bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comparison of Treatment Response, Survival Profiles, as Well as Safety Profiles Between CalliSpheres® Microsphere Transarterial Chemoembolization and Conventional Transarterial Chemoembolization in Huge Hepatocellular Carcinoma
Authors: Duan Xuhua , Liu Juanfang , Han Xinwei , Ren Jianzhuang , Li Hao , Li Fengyao , Ju Shuguang 
Published: January 2022

PurposeCalliSpheres® microspheres (CSM) are the first drug-eluting beads (DEB) developed in China. This study aimed to compare treatment response, survival, and safety profiles between DEB transarterial chemoembolization (DEB-TACE) with CSM and conventional TACE (cTACE) in huge hepatocellular carcinoma (HCC) patients.MethodsA total of 71 patients with huge HCC who underwent DEB-TACE or cTACE were consecutively enrolled in this retrospective cohort study. Treatment response was assessed at first month (M1), third month (M3), and sixth month (M6) after TACE therapy; progression-free survival (PFS) and overall survival (OS) were evaluated; liver function indexes were recorded before TACE operation (M0), at first week (W1), M1 and M6 after TACE therapy; adverse events which occurred after TACE operation were recorded.ResultsDEB-TACE presented with higher objective response rate (60.0% vs. 29.7%, p &lt; 0.05) and disease control rate (86.7% vs. 59.4%, p &lt; 0.05) compared with cTACE at M3. Regarding survival profiles, PFS [median: 3.3 months (95% CI: 2.8–3.7) vs. 2.1 months (95% CI: 1.7–2.5)] as well as OS [median: 7.8 months (95% CI: 4.6–11.0) vs. 5.7 months (95% CI: 5.0–6.3)] were longer in DEB-TACE group compared with cTACE group (both p &lt; 0.01). Multivariate Cox’s regression further illustrated that DEB-TACE vs. cTACE was an independent protective factor for PFS and OS (both p &lt; 0.01). As for safety profiles, patients’ liver function injury was reduced in the DEB-TACE group compared with the cTACE group. The incidence of fever was lower, and CINV was less severe in the DEB-TACE group compared with the cTACE group (both p &lt; 0.05), while no difference in occurrence of liver abscess, increase of ascites, or moderate pain between two groups was observed.ConclusionDEB-TACE with CSM presents with better treatment response, survival profiles, as well as safety profiles compared with cTACE in treatment for huge HCC patients.
The Effect of Dietary Intervention With High-Oleocanthal and Oleacein Olive Oil in Patients With Early-Stage Chronic Lymphocytic Leukemia: A Pilot Randomized Trial
Authors: Rojas Gil Andrea Paola , Kodonis Ioannis , Ioannidis Anastasios , Nomikos Tzortzis , Dimopoulos Ioannis , Kosmidis Georgios , Katsa Maria Efthymia , Melliou Eleni , Magiatis Prokopios 
Published: January 2022

AimOleocanthal and oleacein (OC/OL) have important in vitro and in vivo antitumor properties; however, there is no data about their anticancer activity in humans. The aim of this pilot study was to test if patients at early stage of chronic lymphocytic leukemia (CLL) could adhere to and tolerate an intervention with high OC/OL extra virgin olive oil (EVOO) and if this intervention could lead to any changes in markers related to the disease.MethodsA pilot dietary intervention (DI) was made in patients with CLL in Rai stages 0–II who did not follow any treatment (NCT04215367). In the first intervention (DI1), 20 CLL patients were included in a blind randomized study and were separated into two groups. One group (A) of 10 patients consumed 40 ml/day of high OC/OL-EVOO (416 mg/Kg OC and 284 mg/kg OL) for 3 months. A second group (B) of 10 patients consumed 40 ml/day of low OC/OL (82 mg/kg OC and 33 mg/kg OL) for 3 months. After a washout period of 9–12 months, a second intervention (DI2) only with High OC/OL-EVOO for 6 months was performed with 22 randomly selected patients (16 from the DI1 (8 from each group) and 6 new). Hematological, biochemical, and apoptotic markers were analyzed in the serum of the patients. In addition, cellular proliferation and apoptosis markers were studied in isolated proteins from peripheral blood mononuclear cells.ResultsThe results of the DI1 showed beneficial effects on hematological and apoptotic markers only with High OC/OL-EVOO. During the DI2, a decrease in the white blood cell and lymphocyte count was observed (p ≤0.05), comparing 3 months before the intervention and 6 months after it. After 3 and 6 months of DI2, an increase (p ≤0.05) was observed in the apoptotic markers ccK18 and Apo1-Fas, and also in the cell cycle negative regulator p21, and also a decrease in the antiapoptotic protein Survivin, and in the cellular proliferation marker Cyclin D.ConclusionsThis is the first clinical trial with High OC/OL-EVOO that indicates that it could be a promising dietary feature for the improvement of CLL inducing the apoptosis of their cancer cells and improving the metabolism of the patients.Clinical Trial Registrationhttps://clinicaltrials.gov/ct2/show/NCT04215367, identifier: NCT04215367.
Low Vitamin D Levels at Birth and Early Respiratory Outcome in Infants With Gestational Age Less Than 29 Weeks
Authors: Papalia Honoré , Samonini Anais , Buffat Christophe , Gras E. , des Robert Clotilde , Landrier Jean-Francois , Pauly Vanessa , Boubred Farid 
Published: January 2022

BackgroundVitamin D (VitD) is involved in lung development but its influence on respiratory distress syndrome of extremely preterm (EPT) infants have been little investigated. In this study, we examined the influence of low vitamin D status at birth on early respiratory outcomes of this vulnerable infant population.MethodsCord blood 25(OH)D levels ≤ 75 nmol/L were considered as Low vitamin D levels. Stepwise logistic regression and classification regression-tree analyses were used and the primary outcome was the combined outcome of death or mechanical ventilation need by the end of the first week (death or MV DoL7) as a marker od RDS severity.ResultsThe mean (SD) GA and birth weight were 26 (1.4) weeks and 801 (212) gr, respectively; 81/109 (74%) infants had low 25(OH)D levels. Infants with low VitD levels had 25% higher initial FiO2 levels (p &lt; 0.05) and were more likely to be mechanically ventilated on DoL7 (36 vs. 7%, p &lt; 0.05). Adjusted for gestational age, they had 10-fold higher odds of death or MV DoL7 (p &lt; 0.01). By regression tree analysis, the rate of death or MV DoL7 increased from 18 to 71% in infants with GA &lt; 26 weeks and with cord blood 25(OH)D levels higher and lower than 74 nmol/L, respectively (p &lt; 0.05).ConclusionLow vitamin D levels at birth are associated with early adverse respiratory outcomes in infants with GA less 29 weeks. Further largest studies are needed to confirm this association.
Assessing the Value of Nusinersen for Spinal Muscular Atrophy: A Comparative Analysis of Reimbursement Submission and Appraisal in European Countries
Authors: Blonda Alessandra , Barcina Lacosta Teresa , Toumi Mondher , Simoens Steven 
Published: January 2022

Background: Nusinersen is an orphan drug intended for the treatment of spinal muscular atrophy (SMA), a severe genetic neuromuscular disorder. Considering the very high costs of orphan drugs and the expected market entry of cell and gene therapies, there is increased interest in the use of health technology assessment (HTA) for orphan drugs. This study explores the role of the economic evaluation and budget impact analysis on the reimbursement of nusinersen.Methods: Appraisal reports for nusinersen were retrieved from reimbursement and HTA agencies in Belgium, Canada, France, England and Wales, Germany, Italy, Ireland, Scotland, Sweden, the Netherlands, and the United States. Detailed information was extracted on the economic evaluation, the budget impact, the overall reimbursement decision, and the managed entry agreement (MEA). Costs were adjusted for inflation and currency.Results: Overall, the reports included limited data on budget impact, excluding information on the sources of data for cost and patient estimates. Only three jurisdictions reported on total budget impact, estimated between 30 and 40 million euros per year. For early-onset SMA, the incremental cost-effectiveness threshold (ICER) ranged from €464,891 to €6,399,097 per quality-adjusted life year (QALY) gained for nusinersen versus standard of care. For later-onset SMA, the ICER varied from €493,756 to €10,611,936 per QALY. Although none of the jurisdictions found nusinersen to be cost-effective, reimbursement was granted in each jurisdiction. Remarkably, only four reports included arguments in favor of reimbursement. However, the majority of the jurisdictions set up an MEA, which may have promoted a positive reimbursement decision.Conclusion: There is a need for more transparency on the appraisal process and conditions included in the MEA. Additionally, by considering all relevant criteria explicitly during the appraisal process, decision-makers are in a better position to justify their allocation of funds among the rising number of orphan drugs that are coming to the market in the near future.
Inhibitors of Human 5-Lipoxygenase Potently Interfere With Prostaglandin Transport
Authors: Kahnt Astrid S. , Angioni Carlo , Göbel Tamara , Hofmann Bettina , Roos Jessica , Steinbrink Svenja D. , Rörsch Florian , Thomas Dominique , Geisslinger Gerd , Zacharowski Kai , Grösch Sabine , Steinhilber Dieter , Maier Thorsten J. 
Published: January 2022

5-Lipoxygenase (5-LO) is the key enzyme in the formation of pro-inflammatory leukotrienes (LT) which play an important role in a number of inflammatory diseases. Accordingly, 5-LO inhibitors are frequently used to study the role of 5-LO and LT in models of inflammation and cancer. Interestingly, the therapeutic efficacy of these inhibitors is highly variable. Here we show that the frequently used 5-LO inhibitors AA-861, BWA4C, C06, CJ-13,610 and the FDA approved compound zileuton as well as the pan-LO inhibitor nordihydroguaiaretic acid interfere with prostaglandin E2 (PGE2) release into the supernatants of cytokine-stimulated (TNFα/IL-1β) HeLa cervix carcinoma, A549 lung cancer as well as HCA-7 colon carcinoma cells with similar potencies compared to their LT inhibitory activities (IC50 values ranging from 0.1–9.1 µM). In addition, AA-861, BWA4C, CJ-13,610 and zileuton concentration-dependently inhibited bacterial lipopolysaccharide triggered prostaglandin (PG) release into human whole blood. Western Blot analysis revealed that inhibition of expression of enzymes involved in PG synthesis was not part of the underlying mechanism. Also, liberation of arachidonic acid which is the substrate for PG synthesis as well as PGH2 and PGE2 formation were not impaired by the compounds. However, accumulation of intracellular PGE2 was found in the inhibitor treated HeLa cells suggesting inhibition of PG export as major mechanism. Further, experiments showed that the PG exporter ATP-binding cassette transporter multidrug resistance protein 4 (MRP-4) is targeted by the inhibitors and may be involved in the 5-LO inhibitor-mediated PGE2 inhibition. In conclusion, the pharmacological effects of a number of 5-LO inhibitors are compound-specific and involve the potent inhibition of PGE2 export. Results from experimental models on the role of 5-LO in inflammation and pain using 5-LO inhibitors may be misleading and their use as pharmacological tools in experimental models has to be revisited. In addition, 5-LO inhibitors may serve as new scaffolds for the development of potent prostaglandin export inhibitors.
Components of the Endocannabinoid System and Effects of Cannabinoids Against Bone Diseases: A Mini-Review
Authors: Xin Yuqi , Tang Anqun , Pan Shuting , Zhang Jie 
Published: January 2022

Background: The endocannabinoid system (ECS) is involved in multiple physiological processes, including appetite regulation, pain perception, motor function development, and immune response regulation. Cannabinoids have been approved for the clinical treatment of nausea and vomiting caused by cytostatic therapy or cancer chemotherapy, loss of appetite in HIV/AIDS-associated cachexia, refractory spasms induced by multiple sclerosis, chronic pain, and urinary incontinence.Methods: Check out the research on ECS and bone diseases in the past 20 years.Results: Many studies have demonstrated that endocannabinoids (eCBs) and cannabinoid receptors (CBRs) are expressed in bone and synovial tissues, playing important roles in bone metabolism. Preclinical studies using cannabis-based therapies in animal models have shown that cannabinoids (CBs) can alleviate the development of osteoarthritis (OA), prevent osteoporosis (OP), reduce cancer-induced osteolytic destruction, and improve fracture healing, highlighting the therapeutic potential of CBs for human bone diseases.Conclusions: The present review summarizes various components of the ECS in bone diseases and their potential as a therapeutic target.
Does Having a Usual Primary Care Provider Reduce Polypharmacy Behaviors of Patients With Chronic Disease? A Retrospective Study in Hubei Province, China
Authors: Wang Jia , Feng Zhanchun , Dong Zhongxin , Li Wanping , Chen Chaoyi , Gu Zhichun , Wei Anhua , Feng Da 
Published: January 2022

Background: Within China's hierarchical medical system, many patients seek medical care in different hospitals independently without integrated management. As a result, multi-hospital visiting is associated with fragmented service utilization and increased incidence of polypharmacy behaviors, especially for patients with chronic disease. It has been confirmed that factors from the perspective of patients may cause polypharmacy behaviors in Chinese community patients; whether having a usual primary care provider for chronic disease patients could reduce the polypharmacy behaviors and the effect size remains unanswered, and that is what our study aimed to answer.Methods: Our study adopted a cluster sampling method to select 1,196 patients with hypertension or diabetes and measured some information about them. The propensity score weighting method was adopted to eliminate the influence of confounding bias, and then a multivariate logistic regression model was conducted to test the relationship between having a usual primary care provider and polypharmacy behaviors.Results: Patients without usual primary care providers were significantly correlated with polypharmacy behaviors (OR = 2.40, 95%CI: 1.74–3.32, p &lt; 0.001), and the corresponding marginal effect is 0.09 (95%CI: 0.06–0.12). Patients who suffer from two kinds of diseases (OR = 3.05, 95%CI: 1.87–5.10, p &lt; 0.001), with more than three kinds of diseases (OR = 21.03, 95%CI: 12.83–35.65, p &lt; 0.001), with disease history of 20 years and above (OR = 1.66, 95%CI: 1.14–2.42, p = 0.008), who communicate frequently with doctors (OR = 3.14, 95%CI: 1.62–6.19, p &lt; 0.001), alcoholic patients (OR = 2.14, 95%CI: 1.08–4.19, p = 0.027), who used to have meat-based food (OR = 1.42, 95%CI: 1.00–2.00, p = 0.049), and have vegetarian-based diet (OR = 1.42, 95%CI: 1.00–2.00, p = 0.049) are more likely to have polypharmacy behaviors, while patients aged between 65 and 75 years (OR = 0.50, 95%CI: 0.33–0.77, p = 0.020), used to be brain workers (OR = 0.67, 95%CI: 0.45–0.99, p = 0.048), with disease history between 10 and 20 years (OR = 0.56, 95%CI: 0.37–0.83, p = 0.005), have had adverse drug reactions (OR = 0.64, 95%CI: 0.45–0.93, p = 0.019), and participated in medical insurance for urban and rural residents (OR = 0.35, 95%CI: 0.21–0.58, p &lt; 0.001) were less likely to have polypharmacy behaviors.Conclusion: The results suggest that having a usual primary care provider may reduce the incidence of having polypharmacy behaviors; we can take intervention measures to promote establishing a long-term relationship between patients and primary care providers.
Sulforaphane Ameliorates the Severity of Psoriasis and SLE by Modulating Effector Cells and Reducing Oxidative Stress
Authors: Du Pei , Zhang Wenqian , Cui Haobo , He Wei , Lu Shuang , Jia Sujie , Zhao Ming 
Published: January 2022

Background: Sulforaphane, which is found in cruciferous vegetables, has been reported to have anti-inflammatory, antioxidant, and antitumour activities. However, whether sulforaphane has therapeutic effects on inflammatory or autoimmune skin diseases, including psoriasis and systemic lupus erythematosus (SLE), is unclear.Methods: The therapeutic effects of sulforaphane were analyzed in Imiquimod (IMQ)-induced psoriasis-like mice and lupus-prone MRL/lpr mice. In IMQ-induced psoriasis-like mice treated with sulforaphane (55.3 and 110.6 μmol/kg) or vehicle control, the pathological phenotypes were assessed by the psoriasis area and severity index (PASI) score, haematoxylin-eosin staining (H&amp;E) and quantifying of acanthosis and dermal inflammatory cell infiltration. The proportions of T cell subsets in draining lymph nodes (dLNs) and spleens were examined by flow cytometry. In MRL/lpr mice treated with sulforaphane (82.9 μmol/kg) or vehicle control, mortality and proteinuria were observed, and the glomerular pathology was examined by H&amp;E staining. C3 and IgG depositions in kidney sections were examined by immunofluorescence staining. The proportions of plasma cells, follicular helper T (Tfh) cells, neutrophils and dendritic cells in the dLNs and spleens were examined by flow cytometry. Finally, we examined the Malondialdehyde (MDA) concentration by thiobarbituric acid reactive substance assay and the expression of Prdx1, Nqo1, Hmox1, and Gss by reverse transcription-quantitative polymerase chain reaction (RT-qPCR).Results: Sulforaphane ameliorated the skin lesions in IMQ-induced psoriasis-like mice and the renal damage in lupus-prone MRL/lpr mice. In IMQ-induced psoriasis-like mice, sulforaphane reduced the proportions of Th1 and Th17 cells and increased the expression of antioxidant gene Prdx1. In lupus-prone MRL/lpr mice, sulforaphane increased the lifespan and the expression of Prdx1, and decreased the proportions of plasma cells, Tfh cells, neutrophils, and dendritic cells in the dLNs and spleens and the concentration of MDA.Conclusion: Sulforaphane has significant therapeutic effects on IMQ-induced psoriasis-like mice and lupus-like MRL/Lpr mice by reducing inflammatory and autoimmune-related cells and oxidative stress. These findings provide new evidence for developing natural products to treat inflammatory and autoimmune diseases.
Kinsenoside Protects Against Radiation-Induced Liver Fibrosis via Downregulating Connective Tissue Growth Factor Through TGF-β1 Signaling
Authors: Nie Xiaoqi , Yu Qianqian , Li Long , Yi Minxiao , Wu Bili , Huang Yongbiao , Zhang Yonghui , Han Hu , Yuan Xianglin 
Published: January 2022

Radiation-induced liver fibrosis (RILF) is a serious complication of the radiotherapy of liver cancer, which lacks effective prevention and treatment measures. Kinsenoside (KD) is a monomeric glycoside isolated from Anoectochilus roxburghii, which has been reported to show protective effect on the early progression of liver fibrosis. However, the role of KD in affecting RILF remains unknown. Here, we found that KD alleviated RILF via downregulating connective tissue growth factor (CTGF) through TGF-β1 signaling. Sprague-Dawley rats were administered with 20 mg/kg KD per day for 8 weeks after a single 30Gy irradiation on the right part of liver, and tumor-bearing nude mice were administered with 30 mg/kg KD per day after a single fraction of 10Gy on the tumor inoculation site. Twenty-four weeks postirradiation, we found that the administration of KD after irradiation resulted in decreased expression of α-SMA and fibronectin in the liver tissue while had no adverse effect on the tumor radiotherapy. Besides, KD inhibited the activation of hepatic stellate cells (HSCs) postirradiation via targeting CTGF as indicated by the transcriptome sequencing. Results of the pathway enrichment and immunohistochemistry suggested that KD reduced the expression of TGF-β1 protein after radiotherapy, and exogenous TGF-β1 induced HSCs to produce α-SMA and other fibrosis-related proteins. The content of activated TGF-β1 in the supernatant decreased after treatment with KD. In addition, KD inhibited the expression of the fibrosis-related proteins by regulating the TGF-β1/Smad/CTGF pathway, resulting in the intervention of liver fibrosis. In conclusion, this study revealed that KD alleviated RILF through the regulation of TGFβ1/Smad/CTGF pathway with no side effects on the tumor therapy. KD, in combination with blocking the TGF-β1 pathway and CTGF molecule or not, may become the innovative and effective treatment for RILF.
Health Literacy Among University Students: A Systematic Review of Cross-Sectional Studies
Authors: Kühn Lucas , Bachert Philip , Hildebrand Claudia , Kunkel Jule , Reitermayer Jörg , Wäsche Hagen , Woll Alexander 
Published: January 2022

ObjectiveThe aim of this systematic review was to provide an overview of cross-sectional studies that examined health literacy among university students and to identify possible determinants related to health literacy.MethodThe current review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). Three databases (PubMed, Scopus, and Web of Science) were systematically searched for cross-sectional studies that examined health literacy among university students. Results of included studies were narratively summarized.ResultsThe systematic review includes twenty-one research studies. The majority of studies report health literacy scores among university students that are lower compared to reference samples. The health literacy of students is influenced by different variables (age, gender, number of semesters, course of studies/curriculum, parental education, and socioeconomic background).DiscussionHealth literacy activities should target all students. Universities should make use of their resources and offer health literacy courses for students in which content is used from disciplines available at the university (e.g., medicine, health, or psychology). To increase effectiveness, health literacy courses should be adapted according to the different needs and characteristics of the student subgroups.
Avoidable Hospitalization Trends From Ambulatory Care-Sensitive Conditions in the Public Health System in México
Authors: Poblano Verástegui Ofelia , Torres-Arreola Laura del Pilar , Flores-Hernández Sergio , Nevarez Sida Armando , Saturno Hernández Pedro J. 
Published: January 2022

ObjectivesTo estimate and identify the variations in rates of Avoidable Hospitalization for Ambulatory Care Sensitive Conditions (AH-ACSC) in public institutions of the Mexican health system during the period 2010–2017.MethodsSecondary analysis of the hospital discharge database of the Ministry of Health (MoH) from 2010 to 2017. AH for ACSC was calculated by age group and sex per 100,000. Variations per year between institutions were calculated with the extreme quotient (EQ), coefficient of variation (CV) and systematic component of variance (SCV). Adjusted AH rates were calculated by group of causes (acute, chronic and preventable by vaccination). Adjusted AH trend rates were analyzed by Join Point Regression.ResultsFor the period 2010–2017, the number of AH for ACSC decreased from 676,705 to 612,897, going from almost 13% to 10.7% of hospital discharges. There is consistency in terms of relative variance magnitude. But, with regards to SCV, the change remained constant, and in a second period of 2015–2017, high variation was observed by SCV ≥ 3. All-cause AH is diminishing in all institutions. AH rates for diabetes are the highest, but like other chronic diseases, there was a decline in the period from 2010 to 2017. The relative reduction varied from 15% for heart failure to 38% for complications from diabetes or hypertension, to 75% for angina.ConclusionsAH for ACSC is an indirect indicator of quality and access to first-level care. Variations by institutions are observed. This variation in CV and SCV across subsystems and states may be due to inequities in the provision of services. The factors that contribute to the burden of AH for ACSC in the Mexican Health System require detailed analysis.