bluuebunny/crossref_metadata_2025_split huggingface dataset:
Integrating omics reveals that miRNA-guided genetic regulation on plant hormone level and defense response pathways shape resistance to Cladosporium fulvum in the tomato Cf-10-gene-carrying line
Authors: Liu Guan , Liu Fengjiao , Zhang Dongye , Zhao Tingting , Yang Huanhuan , Jiang Jingbin , Li Jingfu , Zhang He , Xu Xiangyang 
Published: May 2023

Invasion of C. fulvum causes the most serious diseases affecting the reproduction of tomatoes. Cf-10-gene-carrying line showed remarkable resistance to Cladosporium fulvum. To exploit its defense response mechanism, we performed a multiple-omics profiling of Cf-10-gene-carrying line and a susceptible line without carrying any resistance genes at non-inoculation and 3 days post-inoculation (dpi) of C. fulvum. We detected 54 differentially expressed miRNAs (DE-miRNAs) between the non-inoculation and 3 dpi in the Cf-10-gene-carrying line, which potentially regulated plant-pathogen interaction pathways and hormone signaling pathways. We also revealed 3,016 differentially expressed genes (DEGs) between the non-inoculated and 3 dpi in the Cf-10-gene-carrying line whose functions enriched in pathways that were potentially regulated by the DE-miRNAs. Integrating DE-miRNAs, gene expression and plant-hormone metabolites indicated a regulation network where the downregulation of miRNAs at 3 dpi activated crucial resistance genes to trigger host hypersensitive cell death, improved hormone levels and upregulated the receptors/critical responsive transcription factors (TFs) of plant hormones, to shape immunity to the pathogen. Notably, our transcriptome, miRNA and hormone metabolites profiling and qPCR analysis suggested that that the downregulation of miR9472 potentially upregulated the expression of SAR Deficient 1 (SARD1), a key regulator for ICS1 (Isochorismate Synthase 1) induction and salicylic acid (SA) synthesis, to improve the level of SA in the Cf-10-gene-carrying line. Our results exploited potential regulatory network and new pathways underlying the resistance to C. fulvum in Cf-10-gene-carrying line, providing a more comprehensive genetic circuit and valuable gene targets for modulating resistance to the virus.
Reducedhumoral response against variants of concern in childhood solid cancer patients compared to adult patients and healthy children after SARS-CoV-2 vaccination
Authors: Ma Yifei , Chen Bocen , Wang Yanqi , Zhu Pengfei , Liu Nianqi , Zhang Zhiying , Zhong Guanqing , Fu Guangzhen , Wang Dao , Cao Lu , Bai Shenrui , Wang Youlong , Chen Shuqin , Wei Xiaolong , Lv Jun , Zhang Ao , Wang Xinjia 
Published: May 2023

IntroductionAlthough there is extended research on the response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines in adult cancer patients (ACP), the immunogenicity to the variants of concern (VOCs) in childhood cancer patients (CCP) and safety profiles are now little known.MethodsA prospective, multi-center cohort study was performed by recruiting children with a solid cancer diagnosis and childhood healthy control (CHC) to receive standard two-dose SARS-CoV-2 vaccines. An independent ACP group was included to match CCP in treatment history. Humoral response to six variants was performed and adverse events were followed up 3 months after vaccination. Responses to variants were compared with ACP and CHC by means of propensity score-matched (PSM) analysis.ResultsThe analysis included 111 CCP (27.2%, median age of 8, quartile 5.5–15 years), 134 CHC (32.8%), and 163 ACP (40.0%), for a total 408 patients. Pathology included carcinoma, neural tumors, sarcoma, and germ cell tumors. Median chemotherapy time was 7 (quartile, 5–11) months. In PSM sample pairs, the humoral response of CCP against variants was significantly decreased, and serology titers (281.8 ± 315.5 U/ml) were reduced, as compared to ACP (p&lt; 0.01 for the rate of neutralization rate against each variant) and CHC (p&lt; 0.01 for the rate of neutralization against each variant) groups. Chemotherapy time and age (Pearson r ≥ 0.8 for all variants) were associated with the humoral response against VOCs of the CHC group. In the CCP group, less than grade II adverse events were observed, including 32 patients with local reactions, and 29 patients had systemic adverse events, including fever (n = 9), rash (n = 20), headache (n = 3), fatigue (n = 11), and myalgia (n = 15). All reactions were well-managed medically.ConclusionsThe humoral response against VOCs after the CoronaVac vaccination in CCP was moderately impaired although the vaccine was safe. Age and chemotherapy time seem to be the primary reason for poor response and low serology levels.
Sex-dependent differences in behavioral and immunological responses to antibiotic and bacteriophage administration in mice
Authors: Grabowski Łukasz , Pierzynowska Karolina , Kosznik-Kwaśnicka Katarzyna , Stasiłojć Małgorzata , Jerzemowska Grażyna , Węgrzyn Alicja , Węgrzyn Grzegorz , Podlacha Magdalena 
Published: May 2023

IntroductionThe problem of antibiotic resistance is a global one, involving many industries and entailing huge financial outlays. Therefore, the search for alternative methods to combat drug-resistant bacteria has a priority status. Great potential is seen in bacteriophages which have the natural ability to kill bacterial cells. Bacteriophages also have several advantages over antibiotics. Firstly, they are considered ecologically safe (harmless to humans, plants and animals). Secondly, bacteriophages preparations are readily producible and easy to apply. However, before bacteriophages can be authorized for medical and veterinary use, they must be accurately characterized in vitro and in vivo to determinate safety.MethodsTherefore, the aim of this study was to verify for the first time the behavioral and immunological responses of both male and female mice (C57BL/6J) to bacteriophage cocktail, composed of two bacteriophages, and to two commonly used antibiotics, enrofloxacin and tetracycline. Animal behavior, the percentage of lymphocyte populations and subpopulations, cytokine concentrations, blood hematological parameters, gastrointestinal microbiome analysis and the size of internal organs, were evaluated.ResultsUnexpectedly, we observed a sex-dependent, negative effect of antibiotic therapy, which not only involved the functioning of the immune system, but could also significantly impaired the activity of the central nervous system, as manifested by disruption of the behavioral pattern, especially exacerbated in females. In contrast to antibiotics, complex behavioral and immunological analyses confirmed the lack of adverse effects during the bacteriophage cocktail administration.DiscussionThe mechanism of the differences between males and females in appearance of adverse effects, related to the behavioral and immune functions, in the response to antibiotic treatment remains to be elucidated. One might imagine that differences in hormones and/or different permeability of the blood-brain barrier can be important factors, however, extensive studies are required to find the real reason(s).
Comparation of time-course, dose-effect, influencing factors and adverse events of biologics in the treatment of adults with moderate to severe plaque psoriasis
Authors: Gao Weiqi , Yu Boran , Yan Ya , Zhao Libo , Zhao Rongsheng 
Published: May 2023

IntroductionBiologics is used for treating moderate to severe plaque psoriasis (MSPP), which represent one of the foremost therapeutic advancements in disease of dermatology. Up to now, the relative efficacy and safety across approved andinvestigational biologics for MSPP is still unclear.MethodsThis study aimed to comparative effectiveness of various biological treatments for MSPP measured by PASI75, PASI90 and PASI100 (The ratio of patients whose Psoriasis Area and Severity Index score (PASI) decreased by ≥ 75%, 90% and 100% compared with baseline, respectively). In addition, random models were used together with a Bayesian method to compare direct and indirect Adverse Events (AEs) of biologics with placebo, to make probabilistic statements and predictions on their AEs. The analytic data set was made up of summarized data from 54 trials, including 27,808 patients, with treatment of 17 biologics. Three mathematic models with nonparametric placebo evaluations were established to characterize the longitudinal direction profile for the three efficacy measures as above mentioned.ResultsOur results showed significant differences among treatments. Bimekizumab, sonelokimab, and ixekizumab were found to be the most effective treatments among the biologics. The effects of covariate were further evaluated, patients’ age, body weight, duration of disease and percentage of patients previously treated with a biological therapy showed impact on the efficacy. In addition, we found that ixekizumab and risankizumab displayed relatively stable as for efficacy and safety.DiscussionOur findings provide valuable insights into the comparative effectiveness and safety of biologics for MSPP treatment. These results may aid in clinical decision-making and ultimately improve patient outcomes.
Screening and characterization of the scFv for chimeric antigen receptor T cells targeting CEA-positive carcinoma
Authors: Zhang Chengcheng , Wang Linling , Zhang Qianzhen , Shen Junjie , Huang Xia , Wang Meiling , Huang Yi , Chen Jun , Xu Yanmin , Zhao Wenxu , Qi Yanan , Li Yunyan , Ou Yanjiao , Yang Zhi , Qian Cheng 
Published: May 2023

IntroductionChimeric antigen receptor T (CAR-T) cell therapy presents a promising treatment option for various cancers, including solid tumors. Carcinoembryonic antigen (CEA) is an attractive target due to its high expression in many tumors, particularly gastrointestinal cancers, while limited expression in normal adult tissues. In our previous clinical study, we reported a 70% disease control rate with no severe side effects using a humanized CEA-targeting CAR-T cell. However, the selection of the appropriate single-chain variable fragment (scFv) significantly affects the therapeutic efficacy of CAR-T cells by defining their specific behavior towards the target antigen. Therefore, this study aimed to identify the optimal scFv and investigate its biological functions to further optimize the therapeutic potential of CAR-T cells targeting CEA-positive carcinoma.MethodsWe screened four reported humanized or fully human anti-CEA antibodies (M5A, hMN-14, BW431/26, and C2-45), and inserted them into a 3rd-generation CAR structure. We purified the scFvs and measured the affinity. We monitored CAR-T cell phenotype and scFv binding stability to CEA antigen through flow cytometry. We performed repeated CEA antigen stimulation assays to compare the proliferation potential and response of the four CAR-T cells, then further evaluated the anti-tumor efficacy of CAR-T cells ex vivo and in vivo.ResultsM5A and hMN-14 CARs displayed higher affinity and more stable CEA binding ability than BW431/26 and C2-45 CARs. During CAR-T cell production culture, hMN-14 CAR-T cells exhibit a larger proportion of memory-like T cells, while M5A CAR-T cells showed a more differentiated phenotype, suggesting a greater tonic signal of M5A scFv. M5A, hMN-14, and BW431/26 CAR-T cells exhibited effective tumor cell lysis and IFN-γ release when cocultured with CEA-positive tumor cells in vitro, correlating with the abundance of CEA expression in target cells. While C2-45 resulted in almost no tumor lysis or IFN-γ release. In a repeat CEA antigen stimulation assay, M5A showed the best cell proliferation and cytokine secretion levels. In a mouse xenograft model, M5A CAR-T cells displayed better antitumor efficacy without preconditioning.DiscussionOur findings suggest that scFvs derived from different antibodies have distinctive characteristics, and stable expression and appropriate affinity are critical for robust antitumor efficacy. This study highlights the importance of selecting an optimal scFv in CAR-T cell design for effective CEA-targeted therapy. The identified optimal scFv, M5A, could be potentially applied in future clinical trials of CAR-T cell therapy targeting CEA-positive carcinoma.
Functional CVIDs phenotype clusters identified by the integration of immune parameters after BNT162b2 boosters
Authors: Piano Mortari Eva , Pulvirenti Federica , Marcellini Valentina , Terreri Sara , Salinas Ane Fernandez , Ferrari Simona , Di Napoli Giulia , Guadagnolo Daniele , Sculco Eleonora , Albano Christian , Guercio Marika , Di Cecca Stefano , Milito Cinzia , Garzi Giulia , Pesce Anna Maria , Bonanni Livia , Sinibaldi Matilde , Bordoni Veronica , Di Cecilia Serena , Accordini Silvia , Castilletti Concetta , Agrati Chiara , Quintarelli Concetta , Zaffina Salvatore , Locatelli Franco , Carsetti Rita , Quinti Isabella 
Published: May 2023

IntroductionAssessing the response to vaccinations is one of the diagnostic criteria for Common Variable Immune Deficiencies (CVIDs). Vaccination against SARS-CoV-2 offered the unique opportunity to analyze the immune response to a novel antigen. We identify four CVIDs phenotype clusters by the integration of immune parameters after BTN162b2 boosters.MethodsWe performed a longitudinal study on 47 CVIDs patients who received the 3rd and 4th vaccine dose of the BNT162b2 vaccine measuring the generation of immunological memory. We analyzed specific and neutralizing antibodies, spike-specific memory B cells, and functional T cells.ResultsWe found that, depending on the readout of vaccine efficacy, the frequency of responders changes. Although 63.8% of the patients have specific antibodies in the serum, only 30% have high-affinity specific memory B cells and generate recall responses.DiscussionThanks to the integration of our data, we identified four functional groups of CVIDs patients with different B cell phenotypes, T cell functions, and clinical diseases. The presence of antibodies alone is not sufficient to demonstrate the establishment of immune memory and the measurement of the in-vivo response to vaccination distinguishes patients with different immunological defects and clinical diseases.
Hepatic and portal vein Doppler ultrasounds in assessing liver inflammation and fibrosis in chronic HBV infection with a normal ALT level
Authors: Tian Li , Tang Shuyao , Wang Na , Deng Huan , Zhang Qunxia , Shi Tongdong 
Published: May 2023

AimsTo discuss the clinical value of hepatic and portal vein Doppler ultrasounds in assessing liver inflammation and fibrosis in patients with chronic hepatitis B virus (HBV) infection, and a normal alanine transaminase (ALT) level.Methods94 patients with chronic HBV infections who had undergone ultrasound-guided liver biopsies were enrolled and grouped by the liver tissue pathological results. Analyzed the differences and correlation between parameters of the hepatic and portal vein Doppler ultrasounds are discussed across different degrees of liver inflammation and fibrosis.ResultsThere were 27 patients with no significant liver damage and 67 patients with significant liver damage, there were significant differences in the parameters of the hepatic and portal vein Doppler ultrasounds between them (p &lt; 0.05). As liver inflammation was aggravated, the inner diameter of the portal vein increased, and the blood flow velocities of the portal and superior mesenteric veins decreased (p &lt; 0.05). When liver fibrosis became more severe, the inner diameter of the portal vein increased, while the blood flow velocities of the portal, superior mesenteric, and splenic veins decreased, and the Doppler waveforms of hepatic veins became unidirectional or flat (p &lt; 0.05). The receiver operating characteristic (ROC) curve showed the assessment efficacy of hepatic and portal vein Doppler ultrasounds was superior to abdominal Doppler ultrasound alone in assessing liver fibrosis, and the combination of the two examination techniques outperformed any technique used alone.ConclusionThe hepatic and portal vein Doppler ultrasounds have important clinical value for assessing liver fibrosis in patients with chronic HBV infection, to aid improve the diagnosis of liver fibrosis.
Application of virtual simulation in clinical skills and operation courses
Authors: Wang Li , Zhang Feng , Xie Hongxiang 
Published: May 2023

AimThis study investigated the effectiveness and prospect of applying virtual simulation operation (VSO) as a novel teaching tool in clinical skill and operation courses.MethodsA comparative test and survey study on the teaching effect of VSO was conducted with the clinical skill and operation course as the test course. The test group students received offline courses combined with online VSO practice. In contrast, the control group students received offline courses combined with instructional video review. The two groups were assessed using the Chinese medical school clinical medicine professional level test and a questionnaire survey.ResultsThe test group students scored significantly higher than the control group in the skills test (score difference: 3.43, 95% CI: 2.05–4.80) (p &lt; 0.001). Additionally, a significant increase in the percentage of high-and intermediate-score ranges and a decrease in the percentage of low-score ranges was observed (p &lt; 0.001). According to the questionnaire survey, 80.56% of the students were willing to continue using virtual simulation in their subsequent clinical skill and operation learning. Further, 85.19% of the students believed that the VSO is superior because it is unrestricted by time and space and can be performed anywhere and anytime compared to traditional operation training.ConclusionVSO teaching can improve skills and examination performance. An entirely online operation that does not need special equipment can break through the spatiotemporal limitations of traditional skills courses. VSO teaching also suits the ongoing COVID-19 pandemic situation. Virtual simulation, a new teaching tool, has good application prospects.
Health-related quality of life of dialysis patients during early COVID-19 lockdowns: a snapshot from a public hospital in Malaysia
Authors: Paneerselvam Ganesh Sritheran , Goh Khang Wen , Kassab Yaman Walid , Farrukh Muhammad Junaid , Goh Bey Hing , Lua Pei Lin , Hermansyah Andi , Ming Long Chiau 
Published: May 2023

BackgroundEnd-stage renal disease is the last stage of chronic kidney disease and can affect the quality of life (QOL) of dialysis patients. The aim of this study was to assess the quality of life and examine its determinants.MethodsA cross-sectional survey involving patients on dialysis in a tertiary hospital was conducted from July 2020 to September 2020. Demographic data were collected using a predesigned questionnaire. QOL was measured using the 36-item KDQOL questionnaire, and statistical analysis was carried out using SPSS version 25.ResultsOf the 108 patients, 59 were men and 49 were women, and the mean age was 48.15 ± 15.4 years. The results showed that there was no significant difference in the mean score of all components of health-related quality of life in different types of dialysis. The demographic data, which included age, gender, ethnicity, marital status, education level, occupation, and monthly income, did not significantly affect the QOL of dialysis patients. Patients with a dialysis duration of more than 5 years had a better QOL compared to other groups. Laboratory parameters such as low albumin and low hemoglobin showed a significant correlation with the health-related quality of life of dialysis patients.ConclusionThe quality of life among patients on dialysis was impaired, especially in terms of burden of the kidney disease. Hypoalbuminemia and anemia were the two factors that influenced QOL.
Comparison of Staphylococcus aureus tolerance between antimicrobial blue light, levofloxacin, and rifampin
Authors: Ong Jemi , Godfrey Rose , Nazarian Alexa , Tam Joshua , Isaacson Brad M. , Pasquina Paul F. , Williams Dustin L. 
Published: May 2023

BackgroundBacterial biofilms readily develop on all medical implants, including percutaneous osseointegrated (OI) implants. With the growing rate of antibiotic resistance, exploring alternative options for managing biofilm-related infections is necessary. Antimicrobial blue light (aBL) is a unique therapy that can potentially manage biofilm-related infections at the skin-implant interface of OI implants. Antibiotics are known to have antimicrobial efficacy disparities between the planktonic and biofilm bacterial phenotypes, but it is unknown if this characteristic also pertains to aBL. In response, we developed experiments to explore this aspect of aBL therapy.MethodsWe determined minimum bactericidal concentrations (MBCs) and antibiofilm efficacies for aBL, levofloxacin, and rifampin against Staphylococcus aureus ATCC 6538 planktonic and biofilm bacteria. Using student t-tests (p &lt; 0.05), we compared the efficacy profiles between the planktonic and biofilm states for the three independent treatments and a levofloxacin + rifampin combination. Additionally, we compared antimicrobial efficacy patterns for levofloxacin and aBL against biofilms as dosages increased.ResultsaBL had the most significant efficacy disparity between the planktonic and biofilm phenotypes (a 2.5 log10 unit difference). However, further testing against biofilms revealed that aBL had a positive correlation between increasing efficacy and exposure time, while levofloxacin encountered a plateau. While aBL efficacy was affected the most by the biofilm phenotype, its antimicrobial efficacy did not reach a maximum.Discussion/conclusionWe determined that phenotype is an important characteristic to consider when determining aBL parameters for treating OI implant infections. Future research would benefit from expanding these findings against clinical S. aureus isolates and other bacterial strains, as well as the safety of long aBL exposures on human cells.