis, helps discover genetic switches that induce the bespoke conversion of carbon flow from “redundant metabolites” to valuable ones for functional food.