bluuebunny/crossref_metadata_2025_split huggingface dataset:
Sarcopenia Was a Poor Prognostic Predictor for Patients With Advanced Lung Cancer Treated With Immune Checkpoint Inhibitors
Authors: Li Shuluan , Liu Zhou , Ren Ya , Liu Jinying , Lv Shiqi , He Pin , Yang Yajing , Sun Yanfen , Chang Jianhua , Luo Dehong , Cong Minghua 
Published: July 2022

BackgroundIt remains not well known whether skeletal muscle mass (SMM) loss has any impact on the effectiveness of immune checkpoint inhibitors (ICIs) in patients with advanced lung cancer. We aimed to evaluate the association between SMM and clinical outcome of patients with advanced lung cancer receiving ICIs as first line or second line.Materials and MethodsFrom March 1st, 2019 to March 31st, 2021 at our hospital, 34 patients with advanced lung cancer treated with first-line or second-line ICIs were enrolled retrospectively. The estimation of skeletal muscle index (SMI) for sarcopenia was assessed at the level of the third lumbar vertebra (L3) on computed tomography (CT) images obtained within 4 weeks before initiation of ICIs treatment. The impact of sarcopenia (low SMI) on progression free survival (PFS) was analyzed using Kaplan-Meier method and log-rank tests. The effect of various variables on PFS was evaluated using Cox proportional hazards regression model with univariate and multivariate analysis. The impact on treatment response including objective response rate (ORR) and disease control rate (DCR) and immunotherapy related adverse events (irAEs) between patients with and without sarcopenia was compared by the chi-squared test. The comparison of SMI value between patients with objective response (OR), disease control (DC) and those without OR and DC was used student t-test or Mann-Whitney U test.ResultsBoth in univariate and multivariate analysis, sarcopenia and treatment lines were the predictive factors for PFS (p &lt; 0.05). Patients with sarcopenia had significantly shorter PFS than that of non-sarcopenic ones [6.57 vs. 16.2 months, hazard ratios (HR) = 2.947 and 3.542, and 95% confidence interval (CI): 1.123–13.183 and 1.11–11.308, p = 0.022 and 0.033]. No significant difference in ORR and irAEs was found. Patients with sarcopenia had lower DCR than those without sarcopenia. The mean SMI value of DCR group and non-DCR group was 32.94 ± 5.49 and 44.77 ± 9.06 cm2/m2, respectively (p = 0.008).ConclusionSarcopenia before immunotherapy might be a significant predictor for poor prognosis including shorter PFS and lower DCR in patients with advanced lung cancer treated with ICIs as first line or second line.
Deep Learning for Automated Contouring of Gross Tumor Volumes in Esophageal Cancer
Authors: Jin Linzhi , Chen Qi , Shi Aiwei , Wang Xiaomin , Ren Runchuan , Zheng Anping , Song Ping , Zhang Yaowen , Wang Nan , Wang Chenyu , Wang Nengchao , Cheng Xinyu , Wang Shaobin , Ge Hong 
Published: July 2022

PurposeThe aim of this study was to propose and evaluate a novel three-dimensional (3D) V-Net and two-dimensional (2D) U-Net mixed (VUMix-Net) architecture for a fully automatic and accurate gross tumor volume (GTV) in esophageal cancer (EC)–delineated contours.MethodsWe collected the computed tomography (CT) scans of 215 EC patients. 3D V-Net, 2D U-Net, and VUMix-Net were developed and further applied simultaneously to delineate GTVs. The Dice similarity coefficient (DSC) and 95th-percentile Hausdorff distance (95HD) were used as quantitative metrics to evaluate the performance of the three models in ECs from different segments. The CT data of 20 patients were randomly selected as the ground truth (GT) masks, and the corresponding delineation results were generated by artificial intelligence (AI). Score differences between the two groups (GT versus AI) and the evaluation consistency were compared.ResultsIn all patients, there was a significant difference in the 2D DSCs from U-Net, V-Net, and VUMix-Net (p=0.01). In addition, VUMix-Net showed achieved better 3D-DSC and 95HD values. There was a significant difference among the 3D-DSC (mean ± STD) and 95HD values for upper-, middle-, and lower-segment EC (p&lt;0.001), and the middle EC values were the best. In middle-segment EC, VUMix-Net achieved the highest 2D-DSC values (p&lt;0.001) and lowest 95HD values (p=0.044).ConclusionThe new model (VUMix-Net) showed certain advantages in delineating the GTVs of EC. Additionally, it can generate the GTVs of EC that meet clinical requirements and have the same quality as human-generated contours. The system demonstrated the best performance for the ECs of the middle segment.
Spontaneous breathing approach in mild congenital diaphragmatic hernia: A resuscitation algorithm
Authors: Horn-Oudshoorn Emily J. J. , Knol Ronny , Cochius-den Otter Suzan C. M. , te Pas Arjan B. , Hooper Stuart B. , Roberts Calum T. , Rafat Neysan , Schaible Thomas , de Boode Willem P. , van der Lee Robin , Debeer Anne , Kipfmueller Florian , Roehr Charles C. , Reiss Irwin K. M. , DeKoninck Philip L. J. 
Published: July 2022

BackgroundInfants with a congenital diaphragmatic hernia (CDH) and expected mild pulmonary hypoplasia have an estimated survival rate of 90%. Current guidelines for delivery room management do not consider the individual patient's disease severity, but an individualized approach with spontaneous breathing instead of routine mechanical ventilation could be beneficial for the mildest cases. We developed a resuscitation algorithm for this individualized approach serving two purposes: improving the success rate by structuring the approach and providing a guideline for other centers.MethodsAn initial algorithm was discussed with all local stakeholders. Afterwards, the resulting algorithm was refined using input from international experts.ResultsEligible CDH infants: left-sided defect, observed to expected lung-to-head ratio ≥50%, gestational age at birth ≥37.0 weeks, and no major associated structural or genetic abnormalities. To facilitate fetal-to-neonatal transition, we propose to start stabilization with non-invasive respiratory support and to adjust this individually.ConclusionsInfants with mild CDH might benefit from an individualized approach for neonatal resuscitation. Herein, we present an algorithm that could serve as guidance for centers implementing this.
Model-Informed Drug Development of New Cefoperazone Sodium and Sulbactam Sodium Combination (3:1): Pharmacokinetic/Pharmacodynamic Analysis and Antibacterial Efficacy Against Enterobacteriaceae
Authors: Ji Xi-Wei , Zhu Xiao , Li Yun , Xue Feng , Kuan Isabelle Hui San , He Qing-Feng , Meng Xiang-Rui , Xiang Xiao-Qiang , Cui Yi-Min , Zheng Bo 
Published: July 2022

Objective: Cefoperazone/sulbactam is a commonly used antibiotic combination against the extended-spectrum beta-lactamases (ESBLs)-producing bacteria. The objective of this study was to evaluate the efficacy of a new cefoperazone/sulbactam combination (3:1) for Enterobacteriaceae infection via model-informed drug development (MIDD) approaches.Methods: Sulperazon [cefoperazone/sulbactam (2:1)] was used as a control. Pharmacokinetic (PK) data was collected from a clinical phase I trial. Minimum inhibitory concentrations (MICs) were determined using two-fold broth microdilution method. The percent time that the free drug concentration exceeded the minimum inhibitory concentration (%fT&gt;MIC) was used as the pharmacokinetic/pharmacodynamic indicator correlated with efficacy. Models were developed to characterize the PK profile of cefoperazone and sulbactam. Monte Carlo simulations were employed to determine the investigational regimens of cefoperazone/sulbactam (3:1) for the treatment of infections caused by Enterobacteriaceae based on the probability of target attainment (PTA) against the tested bacteria.Results: Two 2-compartment models were developed to describe the PK profiles of cefoperazone and sulbactam. Simulation results following the single-dose showed that the regimens of cefoperazone/sulbactam combinations in the ratios of 3:1 and 2:1 achieved similar PTA against the tested bacteria. Simulation results from the multiple-dose showed that the dosing regimen of cefoperazone/sulbactam (4 g, TID, 3 g:1 g) showed slightly better antibacterial effect than cefoperazone/sulbactam (6 g, BID, 4 g:2 g) against the Escherichia coli (ESBL−) and Klebsiella pneumoniae (ESBL−). For the other tested bacteria, the above regimens achieved a similar PTA.Conclusions: Cefoperazone/sulbactam (3:1) showed similar bactericidal activity to sulperazon [cefoperazone/sulbactam (2:1)] against the tested bacteria. For the ESBL-producing and cefoperazone-resistant E. coli and K. pneumoniae, Cefoperazone/sulbactam (3:1) did not exhibit advantage as anticipated. Our study indicated that further clinical trials should be carried out cautiously to avoid the potential risks of not achieving the expected target.
Drug-Related Problems of Children With Chronic Diseases in a Chinese Primary Health Care Institution: A Cross-Sectional Study
Authors: Ni Xiao-Feng , Yang Chun-Song , Zeng Li-Nan , Li Hai-Long , Diao Sha , Li De-Yuan , Wu Jin , Liu Yuan-Chun , Jia Zhi-Jun , Cheng Guo , Zhang Ling-Li 
Published: July 2022

Introduction: Drug-related problems (DRPs) refer to events or circumstances involving drug therapy that actually or potentially interfere with desired health outcomes. DRPs might be severe for children with chronic diseases managed at primary health care institutions, but the relevant research is scarce.Objective: In this cross-sectional study, we aimed to explore the prevalence, types, causes, and influencing factors of DRPs in children with chronic diseases in a Chinese primary health care institution.Methods: We recruited children with chronic diseases who visited the pediatric outpatient department in a primary health care institution from July 1 to 12 October 2021. Clinical pharmacists identified DRPs through medication therapy reviews, classified the types and causes of DRPs, and distinguished the manifested DRPs that affected the outcome and potential DRPs that were going to affect the outcome.Results: A total of 188 children with chronic diseases was included, and 584 DRPs were identified in 89.89% of participants. The most common type of DRPs was “treatment effectiveness” (a manifested problem or potential problem with the effect of the pharmacotherapy; 83.56%), of which 67.29% were potential DRPs. The second common type was “treatment safety” (patient suffers or could suffer from an adverse drug event; 14.21%), of which 89.16% were potential DRPs. The most common cause of DRPs was related to the process of use (42.24%), such as “patient uses/takes less drug than prescribed or does not take the drug at all,” “patient stores drug inappropriately,” and “patient administers/uses the drug in a wrong way.” The second common cause was related to the process of dispensing (29.83%), such as “necessary information not provided or incorrect advice provided” and “prescribed drug is not available.” The third common cause was related to the process of prescribing (26.21%), such as “drug dose is too low” and “no or incomplete drug treatment despite an existing indication.” The number of combined medications was an influencing factor for the frequency of DRPs (p &lt; 0.05).Conclusion: This cross-sectional study showed that the current situation regarding DRPs among children with chronic diseases managed in the primary health care institution was serious. The types of DRPs were mainly related to treatment effectiveness, and improper usage of medications was one of the main causes of DRPs. The number of combined drugs was the influencing factor for the frequency of DRPs. In the future, pharmacists should consider formulating pharmaceutical intervention strategies for this specific group according to the characteristics of DRPs.
Effects of Glycolysis-Related Genes on Prognosis and the Tumor Microenvironment of Hepatocellular Carcinoma
Authors: Zheng Ju-Yan , Liu Jun-Yan , Zhu Tao , Liu Chong , Gao Ying , Dai Wen-Ting , Zhuo Wei , Mao Xiao-Yuan , He Bai-Mei , Liu Zhao-Qian 
Published: July 2022

Background: Hepatocellular carcinoma (HCC) is a common and deadly malignancy worldwide. Current treatment methods for hepatocellular carcinoma have many disadvantages; thus, it is urgent to improve the efficacy of these therapies. Glycolysis is critical in the occurrence and development of tumors. However, survival and prognosis biomarkers related to glycolysis in HCC patients remain to be fully identified.Methods: Glycolysis-related genes (GRGs) were downloaded from “The Molecular Signatures Database” (MSigDB), and the mRNA expression profiles and clinical information of HCC patients were obtained from TCGA. Consensus clustering was performed to classify the HCC patients into two subgroups. We used the least absolute shrinkage and selection operator (LASSO) regression analysis to construct the risk signature model. Kaplan–Meier (K-M) survival analysis was performed to evaluate the prognostic significance of the risk model, and the receiver operating characteristic (ROC) curve analysis was used to evaluate the prediction accuracy. The independent prediction ability of the risk model was validated by univariate and multivariate Cox regression analyses. The differences of immune infiltrates and relevant oncogenic signaling between different risk groups were compared. Finally, biological experiments were performed to explore the functions of screened genes.Results: HCC patients were classified into two subgroups, according to the expression of prognostic-related GRGs. Almost all GRGs categorized in cluster 2 showed upregulated expressions, whereas GRGs in cluster 1 conferred survival advantages. GSEA identified a positive correlation between cluster 2 and the glycolysis process. Ten genes were selected for risk signature construction. Patients were assigned to high-risk and low-risk groups based on the median risk score, and K-M survival analysis indicated that the high-risk group had a shorter survival time. Additionally, the risk gene signature can partially affect immune infiltrates within the HCC microenvironment, and many oncogenic pathways were enriched in the high-risk group, including glycolysis, hypoxia, and DNA repair. Finally, in vitro knockdown of ME1 suppressed proliferation, migration, and invasion of hepatocellular carcinoma cells.Conclusion: In our study, we successfully constructed and verified a novel glycolysis-related risk signature for HCC prognosis prediction, which is meaningful for classifying HCC patients and offers potential targets for the treatment of hepatocellular carcinoma.
Herbal medicine for the treatment of chronic rhinosinusitis: A systematic review and meta-analysis
Authors: Lee Boram , Kwon Chan-Young , Park Man Young 
Published: July 2022

Objectives: Chronic rhinosinusitis (CRS) is a disease with a high prevalence and a high socioeconomic burden. This study aimed to conduct a comprehensive systematic review to update the evidence on the use of herbal medicine (HM) for CRS treatment.Methods: A total of 14 electronic databases for randomized controlled trials (RCTs) evaluating the effects of HM on the treatment of CRS were searched for articles published before July 2021. The primary outcome was CRS severity post-treatment, measured with the Visual Analogue Scale (VAS) and Total Effective Rate (TER). The risk of bias of the included studies and the quality of evidence of the main findings were assessed using the Cochrane Collaboration’s risk of bias tool and the Grading of Recommendations, Assessment, Development, and Evaluations tool.Results: A total of 80 RCTs were included. Compared to placebo, HM significantly improved CRS severity as measured by TER and VAS. When HM was compared with conventional treatment (CT) as monotherapy or adjuvant therapy, CRS severity measured by TER and VAS, quality of life, Lund-Kennedy endoscopy score, Lund-Mackay computed tomography score, and nasal mucociliary function were significantly improved in the HM group. No serious adverse events associated with HM were reported. The risk of bias was generally unclear, and the quality of evidence ranged from moderate to low.Conclusion: This review found some limited clinical evidence that HM or HM combined with CT may be more effective and safer than CT alone in treating CRS. However, the methodological quality of the included studies was generally low, and the quality of the evidence needs to be improved.
Clostridium butyricum Protects Against Pancreatic and Intestinal Injury After Severe Acute Pancreatitis via Downregulation of MMP9
Authors: Yan Qingqing , Jia Lin , Wen Biyan , Wu Yao , Zeng Yanbo , Wang Qing 
Published: July 2022

Background:Evidence have shown that gut microbiota plays an important role in the development of severe acute pancreatitis (SAP). In addition, matrix metalloproteinase-9 (MMP9) plays an important role in intestinal injury in SAP. Thus, we aimed to determine whether gut microbiota could regulate the intestinal injury during SAPviamodulating MMP9.Methods:In this study, the fecal samples of patients with SAP (n= 72) and healthy controls (n= 32) were analyzed by 16S rRNA gene sequencing. In addition, to investigate the association between gut microbiota and MMP9 in intestinal injury during SAP, we established MMP9 stable knockdown Caco2 and HT29 cellsin vitroand generated a MMP9 knockout (MMP9−/−) mouse model of SAPin vivo.Results:We found that the abundance ofClostridium butyricum(C.butyricum) was significantly decreased in the SAP group. In addition, overexpression of MMP9 notably downregulated the expressions of tight junction proteins and upregulated the expressions of p-p38 and p-ERK in Caco2 and HT29 cells (p&lt; 0.05). However, C.butyricumor butyrate treatment remarkably upregulated the expressions of tight junction proteins and downregulated the expressions of MMP9, p-p38 and p-ERK in MMP9-overexpressed Caco2 and HT29 cells (p&lt; 0.05). Importantly, C.butyricumor butyrate could not affect the expressions of tight junction proteins, and MMP9, p-p38 and p-ERK proteins in MMP9-knockdown cells compared with MMP9-knockdown group. Consistently, C.butyricumor butyrate could not attenuate pancreatic and intestinal injury during SAP in MMP9−/− mice compared with the SAP group.Conclusion:Collectively, C.butyricumcould protect against pancreatic and intestinal injury after SAPviadownregulation of MMP9in vitroandin vivo.
Role of 5HT1A Receptors in the Neuroprotective and Behavioral Effects of Cannabidiol in Hypoxic–Ischemic Newborn Piglets
Authors: Barata Lorena , de Hoz-Rivera María , Romero Angela , Martínez María , Silva Laura , Villa María , Campa Leticia , Jiménez-Sánchez Laura , Martínez-Orgado José 
Published: July 2022

Background: Hypoxic–ischemic (HI) insults have important deleterious consequences in newborns, including short-term morbidity with neuromotor and cognitive disturbances. Cannabidiol (CBD) has demonstrated robust neuroprotective effects and shows anxiolytic/antidepressant effects as well. These effects are thought to be related to serotonin 5-HT1A receptor (5HT1AR) activation. We hereby aimed to study the role of 5HT1AR in the neuroprotective and behavioral effects of CBD in HI newborn piglets.Methods: 1-day-old piglets submitted to 30 min of hypoxia (FiO2 10%) and bilateral carotid occlusion were then treated daily with vehicle, CBD 1 mg/kg, or CBD with the 5HT1AR antagonist WAY 100635 1 mg/kg 72 h post-HI piglets were studied using amplitude-integrated EEG to detect seizures and a neurobehavioral test to detect neuromotor impairments. In addition, behavioral performance including social interaction, playful activity, hyperlocomotion, and motionless periods was assessed. Then, brain damage was assessed using histology (Nissl and TUNEL staining) and biochemistry (proton magnetic resonance spectroscopy studies.Results: HI led to brain damage as assessed by histologic and biochemistry studies, associated with neuromotor impairment and increased seizures. These effects were not observed in HI piglets treated with CBD. These beneficial effects of CBD were not reversed by the 5HT1AR antagonist, which is in contrast with previous studies demonstrating that 5HT1AR antagonists eliminated CBD neuroprotection as assessed 6 h after HI in piglets. HI led to mood disturbances, with decreased social interaction and playfulness and increased hyperlocomotion. Mood disturbances were not observed in piglets treated with CBD, but in this case, coadministration of the 5HT1AR antagonist eliminates the beneficial effects of CBD.Conclusion: CBD prevented HI-induced mood disturbances in newborn piglets by acting on 5HT1AR. However, 5HT1AR activation seems to be necessary for CBD neuroprotection only in the first hours after HI.
Neuroprotective Effects and Mechanisms of Senegenin, an Effective Compound Originated From the Roots of Polygala Tenuifolia
Authors: Chen Zhe , Yang Yu , Han Ying , Wang Xijun 
Published: July 2022

Senegenin is the main bioactive ingredient isolated from the dried roots of Polygala tenuifolia Willd. In recent years, senegenin has been proved to possess a variety of pharmacological activities, such as anti-oxidation, anti-inflammation, anti-apoptosis, enhancement of cognitive function. Besides, it has a good development prospect for the treatment of neurodegenerative diseases, depression, osteoporosis, cognitive dysfunction, ischemia-reperfusion injury and other diseases. However, there is no systematic literature that fully demonstrates the pharmacological effects of senegenin. In order to meet the needs of new drug research and precise medication, this review summarized the neuroprotective effects, mechanisms and gastrointestinal toxicity of senegenin based on the literatures published from the past 2 decades. In addition, an in-depth analysis of the existing problems in the current research as well as the future research directions have been conducted in order to provide a basis for the clinical application of this important plant extract.