bluuebunny/crossref_metadata_2025_split huggingface dataset:
The effect of remimazolam-based total intravenous anesthesia versus sevoflurane-based inhalation anesthesia on emergence delirium in children undergoing tonsillectomy and adenoidectomy: study protocol for a prospective randomized controlled trial
Authors: Ma Hong-Yu , Cai Yu-Hang , Zhong John Wei , Chen Jia , Wang Zhen , Lin Chao-Yi , Wang Qiao-Qiao , Liu Hua-Cheng 
Published: June 2024

Background: Remimazolam, a new ultrashort-acting benzodiazepine, is becoming increasingly applied in general anesthesia. This study is designed to investigate the effect of remimazolam-based total intravenous anesthesia and sevoflurane-based inhalation anesthesia on emergence delirium in pediatric tonsillectomy and adenoidectomy.Methods and analysis: This is a monocentric, prospective, randomized, double-blind clinical trial. A total of 90 pediatric patients will be randomized to receive remimazolam-based total intravenous anesthesia (remimazolam group, n = 45) or sevoflurane-based inhalation anesthesia (sevoflurane group, n = 45). The primary outcome will be the incidence of emergence delirium, which will be evaluated using the Pediatric Anesthesia Emergence Delirium (PAED) scale. The secondary outcomes include the extubation time, recovery time, behavior change using the post-hospitalization behavior questionnaire for ambulatory surgery (PHBQ-AS), and adverse events.Ethics and dissemination: This study has been approved by the Institutional Review Board (IRB) of the Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University (2023-K-262-02).Clinical trial registration:ClinicalTrials.gov, identifier NCT06214117.
Mingjing granule inhibits the subretinal fibrovascular membrane of two-stage laser-induced neovascular age-related macular degeneration in rats
Authors: Li Xiaoyu , Li Jiaxian , Zeng Weixin , Wang Baoli , Du Maobo , Liang Lina , Gao Yun 
Published: June 2024

ObjectiveThe study aims to investigate the protective effect of Mingjing granule (MG) in a fibrovascular membrane rat model of neovascular age-related macular degeneration (nAMD) and explore the underlying mechanism.MethodsThe nAMD fibrovascular membrane model was established by two-stage laser photocoagulation. BN rats were randomly divided into four groups: the model group was gavaged with distilled water, the anti-VEGF group was given an intravitreous injection of ranibizumab, the MG + anti-VEGF group was gavaged with MG combined with an intravitreous injection of ranibizumab, and the normal group not modeled only fed conventionally. Lesions were evaluated by color fundus photograph, optical coherence tomography, fundus fluorescein angiography, and retinal pigment epithelial–choroid–sclera flat mount. The changes in the retinal structure were observed by histopathology. The expression of inflammatory cell markers F4/80, Iba-1, and glial fibrillary acidic protein (GFAP); the fibrosis-related factors collagen-1, fibronectin, α-smooth muscle actin (α-SMA), and transforming growth factor-beta (TGF-β); and the complement system-related factors C3a and C3aR in the retina were detected by immunofluorescence or qRT-PCR.ResultsThe current study revealed that MG + anti-VEGF administration more significantly reduced the thickness of fibrovascular lesions, suppressed vascular leakage (exudation area and mean density value), inhibited the area of fibrovascular lesions, and restrained the formation of the fibrovascular membrane than the anti-VEGF agent alone in the two-stage laser-induced rat model. The fluorescence intensities of F4/80, Iba-1, collagen-1, fibronectin, TGF-β, and C3aR showed more significant inhibition in MG + anti-VEGF-treated rats than the anti-VEGF agent alone. The mRNA expression levels of F4/80, Iba-1, GFAP, collagen-1, fibronectin, α-SMA, TGF-β, and C3a showed lower levels in rats treated with MG + anti-VEGF than the anti-VEGF agent alone.ConclusionCombining MG with anti-VEGF treatment inhibits the growth of the fibrovascular membrane more effectively than using anti-VEGF treatment alone. The mechanism underlying this effect may involve limiting inflammatory cell aggregation, controlling complement system activation, and decreasing the expression of the fibrotic protein.
Prediction of immunotherapy response of bladder cancer with a pyroptosis-related signature indicating tumor immune microenvironment
Authors: Xu Zihan , Zhao Yujie , Zhang Yong , Liu Xiaowei , Song Linlin , Chen Meixu , Xiao Guixiu , Ma Xuelei , Shi Hubing 
Published: June 2024

BackgroundAlthough prognostic models based on pyroptosis-related genes (PRGs) have been constructed in bladder cancer (BLCA), the comprehensive impact of these genes on tumor microenvironment (TME) and immunotherapeutic response has yet to be investigated.MethodsBased on expression profiles of 52 PRGs, we utilized the unsupervised clustering algorithm to identify PRGs subtypes and ssGSEA to quantify immune cells and hallmark pathways. Moreover, we screened feature genes of distinct PRGs subtypes and validated the associations with immune infiltrations in tissue using the multiplex immunofluorescence. Univariate, LASSO, and multivariate Cox regression analyses were employed to construct the scoring scheme.ResultsFour PRGs clusters were identified, samples in cluster C1 were infiltrated with more immune cells than those in others, implying a favorable response to immunotherapy. While the cluster C2, which shows an extremely low level of most immune cells, do not respond to immunotherapy. CXCL9/CXCL10 and SPINK1/DHSR2 were identified as feature genes of cluster C1 and C2, and the specimen with high CXCL9/CXCL10 was characterized by more CD8 + T cells, macrophages and less Tregs. Based on differentially expressed genes (DEGs) among PRGs subtypes, a predictive model (termed as PRGs score) including five genes (CACNA1D, PTK2B, APOL6, CDK6, ANXA2) was built. Survival probability of patients with low-PRGs score was significantly higher than those with high-PRGs score. Moreover, patients with low-PRGs score were more likely to benefit from anti-PD1/PD-L1 regimens.ConclusionPRGs are closely associated with TME and oncogenic pathways. PRGs score is a promising indicator for predicting clinical outcome and immunotherapy response.
A real-world pharmacovigilance study of polatuzumab vedotin based on the FDA adverse event reporting system (FAERS)
Authors: Liu Dan , Mao Wei , Hu Bin , Li Xingxing , Zhao Quanfeng , Zhang Lin , Hu Jing 
Published: June 2024

BackgroundPolatuzumab vedotin, the first FDA-approved antibody-drug conjugate (ADC) targeting CD79b, is utilized in the treatment of previously untreated diffuse large B-cell lymphoma (DLBCL) or high-grade B-cell lymphoma (HGBL), as well as relapsed or refractory (R/R) DLBCL. Despite its approval, concerns persist regarding the long-term safety profile of polatuzumab vedotin. This study aims to evaluate the adverse events (AEs) associated with polatuzumab vedotin since its approval in 2019, utilizing data mining strategies applied to the FDA Adverse Event Reporting System (FAERS).MethodsSignal detection employed four methodologies, including reporting odds ratio (ROR), proportional reporting ratio (PRR), bayesian confidence propagation neural network (BCPNN), and multi-item gamma poisson shrinker (MGPS), to evaluate and quantify the signals of polatuzumab vedotin-associated AEs. Additionally, subgroup analyses based on patients age, gender, and fatal cases were conducted to investigate AEs occurrences in specific subpopulations.ResultsA total of 1,521 reports listing polatuzumab vedotin as a “principal suspect (PS)” drug were collected from the FAERS database. Through concurrent compliance with four algorithms, 19 significant Standardized MedDRA Query (SMQ) AEs and 92 significant Preferred Term (PT) AEs were detected. Subgroup analyses revealed a higher incidence of PTs in male patients compared to female patients, increased likelihood of polatuzumab vedotin-associated AEs in elder patients (&gt;65 years), and AEs with a high risk of fatal cases include: blood lactate dehydrogenase increased, cytopenia, and hydronephrosis. The median time to AEs occurrence following polatuzumab vedotin initiation was 18.5 (5∼57.75) days, with 95% of AEs occurred within 162 days.ConclusionThis study identified various AEs associated with polatuzumab vedotin, offering critical insights for clinical monitoring and risk identification in patients receiving polatuzumab vedotin therapy.
Ginseng extract improves pancreatic islet injury and promotes β-cell regeneration in T2DM mice
Authors: Yin Jianying , Huang Yuanfeng , Wang Ke , Zhong Qin , Liu Yuan , Ji Zirui , Liao Yiwen , Ma Zhiyuan , Bei Weijian , Wang Weixuan 
Published: June 2024

IntroductionPanax ginseng C. A. Mey. (Araliaceae; Ginseng Radix et Rhizoma), a traditional plant commonly utilized in Eastern Asia, has demonstrated efficacy in treating neuro-damaging diseases and diabetes mellitus. However, its precise roles and mechanism in alleviating type 2 diabetes mellitus (T2DM) need further study. The objective of this study is to explore the pharmacological effects of ginseng extract and elucidate its potential mechanisms in protecting islets and promoting β-cell regeneration.MethodsThe T2DM mouse model was induced through streptozotocin combined with a high-fat diet. Two batches of mice were sacrificed on the 7th and 28th days following ginseng extract administration. Body weight, fasting blood glucose levels, and glucose tolerance were detected. Morphological changes in the pancreatic islets were examined via H &amp; E staining. Levels of serum insulin, glucagon, GLP-1, and inflammatory factors were measured using ELISA. The ability of ginseng extract to promote pancreatic islet β-cell regeneration was evaluated through insulin &amp; PCNA double immunofluorescence staining. Furthermore, the mechanism behind β-cells regeneration was explored through insulin &amp; glucagon double immunofluorescence staining, accompanied by immunohistochemical staining and western blot analyses.Results and DiscussionThe present research revealed that ginseng extract alleviates symptoms of T2DM in mice, including decreased blood glucose levels and improved glucose tolerance. Serum levels of insulin, GLP-1, and IL-10 increased following the administration of ginseng extract, while levels of glucagon, TNF-α, and IL-1β decreased. Ginseng extract preserved normal islet morphology, increased nascent β-cell population, and inhibited inflammatory infiltration within the islets, moreover, it decreased α-cell proportion while increasing β-cell proportion. Mechanistically, ginseng extract might inhibit ARX and MAFB expressions, increase MAFA level to aid in α-cell to β-cell transformation, and activate AKT-FOXM1/cyclin D2 to enhance β-cell proliferation. Our study suggests that ginseng extract may be a promising therapy in treating T2DM, especially in those with islet injury.
β-blockades and the risk of atrial fibrillation in patients with cardiovascular diseases
Authors: Gu Xun-Hu , Li Weichao , Li Heng , Guo Xun , He Jiang , Liu Yuyan , Gong Jianping , Huang Yizhou , Zhang Bin 
Published: June 2024

Backgroundβ-blockers have been widely used in patients with extensive cardiovascular disease (CVD) and have provided benefits. However, they are more likely to cause symptomatic bradycardia, hypotension, or glucose metabolism disorders, which may lead to an increased risk of atrial fibrillation (AF), but evidence is lacking.AimsThis study was to analyze the association between the use of β-blockers and the risk of developing AF.MethodsThis nationwide, prospective cohort study utilized data from the 2013–2020 National Health and Nutrition Examination Survey (NHANES). The patients were stratified into a β-blocker treatment group (n = 2585) and a non-β-blocker treatment group (n = 8525). Univariate and multivariate logistic regression analyses were performed to identify the relationship between β-blockades and the risk of AF. Propensity matching analysis was used to balance patient baseline characteristics and to control for confounders.ResultsA total of 11,110 subjects were included in this study (mean [SD] age, 59.89 [15.07] years; 5657 [49.7%] males). A total of 111/2585 subjects developed AF in the β-blocker treatment group, and 75/8525 developed AF in the non-β-blocker treatment group (incidence rate, 4.2% vs. 0.8%). Compared with the non-β-blocker group, the β-blocker group had an increased risk of incident AF (aOR, 2.339; 95% CI, 1.614–3.410). Some sensitivity analyses also revealed consistent findings of increased AF risk associated with β-blocker treatment.ConclusionThe findings from this study suggest that β-blocker treatment is associated with an increased risk of incident AF and may help physicians select a modest medication for patients while also assessing the risk of AF.
Sugar feeding in triatomines: a new perspective for controlling the transmission of Chagas disease
Authors: Costa Mariana C. , Moreira Carlos J. C. , Oliveira Pedro Lagerblad de , Juberg José , Castro Daniele Pereira de , Genta Fernando Ariel 
Published: June 2024

Introduction: Triatomines are vectors of Trypanosoma cruzi, the etiological agent of Chagas disease. Currently, there is no vaccine against this disease. Thus, control of the insect vector population is the main strategy available to reduce the number of cases. Triatomines are considered obligate hematophagous, but different alternative feeding behaviors were described, such as haemolymphagy or plant feeding.Methods: To determine the preference for sugar feeding in nymphs and adults of Rhodnius prolixus, the insects were exposed a piece of cotton containing bromophenol blue plus sucrose. In addition, we offered several sugars for different species of triatomines, and tested sugar meals as a route of delivery of insecticides in first-instar nymphs of R. prolixus. The effect of sugar feeding on the physiology of these different species of triatomines was recorded.Results: First instar nymphs ingested sucrose more strongly than other stages, and showed high mortality rates. In different species of triatomines, sucrose induced an ingestion, but engorgement varied according to the species. R. prolixus nymphs showed an indiscriminate intake of various sugars, with very different physiological effects. Furthermore, ingesting different combinations of insecticides + sugar significantly reduced insect survival.Discussion: In summary, we described for the first-time sugar feeding as a widespread behavior in several species of triatomines, and the possibility of the use of toxic sugar baits for the control of these vectors. The knowledge of feeding behavior in these insects can be fundamental for the development of new strategies to control Chagas disease.
Intermittent hypoxia training does not change erythrocyte aggregation indicators in young, healthy men
Authors: Mardyła Mateusz , Maciejczyk Marcin , Pałka Tomasz , Więcek Magdalena , Kusmierczyk Justyna , Szymura Jadwiga , Szygula Zbigniew 
Published: June 2024

BackgroundThe increasing popularity of hypoxic training as a training method to improve physical performance indicates the need to study the effects of this type of intervention on blood morphological and rheological indices, since the adaptive changes that follow such training mainly affect blood indices. In this study, the effects of a 4 weeks of intermittent hypoxic training on blood morphological and rheological indicators in physically active men were assessed.MethodsForty-eight young, physically active men, participated in the study. Participants were randomly divided into three groups: two training groups and a control group without intervention (CTRL). Each group consisted of 16 participants. Training groups performed interval training (three times per week, 4 weeks, 12 workouts) under different conditions: in hypoxia (IHT; fraction of inspired oxygen (FiO2) = 14.4%) or in normoxia (NT; FiO2 = 20.9%). The control group performed only two workouts 4 weeks apart. Blood was taken during the first and last training session at rest, and 3 minutes after training.ResultsAfter the last training session, there was a significant increase in mean corpuscular volume and a decrease in mean corpuscular haemoglobin concentration measured at rest only in the IHT group. There was also a significant decrease in resting aggregation amplitude for the IHT and CTRL groups. There was no difference in change of post-exercise plasma volume between first and last training session.ConclusionThe applied intermittent interval training in conditions of normoxia and hypoxia had no significant impact on resting aggregation parameters. This suggest that training under hypoxic conditions does not cause adverse rheological changes.
A correlation of serum fibroblast growth factor 21 level with inflammatory markers and indicators of nutritional status in patients with inflammatory bowel disease
Authors: Łukawska Agata , Mulak Agata 
Published: June 2024

BackgroundFibroblast growth factor 21 (FGF21) is a stress-inducible hormone that regulates nutrient and metabolic homeostasis. Inflammatory state is one of the stimulators of FGF21 secretion. The aim of the study was to assess correlations between serum FGF21 level and inflammatory markers as well as nutritional status indicators in patients with inflammatory bowel disease (IBD).MethodsFasting serum FGF21 level was measured using ELISA test in 105 IBD patients and 17 healthy controls. There were 31 subjects with active ulcerative colitis (UC), 16 with inactive UC, 36 with active Crohn’s disease (CD), and 22 with inactive CD. Clinical and endoscopic activity of IBD was evaluated based on validated scales and indices. Fecal calprotectin, serum CRP, and selected parameters of nutritional status were tested in all patients.ResultsSerum FGF21 level was characterized by fluctuations depending on the IBD activity. FGF21 level was significantly higher in both active UC and CD compared to inactive phases of the diseases and to the controls. A correlation between FGF21 and fecal calprotectin levels was also found in UC and CD. Additionally, in CD, FGF21 level positively correlated with CRP level. In both UC and CD, a negative correlation was noted between FGF21 level and nutritional status parameters including cholesterol, protein, albumin levels, and BMI.ConclusionThe intensity of intestinal inflammation is related to FGF21 level, which correlates negatively with nutritional status indicators in IBD. The disturbances in FGF21 secretion may contribute to the multifactorial pathogenesis of malnutrition and weight loss in IBD patients.
The relationship between script memory for everyday events and schizotypy: an investigation through a development of Japanese Situational Feature Recognition Test
Authors: Kikutani Mariko , Takiguchi Yuta , Ebina Kota , Matsui Mie 
Published: June 2024

BackgroundScript memory is stored information about a sequential structure of an activity (e.g., going shopping), including what actors do, the purpose of the activity, and the likely consequences of the actor’s actions. It has been reported that script memory is impaired among schizophrenia patients. The present research investigated the relationship between schizotypal personality tendencies (schizotypy) and script memory by testing Japanese individuals.MethodFirst, a new test to measure the intactness of the script memory was created by asking the public to report activities they often perform and what behaviors each activity contains. The test contains 15 everyday activities, each accompanied by 15 behavior choices, either strongly associated, completely unrelated, or weakly associated with the activity. Next, undergraduate participants were presented with the test and chose appropriate behaviors for each activity (Study 1 and 2). Their extent of schizotypy was measured using Schizotypal Personality Questionnaire Brief (SPQ-B). Study 3 targeted the public of various ages. In addition to Study 2 procedure, participants reported the extent of psychological burden for performing each activity, their life satisfaction, and subjective evaluation of their memory ability.ResultsAll studies consistently found that the script memory performance was worse for individuals with higher schizotypy. Signal detection indices for accurate discrimination between correct and incorrect choices, which were A’ in Study 1 and C in Study 2 and 3, negatively correlated with the SPQ-B scores (r = -0.16, -0.11, -0.17, respectively). Study 3 found that the relationship between schizotypy and memory task performance was mediated by the extent of psychological burden. When a signal detection index (d’) for the memory task was regressed on the SPQ-B, while the psychological burden scores being a mediator, the mediation effect was significant (B = 0.003, SE = 0.001, 95% CI [0.001, 0.005]).ConclusionIndividuals with higher schizotypy seem to associate unrelated behaviors to an event, forming script memory with irrelevant information, maybe due to the schizotypy symptom of having peculiar thoughts. The newly created test must be validated using a clinical population to expand its potential to be used in clinical research.
Maternal smoking during pregnancy and offspring risk of intellectual disability: a UK-based cohort study
Authors: Madley-Dowd Paul , Thomas Richard , Boyd Andy , Zammit Stanley , Heron Jon , Rai Dheeraj 
Published: June 2024

BackgroundObservational studies have described associations of maternal smoking during pregnancy with intellectual disability (ID) in the exposed offspring. Whether these results reflect a causal effect or unmeasured confounding is still unclear.MethodsUsing a UK-based prospectively collected birth cohort (the Avon Longitudinal Study of Parents and Children) of 13,479 children born between 1991 and 1992, we assessed the relationship between maternal smoking at 18 weeks’ gestation and offspring risk of ID, ascertained through multiple sources of linked information including primary care diagnoses and education records. Using confounder-adjusted logistic regression, we performed observational analyses and a negative control analysis that compared maternal with partner smoking in pregnancy under the assumption that if a causal effect were to exist, maternal effect estimates would be of greater magnitude than estimates for partner smoking if the two exposures suffer from comparable biases.ResultsIn observational analysis, we found an adjusted odds ratio for ID of 0.75 (95% CI = 0.49–1.13) for any maternal smoking and 0.97 (95% CI = 0.71–1.33) per 10-cigarette increase in number of cigarettes smoked per day. In negative control analysis, comparable effect estimates were found for any partner smoking (OR = 0.94; 95% CI = 0.63–1.40) and number of cigarettes smoked per day (OR = 0.94; 95% CI = 0.74–1.20).ConclusionsThe results are not consistent with a causal effect of maternal smoking during pregnancy on offspring ID.