bluuebunny/crossref_metadata_2025_split huggingface dataset:
Lessons learned from annotation of VAERS reports on adverse events following influenza vaccination and related to Guillain-Barré syndrome
Authors: Sankaranarayanapillai Madhuri , Wang Su , Ji Hangyu , Song Hsing-Yi , Tao Cui 
Published: January 2024

Abstract
Background
Vaccine Adverse Events ReportingSystem (VAERS) is a promising resource of tracking adverse events following immunization. Medical Dictionary for Regulatory Activities (MedDRA) terminology used for coding adverse events in VAERS reports has several limitations. We focus on developing an automated system for semantic extraction of adverse events following vaccination and their temporal relationships for a better understanding of VAERS data and its integration into other applications. The aim of the present studyis to summarize the lessons learned during the initial phase of this project in annotating adverse events following influenza vaccination and related to Guillain-Barré syndrome (GBS). We emphasize on identifying the limitations of VAERS and MedDRA.

Results
We collected 282 VAERS reports documented between 1990 and 2016 and shortlisted those with at least 1,100 characters in the report. We used a subset of 50 reports for the preliminary investigation and annotated all adverse events following influenza vaccination by mapping to representative MedDRA terms. Associated time expressions were annotated when available. We used 16 System Organ Class (SOC) level MedDRA terms to map GBS related adverse events and expanded some SOC terms to Lowest Level Terms (LLT) for granular representation. We annotated three broad categories of events such as problems, clinical investigations, and treatments/procedures. The inter-annotator agreement of events achieved was 86%. Incomplete reports, typographical errors, lack of clarity and coherence, repeated texts, unavailability of associated temporal information, difficulty to interpret due to incorrect grammar, use of generalized terms to describe adverse events / symptoms, uncommon abbreviations, difficulty annotating multiple events with a conjunction / common phrase, irrelevant historical events and coexisting events were some of the challenges encountered. Some of the limitations we noted are in agreement with previous reports.

Conclusions
We reported the challenges encountered and lessons learned during annotation of adverse events in VAERS reports following influenza vaccination and related to GBS. Though the challenges may be due to the inevitable limitations of public reporting systems and widely reported limitations of MedDRA, we emphasize the need to understand these limitations and extraction of other supportive information for a better understanding of adverse events following vaccination.
Nurses’ knowledge of and attitude toward postoperative patient-controlled analgesia (PCA) and the associated factors
Authors: Chen Ying-Ru , Chen Cheryl Chia-Hui , Wu Wei-Wen , Tang Fu-Ing , Lu Ling-Chun 
Published: January 2024

Abstract
Background
Postoperative pain control is pivotal for surgical care; it facilitates patient recovery. Although patient-controlled analgesia (PCA) has been available for decades, inadequate pain control remains. Nurses’ knowledge of and attitude toward PCA may influence the efficacy on clinic application.

Purpose
The purpose of this study is to evaluate nurses’ knowledge of and attitude toward postoperative PCA and investigate the associated factors.

Methods
This is a cross-sectional study. We enrolled registered nurses from a 2200-bed medical center in northern Taiwan within one year. The participants completed an anonymous self-reported PCA knowledge inventory and PCA attitude inventory. Data were analyzed descriptively and associated were tested using logistic regression.

Results
With 303 participants enrolled, we discovered that nurses had limited knowledge of and a negative attitude toward PCA. Under half of the participants know how to set up a bolus dose and lockout intervals. The majority held misconceptions regarding side effect management for opioids. The minority agree to increase the dose when a patient experienced persistent pain or suggested the use of PCA. Surprisingly, participants with a bachelor’s or master’s degree had lower knowledge scores than those with a junior college degree. Those with 6–10 years of work experience also are lower than those with under 5 years of experience. However, the participants with experience of using PCA for patient care had higher knowledge scores and a more positive attitude.

Conclusions
Although postoperative PCA has been available for decades and education programs are routinely provided, nurses had limited knowledge of and a negative attitude toward PCA. A higher education level and longer work experience were not associated with more knowledge. The current education programs on PCA should be revised to enhance their efficacy in delivering up-to-date knowledge and situation training which may convey supportive attitude toward clinical application of PCA.
Identifying factors in the provision of intravenous stroke thrombolysis in Malaysia: a multiple case study from the healthcare providers’ perspective
Authors: Hwong Wen Yea , Ng Sock Wen , Tong Seng Fah , Ab Rahman Norazida , Law Wan Chung , Wong Sing Keat , Puvanarajah Santhi Datuk , Mohd Norzi Aisyah , Lian Fiona Suling , Sivasampu Sheamini 
Published: January 2024

Abstract
Background
Translation into clinical practice for use of intravenous thrombolysis (IVT) for the management of ischemic stroke remains a challenge especially across low- and middle-income countries, with regional inconsistencies in its rate. This study aimed at identifying factors that influenced the provision of IVT and the variation in its rates in Malaysia.

Methods
A multiple case study underpinning the Tailored Implementation for Chronic Diseases framework was carried out in three public hospitals with differing rates of IVT using a multiple method design. Twenty-five in-depth interviews and 12 focus groups discussions were conducted among 89 healthcare providers, along with a survey on hospital resources and a medical records review to identify reasons for not receiving IVT. Qualitative data were analysed using reflective thematic method, before triangulated with quantitative findings.

Results
Of five factors identified, three factors that distinctively influenced the variation of IVT across the hospitals were: 1) leadership through quality stroke champions, 2) team cohesiveness which entailed team dynamics and its degree of alignment and, 3) facilitative work process which included workflow simplification and familiarity with IVT. Two other factors that were consistently identified as barriers in these hospitals included patient factors which largely encompassed delayed presentation, and resource constraints. About 50.0 – 67.6% of ischemic stroke patients missed the opportunity to receive IVT due to delayed presentation.

Conclusions
In addition to the global effort to explore sustainable measures to improve patients’ emergency response for stroke, attempts to improve the provision of IVT for stroke care should also consider the inclusion of interventions targeting on health systems perspectives such as promoting quality leadership, team cohesiveness and workflow optimisation.
Spotlight on therapeutic efficiency of green synthesis metals and their oxide nanoparticles in periodontitis
Authors: Kiarashi Mohammad , Mahamed Parham , Ghotbi Nader , Tadayonfard Azadeh , Nasiri Kamyar , Kazemi Parisa , Badkoobeh Ashkan , Yasamineh Saman , Joudaki Ali 
Published: January 2024

AbstractPeriodontitis, one of the most prevalent dental diseases, causes the loss of bone and gum tissue that hold teeth in place. Several bacteria, commonly present in clinically healthy oral cavities, may induce and perpetuate periodontitis when their concentration rises in the gingival sulcus. Antibacterial effect against various Gram-negative and Gram-positive bacteria, including pathogenic and drug-resistant ones, has been shown for several distinct transient metal and metal oxide NPs. Therefore, NPs may be used in biomedicine to treat periodontal problems and in nanotechnology to inhibit the development of microorganisms. Instead of using harmful chemicals or energy-intensive machinery, biosynthesis of metal and metal oxide nanoparticles (NPs) has been suggested. To produce metal and metal oxide NPs, the ideal technique is “Green” synthesis because of its low toxicity and safety for human health and the environment. Gold NPs (AuNPs) appear to be less toxic to mammalian cells than other nanometals because their antibacterial activity is not dependent on reactive oxygen species (ROS). AgNPs also possess chemical stability, catalytic activity, and superior electrical and thermal conductivity, to name a few of their other advantageous characteristics. It was observed that zinc oxide (ZnO) NPs and copper (Cu) NPs exhibited discernible inhibitory effects against gram-positive and gram-negative bacterial strains, respectively. ZnO NPs demonstrated bactericidal activity against the microorganisms responsible for periodontitis. Medications containing magnetic NPs are highly effective against multidrug-resistant bacterial and fungal infections. The titanium dioxide (TiO2) NPs are implicated in elevating salivary peroxidase activity in individuals diagnosed with chronic periodontitis. Furthermore, specific metallic NPs have the potential to enhance the antimicrobial efficacy of periodontitis treatments when combined. Therefore, these NPs, as well as their oxide NPs, are only some of the metals and metal oxides that have been synthesized in environmentally friendly ways and shown to have therapeutic benefits against periodontitis.Graphical Abstract
Transcriptomic insights into UTUC: role of inflammatory fibrosis and potential for personalized treatment
Authors: Li Keqiang , Huang Zhenlin , Xie Guoqing , Huang Budeng , Song Liang , Zhang Yu , Yang Jinjian 
Published: January 2024

Abstract
Background
Upper tract urothelial carcinoma (UTUC) is a rare disease, belonging to the same category of urothelial cancers as bladder cancer (BC). Despite sharing similar non-surgical treatment modalities, UTUC demonstrates a higher metastasis propensity than BC. Furthermore, although both cancers exhibit similar molecular disease emergence mechanisms, sequencing data reveals some differences. Our study investigates the transcriptomic distinctions between UTUC and BC, explores the causes behind UTUC's heightened metastatic tendency, constructs a model for UTUC metastasis and prognosis, and propose personalized treatment strategies for UTUC.

Methods
In our research, we utilized differential gene expression analysis, interaction networks, and Cox regression to explore the enhanced metastatic propensity of UTUC. We formulated and validated a prognostic risk model using diverse techniques, including cell co-culture, reverse transcription quantitative polymerase chain reaction (rt-qPCR), western blotting, and transwell experiments. Our methodological approach also involved survival analysis, risk model construction, and drug screening leveraging the databases of CTRPv2, PRISM and CMap. We used the Masson staining technique for histological assessments. All statistical evaluations were conducted using R software and GraphPad Prism 9, reinforcing the rigorous and comprehensive nature of our research approach.

Results
Screening through inflammatory fibrosis revealed a reduction of extracellular matrix and cell adhesion molecules regulated by proteoglycans in UTUC compared with BC, making UTUC more metastasis-prone. We demonstrated that SDC1, LUM, VEGFA, WNT7B, and TIMP3, are critical in promoting UTUC metastasis. A risk model based on these five molecules can effectively predict the risk of UTUC metastasis and disease-free survival time. Given UTUC's unique molecular mechanisms distinct from BC, we discovered that UTUC patients could better mitigate the issue of poor prognosis associated with UTUC's easy metastasis through tyrosine kinase inhibitors (TKIs) alongside the conventional gemcitabine and cisplatin chemotherapy regimen.

Conclusions
The poor prognosis of UTUC because of its high metastatic propensity is intimately tied to inflammatory fibrosis induced by the accumulation of reactive oxygen species. The biological model constructed using the five molecules SDC1, LUM, VEGFA, WNT7B, and TIMP3 can effectively predict patient prognosis. UTUC patients require specialized treatments in addition to conventional regimens, with TKIs exhibiting significant potential.
(Pro)renin receptor mediates tubular epithelial cell pyroptosis in diabetic kidney disease via DPP4-JNK pathway
Authors: Xie Shiying , Song Shicong , Liu Sirui , Li Qiong , Zou Wei , Ke Jianting , Wang Cheng 
Published: January 2024

Abstract
Background
(Pro)renin receptor (PRR) is highly expressed in renal tubules, which is involved in physiological and pathological processes. However, the role of PRR, expressed in renal tubular epithelial cells, in diabetic kidney disease (DKD) remain largely unknown.

Methods
In this study, kidney biopsies, urine samples, and public RNA-seq data from DKD patients were used to assess PRR expression and cell pyroptosis in tubular epithelial cells. The regulation of tubular epithelial cell pyroptosis by PRR was investigated by in situ renal injection of adeno-associated virus9 (AAV9)-shRNA into db/db mice, and knockdown or overexpression of PRR in HK-2 cells. To reveal the underlined mechanism, the interaction of PRR with potential binding proteins was explored by using BioGrid database. Furthermore, the direct binding of PRR to dipeptidyl peptidase 4 (DPP4), a pleiotropic serine peptidase which increases blood glucose by degrading incretins under diabetic conditions, was confirmed by co-immunoprecipitation assay and immunostaining.

Results
Higher expression of PRR was found in renal tubules and positively correlated with kidney injuries of DKD patients, in parallel with tubular epithelial cells pyroptosis. Knockdown of PRR in kidneys significantly blunted db/db mice to kidney injury by alleviating renal tubular epithelial cells pyroptosis and the resultant interstitial inflammation. Moreover, silencing of PRR blocked high glucose-induced HK-2 pyroptosis, whereas overexpression of PRR enhanced pyroptotic cell death of HK-2 cells. Mechanistically, PRR selectively bound to cysteine-enrich region of C-terminal of DPP4 and augmented the protein abundance of DPP4, leading to the downstream activation of JNK signaling and suppression of SIRT3 signaling and FGFR1 signaling, and then subsequently mediated pyroptotic cell death.

Conclusions
This study identified the significant role of PRR in the pathogenesis of DKD; specifically, PRR promoted tubular epithelial cell pyroptosis via DPP4 mediated signaling, highlighting that PRR could be a promising therapeutic target in DKD.
The 4th NextGen therapies of SJIA and MAS, part 4: it is time for IL-18 based trials in systemic juvenile idiopathic arthritis?
Authors: Canna Scott W. , De Benedetti Fabrizio 
Published: January 2024

AbstractSince IL-18 has recently emerged as a biomarker associated with refractory disease course in SJIA, the focus of the discussion was the feasibility of the biomarker-driven drug development to SJIA. Overall, there was broad agreement on the conclusion that IL-18 is a uniquely specific biomarker for many of the subsets of SJIA most in need of new therapies, and it may define a class of diseases mediated by IL-18 excess. The consensus was that leveraging IL-18 remains our most promising “lead” for use in refractory SJIA as it may mechanistically explain the disease pathophysiology and lead to more targeted therapies.
Production of recombinant HPV11/16 E6/E7-MBP-His6 fusion proteins and their potential to induce cytokine secretion by immune cells in peripheral blood
Authors: Xu Mei-nian , Zhong Mei-zhen , Feng Si-ning , Xu Yan-qin , Peng Xiao-ming , Zeng Kang , Huang Xiao-wen 
Published: January 2024

AbstractHuman papillomavirus (HPV) infection poses a significant threat to public health worldwide. Targeting the function of HPV E6 and E7 proteins and activating the host immune response against these proteins represent promising therapeutic strategies for combating HPV-related diseases. Consequently, the efficient production of soluble, high-purity E6 and E7 proteins is crucial for function and host immune response studies. In this context, we selected the pMCSG19 protein expression vector for Escherichia coli to produce soluble MBP-His6 tagged HPV11/16 E6/E7 proteins, achieving relatively high purity and yield. Notably, these proteins exhibited low toxicity to peripheral blood mononuclear cells (PBMCs) and did not compromise their viability. Additionally, the recombinant proteins were capable of inducing the secretion of multiple cytokines by immune cells in peripheral blood, indicating their potential to elicit immune responses. In conclusion, our study offers a novel approach for the production of HPV11/16 E6/E7 fusion proteins with relatively high purity and yield. The fusing HPV11/16 E6/E7 proteins to MBP-His6 tag may serve as a valuable method for large-scale protein production in future research endeavors.
Systematic evaluation of the degree of joint amnesia in patients after total hip arthroplasty with direct anterior approach (DAA) compared with posterior approach (PA)
Authors: Zhang Fukang , Zhang Zhuangzhuang , Fan Hua , Cheng Qinghao , Guo Hongzhang 
Published: January 2024

Abstract
Objective
A comparative study of joint amnesia in patients undergoing total hip arthroplasty with the direct anterior approach and posterior approach was conducted through a comprehensive evaluation.

Methods
The literature on joint amnesia in postoperative patients who underwent total hip arthroplasty by the direct anterior approach and the posterior approach was systematically searched in PubMed, Embase, Web of Science, Cochrane Library, CNKI, CBM, Wanfang, and VIP databases from the time of library construction until February 13, 2023. Meta-analysis was performed using RevMan 5.3 software after independent searching, screening of the literature, data extraction, and quality assessment of the included studies by two investigators in strict accordance with the guidelines for conducting meta-analyses.

Results
A total of one RCT and six cohort studies were included in this meta-analysis. Meta-analysis results indicated that at 1 month postoperatively (MD = 2.08, 95% CI (0.20, 3.96), P = 0.03), 3 months (MD = 10.08, 95% CI (1.20, 18.96), P = 0.03), and 1 year (MD = 6.74, 95% CI (1.30, 12.19), P = 0.02), DAA total hip arthroplasty was associated with better FJS compared to PA at 1 year postoperatively. However, there was no statistical significance in FJS between the two groups at 5 years postoperatively (MD = 1.35, 95% CI (− 0.58, 3.28), P = 0.17).

Conclusion
Current evidence suggests that the degree of joint amnesia after THA for DAA was not found to be superior to that of PA. Further, these findings require confirmation by including a larger number of high-quality randomized controlled studies.

Study design
Systematic review; Level of evidence, 3.
Combination of mangiferin and T0901317 targeting autophagy promotes cholesterol efflux from macrophage foam cell in atherosclerosis
Authors: Chen Qian , Wang Sijian , Bao Ruixia , Wang Dan , Wu Yuzheng , Zhang Yi , Liu Mengyang , Wang Tao 
Published: January 2024

Abstract
Background
The synthetic liver X receptor ligand (LXR) T0901317 (T0) has been reported to attenuate atherosclerosis (AS) without hyperglyceridemia due to innovative drug combination or nano-sized drug delivery. Given the key roles of mangiferin (MGF) in lipid metabolism and atherogenesis, it is critical to investigate progression of atherosclerotic lesion after combined treatment of MGF and T0.

Methods
Atherosclerotic plaque formation and hepatic lipid accumulation were compared in Apoe−/− mice among T0 and/or MGF treatment. The in vitro functions of MGF and T0 were analyzed by Oil-red O staining, cholesterol efflux assay, transmission electron microscopy and western blot analyses with or without acetylated low density lipoprotein.

Results
The combination therapy are effective regulators for atherosclerotic plaque formation in Apoe−/− mice, due to upregulation of ABCA1 and ABCG1 induced by LXR activation. Subsequently, we identified autophagy promoted by MGF and T0 treatment establishes a positive feedback loop that increases cholesterol efflux, resulted from LXRα activation. Under atherogenic conditions, the autophagy inhibitor CQ abolished the enhancement effect on cholesterol outflow of MGF and T0. Mechanically, MGF and T0 promotes LXRα and mTOR/AMPK signaling cascade in macrophage, and promotes AMPK signaling cascade in hepatocyte, leading to lipid metabolic homeostasis.

Conclusions
Altogether, our findings reveal that MGF and T0 engages in AS therapy without side effects by activating AMPK-dependent autophagy to promote macrophage cholesterol efflux, and MGF might serve as a natural compound to assist T0 in AS via targeting autophagy.
Targeting tumor–stromal interactions in triple-negative breast cancer using a human vascularized micro-tumor model
Authors: Hachey Stephanie J. , Hatch Christopher J. , Gaebler Daniela , Mocherla Aneela , Nee Kevin , Kessenbrock Kai , Hughes Christopher C. W. 
Published: January 2024

AbstractTriple-negative breast cancer (TNBC) is highly aggressive with limited available treatments. Stromal cells in the tumor microenvironment (TME) are crucial in TNBC progression; however, understanding the molecular basis of stromal cell activation and tumor–stromal crosstalk in TNBC is limited. To investigate therapeutic targets in the TNBC stromal niche, we used an advanced human in vitro microphysiological system called the vascularized micro-tumor (VMT). Using single-cell RNA sequencing, we revealed that normal breast tissue stromal cells activate neoplastic signaling pathways in the TNBC TME. By comparing interactions in VMTs with clinical data, we identified therapeutic targets at the tumor–stromal interface with potential clinical significance. Combining treatments targeting Tie2 signaling with paclitaxel resulted in vessel normalization and increased efficacy of paclitaxel in the TNBC VMT. Dual inhibition of HER3 and Akt also showed efficacy against TNBC. These data demonstrate the potential of inducing a favorable TME as a targeted therapeutic approach in TNBC.