bluuebunny/crossref_metadata_2025_split huggingface dataset:
miR-34a mimic or pre-mir-34a, which is the better option for cancer therapy? KatoIII as a model to study miRNA action in human gastric cancer cells
Authors: Jafari Narjes , Abediankenari Saeid , Hossein-Nataj Hadi 
Published: March 2021

Abstract
Background
Aberrantly expressed microRNAs play important roles in gastric tumorigenesis. However, use of miRNAs as a therapeutic option in gastric cancer still remains as a challenging problem.

Methods
We performed transient transfection of miR-34a-5p mimic and stable transfection of pre-mir-34a into KatoIII cells. Then, we evaluated the effect of transfected miRNAs on numerous cellular and molecular processes.

Results
Following transient transfection of miR-34a-5p mimic at 25 nM—a commonly used concentration—into KatoIII cells, inhibition of two target genes expression, namely Notch1 and β-catenin, was not observed, but a non-significant marginal increase of these genes was detected. No changes were detected in the percentage of apoptotic cells as well as in CD44 + and EpCAM + cells after 25 nM miR-34a-5p mimic transfection. Interestingly, stable transfection of pre-mir-34a into KatoIII cells (named as KatoIII-pGFPC1-34a cells) caused a significant repression in β-catenin protein and Notch1 mRNA levels (p < 0.05 and p < 0.01, respectively) relative to equivalent control (KatoIII- pGFPC1-empty cells). The percentage of CD44 + cells in the KatoIII-pGFPC1-34a cells (< 40%) was significantly lower than that in control cells (~ 95%) (p < 0.05). An increase of ~ 3.5% in apoptotic cells and a slower proliferation rate were detected in KatoIII-pGFPC1-34a cells.

Conclusions
Our study revealed that the effect of miR mimic in target gene repression can be dependent to its concentration as well as to the cell type. Meanwhile, our findings further support a regulatory function for pre-miRNAs in target repression and will help to develop effective therapeutic strategies in cancer treatment.
Micro/nano-textured hierarchical titanium topography promotes exosome biogenesis and secretion to improve osseointegration
Authors: Zhang Zhengchuan , Xu Ruogu , Yang Yang , Liang Chaoan , Yu Xiaolin , Liu Yun , Wang Tianlu , Yu Yi , Deng Feilong 
Published: March 2021

Abstract
Background
Micro/nano-textured hierarchical titanium topography is more bioactive and biomimetic than smooth, micro-textured or nano-textured titanium topographies. Bone marrow mesenchymal stem cells (BMSCs) and exosomes derived from BMSCs play important roles in the osseointegration of titanium implants, but the effects and mechanisms of titanium topography on BMSCs-derived exosome secretion are still unclear. This study determined whether the secretion behavior of exosomes derived from BMSCs is differently affected by different titanium topographies both in vitro and in vivo.

Results
We found that both micro/nanonet-textured hierarchical titanium topography and micro/nanotube-textured hierarchical titanium topography showed favorable roughness and hydrophilicity. These two micro/nano-textured hierarchical titanium topographies enhanced the spreading areas of BMSCs on the titanium surface with stronger promotion of BMSCs proliferation in vitro. Compared to micro-textured titanium topography, micro/nano-textured hierarchical titanium topography significantly enhanced osseointegration in vivo and promoted BMSCs to synthesize and transport exosomes and then release these exosomes into the extracellular environment both in vitro and in vivo. Moreover, micro/nanonet-textured hierarchical titanium topography promoted exosome secretion by upregulating RAB27B and SMPD3 gene expression and micro/nanotube-textured hierarchical titanium topography promoted exosome secretion due to the strongest enhancement in cell proliferation.

Conclusions
These findings provide evidence that micro/nano-textured hierarchical titanium topography promotes exosome biogenesis and extracellular secretion for enhanced osseointegration. Our findings also highlight that the optimized titanium topography can increase exosome secretion from BMSCs, which may promote osseointegration of titanium implants.
Individual or combined transcatheter arterial chemoembolization and radiofrequency ablation for hepatocellular carcinoma: a time-to-event meta-analysis
Authors: Jiang Chuang , Cheng Gong , Liao Mingheng , Huang Jiwei 
Published: March 2021

Abstract
Background
There is still some debate as to whether transcatheter arterial chemoembolization (TACE) plus radiofrequency ablation (RFA) is better than TACE or RFA alone. This meta-analysis aimed to compare the efficacy and safety of TACE plus RFA for hepatocellular carcinoma (HCC) with RFA or TACE alone.

Methods
We searched PubMed, MEDLINE, Embase, Cochrane Library, and CNKI (China National Knowledge Infrastructure) for all relevant randomized controlled trials and retrospective studies reporting overall survival (OS), recurrence-free survival (RFS), and complications of TACE plus RFA for HCC, compared with RFA or TACE alone.

Results
Twenty-one studies involving 3413 patients were included. TACE combined with RFA was associated with better OS (hazard ratio [HR]=0.62, 95% confidence intervals [CI] = 0.55–0.71, P < 0.001) and RFS (HR = 0.52, 95% CI = 0.39–0.69, P < 0.001) than TACE alone; compared with RFA alone, TACE plus RFA resulted in longer OS (HR = 0.63, 95% CI = 0.53–0.75, P < 0.001) and RFS (HR = 0.60, 95% CI = 0.51–0.71, P < 0.001). Subgroup analyses by tumor size also showed that combined treatment resulted in better OS and RFS compared with RFA alone in patients with HCC larger than 3 cm. Combined treatment resulted in similar rate of major complications compared with TACE or RFA alone (OR = 1.78, 95% CI = 0.99–3.20, P = 0.05; OR = 1.00, 95% CI = 0.42–2.38, P = 1.00, respectively).

Conclusions
TACE combined with RFA was more effective for HCC than TACE alone. For patients with a tumor larger than 3 cm, the combined treatment also achieved a better effect than RFA alone.
Rectal washout does not increase the complication risk after anterior resection for rectal cancer
Authors: Teurneau-Hermansson Karl , Svensson Neufert Rebecca , Buchwald Pamela , Jörgren Fredrik 
Published: March 2021

Abstract
Background
To reduce local recurrence risk, rectal washout (RW) is integrated in the total mesorectal excision (TME) technique when performing anterior resection (AR) for rectal cancer. Although RW is considered a safe practice, data on the complication risk are scarce. Our aim was to examine the association between RW and 30-day postoperative complications after AR for rectal cancer.

Methods
Patients from the Swedish Colorectal Cancer Registry who underwent AR between 2007 and 2013 were analysed using multivariable methods.

Results
A total of 4821 patients were included (4317 RW, 504 no RW). The RW group had lower rates of overall complications (1578/4317 (37%) vs. 208/504 (41%), p = 0.039), surgical complications (879/4317 (20%) vs. 140/504 (28%), p < 0.001) and 30-day mortality (50/4317 (1.2%) vs. 12/504 (2.4%), p = 0.020). In multivariable analysis, RW was a risk factor neither for overall complications (OR 0.73, 95% CI 0.60–0.90, p = 0.002) nor for surgical complications (OR 0.62, 95% CI 0.50–0.78, p < 0.001).

Conclusions
RW is a safe technique that does not increase the 30-day postoperative complication risk after AR with TME technique for rectal cancer.
Anti-SAE autoantibody-positive Japanese patient with juvenile dermatomyositis complicated with interstitial lung disease - a case report
Authors: Kishi Takayuki , Tani Yumi , Okiyama Naoko , Mizuochi Kiyoshi , Ichimura Yuki , Harigai Masayoshi , Nagata Satoru , Miyamae Takako 
Published: March 2021

Abstract
Background
Clinical phenotypes and outcomes in juvenile dermatomyositis (JDM) have been defined by various myositis-specific autoantibodies (MSAs). One of the recently described MSAs associated with DM is targeted against the small ubiquitin-like modifier 1 activating enzyme (SAE). We report an anti-SAE autoantibody-positive JDM patient complicated with interstitial lung disease (ILD).

Case presentation
An 8-year-8-month-old Japanese girl presented with bilateral eyelid edema and facial erythema. At 8 years 4 months, she had dry cough and papules with erythema on the dorsal side of the interphalangeal joints of both hands. Her facial erythema gradually worsened and did not improve with topical steroids. At the first visit to our department at 8 years 8 months of age, she had a typical heliotrope rash and Gottron’s papules, with no fever or weight loss, and a chest computed tomography scan showed ground-glass opacity under visceral pleura. There was no clinical evidence of myositis, muscle weakness, myalgia, or muscle magnetic resonance imaging (MRI) findings. She had mild dry cough, without any signs of respiratory distress. Laboratory tests showed no elevated inflammatory markers. She had a normal serum creatine kinase level with a slightly elevated aldolase level, and serum anti-SAE autoantibody was detected by immunoprecipitation—western blotting. She was diagnosed with juvenile amyopathic DM complicated by ILD and received two courses of methylprednisolone pulse therapy followed by oral corticosteroid and cyclosporin A. We gradually reduced the corticosteroid dose as her skin rash improved after treatment initiation. There was no progression of muscle symptoms, dysphagia, or disease flare during a 24-month follow-up period.

Conclusions
We report a patient with anti-SAE autoantibody-positive JDM complicated by interstitial pneumonia. This patient had no progression of muscle symptoms and dysphagia during a 24-month follow-up period, which differs from previous reports in adult patients with MSAs. There have been no previous reports of pediatric patients with SAE presenting with ILD. However, ILD seen in this case was not rapidly progressive and did not require cytotoxic agents. To prevent overtreatment, appropriate treatment choices are required considering the type of ILD.
A cluster randomized stepped-wedge trial to de-implement unnecessary post-operative antibiotics in children: the optimizing perioperative antibiotic in children (OPerAtiC) trial
Authors: Malone Sara , McKay Virginia R. , Krucylak Christina , Powell Byron J. , Liu Jingxia , Terrill Cindy , Saito Jacqueline M. , Rangel Shawn J. , Newland Jason G. 
Published: March 2021

Abstract
Background
Antibiotic-resistant infections have become a public health crisis that is driven by the inappropriate use of antibiotics. In the USA, antibiotic stewardship programs (ASP) have been established and are required by regulatory agencies to help combat the problem of antibiotic resistance. Post-operative antibiotic use in surgical cases deemed low-risk for infection is an area with significant overuse of antibiotics in children. Consensus among leading public health organizations has led to guidelines eliminating post-operative antibiotics in low-risk surgeries. However, the best strategies to de-implement these inappropriate antibiotics in this setting are unknown.

Methods/design
A 3-year stepped wedge cluster randomized trial will be conducted at nine US Children’s Hospitals to assess the impact of two de-implementation strategies, order set change and facilitation training, on inappropriate post-operative antibiotic prescribing in low risk (i.e., clean and clean-contaminated) surgical cases. The facilitation training will amplify order set changes and will involve a 2-day workshop with antibiotic stewardship teams. This training will be led by an implementation scientist expert (VRM) and a pediatric infectious diseases physician with antibiotic stewardship expertise (JGN). The primary clinical outcome will be the percentage of surgical cases receiving unnecessary post-operative antibiotics. Secondary clinical outcomes will include the rate of surgical site infections and the rate of Clostridioides difficile infections, a common negative consequence of antibiotic use. Monthly semi-structured interviews at each hospital will assess the implementation process of the two strategies. The primary implementation outcome is penetration, which will be defined as the number of order sets changed or developed by each hospital during the study. Additional implementation outcomes will include the ASP team members’ assessment of the acceptability, appropriateness, and feasibility of each strategy while they are being implemented.

Discussion
This study will provide important information on the impact of two potential strategies to de-implement unnecessary post-operative antibiotic use in children while assessing important clinical outcomes. As more unnecessary medical practices are identified, de-implementation strategies, including facilitation, need to be rigorously evaluated. Along with this study, other rigorously designed studies evaluating additional strategies are needed to further advance the burgeoning field of de-implementation.

Trial registration
NCT04366440. Registered April 28, 2020, https://clinicaltrials.gov/ct2/show/NCT04366440.
Implementation science should give higher priority to health equity
Authors: Brownson Ross C. , Kumanyika Shiriki K. , Kreuter Matthew W. , Haire-Joshu Debra 
Published: March 2021

Abstract
Background
There is growing urgency to tackle issues of equity and justice in the USA and worldwide. Health equity, a framing that moves away from a deficit mindset of what society is doing poorly (disparities) to one that is positive about what society can achieve, is becoming more prominent in health research that uses implementation science approaches. Equity begins with justice—health differences often reflect societal injustices. Applying the perspectives and tools of implementation science has potential for immediate impact to improve health equity.

Main text
We propose a vision and set of action steps for making health equity a more prominent and central aim of implementation science, thus committing to conduct implementation science through equity-focused principles to achieve this vision in U.S. research and practice. We identify and discuss challenges in current health disparities approaches that do not fully consider social determinants. Implementation research challenges are outlined in three areas: limitations of the evidence base, underdeveloped measures and methods, and inadequate attention to context. To address these challenges, we offer recommendations that seek to (1) link social determinants with health outcomes, (2) build equity into all policies, (3) use equity-relevant metrics, (4) study what is already happening, (5) integrate equity into implementation models, (6) design and tailor implementation strategies, (7) connect to systems and sectors outside of health, (8) engage organizations in internal and external equity efforts, (9) build capacity for equity in implementation science, and (10) focus on equity in dissemination efforts.

Conclusions
Every project in implementation science should include an equity focus. For some studies, equity is the main goal of the project and a central feature of all aspects of the project. In other studies, equity is part of a project but not the singular focus. In these studies, we should, at a minimum, ensure that we “leave no one behind” and that existing disparities are not widened. With a stronger commitment to health equity from funders, researchers, practitioners, advocates, evaluators, and policy makers, we can harvest the rewards of the resources being invested in health-related research to eliminate disparities, resulting in health equity.
Fiducial-based image-guided SBRT for pancreatic adenocarcinoma: Does inter-and intra-fraction treatment variation warrant adaptive therapy?
Authors: Hill Colin S. , Han-Oh Sarah , Cheng Zhi , Wang Ken Kang-Hsin , Meyer Jeffrey J. , Herman Joseph M. , Narang Amol K. 
Published: March 2021

Abstract
Purpose
Variation in target positioning represents a challenge to set-up reproducibility and reliability of dose delivery with stereotactic body radiation therapy (SBRT) for pancreatic adenocarcinoma (PDAC). While on-board imaging for fiducial matching allows for daily shifts to optimize target positioning, the magnitude of the shift as a result of inter- and intra-fraction variation may directly impact target coverage and dose to organs-at-risk. Herein, we characterize the variation patterns for PDAC patients treated at a high-volume institution with SBRT.

Methods
We reviewed 30 consecutive patients who received SBRT using active breathing coordination (ABC). Patients were aligned to bone and then subsequently shifted to fiducials. Inter-fraction and intra-fraction scans were reviewed to quantify the mean and maximum shift along each axis, and the shift magnitude. A linear regression model was conducted to investigate the relationship between the inter- and intra-fraction shifts.

Results
The mean inter-fraction shift in the LR, AP, and SI axes was 3.1 ± 1.8 mm, 2.9 ± 1.7 mm, and 3.5 ± 2.2 mm, respectively, and the mean vector shift was 6.4 ± 2.3 mm. The mean intra-fraction shift in the LR, AP, and SI directions were 2.0 ± 0.9 mm, 2.0 ± 1.3 mm, and 2.3 ± 1.4 mm, respectively, and the mean vector shift was 4.3 ± 1.8 mm. A linear regression model showed a significant relationship between the inter- and intra-fraction shift in the AP and SI axis and the shift magnitude.

Conclusions
Clinically significant inter- and intra-fraction variation occurs during treatment of PDAC with SBRT even with a comprehensive motion management strategy that utilizes ABC. Future studies to investigate how these variations could lead to variation in the dose to the target and OAR should be investigated. Strategies to mitigate the dosimetric impact, including real time imaging and adaptive therapy, in select cases should be considered.
Spindle cell sarcoma of the right atrium causing right atrial pseudoaneurysm: a case report and review of the literature
Authors: Wang Xiaofang , Dong Aiqiang , Yang Weijun , Duan Qunjun 
Published: March 2021

Abstract
Background
Spindle cell sarcomas of the right atrium are extremely rare primary cardiac tumours, with very few cases reported in the medical literature. Pseudoaneurysms caused by cardiac spindle cell sarcoma have never been reported worldwide.

Case presentation
A 32-year-old woman was referred to our hospital for recurrent pericardial haemorrhagic effusion and pleural effusion. Three-dimensional transthoracic echocardiogram, contrast chest CT, and contrast MRI revealed a pseudoaneurysm on the right side of the right atrium with a thrombus. There was a defect between the pseudoaneurysm and the right atrium. PET-CT suggested that FDG metabolism inhomogeneity increased in the mass in the right atrium. Exfoliative cytology detection of massive pericardial effusion and pleural effusion revealed no tumour cells. Spindle cell sarcoma of the right atrium was not confirmed until the patient underwent right thoracic exploration and biopsy. Before a confirmed diagnosis, symptomatic treatment, such as chest effusion and pericardium effusion drainage, and transfusion of red blood cells were mainly used to relieve the patient’s symptoms. Unfortunately, the patient was lost to optimal treatments and passed away 20 days after the pathological diagnosis was made.

Conclusion
The prognosis of spindle cell sarcomas remains poor due to delays in diagnosis, early metastasis and few available therapeutic options. Recurrent pericardial effusion and pleural effusion, especially in the nature of haemorrhagic effusion, and/or right atrial pseudoaneurysm shown on the transthoracic echocardiogram must be considered and highly suspected as malignancy by patients and physicians. If the diagnosis cannot be confirmed, histopathology should be performed as soon as possible to avoid losing the best treatment opportunity.
Integrating metabolomic data with machine learning approach for discovery of Q-markers from Jinqi Jiangtang preparation against type 2 diabetes
Authors: Yang Lele , Xue Yan , Wei Jinchao , Dai Qi , Li Peng 
Published: March 2021

Abstract
Background
Jinqi Jiangtang (JQJT) has been widely used in clinical practice to prevent and treat type 2 diabetes. However, little research has been done to identify and classify its quality markers (Q-markers) associated with anti-diabetes bioactivity. In this study, a strategy combining mass spectrometry-based untargeted metabolomics with backpropagation artificial neural network (BP-ANN)-based machine learning approach was proposed to screen Q-markers from JQJT preparation.

Methods
This strategy mainly involved chemical profiling of herbal medicines, statistic processing of metabolomic datasets, detection of different anti-diabetes activities and establishment of BP-ANN model. The chemical features of seventy-eight batches of JQJT extracts were first profiled by using the untargeted UPLC-LTQ-Orbitrap metabolomic approach. The chemical features obtained which were associated with different anti-diabetes activities based on three modes of action were normalized, ranked, and then pre-selected by using ReliefF feature selection. BP-ANN model was then established and optimized to screen Q-markers based on mean impact value (MIV).

Results
Optimized BP-ANN architecture was established with high accuracy of R > 0.9983 and relative low error of MSE < 0.0014, which showed better performance than that of partial least square (PLS) model (R2 < 0.5). Meanwhile, the BP-ANN model was subsequently applied to further screen potential bioactive components from the pre-selected chemical features by calculating their MIVs. With this machine learning model, 10 potential Q-markers with bioactivity were discovered from JQJT. The tested anti-diabetes bioactivities of 78 batches of JQJT could be accurately predicted.

Conclusions
This proposed artificial intelligence approach is desirable for quick and easy identification of Q-markers with bioactivity from JQJT preparation.
Signal amplification and optimization of riboswitch-based hybrid inputs by modular and titratable toehold switches
Authors: Hwang Yunhee , Kim Seong Gyeong , Jang Sungho , Kim Jongmin , Jung Gyoo Yeol 
Published: March 2021

Abstract
Background
Synthetic biological circuits are widely utilized to control microbial cell functions. Natural and synthetic riboswitches are attractive sensor modules for use in synthetic biology applications. However, tuning the fold-change of riboswitch circuits is challenging because a deep understanding of the riboswitch mechanism and screening of mutant libraries is generally required. Therefore, novel molecular parts and strategies for straightforward tuning of the fold-change of riboswitch circuits are needed.

Results
In this study, we devised a toehold switch-based modulator approach that combines a hybrid input construct consisting of a riboswitch and transcriptional repressor and de-novo-designed riboregulators named toehold switches. First, the introduction of a pair of toehold switches and triggers as a downstream signal-processing module to the hybrid input for coenzyme B12 resulted in a functional riboswitch circuit. Next, several optimization strategies that focused on balancing the expression levels of the RNA components greatly improved the fold-change from 260- to 887-fold depending on the promoter and host strain. Further characterizations confirmed low leakiness and high orthogonality of five toehold switch pairs, indicating the broad applicability of this strategy to riboswitch tuning.

Conclusions
The toehold switch-based modulator substantially improved the fold-change compared to the previous sensors with only the hybrid input construct. The programmable RNA-RNA interactions amenable to in silico design and optimization can facilitate further development of RNA-based genetic modulators for flexible tuning of riboswitch circuitry and synthetic biosensors.