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Abstract BackgroundThe traditional clinical trial data collection process requires a clinical research coordinator who is authorized by the investigators to read from the hospital’s electronic medical record. Using electronic source data opens a new path to extract patients’ data from electronic health records (EHRs) and transfer them directly to an electronic data capture (EDC) system; this method is often referred to as eSource. eSource technology in a clinical trial data flow can improve data quality without compromising timeliness. At the same time, improved data collection efficiency reduces clinical trial costs. ObjectiveThis study aims to explore how to extract clinical trial–related data from hospital EHR systems, transform the data into a format required by the EDC system, and transfer it into sponsors’ environments, and to evaluate the transferred data sets to validate the availability, completeness, and accuracy of building an eSource dataflow. MethodsA prospective clinical trial study registered on the Drug Clinical Trial Registration and Information Disclosure Platform was selected, and the following data modules were extracted from the structured data of 4 case report forms: demographics, vital signs, local laboratory data, and concomitant medications. The extracted data was mapped and transformed, deidentified, and transferred to the sponsor’s environment. Data validation was performed based on availability, completeness, and accuracy. ResultsIn a secure and controlled data environment, clinical trial data was successfully transferred from a hospital EHR to the sponsor’s environment with 100% transcriptional accuracy, but the availability and completeness of the data could be improved. ConclusionsData availability was low due to some required fields in the EDC system not being available directly in the EHR. Some data is also still in an unstructured or paper-based format. The top-level design of the eSource technology and the construction of hospital electronic data standards should help lay a foundation for a full electronic data flow from EHRs to EDC systems in the future.

ABSTRACT5-Methylcytosine (m5C) is a widespread post-transcriptional RNA modification and is reported to be involved in manifold cellular responses and biological processes through regulating RNA metabolism. However, its regulatory role in antiviral innate immunity has not yet been elucidated. Here, we report that NSUN2, a typical m5C methyltransferase, negatively regulates type I interferon responses during various viral infections, including SARS-CoV-2. NSUN2 specifically mediates m5C methylation of IRF3 mRNA and accelerates its degradation, resulting in low levels of IRF3 and downstream IFN-β production. Knockout or knockdown of NSUN2 enhanced type I interferon and downstream ISGs during various viral infection in vitro. And in vivo, the antiviral innate response is more dramatically enhanced in Nsun2+/− mice than in Nsun2+/+ mice. The highly m5C methylated cytosines in IRF3 mRNA were identified, and their mutation enhanced cellular IRF3 mRNA levels. Moreover, infection with Sendai virus (SeV), vesicular stomatitis virus (VSV), herpes simplex virus 1 (HSV-1), or Zika virus (ZIKV) resulted in a reduction of endogenous NSUN2 levels. Especially, SARS-CoV-2 infection (WT strain and BA.1 omicron variant) also decreased endogenous levels of NSUN2 in COVID-19 patients and K18-hACE2 KI mice, further increasing type I interferon and downstream ISGs. Together, our findings reveal that NSUN2 serves as a negative regulator of interferon response by accelerating the fast turnover of IRF3 mRNA, while endogenous NSUN2 levels decrease during SARS-CoV-2 and various viral infections to boost antiviral responses for effective elimination of viruses.

BackgroundClinical research associates (CRAs) monitor the progress of a trial, verify the data collected, and ensure that the trial is carried out and reported in accordance with the trial protocol, standard operating procedures, and relevant laws and regulations. In response to monitoring challenges during the COVID-19 pandemic, Peking University Cancer Hospital launched a remote monitoring system and established a monitoring model, combining on-site and remote monitoring of clinical trials. Considering the increasing digitization of clinical trials, it is important to determine the optimal monitoring model for the general benefit of centers conducting clinical trials worldwide. ObjectiveWe sought to summarize our practical experience of a hybrid model of remote and on-site monitoring of clinical trials and provide guidance for clinical trial monitoring management. MethodsWe evaluated 201 trials conducted by our hospital that used on-site monitoring alone or a hybrid monitoring model, of which 91 trials used on-site monitoring alone (arm A) and 110 used a hybrid model of remote and on-site monitoring (arm B). We reviewed trial monitoring reports from June 20, 2021, to June 20, 2022, and used a customized questionnaire to collect and compare the following information: monitoring cost of trials in the 2 models as a sum of the CRAs’ transportation (eg, taxi fare and air fare), accommodation, and meal costs; differences in monitoring frequency; the number of monitored documents; and monitoring duration. ResultsFrom June 20, 2021, to June 20, 2022, a total of 320 CRAs representing 201 sponsors used the remote monitoring system for source data review and the verification of data from 3299 patients in 320 trials. Arm A trials were monitored 728 times and arm B trials were monitored 849 times. The hybrid model in arm B had 52.9% (449/849) remote visits and 48.1% (409/849) on-site visits. The number of patients’ visits that could be reviewed in the hybrid monitoring model increased by 34% (4.70/13.80; P=.004) compared with that in the traditional model, whereas the duration of monitoring decreased by 13.8% (3.96/28.61; P=.03) and the total cost of monitoring decreased by 46.2% (CNY ¥188.74/408.80; P

As of 10 May 2022, at least 450 cases of pediatric patients with acute hepatitis of unknown cause have been reported worldwide. Human adenoviruses (HAdVs) have been detected in at least 74 cases, including the F type HAdV41 in 18 cases, which indicates that adenoviruses may be associated with this mysterious childhood hepatitis, although other infectious agents or environmental factors cannot be excluded. In this review, we provide a brief introduction of the basic features of HAdVs and describe diseases caused by different HAdVs in humans, aiming to help understand the biology and potential risk of HAdVs and cope with the outbreak of acute child hepatitis.

While the significance of N6-methyladenosine (m6A) in viral regulation has been extensively studied, the functions of 5-methylcytosine (m5C) modification in viral biology remain largely unexplored. In this study, we demonstrate that m5C is more abundant than m6A in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and provide a comprehensive profile of the m5C landscape of SARS-CoV-2 RNA. Knockout of NSUN2 reduces m5C levels in SARS-CoV-2 virion RNA and enhances viral replication. Nsun2 deficiency mice exhibited higher viral burden and more severe lung tissue damages. Combined RNA-Bis-seq and m5C-MeRIP-seq identified the NSUN2-dependent m5C-methylated cytosines across the positive-sense genomic RNA of SARS-CoV-2, and the mutations of these cytosines enhance RNA stability. The progeny SARS-CoV-2 virions from Nsun2 deficiency mice with low levels of m5C modification exhibited a stronger replication ability. Overall, our findings uncover the vital role played by NSUN2-mediated m5C modification during SARS-CoV-2 replication and propose a host antiviral strategy via epitranscriptomic addition of m5C methylation to SARS-CoV-2 RNA. [ABSTRACT FROM AUTHOR]

Background Rituximab plus CHOP (R-CHOP) significantly improved the outcome of diffuse large B cell lymphoma (DLBCL), a common sub-type of non-Hodgkin lymphoma. But 40% - 50% of DLBCL patients cannot be cured by this regimen. Some clinical trials showed that bevacizumab might be useful in the treatment of DLBCL. This study evaluated the safety and efficacy of bevacizumab combined with the R-CHOP (A-R-CHOP) regimen in Chinese patients with previously untreated DLBCL. Methods Patients with previously untreated DLBCL received A-R-CHOP regimen therapy. All patients with complete response (CR)/ unconfirmed complete response(CRu) after 8 cycles of A-R-CHOP received the bevacizumab maintenance therapy once every 3 weeks. The remained bulky disease was treated with radiotherapy. Results Seven Chinese patients were treated. All of them had bulky diseases. One patient had progressive disease after 4 cycles of A-R-CHOP therapy. The rest six patients completed 8 cycles of A-R-CHOP treatment. All of these six patients reached CR/CRu (5 CR, 1 CRu). Bevacizumab maintenance therapy was given to 4 CR patients. All 7 patients experienced Grade 3/4 hematologic adverse events; additionally, one had Grade 3 gastrointestinal toxicity and one had Grade 1 epistaxis. During bevacizumab maintenance therapy, one patient had Grade 1 gingival bleeding, another experienced Grade 1 proteinuria and then Grade 3 congestive heart failure 4 months after completion of maintenance therapy. At the end of July 2013, the patient who had progressive disease after 4 cycles of A-R-CHOP died of progressive disease, the other six remained CR response. Conclusions The A-R-CHOP regimen is effective for untreated DLBCL, but may cause bevacizumabspecific toxicities, which should be monitored. [ABSTRACT FROM AUTHOR]

Background: R-CHOP has significantly improved survival rates of patients with diffuse large B cell lymphoma (DLBCL) by ∼20% as compared to CHOP. CD20 antigen, highly expressed on more than 80% of B-cell lymphomas, is the target for rituximab. The goal of our study was to examine polymorphism in the CD20 gene in Chinese DLBCL population and whether CD20 gene polymorphism is associated with clinical response to R-CHOP. Method: CD20 gene polymorphism was detected in the entire coding regions including 6 exons by polymerase chain reaction (PCR)-sequencing assay in 164 patients with DLBCL. Among them, 129 patients treated with R-CHOP as frontline therapy (R ≥ 4 cycles) were assessable for the efficacy. Results: Polymorphisms at three single nucleotides (SNP) were identified in the entire coding regions of the CD20 gene in the 164 patients. One of them, CD20 Exon2 [216] was found to be highly correlated with response to RCHOP. Patients with homozygous C genotype showed a trend toward higher overall response rate than others with CT plus TT genotype (90.6% vs. 79.5%; P =0.166). A trend toward higher complete remission (CR) rate was observed in patients with homozygous C genotype (67.4%) compared with CT plus TT genotype (47.1%) (P = 0.091). Conclusion: These results suggest that there are 3 SNPs in CDS of the CD20 gene in Chinese DLBCL population. The CC genotype at Exon2 [216] appears to be associated with favourable response to R-CHOP. [ABSTRACT FROM AUTHOR]