bluuebunny/crossref_metadata_2025_split huggingface dataset:
Novel miRNA-based drug CD5-2 reduces liver tumor growth in diethylnitrosamine-treated mice by normalizing tumor vasculature and altering immune infiltrate
Authors: Liu Ken , Chen Jinbiao , Zhao Yang , Boland Jade , Ting Ka Ka , Lockwood Glen , McKenzie Catriona , Kench James , Vadas Mathew A. , Gamble Jennifer R. , McCaughan Geoffrey W. 
Published: September 2023

IntroductionLiver cancers exhibit abnormal (leaky) vasculature, hypoxia and an immunosuppressive microenvironment. Normalization of tumor vasculature is an emerging approach to treat many cancers. Blockmir CD5-2 is a novel oligonucleotide-based inhibitor of the miR-27a interaction with VE-Cadherin, the endothelial-specific cadherin. The combination of a vasoactive medication with inhibition of immune checkpoints such as programmed cell death protein 1 (PD1) has been shown to be effective in treating liver cancer in humans. We aimed to study the effect of CD5-2 combined with checkpoint inhibition (using an antibody against PD1) on liver tumor growth, vasculature and immune infiltrate in the diethylnitrosamine (DEN)-induced liver tumor mouse model.MethodsWe first analyzed human miR-27a and VE-Cadherin expression data from The Cancer Genome Atlas for hepatocellular carcinoma. CD5-2 and/or anti-PD1 antibody were given to the DEN-treated mice from age 7-months until harvest at age 9-months. Tumor and non-tumor liver tissues were analyzed using histology, immunohistochemistry, immunofluorescence and scanning electron microscopy.ResultsHuman data showed high miR-27a and low VE-Cadherin were both significantly associated with poorer prognosis. Mice treated with CD5-2 plus anti-PD1 antibody had significantly smaller liver tumors (50% reduction) compared to mice treated with either agent alone, controls, or untreated mice. There was no difference in tumor number. Histologically, tumors in CD5-2-treated mice had less leaky vessels with higher VE-Cadherin expression and less tumor hypoxia compared to non-CD5-2-treated mice. Only tumors in the combination CD5-2 plus anti-PD1 antibody group exhibited a more favorable immune infiltrate (significantly higher CD3+ and CD8+ T cells and lower Ly6G+ neutrophils) compared to tumors from other groups.DiscussionCD5-2 normalized tumor vasculature and reduced hypoxia in DEN-induced liver tumors. CD5-2 plus anti-PD1 antibody reduced liver tumor size possibly by altering the immune infiltrate to a more immunosupportive one.
Alkaline arginine promotes the gentamicin-mediated killing of drug-resistant Salmonella by increasing NADH concentration and proton motive force
Authors: Zhu Chunyang , Zhou Yanhong , Kang Jian , Yang Heng , Lin Jinglin , Fang Binghu 
Published: September 2023

IntroductionAntimicrobial resistance, especially the development of multidrug-resistant strains, is an urgent public health threat. Antibiotic adjuvants have been shown to improve the treatment of resistant bacterial infections.MethodsWe verified that exogenous L-arginine promoted the killing effect of gentamicin against Salmonella in vitro and in vivo, and measured intracellular ATP, NADH, and PMF of bacteria. Gene expression was determined using real-time quantitative PCR.ResultsThis study found that alkaline arginine significantly increased gentamicin, tobramycin, kanamycin, and apramycin-mediated killing of drug-resistant Salmonella, including multidrug-resistant strains. Mechanistic studies showed that exogenous arginine was shown to increase the proton motive force, increasing the uptake of gentamicin and ultimately inducing bacterial cell death. Furthermore, in mouse infection model, arginine effectively improved gentamicin activity against Salmonella typhimurium.DiscussionThese findings confirm that arginine is a highly effective and harmless aminoglycoside adjuvant and provide important evidence for its use in combination with antimicrobial agents to treat drug-resistant bacterial infections.
Preferred physical characteristics of lidocaine thin film for women with vestibulodynia
Authors: Silverstein R. Gina , Cromeens Martha Grace , Rowland Caroline , Ogbansiegbe Joseph A. , Mihas Paul , Benhabbour S. Rahima , Carey Erin T. 
Published: September 2023

IntroductionVestibulodynia (VBD) is the most common cause of sexual pain in the United States, affecting up to 15% of reproductive-aged women during their lifetime with limited treatment options. The purpose of this study was to describe ideal physical characteristics of a vulvar film designed for insertional sexual pain in sexually active women with VBD.MethodsTwenty women were recruited to participant in one of six, semi-structured 60-minute focus group discussions regarding treatment options for VBD. Heterosexual women, aged 18–51 years old with a diagnosis of vulvodynia, vestibulodynia or insertional dyspareunia fit the inclusion criteria. Those who reported no episodes of vaginal intercourse in the prior 18 months were excluded. A new vulvar film technology loaded with 50 mg of 5% lidocaine was introduced to the group. Participants took part in focus groups on a rolling basis depending on availability. Focus group discussions were audio-recorded and transcribed verbatim. Two study investigators coded the transcripts using inductive coding and merged their respective projects to resolve disagreements. We analyzed data related to each code to develop code clusters and higher-level primary topics regarding device preferences. Data related to each of these primary topics was analyzed to assess the range of participant attitudes and preferences and to identify patterns within each primary topic.ResultsOne hundred and sixteen women were recruited, and twenty women were enrolled. The mean age for the participants was 33.3 years. Most women were educated with at least some college (93%), White (78.6%), married (75%), and had income greater than $100,000 (50%). Analysis of the focus group discussions identified five common topics addressed by participants: desired loaded medication, film size, film shape, film flexibility, and ease and accuracy of use. Concerns across topics included comfort, sexual spontaneity, and efficacy. Interest in loading the device with other acceptable medications or combination with lidocaine was independently noted in 2/6 (33%) of the focus groups.DiscussionMucoadhesive vulvar thin films may be an acceptable drug delivery system for insertional sexual pain for women with VBD.
Can the Chinese study on the normal range of FeNO in children evaluate standardized asthma treatment efficacy in 6- to 12-year-old children?
Authors: Yang Qiuyan , Cai Chunling , Xu Qingrong , Zheng Yuehong , Li Aijun , Liu Ying , Li Shufang , Zhang Yanli 
Published: September 2023

ObjectiveBy examining fractional exhaled nitric oxide (FeNO) levels and performing pulmonary function testing, this study explored whether the multicenter study on the normal range of FeNO in children in China can be used to evaluate standardized treatment efficacy in 6- to 12-year-old children with asthma.MethodsA total of 115 children aged 6–12 years old who were first diagnosed with asthma and received standardized asthma treatment from April 2018 to July 2022 were selected. According to the FeNO level at the first visit, the subjects were divided into different high- and low-FeNO groups according to the American Thoracic Society (ATS) guidelines and the Chinese multicenter study recommendations. The consistency of the two grouping methods and the differences between the high- and low-FeNO groups were compared after standardized treatment. The grouping method that was the most suitable for children in the cross group was discussed.Results(i) There was fair consistency between the Chinese multicenter study recommendations and the ATS guidelines regarding the classification of high- and low-FeNO groups (Kappa = 0.338). (ii) Repeated-measures ANOVA showed that the level of improvement in FVC%, FEV1%, FEF25%, FEF50%, and FeNO in the American high- and low-FeNO groups differed with the duration of therapy (P &lt; 0.05), however, there was no significant difference between the Chinese groups. (iii) FEV1% and FeNO improved more after treatment in the fixed high-FeNO group than in the cross group (P &lt; 0.05).ConclusionThe Chinese multicenter study on the normal range of FeNO in children in China has a limited role in evaluating standardized asthma treatment efficacy in 6- to 12-year-old children. The ATS guidelines are currently recommended for clinical assessment of asthma treatment efficacy.
Pilot study shows skin-to-skin care with parents improves heart rate variability in preterm infants in the neonatal intensive care unit
Authors: Swieter Erin , Gross Jessica M. , Stephen Julia , Watterberg Kristi , Maxwell Jessie R. 
Published: September 2023

BackgroundSkin-to-skin care in the newborn intensive care unit typically lasts for short periods of time and enhances breastfeeding, attachment, and parental self-esteem. Heart rate variability (HRV) increases with gestational age and is a measure of maturation of parasympathetic vs. sympathetic autonomic nervous system activity. HRV measurements may be useful in capturing changes in autonomic regulation in response to skin-to-skin care.ObjectiveTo analyze the effects of skin-to-skin care on HRV in preterm infants receiving respiratory support. We hypothesized that skin-to-skin care would result in a more mature pattern of parasympathetic activity.MethodsIn this prospective crossover study, infants &lt;30 weeks' gestation and 1–6 weeks postnatal age had HRV recorded for 30 min before, during, and after skin-to-skin care sessions. HRV characteristics analyzed included the standard deviation of the normal-to-normal interval (SDNN), the root mean squared of successive differences of normal-to-normal intervals (RMSSD), and the standard deviation of decelerations (SDDec).Results10 infants between 25 5/7–29 6/7 weeks gestational age and 7–41 days postnatal age completed 22 sessions while receiving respiratory support (positive pressure ventilation or nasal cannula oxygen). Two measures of HRV (SDNN and RMSSD) were significantly decreased by the end of the skin-to-skin sessions, compared to pre-session values. SDNN decreased from a median of 10.44 ms before the session to 6.70 ms after being placed back in bed (p &lt; 0.05), with RMSSD decreasing from a median of 6.80 ms before the session to 4.32 ms while being held at the end of 30 min (p &lt; 0.05).DiscussionSkin-to-skin care with a parent resulted in a more mature autonomic nervous system pattern in preterm infants receiving respiratory support, suggesting physiologic benefit for the infant. No adverse events were seen during any session.
G. lucidum triterpenes restores intestinal flora balance in non-hepatitis B virus-related hepatocellular carcinoma: evidence of 16S rRNA sequencing and network pharmacology analysis
Authors: Xiong Wei , Yang Ce , Xia Jing , Wang Wenxiang , Li Ning 
Published: September 2023

Background: Ganoderma lucidum (G. lucidum) is a popular traditional remedy medicine used in Asia to promote health and longevity, which has also been highlighted for anti-cancer effects. This study investigated the molecular pharmacological mechanism of G. lucidum triterpenes in influencing intestinal flora imbalance in non-hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) based on 16S rRNA sequencing technology and network pharmacology analysis.Methods: 16S rRNA sequencing data of fecal samples from normal controls and HCC patients were obtained from the SRA database. G. lucidum triterpenes and HCC-related targets were screened by BATMAN-TCM, ETCM, and GeneCards databases. The TCGA-LIHC dataset was downloaded through the TCGA database to analyze the differential expression of key genes. NHBV-related HCC-related transcriptome RNA sequencing dataset was downloaded via the GEO database.Results: Abundance of intestinal flora in the HBV-related HCC and NHBV-related samples was higher than that of control samples. The intestinal flora of NHBV samples was mainly enriched in apoptosis and p53 pathways. Totally, 465 G. lucidum triterpenes-related targets were intersected with 4186 HCC-related targets, yielding 176 intersected targets. Among them, apoptosis and p53 pathway factors were located at the core of the protein-protein interactions network. Ganosporelactone B, the active component of G. lucidum triterpenes, had the lowest binding free energy to CASP3. CASP3 expression were upregulated in HCC tissue samples, and had higher predictive value in NHBV-related HCC patients.Conclusion: Therefore, Ganosporelactone B, the active ingredient of G. lucidum triterpenes, improves the imbalance of intestinal flora and ultimately curtails development of NHBV-related HCC.
The influence of adjunctive traditional Chinese medicine therapy on survival in primary liver cancer: a real-world study based on electronic medical records
Authors: Zhao Ruixia , Wang Linlin , Liu Yibing , Shao Mingyi , Yang Wei , Fu Yu , Gao Qilong , Feng Jun’an , Xing Yunfei , Xiang Xinghua 
Published: September 2023

Background: Traditional Chinese medicine (TCM) effectively improves the survival rate and quality of life of primary liver cancer patients, but high-level evidence is lacking.Patients and methods: Patients were selected from 5 tertiary hospitals in Henan Province, China. Two thousand sixty-seven patients with primary liver cancer were included in the study. The electronic medical records (EMRs) of the patients were collected. Patients who received adjunctive TCM treatment and underwent treatment cumulative time for more than 1 month were classified as the TCM intervention cohort. Patients who did not receive adjunctive TCM treatment or underwent treatment cumulative time for less than 1 month were classified as the non-TCM intervention cohort. The main outcome indicators were the survival rate and overall survival time. The propensity score inverse probability weighting method was used to balance the differences between the groups.Results: The primary cohort comprised 2,067 patients, including 462 patients who received adjunctive TCM treatment and 1,605 patients who did not receive adjunctive TCM treatment. The results of the Kaplan‒Meier survival curve indicated that the survival rate and median survival time of the exposure group before and after propensity score weighting were greater than those of the control group (p &lt; 0.0001). Univariate Cox regression analysis after propensity score weighting showed that adjunctive TCM treatment was an independent protective factor for survival [regression coefficient = −0.215, hazard ratio (HR) = 0.8066, 95% confidence interval (CI) (0.6609–0.9844)].Conclusion: Adjuvant treatment with TCM has a protective effect on the prognosis of patients with primary liver cancer; it can reduce the mortality and prolong the survival time.
Comparison of the respiratory effects of commonly utilized general anaesthesia regimes in male Sprague-Dawley rats
Authors: Ballók Bence , Schranc Álmos , Tóth Ibolya , Somogyi Petra , Tolnai József , Peták Ferenc , Fodor Gergely H. 
Published: September 2023

Background: Respiratory parameters in experimental animals are often characterised under general anaesthesia. However, anaesthesia regimes may alter the functional and mechanical properties of the respiratory system. While most anaesthesia regimes have been shown to affect the respiratory system, the effects of general anaesthesia protocols commonly used in animal models on lung function have not been systematically compared.Methods: The present study comprised 40 male Sprague-Dawley rats divided into five groups (N = 8 in each) according to anaesthesia regime applied: intravenous (iv) Na-pentobarbital, intraperitoneal (ip) ketamine-xylazine, iv propofol-fentanyl, inhaled sevoflurane, and ip urethane. All drugs were administered at commonly used doses. End-expiratory lung volume (EELV), airway resistance (Raw) and tissue mechanics were measured in addition to arterial blood gas parameters during mechanical ventilation while maintaining positive end-expiratory pressure (PEEP) values of 0, 3, and 6 cm H2O. Respiratory mechanics were also measured during iv methacholine (MCh) challenges to assess bronchial responsiveness.Results: While PEEP influenced baseline respiratory mechanics, EELV and blood gas parameters (p &lt; 0.001), no between-group differences were observed (p &gt; 0.10). Conversely, significantly lower doses of MCh were required to achieve the same elevation in Raw under ketamine-xylazine anaesthesia compared to the other groups.Conclusion: In the most frequent rodent model of respiratory disorders, no differences in baseline respiratory mechanics or function were observed between commonly used anaesthesia regimes. Bronchial hyperresponsiveness in response to ketamine-xylazine anaesthesia should be considered when designing experiments using this regime. The findings of the present study indicate commonly used anaesthetic regimes allow fair comparison of respiratory mechanics in experimental animals undergoing any of the examined anaesthesia protocols.
Genetic improvement of tocotrienol content enhances the oxidative stability of canola oil
Authors: Deng Min , Chen Hao , Zhang Wei , Cahoon Edgar B. , Zhou Yongming , Zhang Chunyu 
Published: September 2023

BackgroundTocotrienols and tocopherols, which are synthesized in plastids of plant cells with similar functionalities, comprise vitamin E to serve as a potent lipid-soluble antioxidant in plants. The synthesis of tocopherols involves the condensation of homogentisic acid (HGA) and phytyl diphosphate (PDP) under the catalysis of homogentisate phytyltransferase (HPT). Tocotrienol synthesis is initiated by the condensation of HGA and geranylgeranyl diphosphate (GGDP) mediated by homogentisate geranylgeranyl transferase (HGGT). As one of the most important oil crops, canola seed is regarded as an ideal plant to efficiently improve the production of vitamin E tocochromanols through genetic engineering approaches. However, only a modest increase in tocopherol content has been achieved in canola seed to date.MethodsIn this study, we transformed barley HGGT (HvHGGT) into canola to improve total tocochromanol content in canola seeds.Results and discussionThe results showed that the total tocochromanol content in the transgenic canola seeds could be maximally increased by fourfold relative to that in wild-type canola seeds. Notably, no negative impact on important agronomic traits was observed in transgenic canola plants, indicating great application potential of the HvHGGT gene in enhancing tocochromanol content in canola in the future. Moreover, the oil extracted from the transgenic canola seeds exhibited significantly enhanced oxidative stability under high temperature in addition to the increase in total tocochromanol content, demonstrating multiple desirable properties of HvHGGT.
Emotions, COVID-19 related thoughts and satisfaction with life during the critical period from control to relaxation
Authors: Diao Chunting , Tan Huiping , Wen Yanhui , Zhu Ruiyue , Wu Xiaoyue , Zhang Shiqi , Zhao Yongzhi , Liu Nian , Zhou Xuan , Hu Zhen 
Published: September 2023

IntroductionIn the context of declining mortality rates and increasing infectivity, it has become unavoidable for the majority of individuals to experience a COVID-19 infection at some point. This study aimed to investigate the psychological well-being of the general population during China’s transition period from strict control measures to relaxed policies in COVID-19 prevention and control, as well as the impact of COVID-19 related thoughts on emotion and life satisfaction during widespread infections.MethodsA cross-sectional study was conducted involving a sample size of 1578 participants. Participants completed self-report questionnaires assessing positive and negative emotions, thoughts about COVID-19, and satisfaction with life. Demographic characteristics such as sex, age, and education level were controlled for in the analysis.ResultsThe findings revealed that individuals who had been infected with COVID-19 (specifically the Omicron variant BA.5.2 or BF.7) reported lower levels of positive emotions compared to those who were uninfected or had recovered from the infection. There was a significant relationship between COVID-19-related thoughts, emotions, and life satisfaction. Positive COVID-19 related thoughts were found to mediate the relationship between negative emotions and satisfaction with life.DiscussionThis study represents a comprehensive examination conducted in China, focusing on assessing the impact of the COVID-19 pandemic on the general population during the critical transition period from control to relaxation. Throughout this period, the number of infections experienced fluctuations, initially rising but eventually declining over a one-month span. In such a momentous historical period, maintaining a positive perspective on COVID-19 and its management becomes paramount in enhancing the emotional well-being, life satisfaction and overall well-being of individuals.
Self-efficacy assessment hinders improvement on a deliberate cricket bowling practice task
Authors: Raman Dhruv , Rajaraman Bittu 
Published: September 2023

IntroductionPrevious research indicates that external focused attention is linked to superior performance on motor tasks. This study examined how attention directed toward one’s self-efficacy affected performance in a cricket bowling task.MethodsIn the pre-test phase, participants attempted to bowl in a designated “good length” zone across 12 trials. Following this, participants were randomly assigned to either an experimental group, where they rated their own general and task-specific self-efficacy, or a control group, where they rated someone else’s ability. They each then bowled 12 more trials. Their performance was measured based on the number of trials that were bowled within the standard “good length” zone.ResultsPaired t-tests showed that while the performance of the control group improved significantly from pre-test to post-test, t = 2.613, p = 0.008; the experimental group did not show a significant improvement, t = 1.156, p = 0.131.DiscussionResults indicate that asking people to rate their self-efficacy level may reduce their improvement on a deliberate practice task. Implications for sport performance and researchers are discussed.