bluuebunny/crossref_metadata_2025_split huggingface dataset:
Adjuvant crizotinib in high-risk uveal melanoma following definitive therapy
Authors: Khan Shaheer , Lutzky Jose , Shoushtari Alexander N. , Jeter Joanne , Marr Brian , Olencki Thomas E. , Cebulla Colleen M. , Abdel-Rahman Mohamed , Harbour J. William , Sender Naomi , Nesson Alexandra , Singh-Kandah Shahnaz , Hernandez Susana , King Jeanelle , Katari Manpreet S. , Dimapanat Lyssa , Izard Stephanie , Ambrosini Grazia , Surriga Oliver , Rai Alex J. , Chiuzan Codruta , Schwartz Gary K. , Carvajal Richard D. 
Published: August 2022

IntroductionApproximately 40% of patients with uveal melanoma (UM) will develop metastatic disease. Tumors measuring at least 12mm in basal diameter with a class 2 signature, as defined by a widely used gene expression-profiling test, are associated with significantly higher risk of metastasis, with a median time to recurrence of 32 months. No therapy has been shown to reduce this risk.Materials and MethodsThis was a single-arm, multicenter study in patients with high-risk UM who received definitive treatment of primary disease and had no evidence of metastasis. Patients were consecutively enrolled to receive 12 four-week cycles of adjuvant crizotinib at a starting dose of 250mg twice daily and were subsequently monitored for 36 months. The primary outcome of this study was to assess recurrence-free survival (RFS) of patients with high-risk UM who received adjuvant crizotinib.Results34 patients enrolled and received at least one dose of crizotinib. Two patients were unevaluable due to early withdrawal and loss to follow-up, leaving 32 patients evaluable for efficacy. Eight patients (25%) did not complete the planned 48-week course of treatment due to disease recurrence (n=5) or toxicity (n=3). All patients experienced at least one adverse event (AE), with 11/34 (32%) experiencing a Common Terminology Criteria for Adverse Events (CTCAE) grade 3 or 4 AE. After a median duration of follow up of 47.1 months, 21 patients developed distant recurrent disease. The median RFS was 34.9 months (95% CI (Confidence Interval), 23-55 months), with a 32-month recurrence rate of 50% (95% CI, 33-67%). Analysis of protein contents from peripheral blood extracellular vesicles in a subset of patient samples from baseline, on-treatment, and off-treatment, revealed a change in protein content associated with crizotinib exposure, however without a clear association with disease outcome.ConclusionsThe use of adjuvant crizotinib in patients with high-risk UM did not result in improved RFS when compared to historical controls. Analysis of blood extracellular vesicles revealed changes in protein content associated with treatment, raising the possibility of future use as a biomarker. Further investigation of adjuvant treatment options are necessary for this challenging disease.
Leveraging teachable moments in cancer prevention by improving HPV vaccination in health professional students (HPS): A systematic review
Authors: Levy Morgan S. , Finch Lindsey , Lindsay Kara A. , Jeudin Patricia , Huang Marilyn 
Published: August 2022

IntroductionVaccination against HPV is safe and effective in cancer prevention, yet vaccination uptake remains low. Strong recommendation of HPV vaccination by healthcare providers increases immunization rates, but gaps in knowledge persist surrounding HPV and HPV vaccination amongst health professional students (HPS). It is critical to educate HPS in all professions to maximize vaccination opportunities and increase vaccine uptake. The objective of this study is to evaluate evidence on HPV knowledge, vaccine uptake, and educational interventions in HPS to identify specific deficits to improve education.MethodsA systematic literature search for articles on HPV vaccine uptake, knowledge, and educational interventions in HPS was performed in PubMed, Embase, Web of Science, CINAHL, and Scopus from January 1, 2006 – July 21, 2021. Included studies assessed HPS for HPV vaccine uptake, knowledge, counseling comfort, or educational interventions to increase HPV vaccine knowledge. Studies were screened for inclusion by 2 independent reviewers and evaluated for risk of bias. PRISMA guidelines for reporting were followed.ResultsTwenty-one unique articles met inclusion criteria and were included in the analysis. Of the studies included, 20 included knowledge, 11 included vaccine uptake, 8 included interventions, and 12 included counseling comfort. The students in the studies included medical (n=14), dental (n=7), dental hygiene (n=6), nursing (n=3), physician assistant (n=2), public health (n=1), and pharmacy (n=1). Across studies, HPV vaccine series initiation ranged from 34.6-70.3%, with 28.3-58.3% up to date on vaccination. Most students knew that HPV causes cervical cancer (99%), but fewer knew that HPV causes head and neck cancer (40-47%) and oropharyngeal cancer (45%). Educational interventions included team-based approaches and lectures, and improved outcomes including vaccine knowledge, vaccination schedule, and cancer knowledge. Medical students with lower knowledge of HPV were more hesitant to recommend vaccination at baseline but were more likely to recommend vaccination after an education session.DiscussionAcross HPS, inadequacies persist in HPV vaccine uptake, knowledge, and counseling comfort. It is critical to target vaccine uptake in this population and improve existing educational efforts to reduce preventable cancers. Institutions must prioritize HPV vaccine education to impact HPV related death.
Quantitative comparison of the efficacies and safety profiles of three first-line non-platinum chemotherapy regimens for advanced non-small cell lung cancer
Authors: Yang Qian-Yu , Zhu Lin , Liu Hong-Xia , Zheng Qing-Shan , Li Lu-Jin 
Published: August 2022

Objectives:The purpose of this study was to quantify the efficacies and safety profiles of the three first-line non-platinum chemotherapy regimens recommended in the National Comprehensive Cancer Network guidelines.Materials and Methods:The PubMed and Cochrane Library databases were searched comprehensively, and clinical trials involving patients with advanced non-small cell lung cancer treated with one of three first-line non-platinum regimens (gemcitabine combined with vinorelbine, gemcitabine combined with docetaxel, or gemcitabine alone) were included in the analysis. A parametric proportional hazard survival model was established to analyze the time course of overall survival (OS). The objective response rate (ORR) and incidence rates of grade 3–4 adverse events (AEs) were summarized using a single-arm meta-analysis with a random-effects model.Results:Seventeen studies met the inclusion criteria. Age and performance status (PS) scores were significant predictors of OS. For each 10-years increase in age, mortality risk increased by 18.5%, and the mortality risk increased by 4% for every 10% increase in the proportion of patients with a PS score of 2. After correcting for the above factors, we found that the three first-line non-platinum chemotherapy regimens did not differ based on OS or toxicity.Conclusion:There was no significant difference in OS or toxicity among the three first-line non-platinum chemotherapy regimens. Age and PS scores were significant predictors of OS, and their heterogeneity across different studies should be considered in cross-study comparisons and sample size estimations when designing clinical trials.
Study on plasma metabolomics for HIV/AIDS patients treated by HAART based on LC/MS-MS
Authors: Lao Donghui , Liu Rong , Liang Jianying 
Published: August 2022

Background: Metabolomics can be applied to the clinical diagnosis and treatment evaluation of acquired immune deficiency syndrome (AIDS). AIDS biomarkers have become a new direction of AIDS research providing clinical guidance for diagnosis.Objective: We sought to apply both untargeted and targeted metabolomic profiling to identify potential biomarkers for AIDS patients.Methods: A liquid chromatography-tandem mass spectrometry (LC-MS/MS) based untargeted metabolomic profiling was performed on plasma samples of patients before and after highly active antiretroviral therapy (HAART) treatment as well as healthy volunteers to identify potential AIDS biomarkers. Targeted quantitative analysis was performed on the potential biomarkers screened from untargeted metabolic profiling for verification.Results: Using the Mass Profiler Professional and the MassHunter, several potential biomarkers have been found by LC-MS/MS in the untargeted metabolomic study. High-resolution MS and MS/MS were used to analyze fragmentation rules of the metabolites, with comparisons of related standards. Several potential biomarkers have been identified, including PS(O-18:0/0:0), sphingosine, PE (21:0/0:0), and 1-Linoleoyl Glycerol. Targeted quantitative analysis showed that sphingosine and 1-Linoleoyl Glycerol might be closely related to HIV/AIDS, which may be the potential biomarkers to the diagnosis.Conclusion: We conducted untargeted metabolomic profiling, which indicates that several metabolites should be considered potential biomarkers for AIDS patients. Further targeted metabolomic research verified that d-Sphingosine and 1-Linoleoyl glycerol as the diagnostic biomarker of AIDS.
Arecae pericarpium water extract alleviates chronic pancreatitis by deactivating pancreatic stellate cells
Authors: Kweon Bitna , Kim Dong-Uk , Oh Jin-Young , Oh Hyuncheol , Kim Youn-Chul , Mun Yeun-Ja , Bae Gi-Sang , Park Sung-Joo 
Published: August 2022

Chronic pancreatitis (CP) is a chronic inflammatory disease of the pancreas with irreversible morphological changes. Arecae pericarpium (ARP), known to improve gastrointestinal disorders, has not yet been reported to inhibit fibrosis in CP. Therefore, we investigated the beneficial effects of ARP on cerulein-induced CP. Cerulein (50 μg/kg) was administered intraperitoneally to mice every hour, six times a day, four times a week for a total of 3 weeks to induce CP. To ascertain the prophylactic effects of ARP, ARP water extract (50, 100, or 200 mg/kg) or saline was administered intraperitoneally 1 h before the onset of CP. To determine the therapeutic effects of ARP, ARP water extract (200 mg/kg) or saline was administered for a total of 1 week or 2 weeks, starting 2 weeks or 1 week after the onset of CP. The pancreas was collected immediately for histological analysis. Additionally, to determine the effectiveness and mechanism of ARP in alleviating pancreatic fibrosis, pancreatic stellate cells (PSCs) were isolated. ARP treatment considerably improved glandular atrophy and inflammation and repressed collagen deposition in the pancreas. Furthermore, ARP water extract inhibited extracellular matrix (ECM) constituents such as alpha-smooth muscle actin (α-SMA), collagen I, and fibronectin 1 (FN1) in pancreatic tissue and PSCs. ARP also suppressed transforming growth factor-β (TGF-β) signaling by inhibiting Smad2 phosphorylation. Our study suggests that ARP exhibits anti-fibrotic effects in cerulein-induced CP by inhibiting TGF-β/Smad signaling.
Treatment options of traditional Chinese patent medicines for dyslipidemia in patients with prediabetes: A systematic review and network meta-analysis
Authors: Jiang Li , Wang Shidong , Zhao Jinxi , Chien Chieh , Zhang Yaofu , Su Guanxun , Chen Xiaoyu , Song Dechao , Chen Yu , Huang Weijun , Xiao Yonghua , Cao Yandong , Hu Zixian 
Published: August 2022

Objective: To compare the clinical efficacy and safety of SIX Traditional Chinese Patent Medicines (TCPM) recommended by guidelines in improving lipids for patients with prediabetes by network meta-analysis.Methods: Randomized controlled trials of 6 TCPM in the treatment of prediabetes were searched systematically in various databases. After extracting effective data, the risk of bias was assessed using Review Manager 5.3 and Cochrane Collaboration Systems Evaluator’s Manual. Network meta-analysis was performed using STATA 15.0 based on the frequency statistical model. The effect size and credibility of the evidence for the intervention were summarized based on a minimal contextualized framework.Results: A total of 27 studies involving 2,227 patients were included. Compared with lifestyle modification (LM), Shenqi + LM [SMD −0.49 (95% CI: −0.85, −0.12)] and Jinqi + LM [SMD −0.44 (95% CI: −0.81, −0.06)] showed statistically significant effect in lowering TG, Shenqi + LM [SMD −0.51 (95%CI: −0.86, −0.17)] and Jinqi + LM [SMD −0.44 (95%CI: −0.80, −0.08)] in lowering TC, Jinlida + LM [SMD −0.31 (95%CI: −0.59, −0.04)] in lowering LDL-C, Shenqi + LM [SMD 0.29 (95%CI: 0.06, 0.51)] and Jinqi + LM [SMD 0.16 (95%CI: 0.01, 0.31)] in increasing HDL-C.Conclusion: For patients with prediabetes, Traditional Chinese patent medicine Jinqi and Shenqi combined with lifestyle modification were associated with a significant reduction in TG and TC, while Shenqi + LM was among the most effective. Jinlida + LM was among the least effective.Systematic Review Registration:https://clinicaltrials.gov/, identifier PROSPERO(CRD42021279332).
Comparison of prognosis between neoadjuvant imatinib and upfront surgery for GIST: A systematic review and meta-analysis
Authors: Liu Zhen , Zhang Zimu , Sun Juan , Li Jie , Zeng Ziyang , Ma Mingwei , Ye Xin , Feng Fan , Kang Weiming 
Published: August 2022

Background: Significant survival benefit of adjuvant imatinib therapy has been observed in gastrointestinal stromal tumor (GIST). However, the impact of neoadjuvant imatinib on prognosis of GIST remains unclear. This meta-analysis aimed to compare the prognostic impact between upfront surgery and neoadjuvant imatinib plus surgery on GIST.Methods: A comprehensive literature search was performed to identify eligible studies up to 30 Sep 2021, through PubMed, Embase, Web of Science, and Cochrane Library. Studies compared the impact of upfront surgery and neoadjuvant imatinib plus surgery on disease-free (DFS) or overall survival (OS) in patients with GIST were selected.Results: Seven eligible studies with 17,171 patients were included. The reduction rates of tumor size in rectal and mixed site GIST were 33% and 29.8%, respectively. Neoadjuvant imatinib was not significantly associated with DFS compared with no-neoadjuvant therapy in rectal GIST (HR: 0.71, 95% CI: 0.35–1.41). The OS of rectal GIST was significantly improved by neoadjuvant imatinib compared with no-neoadjuvant therapy (HR: 0.36, 95% CI: 0.17–0.75).Conclusion: Neoadjuvant imatinib therapy contributed to tumor shrinkage and R0 resection of rectal GIST. Neoadjuvant imatinib plus surgery significantly improved overall survival of rectal GIST in comparison with upfront surgery.
Population pharmacokinetics of intravenous colistin sulfate and dosage optimization in critically ill patients
Authors: Xie Yue-liang , Jin Xin , Yan Shan-shan , Wu Cui-fang , Xiang Bi-xiao , Wang Hui , Liang Wu , Yang Bing-chang , Xiao Xue-fei , Li Zhi-ling , Pei Qi , Zuo Xiao-cong , Peng Yue 
Published: August 2022

Aims: To explore the population pharmacokinetics of colistin sulfate and to optimize the dosing strategy for critically ill patients.Methods: The study enrolled critically ill adult patients who received colistin sulfate intravenously for more than 72 h with at least one measurement of plasma concentration. Colistin concentrations in plasma or urine samples were measured by ultraperformance liquid chromatography tandem mass spectrometry (LC-MS/MS). The population pharmacokinetics (PPK) model for colistin sulfate was developed using the Phoenix NLME program. Monte Carlo simulation was conducted to evaluate the probability of target attainment (PTA) for optimizing dosing regimens.Results: A total of 98 plasma concentrations from 20 patients were recorded for PPK modeling. The data were adequately described by a two-compartment model with linear elimination. During modeling, creatinine clearance (CrCL) and alanine aminotransferase (ALT) were identified as covariates of the clearance (CL) and volume of peripheral compartment distribution (V2), respectively. In addition, colistin sulfate was predominantly cleared by the nonrenal pathway with a median urinary recovery of 10.05% with large inter-individual variability. Monte Carlo simulations revealed a greater creatinine clearance associated with a higher risk of sub-therapeutic exposure to colistin sulfate. The target PTA (≥90%) of dosage regimens recommended by the label sheet was achievable only in patients infected by pathogens with MIC ≤0.5 mg/L or with renal impairments.Conclusion: Our study showed that the dose of intravenous colistin sulfate was best adjusted by CrCL and ALT. Importantly, the recommended dosing regimen of 1.0–1.5 million units daily was insufficient for patients with normal renal functions (CrCL ≥80 ml/min) or those infected by pathogens with MIC ≥1.0 mg/L. The dosage of colistin sulfate should be adjusted according to renal function and drug exposure.
Efficacy of Ficus tikoua Bur. extract in ethylene glycol-induced urolithiasis model in SD rats
Authors: Bervinova Arina V. , Palikov Viktor A. , Mikhailov Evgeny S. , Palikova Yulia A. , Borozdina Natalya A. , Kazakov Vitaly A. , Rudenko Pavel A. , Tukhovskaya Elena A. , Dyachenko Igor A. , Slashcheva Gulsara A. , Goryacheva Natalya A. , Sadovnikova Elena S. , Kravchenko Irina N. , Kalabina Elena A. , Shinelev Maksim V. , Wu Peng , Murashev Arkady N. 
Published: August 2022

The development of new herbal preparations for the treatment of urolithiasis is an urgent task of medical science. Ficus have attracted the attention of pharmacologists due to a wide range of biological properties, including antioxidant, anti-inflammatory, antibacterial and antifungal activity. We studied the effectiveness of Ficus tikoua Bur. in SD rats in which urolithiasis was induced by 6 weeks of oral administration of ethylene glycol 0.5% ad libitum instead of drinking water. Administration of the extract of Ficus tikoua Bur., as well as comparative drug Cystone® after modeling of urolithiasis lead to the restoration of diuresis and the concentration of inorganic phosphates starting from the 6th week of the experiment. The use of the Ficus tikoua Bur. extract for 6 weeks, both during the modeling of urolithiasis and during the recovery period, led to the restoration of the percentage of lymphocytes in the blood, content of sodium, chlorine and inorganic phosphates in the blood to the control level. Thus, the extract of Ficus tikoua Bur. seems to be a promising drug for effective treatment of the initial stages of the development of urolithiasis.
Medicine-related problems: A recurrent issue among residents living in nursing homes
Authors: Dorj Gereltuya , Lim Renly , Ellett Lisa Kalisch , Kelly Thu-Lan , Andrade Andre , Widagdo Imaina , Pratt Nicole , Bilton Rebecca , Roughead Elizabeth 
Published: August 2022

Aim: To examine the incidence and nature of medicine-related problems over time experienced by nursing home residents.Method: We analyzed records collected in the Reducing Medicine-Induced Deterioration and Adverse Events (ReMInDAR) trial. The trial pharmacists provided services to reduce medicine-induced deterioration and adverse reactions for residents every 8-weeks over a year. The problems identified by the pharmacists were documented in reports and subsequently classified independently by research pharmacists using the D.O.C.U.M.E.N.T system. The number and type of problems at each service and time to develop a new problem post first session were assessed. All analyses were performed using R software (Version 4.1.1).Results: The cohort was 115 nursing home residents who received 575 services. In the 12-months, a total of 673 medicine-related problems or symptom reports were identified in 112 residents. Most residents (75%) experienced a new medicine-related problem by the fourth month post the first assessment. After the first session, the proportion of residents with a new medicine-related problem or symptom report declined at each repeated pharmacy session (59% at visit 2 vs. 28% at visit 6, p &lt; 0.01).Conclusion: Residents living in nursing homes frequently experience medicine-related problems. Our results suggest clinical pharmacist services performed every 4-months may have the potential to reduce the medicine-related problems in nursing homes.
Effects of torso mesh density and electrode distribution on the accuracy of electrocardiographic imaging during atrial fibrillation
Authors: Molero Rubén , González-Ascaso Ana , Hernández-Romero Ismael , Lundback-Mompó David , Climent Andreu M. , Guillem María S. 
Published: August 2022

Introduction: Electrocardiographic Imaging (ECGI) allows computing the electrical activity in the heart non-invasively using geometrical information of the patient and multiple body surface signals. In the present study we investigate the influence of the number of nodes of geometrical meshes and recording ECG electrodes distribution to compute ECGI during atrial fibrillation (AF).Methods: Torso meshes from 100 to 2000 nodes heterogeneously and homogeneously distributed were compared. Signals from nine AF realistic mathematical simulations were used for computing the ECGI. Results for each torso mesh were compared with the ECGI computed with a 4,000 nodes reference torso. In addition, real AF recordings from 25 AF patients were used to compute ECGI in torso meshes from 100 to 1,000 nodes. Results were compared with a reference torso of 2000 nodes. Torsos were remeshed either by reducing the number of nodes while maximizing the overall shape preservation and then assigning the location of the electrodes as the closest node in the new mesh or by forcing the remesher to place a node at each electrode location. Correlation coefficients, relative difference measurements and relative difference of dominant frequencies were computed to evaluate the impact on signal morphology of each torso mesh.Results: For remeshed torsos where electrodes match with a geometrical node in the mesh, all mesh densities presented similar results. On the other hand, in torsos with electrodes assigned to closest nodes in remeshed geometries performance metrics were dependent on mesh densities, with correlation coefficients ranging from 0.53 ± 0.06 to 0.92 ± 0.04 in simulations or from 0.42 ± 0.38 to 0.89 ± 0.2 in patients. Dominant frequency relative errors showed the same trend with values from 1.14 ± 0.26 to 0.55 ± 0.21 Hz in simulations and from 0.91 ± 0.56 to 0.45 ± 0.41 Hz in patients.Conclusion: The effect of mesh density in ECGI is minimal when the location of the electrode is preserved as a node in the mesh. Torso meshes constructed without imposing electrodes to constitute nodes in the torso geometry should contain at least 400 nodes homogeneously distributed so that a distance between nodes is below 4 cm.