bluuebunny/crossref_metadata_2025_split huggingface dataset:
Uric Acid and Clinical Outcomes Among Intracerebral Hemorrhage Patients: Results From the China Stroke Center Alliance
Authors: Liu Xinmin , Cao Zhentang , Gu Hongqiu , Yang Kaixuan , Ji Ruijun , Li Zixiao , Zhao Xingquan , Wang Yongjun 
Published: December 2020

Background and Purpose: The effect of uric acid (UA) levels on severity and prognosis of spontaneous intracerebral hemorrhage (ICH) remains controversial. We aimed to explore the association of admission UA levels with stroke severity and outcomes in ICH patients.Materials and Methods: The patients enrolled in this study were from the China Stroke Center Alliance study (CSCA). Patients were divided into four groups (Q1–Q4) according to the quartiles of UA levels at admission. The primary outcome was in-hospital mortality. The secondary outcomes included stroke severity, in-hospital complications, and discharge disposition. Multivariate logistic regression was adopted to explore the association of UA levels with outcomes after ICH.Results: Patients (84,304) with acute ICH were included in the final analysis; the median (interquartile range) of UA was 277 (210, 354) μmol/L. The four groups were defined as follows: Q1 ≤ 210 μmol/L, 210 μmol/L &lt; Q2 ≤ 277 μmol/L, 277 μmol/L &lt; Q3 ≤ 354 μmol/L, Q4 &gt; 354 μmol/L. There was no significant evidence indicating that UA levels were correlated with the discharge disposition and in-hospital mortality after ICH. However, compared to Q1, the patients with higher UA levels had decreased odds of severe stroke (NIHSS ≥ 16) at admission (OR 0.89, 95% CI 0.86–0.92). An L-shaped association was found between UA and severe stroke. Among in-hospital complications, decrease in pneumonia, poor swallow function, gastrointestinal bleeding, and deep vein thrombosis (DVT) were significantly associated with higher UA levels compared to Q1 (P for trend &lt; 0.0001).Conclusions: UA was a protective factor for stroke severity and in-hospital complications such as pneumonia, poor swallow function, gastrointestinal bleeding, and DVT. However, no significant evidence indicated that UA levels were predictive of the discharge disposition and in-hospital mortality after ICH.
Delta Radiomics Can Predict Distant Metastasis in Locally Advanced Rectal Cancer: The Challenge to Personalize the Cure
Authors: Chiloiro Giuditta , Rodriguez-Carnero Pablo , Lenkowicz Jacopo , Casà Calogero , Masciocchi Carlotta , Boldrini Luca , Cusumano Davide , Dinapoli Nicola , Meldolesi Elisa , Carano Davide , Damiani Andrea , Barbaro Brunella , Manfredi Riccardo , Valentini Vincenzo , Gambacorta Maria Antonietta 
Published: December 2020

PurposeDistant metastases are currently the main cause of treatment failure in locally advanced rectal cancer (LARC) patients. The aim of this research is to investigate a correlation between the variation of radiomics features using pre- and post-neoadjuvant chemoradiation (nCRT) magnetic resonance imaging (MRI) with 2 years distant metastasis (2yDM) rate in LARC patients.Methods and MaterialsDiagnostic pre- and post- nCRT MRI of LARC patients, treated in a single institution from May 2008 to June 2015 with an adequate follow-up time, were retrospectively collected. Gross tumor volumes (GTV) were contoured by an abdominal radiologist and blindly reviewed by a radiation oncologist expert in rectal cancer. The dataset was firstly randomly split into 90% training data, for features selection, and 10% testing data, for the validation. The final set of features after the selection was used to train 15 different classifiers using accuracy as target metric. The models’ performance was then assessed on the testing data and the best performing classifier was then selected, maximising the confusion matrix balanced accuracy (BA).ResultsData regarding 213 LARC patients (36% female, 64% male) were collected. Overall 2yDM was 17%. A total of 2,606 features extracted from the pre- and post- nCRT GTV were tested and 4 features were selected after features selection process. Among the 15 tested classifiers, logistic regression proved to be the best performing one with a testing set BA, sensitivity and specificity of 78.5%, 71.4% and 85.7%, respectively.ConclusionsThis study supports a possible role of delta radiomics in predicting following occurrence of distant metastasis. Further studies including a consistent external validation are needed to confirm these results and allows to translate radiomics model in clinical practice. Future integration with clinical and molecular data will be mandatory to fully personalized treatment and follow-up approaches.
The Expression of Glycoprotein Genes in the Inflammatory Process of Kawasaki Disease
Authors: Kuo Kuang-Che , Yang Ya-Ling , Lo Mao-Hung , Cai Xin-Yuan , Kuo Ho-Chang , Huang Ying-Hsien 
Published: December 2020

Background: Kawasaki disease (KD) is the most common form of febrile coronary vasculitis disease to occur in children. Early diagnosis and proper therapy can prevent the complication of coronary artery lesions (CAL). The main pathogenesis of KD is an inflammatory process related to the host's genetic characteristics. In innate human immunity, the interaction of leukocytes and glycoprotein plays an important role against microbes. The purpose of our study was to understand the role of leukocytes' glycoprotein genes during the acute phase of KD.Materials and Methods: We enrolled a total of 97 subjects from a medical center. Of those, 24 subjects were healthy controls, and 24 subjects were fever controls; the other 49 subjects were KD patients who had had blood samples taken both before and after IVIG treatment. We collected the total RNA from leukocytes and performed a quantitative polymerase chain reaction for the HP, GRP84, and CLEC4D genes in real time.Results: Compared with both the healthy and fever controls, the upregulation of HP, GRP84, and CLEC4D genes was significant in peripheral leukocytes during acute-phase KD. The transcriptional level of these respective genes not only demonstrated a positive correlation with each other, but were also effective predictors for KD (all auROC &gt;0.87) according to the ROC curve analysis. The hyper-expression of these three genes was significantly associated with IVIG resistance, but not CAL formation.Conclusions: Our study demonstrates that the expression of HP, GRP84, and CLEC4D genes of leukocytes play an important role in the pathogenesis and primary IVIG response during the acute inflammatory process of KD.
Pharmacological Characterization of Orofacial Nociception in Female Rats Following Nitroglycerin Administration
Authors: Caudle Robert M. , Caudle Stephanie L. , Flenor Natalie D. , Rohrs Eric L. , Neubert John K. 
Published: December 2020

Rodent models of human disease can be valuable for understanding the mechanisms of a disease and for identifying novel therapies. However, it is critical that these models be vetted prior to committing resources to developing novel therapeutics. Failure to confirm the model can lead to significant losses in time and resources. One model used for migraine headache is to administer nitroglycerin to rodents. Nitroglycerin is known to produce migraine-like pain in humans and is presumed to do the same in rodents. It is not known, however, if the mechanism for nitroglycerin headaches involves the same pathological processes as migraine. In the absence of known mechanisms, it becomes imperative that the model not only translates into successful clinical trials but also successfully reverse translates by demonstrating efficacy of current therapeutics. In this study female rats were given nitroglycerin and nociception was evaluated in OPADs. Estrous was not monitored. Based on the ED50 of nitroglycerin a dose of 10 mg/kg was used for experiments. Sumatriptan, caffeine, buprenorphine and morphine were administered to evaluate the reverse translatability of the model. We found that nitroglycerin did not produce mechanical allodynia in the face of the rats, which is reported to be a consequence of migraine in humans. Nitroglycerin reduced the animals’ participation in the assay. The reduced activity was verified using an assay to measure exploratory behavior. Furthermore, the effects of nitroglycerin were not reversed or prevented by agents that are effective acute therapies for migraine. Two interesting findings from this study, however, were that morphine and nitroglycerin interact to increase the rats’ tolerance of mechanical stimuli on their faces, and they work in concert to slow down the central motor pattern generator for licking on the reward bottle. These interactions suggest that nitroglycerin generated nitric oxide and mu opioid receptors interact with the same neuronal circuits in an additive manner. The interaction of nitroglycerin and morphine on sensory and motor circuits deserves additional examination. In conclusion, based on the results of this study the use of nitroglycerin at these doses in naïve female rats is not recommended as a model for migraine headaches.
Pain Modulation in WAG/Rij Epileptic Rats (A Genetic Model of Absence Epilepsy): Effects of Biological and Pharmacological Histone Deacetylase Inhibitors
Authors: De Caro Carmen , Di Cesare Mannelli Lorenzo , Branca Jacopo Junio Valerio , Micheli Laura , Citraro Rita , Russo Emilio , De Sarro Giovambattista , Ghelardini Carla , Calignano Antonio , Russo Roberto 
Published: December 2020

Epigenetic mechanisms are involved in epilepsy and chronic pain development. About that, we studied the effects of the natural histone deacetylase (HDAC) inhibitor sodium butyrate (BUT) in comparison with valproic acid (VPA) in a validated genetic model of generalized absence epilepsy and epileptogenesis. WAG/Rij rats were treated with BUT (30 mg/kg), VPA (300 mg/kg), and their combination (BUT + VPA) daily per os for 6 months. Rats were subjected at Randall–Selitto, von Frey, hot plate, and tail flick tests after 1, 3, and 6 months of treatment to evaluate hypersensitivity to noxious and non-noxiuous stimuli. Moreover, PPAR-γ (G3335 1 mg/kg), GABA-B (CGP35348 80 mg/kg), and opioid (naloxone 1 mg/kg) receptor antagonists were administrated to investigate the possible mechanisms involved in analgesic activity. The expression of NFkB, glutathione reductase, and protein oxidation (carbonylation) was also evaluated by Western blot analysis. WAG/Rij rats showed an altered pain threshold throughout the study (p &lt; 0.001). BUT and BUT + VPA treatment reduced hypersensitivity (p &lt; 0.01). VPA was significantly effective only after 1 month (p &lt; 0.01). All the three receptors are involved in BUT + VPA effects (p &lt; 0.001). BUT and BUT + VPA decreased the expression of NFkB and enhanced glutathione reductase (p &lt; 0.01); protein oxidation (carbonylation) was reduced (p &lt; 0.01). No effect was reported with VPA. In conclusion BUT, alone or in coadministration with VPA, is a valuable candidate for managing the epilepsy-related persistent pain.
Severe Potential Drug-Drug Interactions and the Increased Length of Stay of Children in Intensive Care Unit
Authors: Lima Elisangela da Costa , Camarinha Barbara Dias , Ferreira Bezerra Nathalia Cristina , Panisset Anderson Gonçalves , Belmino de Souza Raquel , Silva Marcus Tolentino , Lopes Luciane Cruz 
Published: December 2020

Children are exposed to drug-drug interactions (DDI) risks due to their organism’s complexity and the need for several medicines prescriptions in pediatric intensive care units (PICU). This study aimed to assess the prevalence of potential DDIs in a Brazilian PICU. We carried out a cross-sectional study at a pediatric teaching hospital from Rio de Janeiro (Brazil) over one year. Potential DDIs (pDDIs) between prescribed medicines for hospitalized children in PICU (n = 143) were analyzed according to severity using Micromedex®. Sex, age group, number of drugs prescribed, vasoactive amines use (a proxy of clinical complexity), and the PICU length of stay were summarized using descriptive statistics. Association between the PICU length stay, and variables sex, age, clinical condition complexity, number of drugs prescribed, and severity of pDDI were examined by univariate and multiple linear regression. Seventy percent of patients aged three days to 14 years old were exposed at least one potential DDIs during PICU stay. Two hundred eighty-four different types of pDDIs were identified, occurring 1,123 times. Nervous system drugs were implicated in 55% of the interactions, and fentanyl (10%) was most involving in pDDIs. Most pDDIs were classified as higher severity (56.2%), with reasonable documentation (64.6%) and unspecified onset time (63.8%). Worse clinical condition, ten or more drugs prescribed, and most severe pDDIs were associated with a longer PICU length of stay. Multiple linear regression analysis showed an increase of 9.83 days (95% confidence interval: 3.61–16.05; p = 0.002) in the PICU length of stay in children with major or contraindicated pDDIs. The results of this research may support the monitoring and prevention of pDDIs related to adverse events in children in intensive care and the design and conduction of new studies.
Pharmacokinetics and Bioequivalence of Rasagiline Tablets in Chinese Healthy Subjects Under Fasting and Fed Conditions: An Open, Randomized, Single-Dose, Double-Cycle, Two-Sequence, Crossover Trial
Authors: Li Yinjuan , Qi Lu , Bai Haihong , Liu Ying , Fan Rongxia , Tu Yongrui , Sun Yongqiang , Wang Juxiang , Qi Qi , Feng Xiaohui , Zhou Da , Wang Xinghe 
Published: December 2020

Objective: This study evaluated the pharmacokinetics, safety, and bioequivalence (BE) of two formulations of rasagiline tablets in healthy Chinese subjects under fasting and fed conditions.Methods: An open, randomized, single-dose, double-cycle, two-sequence, self-crossover pharmacokinetic study in healthy Chinese subjects under fasting and high-fat postprandial conditions was performed. A total of 108 healthy subjects (36 in the fasting group and 72 in the postprandial group) were recruited. In each cycle of the study under both conditions, subjects received a single oral dose of 1 mg of a test or reference preparation of rasagiline tablets (1 mg each). A washout period of 3 days was observed. Blood samples were obtained up to 10 h post-intake. Primary endpoints were the BE of major pharmacokinetic parameters (AUC0–t and AUC0–∞) and the maximum observed serum concentration (Cmax). Secondary endpoints were safety parameters.Results: The 90% confidence interval (CI) of the geometric mean ratio (GMR) of the test drug vs. the reference drug for rasagiline was 94.16–105.35% for the AUC0–t under fasting conditions and 99.88–107.07% under postprandial conditions. The 90% CIs for the AUC0–∞ were 93.55–105.01% and 99.59–107.05% under fasting and postprandial conditions, respectively. The 90% CIs for the Cmax were 88.26–108.46% and 89.54–118.23% under fasting and postprandial conditions, respectively. The 90% CIs for the test/reference AUC ratio and Cmax ratio were within the acceptable range (0.80–1.25) for BE. In this BE study, there were no serious adverse events (AEs).Conclusion: BE between the test and the reference products was established in both fasting and postprandial conditions. The two formulations of rasagiline showed good tolerability and a similar safety profile.Clinical Trial Registration:chinaDrugtrials.org.cn, identifier CTR20181466.
Companies’ Health Technology Assessment Strategies and Practices in Australia, Canada, England, France, Germany, Italy and Spain: An Industry Metrics Study
Authors: Wang Ting , McAuslane Neil , Liberti Lawrence , Gardarsdottir Helga , Goettsch Wim , Leufkens Hubert 
Published: December 2020

Background:Health technology assessment (HTA) has increased in importance in supporting payer decision making by assessing the relative effectiveness and cost effectiveness of new medicines. Thus, pharmaceutical companies need to address the HTA requirements early during development to improve reimbursement outcomes. Currently, there is a lack of research to assess the impact of HTA on development and jurisdictional outcome from companies’ perspectives. This study aimed to assess companies’ HTA strategy and characterise HTA practice in seven jurisdictions.Methods:A multi-year, annual study collected information for individual products, focusing on development activities regarding inclusion of HTA requirements and selection of global comparators. The generation of local contextual information, submission strategies and predictability of HTA outcomes was examined jurisdictionally in Australia, Canada, England, France, Germany, Italy and Spain. The study questionnaire was built into a secure online data collection platform and data were provided annually by participating companies.Results:Data for 169 compounds were provided by nine international companies between 2014 and 2018. HTA requirements were implemented in evidence generation plan for 63% of products during development. Global comparators were accepted by HTA bodies for more than half of studied products; Spain showed the highest acceptance rate (85%). Companies took advantages of parallel process in Australia and Canada to shorten product rollout time. Australia demonstrated general consistency in HTA review time, and England had the longest variation (interquartile range, 216 days). Requirements for additional information after submission occurred at all HTA bodies. Germany and Italy showed the highest percentage of products being reimbursed as per regulatory label (80 and 68%, respectively). Canada was the most predictable jurisdiction, with the highest proportion of review outcome (90%) that met companies’ expectations.Conclusion:Companies are addressing HTA requirements during development for many products; however, they are challenged by varying requirements and practices and product success ultimately depends on how HTA organisations and payers assess added value in the context of the national healthcare systems. This ongoing study created a baseline to help capture fact-based changes for company HTA strategies and HTA body practices.
Physical Activity, Sedentary Behavior, Anxiety, and Pain Among Musicians in the United Kingdom
Authors: Matei Raluca , Ginsborg Jane 
Published: December 2020

Context and AimsAlthough some exercise-based interventions have been associated with lower levels of pain and performance-related musculoskeletal disorders (PRMDs) among musicians, the evidence is still mixed. Furthermore, little is known about musicians’ general engagement in physical activity (PA), their knowledge of PA guidelines, or the relevant training they receive on pain prevention and the sources of such training. Similarly, little is known about the relationship between PA and PRMDs and other risk factors for PRMDs.MethodsFollowing a cross-sectional correlational study design, both standardized andad hocmeasurements were used to investigate self-reported PA [International Physical Activity Questionnaire – Short Form (IPAQ-SF)], knowledge of PA guidelines, and barriers to engaging in PA [Centers for Disease Control (CDC); Determinants of Physical Activity Questionnaire (DPAQ)]; sedentary behavior [Sedentary Behavior Questionnaire (SBQ)]; pain [36-Item Short Form Survey Instrument (SF-36)] and PRMDs (frequency and severity); reported physical exertion (RPE); anxiety [Hospital Anxiety and Depression Scale (HADS)]; practice behaviors (e.g., practice time; taking breaks frequency; warming up); and relevant training among conservatoire students in the United Kingdom. The entire set of questionnaires was administered both online and via hard copies between June 2017 and April 2018.ResultsDemographic information was obtained from 111 respondents, mostly undergraduate students (UGs) from seven conservatoires. They reported high levels of engagement in PA, despite poor knowledge of PA guidelines. Teachers were the most frequently mentioned source of pain prevention information (by 43% of respondents), and 62% agreed that they had received advice on why they should engage in cardio PA. Sedentary behavior was comparable to normative data. Levels of bodily pain and PRMDs were low, but 43% showed “abnormal” clinical anxiety and found playing their instruments “somewhat hard” (RPE) on average. Bodily pain interfering with practice and performance was positively correlated with frequency and severity of PRMDs, anxiety, and RPE. Frequency and severity of PRMDs were also associated with sedentary behavior at the weekend. Anxiety was associated with RPE. No association was found between PA and PRMDs.ConclusionThe relationship between PA and PRMDs and pain remains unclear and needs further investigation. While health education needs to be improved, other pathways may need to be taken. Given the high levels of anxiety, the ideology of Western classical music itself may need to be challenged.
Testing the Treatment Integrity of the Managing Cancer and Living Meaningfully Psychotherapeutic Intervention for Patients With Advanced Cancer
Authors: Koranyi Susan , Philipp Rebecca , Quintero Garzón Leonhard , Scheffold Katharina , Schulz-Kindermann Frank , Härter Martin , Rodin Gary , Mehnert-Theuerkauf Anja 
Published: December 2020

IntroductionThe Managing Cancer and Living Meaningfully (CALM) therapy for patients with advanced cancer was tested against a supportive psycho-oncological counseling intervention (SPI) in a randomized controlled trial (RCT). We investigated whether CALM was delivered as intended (therapists’ adherence); whether CALM therapists with less experience in psycho-oncological care show higher adherence scores; and whether potential overlapping treatment elements between CALM and SPI can be identified (treatment differentiation).MethodsTwo trained and blinded raters assessed on 19 items four subscales of the Treatment Integrity Scale covering treatment domains of CALM (SC: Symptom Management and Communication with Health Care Providers; CSR: Changes in Self and Relationship with Others; SMP: Spiritual Well-being and Sense of Meaning and Purpose; FHM: Preparing for the Future, Sustaining Hope and Facing Mortality). A random sample of 150 audio recordings (75 CALM, 75 SPI) were rated on a three-point Likert scale with 1 = “adherent to some extent,” 2 = “adherent to a sufficient extent,” 3 = “very adherent.”ResultsAll 19 treatment elements were applied, but in various frequencies. CALM therapists most frequently explored symptoms and/or relationship to health care providers (SC_1: n_applied = 62; 83%) and allowed expression of sadness and anxiety about the progression of disease (FHM_2: n_applied = 62; 83%). The exploration of CALM treatment element SC_1 was most frequently implemented in a satisfactory or excellent manner (n_sufficient or very adherent = 34; 45%), whereas the treatment element SMP_4: Therapist promotes acknowledgment that some life goals may no longer be achievable (n_sufficient or very adherent = 0; 0%) was not implemented in a satisfactory manner. In terms of treatment differentiation, no treatment elements could be identified which were applied significantly more often by CALM therapists than by SPI therapists.ConclusionResults verify the application of CALM treatment domains. However, CALM therapists’ adherence scores indicated manual deviations. Furthermore, raters were not able to significantly distinguish CALM from SPI, implying that overlapping treatment elements were delivered to patients.