bluuebunny/crossref_metadata_2025_split huggingface dataset:
Safety and Efficacy of Intermittent Presumptive Treatment with Sulfadoxine-Pyrimethamine Using Rapid Diagnostic Test Screening and Treatment with Dihydroartemisinin-Piperaquine at the First Antenatal Care Visit (IPTp-SP+): Study Protocol for a Randomized Controlled Trial
Authors: Kabuya Jean-Bertin Bukasa , Ippolito Matthew M. , Sikalima Jay , Tende Clifford , Champo Davies , Mwakazanga David , Young Anna Marie P. , Mulenga Modest , Chongwe Gershom , Manyando Christine 
Published: June 2021

Abstract
Background: Intermittent preventive treatment in pregnancy (IPTp) with sulfadoxine-pyrimethamine (SP) is recommended by the World Health Organization for the prevention of malaria in pregnancy (MIP)-associated adverse outcomes in high burden areas. However, the efficacy of IPTp-SP has decreased in step with increasing parasite drug resistance. Suitable alternative strategies are needed. Methods: This is a protocol for a phase IIIb open-label, two-armed randomized controlled superiority trial to assess the safety and efficacy of a hybrid approach to IPTp combining screening and treatment with dihydroartemisinin-piperaquine (DP) to the current IPTp-SP regimen at the first antenatal care clinic visit. Pregnant women without HIV infection and without signs or symptoms of malaria will be randomized to either standard IPTp-SP or hybrid IPTp-SP plus screening and treatment (IPTp-SP+). In the IPTp-SP+ arm, participants who screen positive by rapid diagnostic test for P. falciparum will be treated with DP at the first antenatal visit while those who screen negative will receive SP per current guidelines. All participants will be administered SP on days 35 and 63 and will be actively followed biweekly up to day 63 and then monthly until delivery. Infants will be followed until 1 year after delivery. The primary endpoint is incident PCR-confirmed MIP at day 42. Secondary endpoints include incident MIP at other time points, placental malaria, congenital malaria, hemoglobin trends, birth outcomes, and incidence of adverse events in infants up to the first birthday.Discussion: A hybrid approach to IPTp that combines screening and treatment with an artemisinin-based combination therapy at the first visit with standard IPTp-SP is hypothesized to confer added benefit over IPTp-SP alone in a high malaria transmission area with prevalent SP resistant parasites. Trial Registration {2a and 2b}.Pan African Clinical Trials Registry, ID: PACTR201905721140808. Registered on May 20, 2019 – Retrospectively, http://www.pactr.org
Bibliometric study of ‘overviews of systematic reviews’ of health interventions: evaluation of prevalence, citation and impact factor
Authors: Lunny Carole , Neelakant Trish , Chen Alyssa , Shinger Gavindeep , Stevens Adrienne , Tasnim Sara , Sadeghipouya Shadi , Adams Stephen , Zheng Yi Wen , Lin Lester , Yang Pei Hsuan , Dosanjh Manpreet , Ngsee Peter , Ellis Ursula , Shea Beverley J. , Reid Emma K. , Wright James M. 
Published: June 2021

Abstract
Background: Overviews synthesising the results of multiple systematic reviews help inform evidence-based clinical practice. In this first of two companion papers, we evaluate the bibliometrics of overviews, including their prevalence and factors affecting citation rates and journal impact factor.Methods: We searched MEDLINE, Epistemonikos and Cochrane databases. We included overviews that: (a) synthesised reviews, (b) conducted a systematic search, (c) had a methods section, and (d) examined a healthcare intervention. Multivariate regression was conducted to determine the association between citation density, impact factor and 6 predictor variables. Results: We found 1218 overviews published from 2000 to 2020; the majority (73%) were published in the most recent 5-year period. We extracted a selection of these overviews (n=541; 44%) dated from 2000 to 2018. The 541 overviews were published in 307 journals; Cochrane Database (8%), PLOS ONE (3%) and Sao Paulo Medical Journal (2%) were the most prevalent. The majority (70%) were published in journals with impact factors between 0.05 and 3.97. We found a mean citation count of 10 overviews per year, published in journals with a mean impact factor of 4.4. In multivariate analysis, overviews with a high number of citations and impact factors had more authors, larger sample sizes, were open access and reported the funding source. Conclusions: An 8-fold increase in the number of overviews was found between 2009 and 2020. We identified 332 overviews published in 2020, which is equivalent to 1 overview published per day. Overviews perform above average for the journals in which they publish.
Vibration Therapy as an Intervention for Enhancing Trochanteric Hip Fracture Healing in Elderly Patients: A Randomized Double-Blinded, Placebo-Controlled Clinical Trial
Authors: WONG Ronald Man Yeung , CHOW Simon Kwoon Ho , TANG Ning , CHUNG Yik Lok , GRIFFITH James , LIU Wing Hong , NG Raymond Wai Kit , TSO Chi Yin , Cheung Wing-Hoi 
Published: June 2021

Abstract
BackgroundThere are more than 300,000 hip fractures yearly in the US with mortality rates of 20% within 1 year. The treatment of osteoporotic fractures is a major challenge as bone quality is poor, and healing is expected to delay due to the impaired healing properties with respect to bone formation, angiogenesis and mineralization. Enhancement of osteoporotic fracture healing and function is therefore critical as a major goal in modern fracture management. Previous pre-clinical studies have shown that low-magnitude high-frequency vibration (LMHFV) accelerates osteoporotic fracture healing. The objective of this study is to investigate the effect of LMHFV on accelerating trochanteric hip fracture healing and functional recovery.MethodsThis is a randomized, double-blinded, placebo-controlled clinical trial to evaluate the effect of LMHFV in accelerating trochanteric hip fracture healing. All fractures undergo cephalomedullary nail fixation. The primary outcome of this study is time to fracture healing by X-ray. Computed tomography (CT) and Dual-energy X-ray absorptiometry (DXA) will also be performed. Blood circulation at the fracture site will be assessed by dynamic perfusion magnetic resonance (MR). Clinical results include functional recovery by muscle strength, timed up and go test (TUG), quality of life questionnaire (SF-36), balancing, falls, and mortality. DiscussionPrevious animal studies have demonstrated LMHFV to improve both normal and osteoporotic fracture healing by accelerating callus formation and mineralization. The mechanical stimulation stimulates angiogenesis by significantly enhancing vascular volume and blood flow velocity. This is the first study to translate LMHFV to enhancing hip fracture healing clinically. Positive results would provide a huge impact in the recovery of hip fracture patients and save healthcare costs. Trial registrationClinicaltrials.gov, NCT04063891. Registered on August 21, 2019
Effect of Omega-3 Fatty Acids on TH1/TH2 Polarization in Individuals with High Exposure To Particulate Matter ≤ 2.5 μm (PM2.5): A Randomized, Double-Blind, Placebo-Controlled Clinical Study
Authors: Wang Zhenxing , Wang Xiaomin , Li Shuiqin , Wu Yongcan , Huang Demei , Pei Caixia , Wang Yilan , Shi Shihua , Wang Fei 
Published: June 2021

Abstract
Background: Long-term exposure to high concentrations of PM2.5 may cause immune system dysfunction and damage to the respiratory and cardiovascular systems. PM2.5 may cause CD4 + T helper cells to polarize toward TH1 or TH2 cell types, which may be associated with the onset and progression of many human diseases. Recent studies have shown that omega-3 fatty acids can regulate human immune function and reduce physiological damage caused by air pollution; however, only limited research has examined the therapeutic effects of omega-3 fatty acids on subjects with high exposure to PM2.5 in mass transit systems such as subways.Methods: This study was designed as a prospective, randomized, double-blinded (to participants and researchers), placebo-controlled trial. The research plan is to recruit 120 qualified volunteers in the Chengdu Metro Station. All participants will receive omega-3 fatty acids or placebo for 8 weeks. The primary outcomes will be changes in the TH1/TH2 cell polarization index and changes in serum cytokine concentrations. Secondary outcomes will be changes in early indicators of atherosclerosis, pulmonary function, COOP/WONCA charts, and scores on the Short Form 36 Health Survey for quality of life. Results will be analyzed to evaluate differences in clinical efficacy between the two groups. A six-month follow-up period will be used to assess the long-term value of omega-3 fatty acids for respiratory and cardiovascular disease end-points.Disscussion: We will explore the characteristics of TH1/TH2 cell polarization index in a population with high exposure to PM2.5. Omega-3 fatty acids and placebo will be compared in many ways to test the effect on people exposed to PM2.5 subway stations. This study is expected to provide reliable evidence to support the promotion of omega-3 fatty acids in clinical practice to protect individuals who are highly exposed to PM2.5.Trial registration: Chinese Clinical Trial Registry (ChiCTR2000038065). Registered on September 9, 2020.
Diet or Additional Supplement to Increase Potassium Intake: Protocol For An Adaptive Clinical Trial
Authors: Hiremath Swapnil , Fergusson Dean , Knoll Greg , Ramsay Tim , Kong Jennifer , Ruzicka Marcel 
Published: June 2021

Abstract
Background
High blood pressure is the leading cause of cardiovascular disease worldwide. The prevalence of high blood pressure is steadily rising, with the growing and ageing population. Many medicines are available to decrease blood pressures successfully, as well as many non-medical options, such as dietary changes and exercise. There is a marked preference amongst patients, reiterated in a Hypertension Canada report, for more research into methods for controlling blood pressure without medicines or to reduce the burden of taking many pills to control high blood pressure. Indeed, effective options do exist, especially with diet, specifically decreasing sodium and increasing potassium in diet. Current public health outreach mostly focusses on sodium intake, even as the potassium intake in diet remains low especially in the Western world. Excellent data exist in the published research reporting that increasing potassium intake, either as diet or even as supplements, reduces blood pressure and reduces risk of cardiovascular outcomes such as stroke. However, the advice most often provided is to ‘eat more fruits and vegetables’ which does not get translated into concrete change.
Methods
We propose to do a clinical trial in two stages, with an adaptive trial design. In the first stage, participants with high blood pressure and proven low potassium intake (measured on the basis of a 24 hour urine collection) will get individually tailored dietary advice, reinforced by weekly supportive phone/email support. If at 4 weeks, there has not been a desired increase in potassium intake, they will be prescribed an additional potassium supplement. Testing will be conducted again at 4 weeks post initiating the potassium supplement, to confirm the efficacy of the potassium supplement. Final measurements will be planned at 52 weeks to observe and measure the persistence of the effect of diet or additional supplement. Concurrent measurements of sodium intake, blood pressure, participant satisfaction, and safety measures will also be done.
Discussion
The results of the study would help determine the most effective method of increasing potassium intake, thus reducing blood pressure, need for blood pressure lowering medicines, at the same time potentially increasing participant satisfaction. The current guidelines recommend changes in diet, not supplement, to increase potassium intake, hence the two stage design will only add supplements if the most rigorous dietary advice does not work.
Trial registration:
This study has been registered on ClinicalTrials.gov identifier NCT03809884, registered on January 18, 2019. URL: https://clinicaltrials.gov/ct2/show/NCT03809884
LncRNA ASAP1-IT1 Enhances Cancer Cell Stemness via Regulating miR-509-3p/YAP1 Axis in NSCLC
Authors: Liu Yantao , Yang Yuping , Zhang Lingli , Lin Jiaqiang , Li Bin , Yang Min , Li Honghui , Chen Kangwu , Zhao Wei 
Published: June 2021

Abstract
Background: Non-small cell lung cancer (NSCLC) is a major cause of cancer-related death worldwide, and cancer stem cell is mainly responsible for the poor clinical outcome of NSCLC. Although previous reports indicated long noncoding RNAs (lncRNAs) play important roles in cancer stemness maintain, the underlying causes mechanisms remain is still mysterious. Our study aims to investigate the role of ASAP1 Intronic Transcript 1 (ASAP1-IT1) in cancer cell stemness of NSCLC. Methods: qRT-PCR analysis the expression of ASAP1-IT1 and microRNA-509-3p (miR-509-3p) in NSCLC tissues, cancer cells and spheres of cancer cells-derived cancer stem cells. Knockdown of ASAP1-IT1 or overexpression of miR-509-3p in NSCLC cells by infection or transfection. Sphere formation and colony formation detects NSCLC stem cell-like properties and tumor growth in vitro. Luciferase reporter assays, RNA immunoprecitation (RIP) and qRT-PCR assays analyzed the interaction between lncRNA and miRNA, qRT-PCR and Western blot detect ASAP1-IT1/miR-509-3p axis's regulation on the expression of regulated genes. NSCLC xenograft mice model validates ASAP1-IT1 role in NSCLC stemness and tumor growth in vivo. Results: ASAP1-IT1 was up-regulated in NSCLC tissues, cancer cells, and in spheres of A549-derived cancer stem cells. Downregulated ASAP1-IT1 or miR-509-3p significantly decreased cell colony formation and stem cell-like properties of A549-dereived stem cells with decreased expression of stem cell biomarkers SOX2, CD34, and CD133, and suppressing the expression of cell growth-related genes, Cyclin A1, Cyclin B1, and PCNA. Furthermore, knockdown of ASAP1-IT1 or overexpression of miR-509-3p repressed tumor growth in nude mice via reducing expression of tumorigenic genes. ASAP1-IT1 was found to interact with miR-509-3p. Moreover, overexpression of ASAP1-IT1 blocked miR-509-3p mediated regulation of stem cell-like properties, cell growth, and cell apoptosis of A549-dereived stem cells both in vitro and in vivo. Finally, the level of YAP1 was regulated by ASAP1-IT1 and miR-509-3p.Conclusions: YAP1-involved ASAP1-IT1/miR-509-3p axis promoted NSCLC progression by regulating cancer cell stemness，and targeting related signaling is a promising therapeutic strategy to overcome NSCLC stemness.
Efficacy and Safety of Xiaoyao Pills for Mild to Moderate Depression With Syndrome of Liver Stagnation and Spleen Deficiency: Study Protocol for a Randomized Controlled Trial
Authors: Xue Zhe , Huang Zhen , Cheng Shu-li , Wang Xi-hong , Zhou Xuan , Ma Qing-yu , Chen Jia-xu 
Published: June 2021

Abstract
Background: Depression is one of the most frequent and severe psychiatric conditions. Many chemical drugs to treat depression are associated with adverse reactions and have shortcomings. Traditional Chinese medicine is of great significance in the prevention and treatment of depression. Xiaoyao pills has achieved good results in clinical application, which has the advantages of quick effect and no obvious adverse reactions. The aim of our study is to evaluate the efficacy and safety of Xiaoyao pills on mild to moderate depression patients with syndrome of liver stagnation and spleen deficiency.Methods: This study is a multi-center, double-blinded, randomized and placebo-controlled clinical trial. A total of 108 participants will be assigned to three groups: Xiaoyao pill group taking Xiaoyao pills twice daily for 4 weeks, placebo group taking placebos twice daily for 4 weeks and normal group without taking any drug. The primary and secondary outcome measures are the Hamilton Depression Scale (HAMD) and Traditional Chinese Medicine (TCM) Syndrome Scale. The assessment is at baseline(before treatment initiation), 1 week, 2 weeks 4 weeks after the first treatment. Exploratory outcome is also assessed to explore the mechanism of Xiaoyao pills at baseline and 4 weeks.Discussion: The results from this study will provide clinical evidence on the efficacy and safety of Xiaoyao pills in patients with mild to moderate depression with syndrome of liver stagnation and spleen deficiency.Trial registration: International Standard Randomized Controlled Trial Number Register: ISRCTN12746343. Registered on September 25, 2020.
Fuzheng Xiaoliu granules reduce the 2-year recurrence rate of early-stage hepatitis B virus-related hepatocellular carcinoma after comprehensive minimally invasive surgery: a study protocol for a prospective, multicenter, central randomized, double-blind, placebo-controlled clinical trial
Authors: Chen Xinju , Ma Suping , Chen Xiaoqi , Hao Yaokun , Zhao Qing , Zhang Chuanlei , Wang Xinting , Zhao Qiang , Wang Lei , Zhao Wenxia , Ji Aiying 
Published: June 2021

Abstract
Background: Hepatitis B virus (HBV) infection is one of the most common risk factors for hepatocellular carcinoma (HCC). With the continuous improvement of minimally invasive treatment techniques such as transarterial chemoembolization (TACE) and radiofrequency ablation (RFA), comprehensive minimally invasive treatment (TACE & RFA) has been widely used in the treatment of early-stage (Barcelona Clinic Liver Cancer (BCLC) stage 0 and A) HCC and has good safety and clinical efficacy. However, recurrence and metastasis after comprehensive minimally invasive treatment are still key factors affecting the survival rate of patients. In recent years, Chinese medicine has highlighted its unique advantages in the adjuvant treatment of liver cancer surgery and minimally invasive treatment. Thus, this study aimed to evaluate the efficacy and safety of Fuzheng Xiaoliu granules (FZXLG) for treating early-stage HBV-related HCC after comprehensive minimally invasive treatment and to explore whether FZXLG can delay the progression of HBV-related HCC. Methods: This is a prospective, multicenter, central randomized, double-blind, placebo-controlled clinical trial. A total of 312 patients with early HBV-related HCC who underwent comprehensive minimally invasive treatment within 2 months were randomized in a 1:1 ratio into two groups: the experimental group and the control group. The experimental group will receive basic FZXLG plus Western medicine treatment, and the control group will receive basic FZXLG simulator plus Western medicine treatment. Each group will be treated for 1 year and followed-up for 1 year. The primary outcome measure is the 2-year recurrence rate of patients with early-stage HBV-related HCC after minimally invasive treatment. The secondary outcomes include (1) measurable active lesions, (2) alpha-fetoprotein (AFP), (3) immunological indicators, such as comparison of CD3+, CD4+, CD8+ absolute values, CD4+/CD8+ before and after the test, (4) hepatitis B virus quantity, and (5) Karnofsky functional status score. Discussion: These results will provide research data on the efficacy and safety of FZXLG for the treatment of early-stage HBV-related HCC after comprehensive minimally invasive treatment. These findings will also be based on laboratory indicators and adverse events for safety assessment to determine whether FZXLG can reduce the 2-year recurrence rate of HCC after minimally invasive surgery, which will provide reliable evidence for the clinical treatment of HCC.Trial registration: Chinese Clinical Trial Registry, ChiCTR1900022999. Registered on 5 May 2019.
Linking Industrial Point Sources to PFAS Contamination in Wells: Michigan Case Study
Authors: Schulz Katarina , Filbin Ryan , Silva Marcia R. , Klaper Rebecca , Boyer Tracy 
Published: June 2021

Abstract
In recent years, concern has grown over widespread environmental contamination of per- and polyfluoroalkyl substances (PFAS) in the environment and especially in drinking water. These manmade chemicals were first synthesized in the mid-20th century and contain thousands of individual species, some of which are still used today. A wide variety of industries use or have historically used PFAS in their products and processes. PFAS chemicals are recalcitrant by design and thus do not break down in the environment. Federal and state agencies have begun testing of drinking water and other media for PFAS in order to understand the extent of contamination and determine any necessary regulatory actions. Testing is expensive, however, and it would be beneficial to be able to prioritize wells for testing based on their likely vulnerability. This study presents a methodology for identifying locations of industrial sites likely to use PFAS, and uses Michigan’s robust well testing data alongside industry and environmental factors to identify any spatial relationships that can be used to help prioritize testing of wells.
Understanding And Restoring Dopaminergic Function In Fibromyalgia Patients Using A Mindfulness-Based Psychological Intervention: A [18F]-DOPA PET StudyStudy Protocol For The FIBRODOPA Study- A Randomized Controlled Trial
Authors: Ledermann Katharina , von Känel Roland , Berna-Renella Chantal , Sprott Haiko , Jenewein Josef , Garland Eric , Martin-Sölch Chantal 
Published: June 2021

Abstract
Background: (FM). Fibromyalgia (FM) is a very prevalent and debilitating chronic pain disorder that is difficult to treat. Mindfulness-based techniques are regarded as a very promising approach for the treatment of chronic pain and in particular FM. The Mindfulness-Oriented Recovery Enhancement (MORE) intervention, a mindfulness-based group intervention, has shown beneficial effects in opioid-treated chronic pain patients, including reduced pain severity, functional interference, and opioid dosing, by restoring neurophysiological and behavioral responses to reward. First evidence for a hypodopaminergic state and impaired reward processing in FM have been reported. However, little is known about its impact on dopamine (DA) function and in particular with regard to DA responses to monetary reward in FM. The aim of the present study protocol is to evaluate if MORE is able to restore the DA function in FM patients, in particular with regard to the DA responses to reward, and to reduce pain and mood complaints in FM.Methods/design: The present study is a multi-center RCT with 3 time points: before the intervention, after completion of the intervention and 3-months after completion of the intervention. Eighty FM patients will be randomly assigned to either the MORE intervention (N=40) or to a wait-list control group (N=40). Additionally a comparison group of healthy women (N=20) will be enrolled. The MORE intervention consists of eight 2-hour long group sessions administered weekly over a period of 8 weeks. Before and after the intervention, FM participants will undergo [18F] DOPA Positron Emission Tomography (PET) and functional MR imaging while performing a monetary reward task. The primary outcome will be endogeneous DA changes measured with [18F] DOPA PET at baseline, after the intervention (after 8 weeks for control group), and at 3 months’ follow-up. Secondary outcomes will be (1) clinical pain measures and FM symptoms using standardized clinical scales 2) functional brain changes 3) measures of negative and positive affect, stress and reward experience in daily life using the Experience Sampling method (ESM) 4) biological measures of stress including cortisol and alpha-amylase.Design: If the findings of this study confirm the effectiveness of MORE in restoring DA function, reducing pain and improving mood symptoms, MORE can be judged to be a promising means to improve quality of life in FM patients. The findings of this trial may inform health care providers about the potential use of the MORE intervention as a possible non-pharmacological intervention for FM.Trial registration: ClinicalTrials.gov NCT 04451564. Registered on 3 July 2020. The trial was prospectively registered.