bluuebunny/crossref_metadata_2025_split huggingface dataset:
Roles of hsa-miR-12462 and SLC9A1 in acute myeloid leukemia
Authors: Jia Yan , Liu Wei , Zhan Hui-En , Yi Xiao-Ping , Liang Hui , Zheng Qi-Li , Jiang Xin-Ya , Zhou Hai-Yan , Zhao Liang , Zhao Xie-Lan , Zeng Hui 
Published: July 2020

AbstractMicroRNAs (miRNAs) play important roles in cell proliferation, differentiation, and survival and may be useful for acute myeloid leukemia (AML) diagnosis and prognosis. In this study, we defined a novel miRNA, hsa-miR-12462, through small RNA sequencing of the bone marrow (BM) cells from 128 AML patients. Overexpression of hsa-miR-12462 in AML cells (U937 and HL-60) significantly decreased their growth rate when compared with those of the wild-type and MOCK controls. In a xenograft mouse model, tumor weight and size in the mice bearing the U937 cells with hsa-miR-12462 overexpression were significantly reduced when compared with those bearing the mock cells. The AML cells overexpressing hsa-miR-12462 had increased sensitivity to cytarabine chemotherapy. Combining the data from the MiRDB, an online microRNA database (http://mirdb.org), with the RNA-sequencing results, SLC9A1 was predicted to be one of the targets of hsa-miR-12462. hsa-miR-12462 was further confirmed to bind exclusively to the 3′UTR of SLC9A1 in U937 cells, leading to downregulation of SLC9A1. In summary, a higher level of hsa-miR-12462 in AML cells is associated with increased sensitivity to cytarabine chemotherapy via downregulation of SLC9A1.
Crosstalks between inflammasome and autophagy in cancer
Authors: Chung Chaeuk , Seo Wonhyoung , Silwal Prashanta , Jo Eun-Kyeong 
Published: July 2020

AbstractBoth inflammasomes and autophagy have important roles in the intracellular homeostasis, inflammation, and pathology; the dysregulation of these processes is often associated with the pathogenesis of numerous cancers. In addition, they can crosstalk with each other in multifaceted ways to influence various physiological and pathological responses, including cancer. Multiple molecular mechanisms connect the autophagy pathway to inflammasome activation and, through this, may influence the outcome of pro-tumor or anti-tumor responses depending on the cancer types, microenvironment, and the disease stage. In this review, we highlight the rapidly growing literature on the various mechanisms by which autophagy interacts with the inflammasome pathway, to encourage additional applications in the context of tumors. In addition, we provide insight into the mechanisms by which pathogen modulates the autophagy-inflammasome pathway to favor the infection-induced carcinogenesis. We also explore the challenges and opportunities of using multiple small molecules/agents to target the autophagy/inflammasome axis and their effects upon cancer treatment. Finally, we discuss the emerging clinical efforts assessing the potential usefulness of targeting approaches for either autophagy or inflammasome as anti-cancer strategies, although it remains underexplored in terms of their crosstalks.
A narrative review of estimands in drug development and regulatory evaluation: old wine in new barrels?
Authors: Mitroiu M. , Oude Rengerink K. , Teerenstra S. , Pétavy F. , Roes K. C. B. 
Published: July 2020

Abstract
Background
An estimand defines the target of estimation for a clinical trial through specification of the treatment, target population, variable, population-level summary and of the strategies for intercurrent events. A carefully defined estimand aligns the clinical trial design and analysis with the scientific question of interest and adequately accounts for so-called intercurrent events. The ICH E9(R1) addendum suggests five estimand strategies. We evaluated to what extent current practice in drug development and regulatory assessment fits in the estimand framework.

Methods
We systematically evaluated what estimands, especially what strategies for intercurrent events are advised in European Medicines Agency disease guidelines, used in sponsors’ trials and additionally requested by the European Medicines Agency in assessment dossiers. We selected four therapeutic areas: nervous system, oncology, cardiovascular diseases and respiratory diseases. For each, we evaluated all disease guidelines with approved drugs, the dossiers of the most recently approved drugs matching the guidelines and corresponding regulatory questions.

Results
Strategies for intercurrent events were present in 18 (53%) of 34 guidelines, in all 34 sponsor documentations and in 15 (44%) of 34 sets of regulatory questions. Treatment policy was advised in 13 (38%) guidelines and was applied in 9 corresponding sponsor documentations. Of these 9, it was the sole strategy in 4 cases and accompanied by another strategy in 5 cases. Hypothetical strategy was not advised in guidelines. However, it was the leading strategy applied in 25 (74%) sponsor documentations. Composite strategy was advised in 3 (9%) guidelines and applied accompanied by another strategy in 2 corresponding sponsor documentations. While on treatment strategy was not advised in guidelines, but was applied in 2 sponsor documentations. Principal stratum strategy was advised in 2 guidelines but not applied in corresponding sponsor documentations. Of the regulatory questions, treatment policy was present in 2 cases (6%), hypothetical in 6 cases (18%), composite in 6 cases (18%) and while on treatment in 1 case (3%).

Conclusions
Estimand attributes are present in guidelines, sponsor documentations and regulatory questions, but not described as estimands. Treatment policy was most often advised in guidelines, but hypothetical was the leading strategy applied in sponsor documentations. Thus, results indicate not a full concordance between the regulatory target of estimation and what is actually estimated. The lack of concordance was mostly due to limitations in collection of intercurrent events data to enable a treatment policy strategy. There is, therefore, a need to better define estimands at the design stage and throughout the applications dossiers and assessment reports.
Efficacy of brief dynamic interpersonal therapy in patients with major depressive disorder: a prospective, multicenter randomized controlled trial protocol
Authors: Wang Lanlan , Wang Qian , Jiang Wenhui , Luo Jianfeng , Tong Jun , Li Xiaosi , Fang Fang , Wang Hongyan , Zhao Wenqing , Koszycki Diana , Qiu Jianyin 
Published: July 2020

Abstract
Background
In China, psychodynamic psychotherapies are widely used as a treatment for depression. However, very few efficacy studies of psychodynamic therapies have been conducted with the Chinese population. This paper describes a study protocol of a multicenter randomized controlled trial of dynamic interpersonal psychotherapy (DIT), a brief manualized depression-focused intervention, in Chinese adults with major depressive disorder (MDD).

Methods
Recruitment is planned in five hospitals. Two hundred forty patients with MDD will be randomly allocated on a 1:1:1 basis to either medication plus DIT, medication plus an active control psychotherapy, or medication alone. Patients will be assessed at baseline and at weeks 2, 4, 8, 12, and 16 during the acute treatment phase and 1, 3, 6, and 12 months posttreatment. The primary outcome is change from baseline in the 17-item Hamilton Depression Rating Scale, administered by independent raters who are blind to treatment allocation. The Hamilton Anxiety Rating Scale, Patient Health Questionnaire-9, Generalized Anxiety Disorder 7-item scale, response, remission and relapse rates, self-assessment of overall efficacy and satisfaction of patients, and side effect profiles are secondary measures.

Discussion
This will be the first multicentered RCT in China to assess the efficacy of a brief psychodynamic intervention for MDD. The study has the potential to inform clinical treatment guidelines for the treatment of depression in China.

Trial registration
ChiCTR, ChiCTR1800016970. Registered on July 5, 2018
Communities for Healthy Living (CHL) A Community-based Intervention to Prevent Obesity in Low-Income Preschool Children: Process Evaluation Protocol
Authors: Beckerman-Hsu Jacob P. , Aftosmes-Tobio Alyssa , Gavarkovs Adam , Kitos Nicole , Figueroa Roger , Kalyoncu Z. Begum , Lansburg Kindra , Yu Xinting , Kazik Crystal , Vigilante Adrienne , Leonard Jessie , Torrico Merieka , Jurkowski Janine M. , Davison Kirsten K. 
Published: July 2020

Abstract
Background
Process evaluation can illuminate barriers and facilitators to intervention implementation as well as the drivers of intervention outcomes. However, few obesity intervention studies have documented process evaluation methods and results. Community-based participatory research (CBPR) requires that process evaluation methods be developed to (a) prioritize community members’ power to adapt the program to local needs over strict adherence to intervention protocols, (b) share process evaluation data with implementers to maximize benefit to participants, and (c) ensure partner organizations are not overburdened. Co-designed with low-income parents using CBPR, Communities for Healthy Living (CHL) is a family-centered intervention implemented within Head Start to prevent childhood obesity and promote family well-being. We are currently undertaking a randomized controlled trial to test the effectiveness of CHL in 23 Head Start centers in the greater Boston area. In this protocol paper, we outline an embedded process evaluation designed to monitor intervention adherence and adaptation, support ongoing quality improvement, and examine contextual factors that may moderate intervention implementation and/or effectiveness.

Methods
This mixed methods process evaluation was developed using the Pérez et al. framework for evaluating adaptive interventions and is reported following guidelines outlined by Grant et al. Trained research assistants will conduct structured observations of intervention sessions. Intervention facilitators and recipients, along with Head Start staff, will complete surveys and semi-structured interviews. De-identified data for all eligible children and families will be extracted from Head Start administrative records. Qualitative data will be analyzed thematically. Quantitative and qualitative data will be integrated using triangulation methods to assess intervention adherence, monitor adaptations, and identify moderators of intervention implementation and effectiveness.

Discussion
A diverse set of quantitative and qualitative data sources are employed to fully characterize CHL implementation. Simultaneously, CHL’s process evaluation will provide a case study on strategies to address the challenges of process evaluation for CBPR interventions. Results from this process evaluation will help to explain variation in intervention implementation and outcomes across Head Start programs, support CHL sustainability and future scale-up, and provide guidance for future complex interventions developed using CBPR.

Trial registration
ClinicalTrials.gov, NCT03334669. Registered on October 10, 2017
Ursodeoxycholic acid for the prevention of symptomatic gallstone disease after bariatric surgery: statistical analysis plan for a randomised controlled trial (UPGRADE trial)
Authors: Haal Sylke , Guman Maimoena S. S. , de Brauw L. Maurits , van Veen Ruben N. , Schouten Ruben , Fockens Paul , Gerdes Victor E. A. , Dijkgraaf Marcel G. W. , Voermans Rogier P. 
Published: July 2020

Abstract
Background
Approximately 8–15% of patients undergoing bariatric surgery develop symptomatic gallstone disease within 24 months after surgery. Ursodeoxycholic acid (UDCA) seems to effectively prevent the formation of gallstones detectable by ultrasound after bariatric surgery. The aim of the UPGRADE trial is to provide evidence on the prophylactic use of UDCA in preventing symptomatic gallstone disease postoperatively.

Methods
The UPGRADE trial is designed as a randomised, placebo-controlled, double-blind multicentre trial in patients with morbid obesity undergoing Roux-en-Y gastric bypass (RYGB) or sleeve gastrectomy (SG). Patients are randomly assigned to either UDCA 900 mg daily for 6 months or placebo treatment. This paper details the statistical analysis plan (SAP) of this trial and was submitted before outcome data were available.

Results
The primary endpoint of this trial is symptomatic gallstone disease within 24 months after bariatric surgery, defined as admission or hospital visit for symptomatic gallstone disease. Secondary outcomes consist of the development of gallstones/sludge on ultrasound at 24 months in the gallstone-negative group at baseline, presence of gallstones/sludge on ultrasound at 24 months, number of cholecystectomies, side effects of UDCA, therapy compliance, quality of life, costs and revenues. Analyses will be completed according to this pre-specified SAP. The main analysis will be performed as a standard ITT analysis using the chi-squared test.

Discussion
The UPGRADE trial will show if prophylactic use of UDCA reduces the incidence of symptomatic gallstone disease after bariatric surgery. Unforeseen deviations from the SAP at the time of analysis will be motivated and discussed.

Trial registration
The Netherlands Trial Register NL5954. Registered on 21 November 2016.
Quantification of circulating microRNAs by droplet digital PCR for cancer detection
Authors: Cirillo Priscila D. R. , Margiotti Katia , Mesoraca Alvaro , Giorlandino Claudio 
Published: July 2020

Abstract
Objective
Circulating cell-free microRNAs (miRNAs) which consist of short-sequence RNAs are released from cells into the blood stream and has emerged as new biomarkers in the clinical cancer diagnosis and treatment. For instance, ovarian cancer comprises one of the three major malignant tumor types in the female reproductive system. The mortality rate of this cancer is the highest among all gynecological tumors, with ovarian cancer metastasis constituting an important cause of death. Therefore, development of a diagnostic tool that enables the ovarian cancer diagnosis in earlier stages is urgent.

Results
We have described an efficient protocol for an accurate absolute quantification of circulating miRNAs in healthy and ovarian cancer serum samples. Our data showed that ddPCR methodology can accurately measure circulating miRNAs levels and that can be a useful tool in biomarkers discovery for ovarian cancer detection.
Intracranial alternating current stimulation facilitates neurogenesis in a mouse model of Alzheimer’s disease
Authors: Liu Qian , Jiao Yihang , Yang Weijian , Gao Beiyao , Hsu Daniel K. , Nolta Jan , Russell Michael , Lyeth Bruce , Zanto Theodore P. , Zhao Min 
Published: July 2020

AbstractBackgroundNeurogenesis is significantly impaired in the brains of both human patients and experimental animal models of Alzheimer’s disease (AD). Although deep brain stimulation promotes neurogenesis, it is an invasive technique that may damage neural circuitry along the path of the electrode. To circumvent this problem, we assessed whether intracranial electrical stimulation to the brain affects neurogenesis in a mouse model of Alzheimer’s disease (5xFAD).Methods and resultsWe used Ki67, Nestin, and doublecortin (DCX) as markers and determined that neurogenesis in both the subventricular zone (SVZ) and hippocampus were significantly reduced in the brains of 4-month-old 5xFAD mice. Guided by a finite element method (FEM) computer simulation to approximately estimate current and electric field in the mouse brain, electrodes were positioned on the skull that were likely to deliver stimulation to the SVZ and hippocampus. After a 4-week program of 40-Hz intracranial alternating current stimulation (iACS), neurogenesis indicated by expression of Ki67, Nestin, and DCX in both the SVZ and hippocampus were significantly increased compared to 5xFAD mice who received sham stimulation. The magnitude of neurogenesis was close to the wild-type (WT) age-matched unmanipulated controls.ConclusionOur results suggest that iACS is a promising, less invasive technique capable of effectively stimulating the SVZ and hippocampus regions in the mouse brain. Importantly, iACS can significantly boost neurogenesis in the brain and offers a potential treatment for AD.
Patient with rheumatoid arthritis with deep vein thrombosis presenting as a calf strain: a case report
Authors: Lewis Trevor 
Published: July 2020

Abstract
Background
Patients with rheumatoid arthritis experience various comorbidities, including cardiovascular disease. More data and awareness exist regarding the adverse effects of rheumatoid arthritis affecting the arterial side of the cardiovascular system, such as stroke or myocardial infarction, than regarding adverse venous complications, such as deep vein thrombosis and pulmonary embolism. Rheumatoid arthritis affects more women than men, and the risk of venous thromboembolism in rheumatoid arthritis tends to increase with age; therefore, the presentation in this case report of deep vein thrombosis in a nonsmoking, young, fit man with rheumatoid arthritis is rare. This patient was sent away from a minor injuries unit with a diagnosis of a calf strain. Further assessment at an accident and emergency department later in the day confirmed deep vein thrombosis via ultrasonography. This case report underlines the need for vigilance because deep vein thrombosis is a risk factor in rheumatoid arthritis, even in young, male, and physically fit individuals.

Case presentation
A nonsmoking 39-year-old Caucasian man with a 2-year history of rheumatoid arthritis presented for assessment at a private physiotherapy clinic with a 4-week history of right-sided posterior calf pain that had developed following exercise at a gym. The patient therefore believed his symptoms were due to a calf strain. Findings at physiotherapy assessment suggested that the actual cause of the patient’s symptoms were as a result of deep vein thrombosis. The patient was directed to a local minor injuries unit with a referral letter from the author outlining this diagnosis. Following clinical assessment at the minor injuries unit, the patient was told that there was no likelihood of deep vein thrombosis, and his diagnosis was a calf strain. The patient harbored concerns at this point and decided to seek further medical opinion at a nearby accident and emergency department, where deep vein thrombosis was diagnosed using ultrasonography, and the patient was commenced on anticoagulants.

Conclusions
Venous thromboembolism risk in rheumatoid arthritis is stated as being less recognized as an arterial complication. This is borne out by this patient’s clinical journey, wherein his youth, fitness, athletic appearance, and onset of symptoms during exercise were said to suggest a diagnosis of a calf strain at a minor injuries unit. Ultrasonography at a different accident and emergency unit later that day ultimately was used to diagnose deep vein thrombosis.
Exosomal lncRNAs from mesenchymal stem cells as the novel modulators to cardiovascular disease
Authors: Huang Ying 
Published: July 2020

Abstract
Aim
Mesenchymal stem cells (MSCs) have been identified as potential therapeutic candidates for cardiovascular disease (CVD). However, the molecular mechanism underlying their therapeutic effects is unknown.

Findings
Recently, Chen et al. showed that an exosomal lncRNA derived from MSCs protected against cardiomyocyte apoptosis in vivo, which provided new insight into our understanding of the functions of MSCs. Other exosomal lncRNAs from MSCs have been shown to play pivotal roles in the development of CVD.

Conclusion
Exosomal lncRNAs are important molecules in the application of MSCs, which reveals, at least in part, the functional mechanism of MSCs.
Development of attenuated live vaccine candidates against swine brucellosis in a non-zoonotic B. suis biovar 2 background
Authors: Aragón-Aranda Beatriz , de Miguel María Jesús , Lázaro-Antón Leticia , Salvador-Bescós Miriam , Zúñiga-Ripa Amaia , Moriyón Ignacio , Iriarte Maite , Muñoz Pilar M. , Conde-Álvarez Raquel 
Published: July 2020

AbstractBrucellais a genus of gram-negative bacteria that cause brucellosis. B. abortusandB. melitensisinfect domestic ruminants whileB. suis(biovars 1–3) infect swine, and all these bacteria butB. suisbiovar 2 are zoonotic. Live attenuatedB. abortusS19 andB. melitensisRev1 are effective vaccines in domestic ruminants, though both can infect humans. However, there is no swine brucellosis vaccine. Here, we investigated the potential use as vaccines ofB. suisbiovar 2 rough (R) lipopolysaccharide (LPS) mutants totally lacking O-chain (Bs2ΔwbkF) or only producing internal O-chain precursors (Bs2Δwzm) and mutants with a smooth (S) LPS defective in the core lateral branch (Bs2ΔwadBand Bs2ΔwadD). We also investigated mutants in the pyruvate phosphate dikinase (Bs2ΔppdK) and phosphoenolpyruvate carboxykinase (Bs2ΔpckA) genes encoding enzymes bridging phosphoenolpyruvate and the tricarboxylic acid cycle. When tested in the OIE mouse model at the recommended R or S vaccine doses (108and 105 CFU, respectively), CFU/spleen of all LPS mutants were reduced with respect to the wild type and decreased faster for the R than for the S mutants. At those doses, protection againstB. suiswas similar for Bs2ΔwbkF, Bs2Δwzm,Bs2ΔwadBand the Rev1 control (105 CFU). As described before forB. abortus,B. suisbiovar 2 carried a disabledpckAso that a double mutant Bs2ΔppdKΔpckAhad the same metabolic phenotype as Bs2ΔppdKandppdKmutation was enough to generate attenuation. At 105 CFU, Bs2ΔppdKalso conferred the same protection as Rev1. As compared to otherB. suisvaccine candidates described before, the mutants described here simultaneously carry irreversible deletions easy to identify as vaccine markers, lack antibiotic-resistance markers and were obtained in a non-zoonotic background. Since R vaccines should not elicit antibodies to the S-LPS andwzmmutants carry immunogenic O-chain precursors and did not improve Bs2ΔwbkF, the latter seems a better R vaccine candidate than Bs2Δwzm. However, taking into account that all R vaccines interfere in ELISA and other widely used assays, whether Bs2ΔwbkFis advantageous over Bs2ΔwadBor Bs2ΔppdKrequires experiments in the natural host.
A wavelet denoising approach based on unsupervised learning model
Authors: Bnou Khawla , Raghay Said , Hakim Abdelilah 
Published: July 2020

AbstractImage denoising plays an important role in image processing, which aims to separate clean images from noisy images. A number of methods have been presented to deal with this practical problem over the past several years. The best currently available wavelet-based denoising methods take advantage of the merits of the wavelet transform. Most of these methods, however, still have difficulties in defining the threshold parameter which can limit their capability. In this paper, we propose a novel wavelet denoising approach based on unsupervised learning model. The approach taken aims at exploiting the merits of the wavelet transform: sparsity, multi-resolution structure, and similarity with the human visual system, to adapt an unsupervised dictionary learning algorithm for creating a dictionary devoted to noise reduction. Using the K-Singular Value Decomposition (K-SVD) algorithm, we obtain an adaptive dictionary by learning over the wavelet decomposition of the noisy image. Experimental results on benchmark test images show that our proposed method achieves very competitive denoising performance and outperforms state-of-the-art denoising methods, especially in the peak signal to noise ratio (PSNR), the structural similarity (SSIM) index, and visual effects with different noise levels.