bluuebunny/crossref_metadata_2025_split huggingface dataset:
A multicenter, open-label, randomized, proof-of-concept phase ii clinical trial to Assess the efficacy and safety of icatibant in patients infected with sars-cov-2 (covid-19) And admitted to hospital units without invasive mechanical ventilation. StudyProtocol (icat-covid)
Authors: González Aurema Otero , Malchair Pierre , Giol Jordi , Solanich Xavier , Carnaval Thiago , Fernández-Nistal Alonso , Sánchez-Gabriel Ana , Montoto Carmen , Lleonart Ramon , Videla Sebastian 
Published: October 2021

Abstract
Background: COVID-19 has quickly become a global pandemic with a substantial number of deaths and a substantial burden for healthcare systems worldwide. Although most cases are paucisymptomatic and limited to the viral infection related symptoms, some patients evolve to a second phase, with an impaired inflammatory response (cytokine storm) that may lead to acute respiratory distress syndrome and death. This is thought to be caused by an increased bradykinin synthesis. Methods: ICAT-COVID is a multicenter, randomized, open-label, proof-of-concept phase II clinical trial assessing the clinical efficacy and safety of adding Icatibant on the standard of care in patients hospitalized with COVID-19 without invasive mechanical ventilation. Patients hospitalized with a confirmed COVID-19 pneumonia diagnosis (RT-PCR or antigen test ≤ 10 days prior to randomization, and radiographic evidence of pulmonary infiltrates), rated ‘4’ or ‘5’ on the WHO’s clinical status scale are eligible. Patients will be randomized on a 1:1 ratio to either standard of care-plus-Icatibant (experimental group) or to standard of care alone (control group). The experimental group will receive 30 mg of Icatibant subcutaneously 3 times a day for 3 days (for a total of 9 doses). The expected sample size is of 120 patients (60 per group) gathered from 2 centers in Spain. Primary outcomes are Icatibant’s efficacy and safety. The main efficacy outcome is the number of patients reaching grades ‘2’ or ‘1’ on the WHO Scale within 10 days of treatment start. Among the secondary outcomes are ‘long-term efficacy’: number of patients discharged who do not present any COVID-19-related relapse or comorbidity up until 28 days after discharging, and mortality. Discussion: Icatibant, a bradykinin type 2 receptor antagonist with proven effectiveness and safety against hereditary angioedema attacks, may be beneficial for COVID-19 patients by inhibiting bradykinin’s action on endothelial cells and by inhibiting the SARS-CoV-2 M protease. Our working hypothesis is that treatment with Standard of Care-plus-Icatibant is effective and safe to treat patients infected with SARS-CoV-2 admitted to hospital for pneumonia without invasive mechanical ventilation.Trial registration: EudraCT: 2020-002166-13; ClinicalTrials.gov: NCT04978051
Double-blind Placebo-controlled Randomized Clinical Trial to Assess the Efficacy of Montelukast in Mild to Moderate Respiratory Symptoms of Patients With Long COVID E-SPERANZA COVID PROJECT Study Protocol
Authors: Mera-Cordero Francisco , Monne Sara Bonet , Ortega Jesús Almeda , García-Sangenís Ana , Puèrtolas Oriol Cunillera , Contreras-Martos Sara , Muñoz Gemma Alvarez , Escolà Ramon Monfà , Joué Marina Balanzó , Pedrós Rosa Morros , Salvador-Gonzalez Betlem 
Published: October 2021

Abstract
BackgroundThe coronavirus disease-2019 (COVID-19) pandemic continues to affect the globe. After eighteen months of the SARS-CoV-2 emergence, clinicians have clearly defined a subgroup of patients with lasting, disabling symptoms. While big strides have been made in understanding the acute phase of SARS-CoV-2 infection, the pathophysiology of long COVID is still largely unknown and evidence-based, effective treatments for this condition remain unavailable. ObjectivesTo evaluate the efficacy of 10 mg oral montelukast every 24 hours versus placebo in improving quality of life associated with mild to moderate respiratory symptoms in patients with long COVID as measured with the COPD Assessment Test (CAT) questionnaire. The secondary objectives will evaluate the effect of montelukast versus placebo on improving: exercise capacity; COVID-19 symptoms (asthenia, headache, mental confusion or brain fog, ageusia, and anosmia); oxygen desaturation during exertion; functional status; and mortality. Methods and analysisPhase III, randomized, double-blind clinical trial. We will include 18 to 80 year-old patients with SARS-CoV-2 infection and mild to moderate respiratory symptoms lasting more than 4 weeks. Participants will be randomly allocated in a 1:1 ratio to the intervention (experimental treatment with 10 mg/day montelukast) or the control group (placebo group), during a 28-day treatment. Follow up will finish 56 days after start of treatment. The primary outcome will be health-related quality of life associated with respiratory symptoms according to the COPD Assessment Test 4 weeks after starting treatment. Secondary outcomes a) Exercise capacity and oxygen saturation (1Min Sit-to-Stand test); b) Post-COVID-19 Functional Status scale; c) Other symptoms: asthenia, headache, mental confusion (brain fog), ageusia and anosmia (Likert scale); d) Use of healthcare resources; e) Mortality; f) Sick leave duration in days g) Side effects of montelukast. Ethics and disseminationThis study has been approved by the Clinical Research Ethics Committee of the IDIAPJGol (reference number 21/091-C). The trial results will be published in open access, peer-reviewed journals and explained in webinars to increase awareness and understanding about long COVID among primary health professionals. Trial registrationClinicalTrials.gov Identifier: NCT04695704 first posted on January, 5, 2021. EudraCT number 2021-000605-24). Prospectively registered.
Synthesis and Biological Evaluation of Xanthone Derivatives as Anti-Cancer Agents Targeting Topoisomerase II and DNA
Authors: Song Yali , Zhu Xinyue , Yang Kan , Feng Siran , Zhang Yiwen , Dong Jinjiao , Liu Zhenming , Qiao Xiaoqiang 
Published: October 2021

Abstract
Topoisomerase is one of the most important targets of anticancer drugs. In order to develop effective and low-toxic topoisomerase inhibitors, a series of xanthone derivatives have been designed and synthesized using the principles of skeleton transition. In vitro growth inhibition experiments of human breast cancer(MCF-7), gastric cancer (MGC-803), and cervical cancer(Hela) cell lines were used to evaluate the compound's anti-tumor cell proliferation activity. Most of the compounds showed anti-tumor growth activity, and also showed low toxicity to human normal cells L929. In the enzyme activity inhibition experiment, compounds 7d and 8d showed the best inhibitory activity. The DNA binding studies disclosed that the most potent compounds 7d and 8d can intercalate into DNA, induce apoptosis in MGC-803 cells and arrested at G2/M phase. Molecular docking showed that compounds 7d and 8d could bind with topoisomerase II and DNA through hydrogen bonds and π-stacking interactions.
Effect of Flexible Half-dose Gonadotropin-releasing Hormone Antagonist Protocol on in Vitro Fertilization Outcome in Predicted Normal Responder: A Study Protocol for a Multicentered, Randomized, Non-inferiority, Parallel Controlled Trial
Authors: Ma Ying-Jie , Song Jing-Yan , Li Meng-Yao , Sun Zhengao 
Published: October 2021

Abstract
BackgroundGonadotropin-releasing hormone antagonists (GnRH-ant) are widely used in current in vitro fertilization-embryo transfer (IVF-ET), however, whether the lowest daily dose of GnRH-ant is individualized remains unknown. Due to the negative effect of GnRH-ant on endometrial receptivity, lessening the amount of GnRH-antagonists used during controlled ovarian stimulation may be helpful for embryo implantation. As such, a randomized controlled study is essential to validate the feasibility and efficacy of daily GnRH-ant dose reduction to 0.125 mg geared towards providing scientific evidence for guidance in clinical practice.MethodsIn total, 620 infertile women undergoing in vitro fertilization will be enrolled in the multicentered, randomized, parallel controlled trial. Based on a computer-generated random list, they will be randomly and equally subdivided into half-dose GnRH-ant group or conventional-dose GnRH-ant group. The primary outcome is ongoing pregnancy i.e., intrauterine pregnancy diagnosed by pelvic ultrasonography at more than 12 weeks of gestation accompanied by normal fetal heartbeats. Secondary outcomes include cycle cancellation, premature luteinizing hormone surge, positive pregnancy, embryo implantation rate, clinical pregnancy, early spontaneous abortion, and live birth. The intention-to-treat and per protocol analyses will be used to initially analyze the difference in ongoing pregnancy rate between the two groups, while the multiple imputation method was used to handle missing values in the data.DiscussionAt present, no randomized controlled trials (RCTs) have been performed on the use of the half-dose GnRH-ant protocol (0.125mg/d) to improve reproductive outcomes of IVF-ET in predicted normal responder, compared to conventional-dose GnRH-ant protocol (0.25mg/d). Half-dose GnRH-ant protocol might provide a suitable clinical solution for predicted normal responder undergoing IVF treatment. Thus, it is critical to conduct a well-designed RCT to evaluate the impact of a half-dose GnRH-ant protocol on the reproductive outcomes of IVF-ET in predicted normal responder.Trial registrationThis study was registered in the Chinese Clinical Trials Registry Platform on August 29, 2020. (chictr.org.cn; identifier: ChiCTR2000037629).
INFERR-Iron Infusion in Haemodialysis Study: INtravenous Iron Polymaltose for First Nations Patients With High FERRitin Levels On Haemodialysis A Protocol for a Prospective Open-Label Blinded Endpoint Randomised Controlled Trial
Authors: William Majoni Sandawana , Nelson Jane , Germaine Darren , Hoppo Libby , Long Stephanie , Divakaran Shilpa , Turner Brandon , Graham Jessica , Cherian Sajiv , Pawar Basant , Rathnayake Geetha , Heron Bianca , Maple-Brown Louise , Batey Robert , Morris Peter , Davies Jane , Fernandes David Kiran , Sundaram Madhivanan , Abeyaratne Asanga , Wong Yun Hui Sheryl , Lawton Paul D , Taylor Sean , Barzi Federica , Cass Alan 
Published: October 2021

Abstract
BackgroundThe effectiveness of erythropoiesis stimulating agents, which are the main stay of managing anaemia of chronic kidney disease (CKD) is largely dependent on adequate body iron stores. The iron stores are determined by the levels of serum ferritin concentration and transferrin saturation. These two surrogate markers of iron stores are used to guide iron replacement therapy. Most Aboriginal and/or Torres Islander Australians of the Northern Territory (herein respectively referred to as First Nation Australians) with end stage kidney disease have ferritin levels higher than current guideline recommendations for iron therapy. There is no clear evidence to guide safe and effective treatment with iron in these patients. We aim to assess the impact of intravenous iron treatment on all-cause death and hospitalisation with a principal diagnosis of all-cause infection in First Nation patients on haemodialysis with anaemia, high ferritin levels and low transferrin saturationMethodsIn a prospective open-label blinded endpoint randomised controlled trial, a total 576 participants on maintenance haemodialysis with high ferritin (>700µg/L and ≤2000µg/L) and low transferrin saturation (<40%) from 7 renal units across the Northern Territory of Australia will be randomised 1:1 to receive intravenous iron polymaltose 400mg once monthly (200mg during 2 consecutive haemodialysis sessions) (Arm A) or no IV iron treatment (standard treatment) (Arm B). Rescue therapy will be administered when the ferritin levels fall below 700µg/L or when clinically indicated. The primary outcome will be the differences between the two-study arms in the risk of hospitalisation with all-cause infection or death. An economic analysis and several secondary and tertiary outcomes analyses will also be performed.DiscussionThe INFERR clinical trial will address significant uncertainty on the safety and efficacy of iron therapy in First Nation Australians with CKD with hyperferritinaemia and evidence of iron deficiency. This will hopefully lead to the development of evidence-based guidelines. It will also provide the opportunity to explore the causes of hyperferritinaemia in First Nation Australians. Trial registrationThis trial is registered with The Australian New Zealand Clinical Trials Registry (ANZCTR): ACTRN12620000705987; Registered 29 June 2020https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=378517
Dexmedetomidine Improved One-lung Ventilation-induced Cognitive Dysfunction in Rats
Authors: LI Mengyun , JIN Zhe , ZHAN Jia , WANG Yanlin , CHEN Kai 
Published: October 2021

Abstract
Background: One-lung ventilation (OLV) is widely used in thoracic surgery. However, OLV may also increase CERO2 and aggravate delayed cognitive recovery. Here, we aimed to investigate the effect of dexmedetomidine (DEX) on cognitive function in rats undergoing OLV. Methods: Sprague-Dawley rats were randomly divided into two-lung ventilation (TLV) group, OLV group and OLV treated with DEX group. Group DEX received 25 μg/kg DEX i.p. 30 min before induction. After mechanical ventilation (MV), Morris water maze (MWM) test was carried out to examine spatial memory function. Western blotting was used to detect pERK1/2, pCREB, Bcl-2 and BAX in hippocampal tissues. Transmission electron microscopy (TEM) was used to observe the hippocampal CA1 region. Results: Post-MV, compared with group OLV, group DEX showed increases in percentage of target quadrant time (P<0.05), platform crossings (P<0.05), a reduction in CERO2 (P<0.05), and pERK1/2, pCREB, and Bcl-2 significantly increased (P<0.01 or P<0.05), while BAX significantly decreased (P<0.01), besides, a less damaged synaptic structure was observed in group DEX. Conclusions: DEX improved post-MV cognitive function in rats undergoing OLV, reduced cerebral oxygen consumption, protected synaptic structure and upregulated ERK1/2-CREB anti-apoptotic signaling pathway in hippocampal CA1 region.
Quantitative Weathering Assessment of Rock Slope using CIELAB Color Space and Image Analysis Technique
Authors: Razali Mazlina , Jamal Muhd Herman , Ismail Mohd Ashraf Mohamad , Yusoff Intan Norsheira , Nagendran Sharan Kumar , Zainal Zuraini , Zainuddin Nurul Eilmy , Tobe Hayato , Miyoshi Takako , Date Kensuke , Yokota Yasuhiro 
Published: October 2021

Abstract
Quantitative weathering assessment using color changes is one of the new tools for slope stability assessment. In many other engineering field, CIELAB color space and image analytical tools have aided in enhancing the conventional method or inaccuracy due to the subjective and qualitative nature of visual assessment. This study focuses on the granitic rock slope surface assessment because of the predominant rock formation of granite in Malaysia. The 3D model of the rock slope was analyzed to extract the geological planes using compass plugin in Cloud Compare software and verified by manual compass mapping via scanline survey. Findings show that the a* and b* values increased with an increase in weathering results. This study focuses on the 50 points of measurement of rock slope and indicated a positive correlation of a* and b* with R2=0.9027. The image analysis result of the rock slope shows that major zoning (74%) is susceptible to failure due to structural control whilst another 26% are controlled by significant weathering in the grade IV-VI. This outcome is strongly verified via a geomechanical test, geological structure, and mineralogical assessment. The aforementioned mechanism is recommended in any geotechnical and technical purpose in enhancing the method of weathering assessment because image analysis provides reliable measurements in addition to the manual visual inspection.
Peroxymonosulfate Activation by Co-Doped Magnetic Mn3O4 for Degradation of Oxytetracycline in Water
Authors: He Liyan , Li Hui , Wang Jianzhi , Gao Qifei , Li Xiaoli 
Published: October 2021

Abstract
Co-doped magnetic Mn3O4 was synthesized by the solvothermal method and adopted as an effective catalyst for the degradation of oxytetracycline (OTC) in water. Synergistic interactions between Co-Mn3O4 and Fe3O4 not only resulted in the enhanced catalytic activity through the activation of peroxymonosulfate (PMS) to degrade OTC, but also made Fe3O4/Co-Mn3O4 easy to be separated and recovered from aqueous solution. 94.2% of OTC could be degraded within 60 min at an initial OTC concentration of 10 mg/L, catalyst dosage of 0.2 g/L and PMS concentration of 10 mM, the high efficiency of which was achieved in a wider pH range of 3.0-10.0. The free radical quenching experiments showed that O2•- radicals and 1O2 played the main role in the degradation process. Co3+, Co2+, Fe2+, Fe3+, Mn4+, Mn3+ and Mn2+ on Fe3O4/Co-Mn3O4 were identified as catalytic sites based on XPS analysis. Eventually, the intermediates of OTC degradation were examined and the possible decomposition pathways were proposed. The excellent catalytic performance of Fe3O4/Co-Mn3O4 not only came from the fact that the large specific surface area could provide abundant active sites for the activation of PMS, but also the charged redistribution among atoms to accelerate the reduction of metal ions. The high degradation efficiency of OTC in actual water samples indicated that Fe3O4/Co-Mn3O4 had good potential for practical application.
Unloading Effect of the Shear Resistance of Rock Joints
Authors: Yang Jianan , Wang Shuo , Wang Qiongting , Xing Wenzheng , Fan Pengxian 
Published: October 2021

Abstract
To investigate the stress path dependent of rock joints, a comparative experimental study was conducted using cement mortar replicas of artificially split rock joints. In total, 32 replicas were casted and divided into four groups by joint roughness coefficient (JRC). The effects of morphologic characteristics, normal stress levels and stress paths on the shear strength of joints were investigated through tangential loading tests and normal unloading tests. The comparative analysis on the test results indicated that the shear resistance has a distinct unloading effect. The variation trend of shear/normal stress ratio against the normal stress and JRC of the two test conditions were identical. However, under low normal-stress condition, the stress ratio of the joints under normal unloading stress is the higher one; while under higher normal stress, the relationship becomes converse. Compared to that of the tangential loading condition, shear/normal stress ratio of the unloading stress path reduces rapidly as the increasing of normal stress, and the influence of the morphology is masked under lower normal stress. The comparative study revealed a previously unknown unloading effect on the mechanical behavior of rock joints and will aid the estimation of the rock joints’ stability in a complex stress environment.
Toxoplasma gondii is not an important contributor to poor reproductive performance of primiparous ewes from southern Australia: a prospective cohort study
Authors: Clune Thomas , Lockwood Amy , Hancock Serina , Thompson Andrew , Bruce Mieghan , Beetson Sue , Campbell Angus , Glanville Elsa , Brookes Daniel , Trengove Colin , O’Handley Ryan , Jacobson Caroline 
Published: October 2021

Abstract
Background
Toxoplasma gondii causes reproductive losses in sheep worldwide, including Australia. The reproductive performance of primiparous ewes is typically lower than for mature multiparous ewes, and younger ewes are more likely to be immunologically naïve and therefore more susceptible to reproductive disease if T. gondii infection occurs during pregnancy. The aim of this study was to assess the impact of infection with T. gondii on the reproductive performance of primiparous ewes in southern Australia using a prospective cohort study. This will inform the need for targeted control strategies for T. gondii in Australian sheep.
Results
Toxoplasma gondii seropositivity using indirect ELISA was detected at 16/28 farms located across southern Australia. Apparent seroprevalence was lower in primiparous ewes (1.1%, 95% confidence interval (CI) 0.6, 1.8) compared to mature multiparous ewes (8.1%, 95% CI 6.0, 10.5; P < 0.001). Toxoplasma gondii seroconversion during the gestation and lambing period was confirmed for 11/1097 (1.0%, 95% CI 0.5, 1.7) of pregnant primiparous ewes that failed to raise a lamb, and 1/161 (0.6%, 95% CI 0.1, 2.9) primiparous ewes with confirmed abortion. Toxoplasma gondii was not detected using qPCR in tissue samples from aborted or stillborn lambs (n = 35) from a subset of six farms.
Conclusions
Low seroprevalence and low incidence of seroconversion during gestation suggests that toxoplasmosis was not an important contributor to reproductive losses in primiparous ewes on farms located over a wide geographical area in southern Australia.
Do sustainable palliative single fraction radiotherapy practices proliferate or perish 2 years after a knowledge translation campaign?
Authors: Shahhat Shaheer , Hanumanthappa Nikesh , Chung Youn Tae , Beck James , Koul Rashmi , Bashir Bashir , Cooke Andrew , Dubey Arbind , Butler Jim , Nashed Maged , Hunter William , Rathod Shrinivas , Ong Aldrich , Tran Kim , Kim Julian Oliver 
Published: October 2021

Abstract
BACKGROUND

There is a paucity of data regarding the time-dependent effects of knowledge translation (KT) campaign derived Radiation Oncologist (RO) prescription behaviour. In early 2017, the XXXX and XXXX undertook a comprehensive KT campaign to improve utilization of single fraction radiotherapy (SFRT) over multiple fraction radiotherapy (MFRT) in accordance with clinical guidelines for palliative management of bone metastases. The campaign significantly increased short-term SFRT utilization. We assess the time-dependent effects of KT-derived SFRT utilization 12-24 months removed from the KT campaign in a Canadian Provincial Cancer Program.
METHODS

This retrospective, population-based cohort study identified all patients receiving palliative radiotherapy for bone metastases in XXXX from 1 Jan 2018 to 31 Dec 2018 using provincial radiotherapy databases. Baseline characteristics were tabulated by fractionation schedule. The proportion of patients treated with SFRT in 2018 was compared to 2017 levels overall and by prescribing RO. Logistic regression analyses identified risk factors associated with MFRT receipt.
RESULTS

In 2018, 1,008 patients received palliative radiotherapy for bone metastasis, of which 63.3% received SFRT, a small overall increase in SFRT use over 2017 (59.1%). However, 41.1% of ROs demonstrated year-over-year decreases in SFRT utilization, indicative of a time-dependent loss of SFRT prescription habits derived from KT.
CONCLUSION

Although SFRT use increased slightly overall in 2018, evidence of compliance fatigue was observed suggestive of a time-perishing property of RO prescription behaviours derived from KT methodologies. These findings highlight the need for additional longitudinal KT reinforcement practices in the years following KT campaigns.