bluuebunny/crossref_metadata_2025_split huggingface dataset:
Determination of the 95% effective dose of remimazolam tosylate in anesthesia induction inhibits endotracheal intubation response in senile patients
Authors: Qu Liangchao , Liu Mei , Ouyang Ru , Li Tianyuan , Long Dingde , Jiang Yao , Wang Chengyu , Cheng Liqin 
Published: May 2023

Background and Purpose: The prevalence of elderly patients prompts anesthesiologists to determine the optimal dose of medication due to the altered pharmacokinetics and pharmacodynamics of this population. The present study aimed to determine the 95% effective dose (ED95) of remimazolam tosylate in anesthesia induction to inhibit endotracheal intubation-related cardiovascular reaction in frail and non-frail senile patients.Methods: A prospective sequential allocation dose-finding study of remimazolam tosylate was conducted on 80 elderly patients who received general anesthesia between May and June 2022 at the First Affiliated Hospital of Nanchang University. The initial dose was 0.3 mg/kg. The blood pressure and heart rate fluctuations during intubation were either &lt;20% (negative cardiovascular response) or ≥20% (positive cardiovascular response). If positive, the dose of the next patient was increased by 0.02 mg/kg, while if negative, it was reduced by 0.02 mg/kg according to the 95:5 biased coin design (BCD). The ED95 and 95% confidence intervals (CIs) were determined using R-Foundation isotonic regression and bootstrapping methods.Results: The ED95 of remimazolam tosylate to inhibit the response during tracheal intubation was 0.297 mg/kg (95% CI: 0.231–0.451 mg/kg) and 0.331 mg/kg (95% CI: 0.272–0.472 mg/kg) in frail and non-frail senile patients, respectively.Conculation and Implications: The CI of the two groups overlap, and no difference was detected in the ED95 of remimazolam tosylate in inhibiting endotracheal intubation-related cardiovascular response in frail and non-frail senile patients. These results suggested that remimazolam tosylate is an optimal anesthesia inducer for all elderly patients.Clinical Trial Registration:https://www.chictr.org.cn, identifier ChiCTR2200055709.
The construction of a TCM knowledge graph and application of potential knowledge discovery in diabetic kidney disease by integrating diagnosis and treatment guidelines and real-world clinical data
Authors: Zhao Xiaoliang , Wang Yifei , Li Penghui , Xu Julia , Sun Yao , Qiu Moyan , Pang Guoming , Wen Tiancai 
Published: May 2023

Background: The complexity and rapid progression of lesions in diabetic kidney disease pose significant challenges for clinical diagnosis and treatment. The advantages of Traditional Chinese Medicine (TCM) in diagnosing and treating this condition have gradually become evident. However, due to the disease’s complexity and the individualized approach to diagnosis and treatment in Traditional Chinese Medicine, Traditional Chinese Medicine guidelines have limitations in guiding the treatment of diabetic kidney disease. Most medical knowledge is currently stored in the process of recording medical records, which hinders the understanding of diseases and the acquisition of diagnostic and treatment knowledge among young doctors. Consequently, there is a lack of sufficient clinical knowledge to support the diagnosis and treatment of diabetic kidney disease in Traditional Chinese Medicine.Objective: To build a comprehensive knowledge graph for the diagnosis and treatment of diabetic kidney disease in Traditional Chinese Medicine, utilizing clinical guidelines, consensus, and real-world clinical data. On this basis, the knowledge of Traditional Chinese Medicine diagnosis and treatment of diabetic kidney disease was systematically combed and mined.Methods: Normative guideline data and actual medical records were used to construct a knowledge graph of Traditional Chinese Medicine diagnosis and treatment for diabetic kidney disease and the results obtained by data mining techniques enrich the relational attributes. Neo4j graph database was used for knowledge storage, visual knowledge display, and semantic query. Utilizing multi-dimensional relations with hierarchical weights as the core, a reverse retrieval verification process is conducted to address the critical problems of diagnosis and treatment put forward by experts.Results: 903 nodes and 1670 relationships were constructed under nine concepts and 20 relationships. Preliminarily a knowledge graph for Traditional Chinese Medicine diagnosis and treatment of diabetic kidney disease was constructed. Based on the multi-dimensional relationships, the diagnosis and treatment questions proposed by experts were validated through multi-hop queries of the graphs. The results were confirmed by experts and showed good outcomes.Conclusion: This study systematically combed the Traditional Chinese Medicine diagnosis and treatment knowledge of diabetic kidney disease by constructing the knowledge graph. Furthermore, it effectively solved the problem of “knowledge island”. Through visual display and semantic retrieval, the discovery and sharing of diagnosis and treatment knowledge of diabetic kidney disease were realized.
Intraocular pressure effect of intravitreal conbercept injection for retinopathy of prematurity
Authors: Gao Caifeng , Mu Ge , Zhao Huanhuan , Zheng Jiao , Feng Qingyang , Wu Yining , Li Yinan , Huang Xuelin , Sun Wei 
Published: May 2023

Purpose: Intravitreal injection of conbercept (IVC) is a novel anti-vascular endothelial growth factor (anti-VEGF) treatment for retinopathy of prematurity (ROP). This study aimed to assess the intraocular pressure (IOP) effect of IVC.Methods: All IVC surgeries were performed in the Department of Ophthalmology, Guangdong Women and Children Hospital, from January 2021 to May 2021. In this study, 30 eyes of 15 infants who received intravitreal injections of conbercept at a dose of 0.25 mg/0.025 mL were included. The IOP of all participants was measured prior to administering the injection and subsequently at 2 min, 1 h, 1 day, and 1 week thereafter.Results: We included 30 eyes (10 boys and 5 girls) with ROP. For the male group, the mean birth weight, mean gestational age at birth, and the mean time of postmenstrual age (PMA) at IVC treatment were 1,174.0 ± 446.0 g, 28.4 ± 3.0 weeks, and 37.1 ± 1.6 weeks, respectively; for the female group, they were 1,108 ± 285.5 g, 28.2 ± 2.5 weeks, and 36.8 ± 2.1 weeks, respectively. For the male group, the IOP at baseline, 2 min, 1 h, 1 day, and 1 week after IVC were 12.4 ± 1.5 mmHg, 49.0 ± 3.1 mmHg, 26.3 ± 2.5 mmHg, 13.4 ± 2.2 mmHg, and 11.6 ± 1.7 mmHg, respectively; for the female group, they were 10.7 ± 2.0 mmHg, 47.3 ± 3.2 mmHg, 26.4 ± 3.2 mmHg, 10.7 ± 1.8 mmHg, and 10.2 ± 1.8 mmHg, respectively. In both groups, the IOP immediately (2 min) after the operation was significantly higher than that at any other time point (p &lt; 0.01). IOP values returned to the preoperative baseline level on the first day after surgery, with no significant difference compared with that before injection (p &gt; 0.05). IOP continued to be maintained at the preoperative baseline level on the first week after surgery, with no significant difference compared with that before surgery (p &gt; 0.05).Conclusion: Infants with ROP who received IVC experienced a sharp increase in the IOP immediately after injection, which decreased to below 30 mmHg after 1 h and maintain that level for 1 week or longer.
Computational and experimental pharmacology to decode the efficacy of Theobroma cacao L. against doxorubicin-induced organ toxicity in EAC-mediated solid tumor-induced mice
Authors: Patil Priyanka P. , Kumar Pranjal , Khanal Pukar , Patil Vishal S. , Darasaguppe Harish R. , Bhandare Vishwambhar Vishnu , Bhatkande Arati , Shukla Sudhanshu , Joshi Rajesh K. , Patil Basanagouda M. , Roy Subarna 
Published: May 2023

Background and objective: Doxorubicin is extensively utilized chemotherapeutic drug, and it causes damage to the heart, liver, and kidneys through oxidative stress. Theobroma cacao L (cocoa) is reported to possess protective effects against several chemical-induced organ damages and also acts as an anticancer agent. The study aimed to determine whether the administration of cocoa bean extract reduces doxorubicin-induced organ damage in mice with Ehrlich ascites carcinoma (EAC) without compromising doxorubicin efficacy.Methodology: Multiple in vitro methods such as cell proliferation, colony formation, chemo-sensitivity, and scratch assay were carried out on cancer as well as normal cell lines to document the effect of cocoa extract (COE) on cellular physiology, followed by in vivo mouse survival analysis, and the organ-protective effect of COE on DOX-treated animals with EAC-induced solid tumors was then investigated. In silico studies were conducted on cocoa compounds with lipoxygenase and xanthine oxidase to provide possible molecular explanations for the experimental observations.Results:In vitro studies revealed potent selective cytotoxicity of COE on cancer cells compared to normal. Interestingly, COE enhanced DOX potency when used in combination. The in vivo results revealed reduction in EAC and DOX-induced toxicities in mice treated with COE, which also improved the mouse survival time; percentage of lifespan; antioxidant defense system; renal, hepatic, and cardiac function biomarkers; and also oxidative stress markers. COE reduced DOX-induced histopathological alterations. Through molecular docking and MD simulations, we observed chlorogenic acid and 8′8 methylenebiscatechin, present in cocoa, to have the highest binding affinity with lipoxygenase and xanthine oxidase, which lends support to their potential in ameliorating oxidative stress.Conclusion: The COE reduced DOX-induced organ damage in the EAC-induced tumor model and exhibited powerful anticancer and antioxidant effects. Therefore, COE might be useful as an adjuvant nutritional supplement in cancer therapy.
Modulating retinoid-X-receptor alpha (RXRA) expression sensitizes chronic myeloid leukemia cells to imatinib in vitro and reduces disease burden in vivo
Authors: Rajamani Bharathi M. , Illangeswaran Raveen Stephen Stallon , Benjamin Esther Sathya Bama , Balakrishnan Balaji , Jebanesan Daniel Zechariah Paul , Das Saswati , Pai Aswin Anand , Vidhyadharan Rakhi Thalayattu , Mohan Ajith , Karathedath Sreeja , Abraham Aby , Mathews Vikram , Velayudhan Shaji R. , Balasubramanian Poonkuzhali 
Published: May 2023

Introduction: The ligand-activated transcription factors, nuclear hormone receptors (NHRs), remain unexplored in hematological malignancies except for retinoic acid receptor alpha (RARA).Methods: Here we profiled the expression of various NHRs and their coregulators in Chronic myeloid leukemia (CML) cell lines and identified a significant differential expression pattern between inherently imatinib mesylate (IM)-sensitive and resistant cell lines.Results: Retinoid-X-receptor alpha (RXRA) was downregulated in CML cell lines inherently resistant to IM and in primary CML CD34+ cells. Pre-treatment with clinically relevant RXRA ligands improved sensitivity to IM in-vitro in both CML cell lines and primary CML cells. This combination effectively reduced the viability and colony-forming capacity of CML CD34+ cells in-vitro. In-vivo, this combination reduced leukemic burden and prolonged survival. Overexpression (OE) of RXRA inhibited proliferation and improved sensitivity to IM in-vitro. In-vivo, RXRA OE cells showed reduced engraftment of cells in the bone marrow, improved sensitivity to IM, and prolonged survival. Both RXRA OE and ligand treatment markedly reduced BCR::ABL1 downstream kinase activation, activating apoptotic cascades and improving sensitivity to IM. Importantly, RXRA OE also led to the disruption of the oxidative capacity of these cells.Conclusion: Combining IM with clinically available RXRA ligands could form an alternative treatment strategy in CML patients with suboptimal response to IM.
Does China’s centralized volume-based drug procurement policy facilitate the transition from imitation to innovation for listed pharmaceutical companies? Empirical tests based on double difference model
Authors: Gu Yang , Zhuang Qian 
Published: May 2023

Introduction: The normalized implementation of the centralized volume-based procurement policy for pharmaceuticals is a concerted push for supply-side structural reform of the pharmaceutical industry in China. The impact of the centralized drug procurement policy on pharmaceutical companies' transition from imitation to innovation is investigated to test whether a positive effect occurs in the innovation landscape of the pharmaceutical market. Methods: The double difference method and a series of robustness tests were used based on data from a sample of listed pharmaceutical companies in Shanghai and Shenzhen A-shares between 2015 and 2021. Results: The study found that the centralized drug procurement policy significantly contributed to the increased intensity of innovation input in the Chinese pharmaceutical industry. In terms of regional and firm nature heterogeneity, it was found that firms in the seven provinces belonging to the three economic regions had a better increase in innovation input intensity than other regions. Firms of state-owned nature had a better increase in innovation input intensity than private companies. The mechanism test found a partial mediating effect of nearly 10% for the cost of sales rate on the innovation input intensity of listed companies and a negative mediating effect on corporate operating profit. Discussion: Further research found that the effect of centralized drug procurement policy on the improvement of innovation quality of listed pharmaceutical companies was evident. The innovation development of Chinese pharmaceutical companies no longer focused on the accumulation of innovation quantity.
The effects of essential oil from Lippia origanoides and herbal betaine on performance, intestinal integrity, bone mineralization and meat quality in broiler chickens subjected to cyclic heat stress
Authors: Señas-Cuesta Roberto , Stein Andressa , Latorre Juan D. , Maynard Clay J. , Hernandez-Velasco Xochitl , Petrone-Garcia Victor , Greene Elizabeth S. , Coles Makenly , Gray Latasha , Laverty Lauren , Martin Kristen , Loeza Ileana , Uribe Alvaro J. , Martínez Blanca C. , Angel-Isaza Jaime A. , Graham Danielle , Owens Casey M. , Hargis Billy M. , Tellez-Isaias Guillermo 
Published: May 2023

Essential oils (EO) affect performance, intestinal integrity, bone mineralization, and meat quality in broiler chickens subjected to cyclic heat stress (HS). Day-of-hatch Cobb 500 male broiler chicks (n = 475) were randomly divided into four groups. Group 1: No heat stress (Thermoneutral) + control diets with no antibiotics; Group 2: heat stress control + control diets; Group 3: heat stress + control diets supplemented with thymol chemotype (45 ppm) and herbal betaine (150 ppm) formulation EO1; Group 4: heat stress + control diets supplemented with phellandrene (45 ppm) and herbal betaine (150 ppm) formulation EO2. From day 10–42, the heat stress groups were exposed to cyclic HS at 35°C for 12 h (8:00–20:00). BW, BWG, FI, and FCRc were measured at d 0, 10, 28, and 42. Chickens were orally gavaged with FITC-d on days 10 (before heat stress) and 42. Morphometric analysis of duodenum and ileum samples and bone mineralization of tibias were done. Meat quality was assessed on day 43 with ten chickens per pen per treatment. Heat stress reduced BW by day 28 (p &lt; 0.05) compared to thermoneutral chickens. At the end of the trial, chickens that received both formulations of EO1 and EO2 had significantly higher BW than HS control chickens. A similar trend was observed for BWG. FCRc was impaired by EO2 supplementation. There was a significant increase in total mortality in EO2 compared with EO1 EO1 chickens had lower FITC-d concentrations at day 42 than the HS control. In addition, EO1 treatment is not statistically different if compared to EO2 and thermoneutral. Control HS broilers had significantly lower tibia breaking strength and total ash at day 42 than heat-stressed chickens supplemented with EO1 and EO2. Heat stress affected intestinal morphology more than thermoneutral chickens. EO1 and EO2 improved intestinal morphology in heat-stressed chickens. Woody breast and white striping were more common in thermoneutral chickens than heat stress chickens. In conclusion, the EO-containing diet could improve broiler chicken growth during cyclic heat stress, becoming increasingly relevant in antibiotic-free production in harsh climates.
Variation and stability of rhizosphere bacterial communities of Cucumis crops in association with root-knot nematodes infestation
Authors: Song Liqun , Ping Xingxing , Mao Zhenchuan , Zhao Jianlong , Yang Yuhong , Li Yan , Xie Bingyan , Ling Jian 
Published: May 2023

IntroductionRoot-knot nematodes (RKN) disease is a devastating disease inCucumiscrops production. Existing studies have shown that resistant and susceptible crops are enriched with different rhizosphere microorganisms, and microorganisms enriched in resistant crops can antagonize pathogenic bacteria. However, the characteristics of rhizosphere microbial communities ofCucumiscrops after RKN infestation remain largely unknown.MethodsIn this study, we compared the changes in rhizosphere bacterial communities between highly RKN-resistantCucumis metuliferus(cm3) and highly RKN-susceptibleCucumis sativus(cuc) after RKN infection through a pot experiment.ResultsThe results showed that the strongest response of rhizosphere bacterial communities ofCucumiscrops to RKN infestation occurred during early growth, as evidenced by changes in species diversity and community composition. However, the more stable structure of the rhizosphere bacterial community in cm3 was reflected in less changes in species diversity and community composition after RKN infestation, forming a more complex and positively co-occurrence network than cuc. Moreover, we observed that both cm3 and cuc recruited bacteria after RKN infestation, but the bacteria enriched in cm3 were more abundant including beneficial bacteria Acidobacteria, Nocardioidaceae and Sphingomonadales. In addition, the cuc was enriched with beneficial bacteria Actinobacteria, Bacilli and Cyanobacteria. We also found that more antagonistic bacteria than cuc were screened in cm3 after RKN infestation and most of them werePseudomonas(Proteobacteria, Pseudomonadaceae), and Proteobacteria were also enriched in cm3 after RKN infestation. We hypothesized that the cooperation between Pseudomonas and the beneficial bacteria in cm3 could inhibit the infestation of RKN.DiscussionThus, our results provide valuable insights into the role of rhizosphere bacterial communities on RKN diseases ofCucumiscrops, and further studies are needed to clarify the bacterial communities that suppress RKN inCucumiscrops rhizosphere.
Storage of halved strawberry fruits affects aroma, phytochemical content and gene expression, and is affected by pre-harvest factors
Authors: Baldwin Ashley , Dhorajiwala Rakhee , Roberts Callum , Dimitrova Simone , Tu Sarah , Jones Stephanie , Ludlow Richard A. , Cammarisano Laura , Davoli Daniela , Andrews Robert , Kent Nicholas A. , Spadafora Natasha D. , Müller Carsten T. , Rogers Hilary J. 
Published: May 2023

IntroductionStrawberry fruit are highly valued for their aroma which develops during ripening. However, they have a short shelf-life. Low temperature storage is routinely used to extend shelf-life for transport and storage in the supply chain, however cold storage can also affect fruit aroma. Some fruit continue to ripen during chilled storage; however, strawberries are a non-climacteric fruit and hence ripening postharvest is limited. Although most strawberry fruit is sold whole, halved fruit is also used in ready to eat fresh fruit salads which are of increasing consumer demand and pose additional challenges to fresh fruit storage.MethodsTo better understand the effects of cold storage, volatilomic and transcriptomic analyses were applied to halved Fragaria x ananassa cv. Elsanta fruit stored at 4 or 8°C for up to 12 days over two growing seasons.Results and discussionThe volatile organic compound (VOC) profile differed between 4 or 8°C on most days of storage. Major differences were detected between the two different years of harvest indicating that aroma change at harvest and during storage is highly dependent on environmental factors during growth. The major component of the aroma profile in both years was esters. Over 3000 genes changed in expression over 5 days of storage at 8°C in transcriptome analysis. Overall, phenylpropanoid metabolism, which may also affect VOCs, and starch metabolism were the most significantly affected pathways. Genes involved in autophagy were also differentially expressed. Expression of genes from 43 different transcription factor (TF) families changed in expression: mostly they were down-regulated but NAC and WRKY family genes were mainly up-regulated. Given the high ester representation amongst VOCs, the down-regulation of an alcohol acyl transferase (AAT) during storage is significant. A total of 113 differentially expressed genes were co-regulated with the AAT gene, including seven TFs. These may be potential AAT regulators.
Development of a phenotyping protocol for combined drought and salinity stress at seedling stage in rice
Authors: Kota Suneetha , Vispo Naireen Aiza , Quintana Marinell R. , Cabral Carlo L. U. , Centeno C. Arloo , Egdane James , Maathuis Frans J. M. , Kohli Ajay , Henry Amelia , Singh Rakesh Kumar 
Published: May 2023

IntroductionThe case of combined drought and salinity stress is increasingly becoming a constraint to rice production, especially in coastal areas and river deltas where low rainfall not only reduces soil moisture levels but also reduces the flow of river water, resulting in intrusion of saline sea-water. A standardized screening method is needed in order to systematically evaluate rice cultivars under combined drought+salinity at the same time because sequential stress of salinity followed by drought or vice-versa is not similar to simultaneous stress effects. Therefore, we aimed to develop a screening protocol for combined drought+salinity stress applied to soil-grown plants at seedling stage.MethodsThe study system used 30-L soil-filled boxes, which allowed a comparison of plant growth under control conditions, individual drought and salinity stress, as well as combined drought+salinity. A set of salinity tolerant and drought tolerant cultivars were tested, together with several popular but salinity and drought-susceptible varieties that are grown in regions prone to combined drought+salinity. A range of treatments were tested including different timings of the drought and salinity application, and different severities of stress, in order to determine the most effective that resulted in visible distinction among cultivars. The challenges related to determining a protocol with repeatable seedling stage stress treatment effects while achieving a uniform plant stand are described here.ResultsThe optimized protocol simultaneously applied both stresses by planting into saline soil at 75% of field capacity which was then allowed to undergo progressive drydown. Meanwhile, physiological characterization revealed that chlorophyll fluorescence at seedling stage correlated well with grain yield when drought stress was applied to vegetative stage only.DiscussionThe drought+salinity protocol developed here can be used for screening rice breeding populations as part of a pipeline to develop new rice varieties with improved adaptation to combined stresses.