bluuebunny/crossref_metadata_2025_split huggingface dataset:
Recombinant vaccines in 2022: a perspective from the cell factory
Authors: de Pinho Favaro Marianna Teixeira , Atienza-Garriga Jan , Martínez-Torró Carlos , Parladé Eloi , Vázquez Esther , Corchero José Luis , Ferrer-Miralles Neus , Villaverde Antonio 
Published: October 2022

AbstractThe last big outbreaks of Ebola fever in Africa, the thousands of avian influenza outbreaks across Europe, Asia, North America and Africa, the emergence of monkeypox virus in Europe and specially the COVID-19 pandemics have globally stressed the need for efficient, cost-effective vaccines against infectious diseases. Ideally, they should be based on transversal technologies of wide applicability. In this context, and pushed by the above-mentioned epidemiological needs, new and highly sophisticated DNA-or RNA-based vaccination strategies have been recently developed and applied at large-scale. Being very promising and effective, they still need to be assessed regarding the level of conferred long-term protection. Despite these fast-developing approaches, subunit vaccines, based on recombinant proteins obtained by conventional genetic engineering, still show a wide spectrum of interesting potentialities and an important margin for further development. In the 80’s, the first vaccination attempts with recombinant vaccines consisted in single structural proteins from viral pathogens, administered as soluble plain versions. In contrast, more complex formulations of recombinant antigens with particular geometries are progressively generated and explored in an attempt to mimic the multifaceted set of stimuli offered to the immune system by replicating pathogens. The diversity of recombinant antimicrobial vaccines and vaccine prototypes is revised here considering the cell factory types, through relevant examples of prototypes under development as well as already approved products.
Circular RNA circPVT1 promotes nasopharyngeal carcinoma metastasis via the β-TrCP/c-Myc/SRSF1 positive feedback loop
Authors: Mo Yongzhen , Wang Yumin , Wang Yian , Deng Xiangying , Yan Qijia , Fan Chunmei , Zhang Shuai , Zhang Shanshan , Gong Zhaojian , Shi Lei , Liao Qianjin , Guo Can , Li Yong , Li Guiyuan , Zeng Zhaoyang , Jiang Weihong , Xiong Wei , Xiang Bo 
Published: October 2022

AbstractBackgroundCircular RNAs (circRNAs) act as gene expression regulators and are involved in cancer progression. However, their functions have not been sufficiently investigated in nasopharyngeal carcinoma (NPC).MethodsThe expression profiles of circRNAs in NPC cells within different metastatic potential were reanalyzed. Quantitative reverse transcription PCR and in situ hybridization were used to detect the expression level ofcircPVT1in NPC cells and tissue samples. The association of expression level ofcircPVT1with clinical properties of NPC patients was evaluated. Then, the effects ofcircPVT1expression on NPC metastasis were investigated by in vitro and in vivo functional experiments. RNA immunoprecipitation, pull-down assay and western blotting were performed to confirm the interaction betweencircPVT1and β-TrCP in NPC cells. Co-immunoprecipitation and western blotting were performed to confirm the interaction between β-TrCP and c-Myc in NPC cells.ResultsWe find thatcircPVT1, a circular RNA, is significantly upregulated in NPC cells and tissue specimens. In vitro and in vivo experiments showed thatcircPVT1promotes the invasion and metastasis of NPC cells. Mechanistically,circPVT1inhibits proteasomal degradation of c-Myc by binding to β-TrCP, an E3 ubiquiting ligase. Stablization of c-Myc bycircPVT1alters the cytoskeleton remodeling and cell adhesion in NPC, which ultimately promotes the invasion and metastasis of NPC cells. Furthermore, c-Myc transcriptionally upregulates the expression of SRSF1, an RNA splicing factor, and recruits SRSF1 to enhance the biosynthesis ofcircPVT1through coupling transcription with splicing, which forms a positive feedback forcircPVT1production.ConclusionsOur results revealed the important role ofcircPVT1in the progression of NPC through the β-TrCP/c-Myc/SRSF1 positive feedback loop, andcircPVT1may serve as a prognostic biomarker or therapeutic target in patients with NPC.
Increased cognitive load in immersive virtual reality during visuomotor adaptation is associated with decreased long-term retention and context transfer
Authors: Juliano Julia M. , Schweighofer Nicolas , Liew Sook-Lei 
Published: October 2022

Abstract
Background
Complex motor tasks in immersive virtual reality using a head-mounted display (HMD-VR) have been shown to increase cognitive load and decrease motor performance compared to conventional computer screens (CS). Separately, visuomotor adaptation in HMD-VR has been shown to recruit more explicit, cognitive strategies, resulting in decreased implicit mechanisms thought to contribute to motor memory formation. However, it is unclear whether visuomotor adaptation in HMD-VR increases cognitive load and whether cognitive load is related to explicit mechanisms and long-term motor memory formation.

Methods
We randomized 36 healthy participants into three equal groups. All groups completed an established visuomotor adaptation task measuring explicit and implicit mechanisms, combined with a dual-task probe measuring cognitive load. Then, all groups returned after 24-h to measure retention of the overall adaptation. One group completed both training and retention tasks in CS (measuring long-term retention in a CS environment), one group completed both training and retention tasks in HMD-VR (measuring long-term retention in an HMD-VR environment), and one group completed the training task in HMD-VR and the retention task in CS (measuring context transfer from an HMD-VR environment). A Generalized Linear Mixed-Effect Model (GLMM) was used to compare cognitive load between CS and HMD-VR during visuomotor adaptation, t-tests were used to compare overall adaptation and explicit and implicit mechanisms between CS and HMD-VR training environments, and ANOVAs were used to compare group differences in long-term retention and context transfer.

Results
Cognitive load was found to be greater in HMD-VR than in CS. This increased cognitive load was related to decreased use of explicit, cognitive mechanisms early in adaptation. Moreover, increased cognitive load was also related to decreased long-term motor memory formation. Finally, training in HMD-VR resulted in decreased long-term retention and context transfer.

Conclusions
Our findings show that cognitive load increases in HMD-VR and relates to explicit learning and long-term motor memory formation during motor learning. Future studies should examine what factors cause increased cognitive load in HMD-VR motor learning and whether this impacts HMD-VR training and long-term retention in clinical populations.
Diagnostic challenge in mixed phenotype acute leukemia with T/megakaryocyte or T/myeloid lineages accompanied by t(3;3)
Authors: Jia Yannan , Lin Dong , Wang Zhe , Li Chengwen , Wang Huijun , Wang Jianxiang , Mi Yingchang 
Published: October 2022

Abstract
Background
The diagnosis of mixed phenotype acute leukemia (MPAL) with T/megakaryocyte or T/myeloid lineages accompanied by t(3;3) is always a challenge. Therefore, multiple experimental methods are usually required to avoid misdiagnosis. In this report, we presented a rare case of MPAL with T/myeloid lineages accompanied by t(3;3) and discussed the experience of differential diagnosis and our appreciation of the MPAL with T/megakaryocyte and T/myeloid lineages accompanied by t(3;3).

Case presentation:
A 31-year-old woman was admitted to our hospital due to recurrent fever for 20 days. Two distinct blast populations were detected by flow cytometry analysis: one population fulfills the immunophenotypic criteria for T-lymphoblastic leukemia, while the other population is highly suggestive of megakaryoblasts. These immunophenotypic features support the diagnosis of MPAL (T/megakaryocyte), which is rarely reported​. Interestingly, a complex karyotype was detected afterward by cytogenetics with t(3;3)(q21;q26.2), indicating a diagnosis of AML with t(3;3), a subset of which is also characterized by megakaryocytic markers such as CD41 and CD61. It seems that the second blast population detected by flow cytometry could not be classified into either diagnosis based on the morphology, immunophenotyping, and even cytogenetic findings, posing a real diagnostic problem because of the lack of clear-cut cytogenetic morphological defined criteria to distinguish between acute megakaryocytic leukemia and AML with t(3;3). Combining all of the examination data, this case was ultimately diagnosed as MPAL (T + My)-NOS with t(3;3) through differential diagnosis. Before the cytogenetic results were available, the patient received an acute lymphoblastic leukemia (ALL) regimen for MPAL treatment, but the effect was unsatisfactory. After the diagnosis was clear, she received an AML-like regimen with azacitidine for 7 days and venetoclax for 14 days, and achieved complete morphological remission.

Conclusion
MPAL with either T/megakaryocyte or T/myeloid lineages accompanied by t(3;3) is rare, and it is difficult to make a clear diagnosis. Thus, comprehensive examinations, including bone marrow cell morphology, flow cytometry analysis, cytogenetics, and molecular analysis are recommended to avoid misdiagnosis. AML-like regimen including azacitidine and venetoclax may be effective for treating MPAL (T + My)-NOS with t(3;3).
Ex vivo γH2AX assay for tumor radiosensitivity in primary prostate cancer patients and correlation with clinical parameters
Authors: Marinescu Ioana M. , Rogg Manuel , Spohn Simon , von Büren Moritz , Kamps Marius , Jilg Cordula A. , Fountzila Elena , Papadopoulou Kyriaki , Ceci Lara , Bettermann Alisa , Ruf Juri , Benndorf Matthias , Adebahr Sonja , Zips Daniel , Grosu Anca L. , Schell Christoph , Zamboglou Constantinos 
Published: October 2022

Abstract
Backround
Accurate surrogate parameters for radio resistance are warranted for individualized radiotherapy (RT) concepts in prostate cancer (PCa). The purpose of this study was to assess intertumoral heterogeneity in terms of radio resistance using an ex-vivo γH2AX assay after irradiation of prostate biopsy cores and to investigate its correlation with clinical features of respective patients as well as imaging and genomic features of tumor areas.

Methods
Twenty one patients with histologically-proven PCa and pre-therapeutic multiparametric resonance imaging and prostate-specific membrane antigen positron emission tomography were included in the study. Biopsy cores were collected from 26 PCa foci. Residual γH2AX foci were counted 24 h after ex-vivo irradiation (with 0 and 4 Gy) of biopsy specimen and served as a surrogate for radio resistance. Clinical, genomic (next generation sequencing) and imaging features were collected and their association with the radio resistance was studied.

Results
In total 18 PCa lesions from 16 patients were included in the final analysis. The median γH2AX foci value per PCa lesion was 3.12. According to this, the patients were divided into two groups (radio sensitive vs. radio resistant) with significant differences in foci number (p < 0.0001). The patients in the radio sensitive group had significantly higher prostate specific antigen serum concentration (p = 0.015), tumor areas in the radio sensitive group had higher SUV (standardized uptake values in PSMA PET)-max and -mean values (p = 0.0037, p = 0.028) and lower ADC (apparent diffusion coefficient-mean values, p = 0.049). All later parameters had significant (p < 0.05) correlations in Pearson’s test. One patient in the radio sensitive group displayed a previously not reported loss of function frameshift mutation in the NBN gene (c.654_658delAAAAC) that introduces a premature termination codon and results in a truncated protein.

Conclusion
In this pilot study, significant differences in intertumoral radio resistance were observed and clinical as well as imaging parameters may be applied for their prediction. After further prospective validation in larger patient cohorts these finding may lead to individual RT dose prescription for PCa patients in the future.
Right vertical axillary incision for atrial septal defect: a propensity score matched study
Authors: Yang Xiaohui , Hu Yuan , Dong Jie , Huang Peng , Luo Jinwen , Yang Guangxian , Deng Xicheng 
Published: October 2022

Abstract
Background
Atrial septal defect is one of the most common types of congenital heart disease. This study aims to explore the surgical and cosmetic effects of open-heart surgery with right vertical axillary incision for simple congenital heart disease in infants.

Methods
From June 2018 to October 2021, children who underwent direct surgery of atrial septal defect in our department were selected for a propensity score matched study. Those with direct surgery through the right vertical axillary incision were included in the right vertical axillary incision group. According to age and weight, propensity score matching method was employed to match children from the right vertical axillary incision group with those undergoing direct surgery through median sternotomy (median sternotomy group) at a 1:2 ratio. Surgery outcomes between two groups were compared to evaluate the effectiveness and safety of right vertical axillary incision group.

Results
The median incision length (median, [interquartile range]) in right vertical axillary incision group (4.8 cm, [4.0–5.0]) was shorter than that in median sternotomy group (p < 0.001). The median drainage volume of drainage tube of the right vertical axillary incision group (117.5 ml, [92.8,152.8]) was smaller than that of median sternotomy group (p = 0.021). While no residual bubbles cases in the left and right ventricles and outflow tract were present in the right vertical axillary incision group, 44% of residual air bubble rate in right ventricular outflow tract was detected in median sternotomy group (p = 0.001). Additional sedation and analgesia (p = 0.003), wound infection or poor healing (p = 0.047), thoracic deformity healing (p = 0.029) and appearance satisfaction questionnaire (p = 0.018) in the right vertical axillary incision group were better than those in the median sternotomy group.

Conclusion
Right axillary vertical incision can effectively reduce surgical trauma, accelerate postoperative rehabilitation. This surgical approach also provides better cosmetic effect, which is easily accepted by children’s families and worthy of further clinical application.
Flavokawain A is a natural inhibitor of PRMT5 in bladder cancer
Authors: Liu Shuangjie , Liu Zhuonan , Piao Chiyuan , Zhang Zhe , Kong Chuize , Yin Lei , Liu Xi 
Published: October 2022

Abstract
Background
Protein arginine methyltransferases (PRMTs) regulate protein biological activity by modulating arginine methylation in cancer and are increasingly recognized as potential drug targets. Inhibitors targeting PRMTs are currently in the early phases of clinical trials and more candidate drugs are needed. Flavokawain A (FKA), extracted from kava plant, has been recognized as a potential chemotherapy drug in bladder cancer (BC), but its action mechanism remains unclear.

Methods
We first determined the role of a type II PRMT, PRMT5, in BC tissue samples and performed cytological experiments. We then utilized bioinformatics tools, including computational simulation, virtual screening, molecular docking, and energy analysis, to identify the potential use of PRMT5 inhibitors for BC treatment. In vitro and in vivo co-IP and mutation assays were performed to elucidate the molecular mechanism of PRMT5 inhibitor. Pharmacology experiments like bio-layer interferometry, CETSA, and pull-down assays were further used to provide direct evidence of the complex binding process.

Results
Among PRMTs, PRMT5 was identified as a therapeutic target for BC. PRMT5 expression in BC was correlated with poor prognosis and manipulating its expression could affect cancer cell growth. Through screening and extensive experimental validation, we recognized that a natural product, FKA, was a small new inhibitor molecule for PRMT5. We noticed that the product could inhibit the action of BC, in vitro and in vivo, by inhibiting PRMT5. We further demonstrated that FKA blocks the symmetric arginine dimethylation of histone H2A and H4 by binding to Y304 and F580 of PRMT5.

Conclusions
In summary, our research strongly suggests that PRMT5 is a potential epigenetic therapeutic target in bladder cancer, and that FKA can be used as a targeted inhibitor of PRMT5 for the treatment of bladder cancer.
Investigating the association between cancer and dementia risk: a longitudinal cohort study
Authors: Zhang Dan-Dan , Ou Ya-Nan , Yang Liu , Ma Ya-Hui , Tan Lan , Feng Jian-Feng , Cheng Wei , Yu Jin-Tai 
Published: October 2022

Abstract
Background
Previous studies found that cancer survivors had a reduced risk of dementia compared with the general population. However, these findings were uncertain because of survivor bias and a lack of stratification by cancer types. This current cohort study used data from the UK Biobank to explore these associations.

Methods
Multivariable Cox regression analyses were used to examine the association of cancer status and the risk of dementia with its subtypes after adjusting for age and sex. Hazard ratios (HRs) with 95% confidence intervals (CIs) were calculated as a measure of relative risk by comparing observed dementia incidence among cancer patients.

Results
We included 263,151 participants in the observational analysis. During a median follow-up of 9.18 years, dementia was diagnosed in 472 individuals with cancer and 3685 individuals without cancer, respectively. Cancer patients had lower risks of dementia (hazard ratio: 0.89, confidence interval: 0.81–0.98) and its subtypes (Alzheimer’s disease [AD]: 0.85 [0.74–0.98]; vascular dementia [VD]: 0.81 [0.66–0.99]) in the Cox regression adjusted for age and sex. Individuals with cancers in the male genital system had substantially reduced risks of dementia (0.66 [0.46–0.93]) and AD (0.53 [0.29–0.97]) than those with cancers in other systems. Moreover, non-melanoma skin cancer and prostate cancer were associated with a reduced risk of dementia (0.79 [0.62–0.99]; 0.69 [0.49–0.97]), but not with AD or VD (P>0.05).

Conclusions
The current study supported a negative association between cancer and dementia risk, and encourages further exploration of the mechanistic basis of this inverse relationship to improve understanding.
Painful lower limb nodules as first symptom of resectable pancreatic acinar cell cancer: a case report
Authors: Haenen S. M. , Tol J. A. M. G. , van Steen S. C. J. , Busch O. R. , Sarasqueta A. Farine , Roshani S. , Wolkerstorfer A. , van der Linden M. M. D. , Wilmink J. W. , Post H. C. , Besselink M. G. 
Published: October 2022

Abstract
Background
Pancreatic panniculitis is characterized by subcutaneous fat necrosis and is a rare presentation of an underlying pancreatic disease, appearing in approximately 2–3% of all patients with a pancreatic disease. The nodules usually involve the lower extremities. Pancreatic panniculitis is commonly associated with acute or chronic pancreatitis, and occasionally with pancreatic cancer, especially acinar cell carcinoma.

Case presentation
A 77-year-old Caucasian woman with no significant medical history was referred to our center with multiple painful, itchy, and warm red/blue cutaneous nodules on the left lower leg. These skin lesions were consistent with the clinical diagnosis of panniculitis. The skin biopsy obtained showed a predominantly lobular panniculitis with fat necrosis of which the aspect was highly suspicious for pancreatic panniculitis. Further analysis revealed high lipase serum of > 3000 U/L (normal range < 60 U/L), and on computed tomography scan a mass located between the stomach and the left pancreas was seen. Endoscopic ultrasonography-guided fine-needle biopsy confirmed the diagnosis of acinar cell carcinoma. After discussing the patient in the pancreatobiliary multidisciplinary team meeting, laparoscopic distal pancreatectomy including splenectomy and en bloc wedge resection of the stomach due to tumor in-growth was performed. The cutaneous nodules on both legs disappeared 1–2 days after surgery. No long-term complications were reported during follow-up. One year after surgery, the patient presented with similar symptoms as preoperatively. Computed tomography scan showed local recurrence and distal metastases, which were subsequently confirmed by biopsy. She started with palliative folinic acid–fluorouracil–irinotecan–oxaliplatin chemotherapy but stopped after two cycles because of disease progression. The patient died 2 months later, 13 months after surgical resection.

Conclusion
This case illustrates the importance of clinically recognizing cutaneous nodules and pathological recognizing the specific microscopic changes as sign of a (malignant) pancreatic disease.
Estimating interactions in individual participant data meta-analysis: a comparison of methods in practice
Authors: Walker Ruth , Stewart Lesley , Simmonds Mark 
Published: October 2022

AbstractMedical interventions may be more effective in some types of individuals than others and identifying characteristics that modify the effectiveness of an intervention is a cornerstone of precision or stratified medicine. The opportunity for detailed examination of treatment-covariate interactions can be an important driver for undertaking an individual participant data (IPD) meta-analysis, rather than a meta-analysis using aggregate data. A number of recent modelling approaches are available. We apply these methods to the Perinatal Antiplatelet Review of International Studies (PARIS) Collaboration IPD dataset and compare estimates between them. We discuss the practical implications of applying these methods, which may be of interest to aid meta-analysists in the use of these, often complex models.Models compared included the two-stage meta-analysis of interaction terms and one-stage models which fit multiple random effects and separate within and between trial information. Models were fitted for nine covariates and five binary outcomes and results compared.Interaction terms produced by the methods were generally consistent. We show that where data are sparse and there is low heterogeneity in the covariate distributions across trials, the meta-analysis of interactions may produce unstable estimates and have issues with convergence. In this IPD dataset, varying assumptions by using multiple random effects in one-stage models or using only within trial information made little difference to the estimates of treatment-covariate interaction. Method choice will depend on datasets characteristics and individual preference.
Almost sure exponential stability of nonlinear stochastic delay hybrid systems driven by G-Brownian motion
Authors: Wei Chao 
Published: October 2022

AbstractG-Brownian motion has potential applications in uncertainty problems and risk measures, which has attracted the attention of many scholars. This study investigates the almost sure exponential stability of nonlinear stochastic delay hybrid systems driven by G-Brownian motion. Due to the non-linearity of G-expectation and distribution uncertainty of G-Brownian motion, it is difficult to study this issue. Firstly, the existence of the global unique solution is derived under the linear growth condition and local Lipschitz condition. Secondly, the almost sure exponential stability of the system is analyzed by applying the G-Lyapunov function and G-Itô formula. Finally, an example is introduced to illustrate the stability. The conclusions of this paper can be applied to the stability and risk management of uncertain financial markets.