bluuebunny/crossref_metadata_2025 huggingface dataset:
Suppressing HMGB1-TLR4-Mediated Neuroinflammation Alleviates Morphine Tolerance via Inhibiting AMPK-HO-1 Pathway in The Spinal Cord of Mice
Authors: Lin Tong-Tong , Sheng Lei , Wan Li , Ji Lu-Lu , Li Jin-Can , Sun Xiao-Di , Pan Yin-Bing , Xu Chen-Jie , Hu Liang , Wu Xue-Feng , Han Yuan , Jiang Chun-Yi , Liu Wen-Tao
Published: December 2020

Background and objectives: A major unresolved issue in treating pain is the analgesic tolerance produced by opioids. Neuroinflammation was thought to be important in the development of morphine tolerance. The role of High mobility group box-1 (HMGB1) in morphine tolerance is elusive. Methods: ICR mice were used for tail-flick test to evaluate morphine tolerance. SD rats were used to collect the CSF to investigate whether morphine could induce the efflux of HMGB1 into extracellular environment. The neural cell line SH-SY5Y and the microglial cell line BV-2 were used to investigate the pharmacological effects and the mechanism of morphine-induced neuroinflammation. The activation of microglia was assessed by immunofluorescence staining. Neuroinflammation-related cytokines were measured by western blot and real-time PCR. The level of HMGB1 and related signaling pathway were evaluated by western blot and immunofluorescence staining.Results: Morphine induces the release of HMGB1 from neurons. The released HMGB1 activated microglia and triggered TLR4-mediated inflammatory response, leading to the phosphorylation of nuclear factor-κB (NF-κB) p65 and the upregulation of IL-1β. The secretion of HMGB1 was under the control of AMPK-HO-1 pathway. AMPK inhibitor and HO-1 inhibitor inhibited the release of HMGB1 and suppressed HMGB1-TLR4 mediated neuroinflammation.Conclusion: Our study indicated that morphine-induced extracellular HMGB1 was critical for morphine tolerance. The release of HMGB1 was regulated by AMPK-HO-1 pathway. Our findings may represent a bright prospect for the improvement of morphine tolerance with HMGB1 inhibitor and/or the inhibitors for AMPK-HO-1 axis.
Changes in Particle Size Distribution in Hydroponic Lagoons Working as A Third Stage of Wastewater Treatment
Authors: Bawiec Aleksandra , Pawęska Katarzyna , Pulikowski Krzysztof , Marek Kinga
Published: December 2020

The aim of research was to evaluate changes in the particle size distribution in two hydroponic lagoons working as a third stage of wastewater treatment where purification processes are based on plants and algae activity. Wastewater samples were taken during the winter and summer half of the year. In the samples taken from analyzed hydroponic lagoons the range of particles size was very wide (0.01 – 1000.0 μm). In both of the research facilities, the fractal dimension (Df) of particles was close to 2.0 what decides about developed surface of the particles. The results may indicate the predominance of algae cells in the total amount of suspensions. This information may pay a key role in determination the impact of discharged particles on the receiving water bodies quality as well as can be the main factor that allows to improve the system of suspended solids removal.
LINC01614 Promotes Osteosarcoma Progression as ceRNA to Target SNX3 by Sponging hsa-miR-520a-3p
Authors: Cai Qixuan , Zhao Xin , Wang Yanbing , Li Shuai , Wang Jincheng , Li Fan
Published: December 2020

Long noncoding RNAs (lncRNAs) have been reported as significant biomarkers for diagnosis and prognosis in osteosarcoma (OS), the most malignant bone tumor usually observed in children and adolescents. In the present study, we detected differentially expressed lncRNAs in three OS and paired adjacent tissues through RNA-seq technology. By comprehensively analyzing the expression profile and bioinformatics, we determined the relationship between noncoding RNA and OS-related functions, signal pathway, regulatory network, patient survival information and selected LINC01614 as the study object. Through related in vitro experiments, we confirmed that LINC01614 knockdown could inhibit the proliferation, invasion, and metastasis of OS cells. Furthermore, we used the luciferase reporter assay and qRT-PCR to confirm the regulatory relationship between LINC01614/hsa-miR-520a-3p/SNX3. We performed relevant in vitro experiments to prove that LINC01614 promotes the proliferation, invasion, and metastasis of OS cells through the LINC01614/hsa-miR-520a-3p/SNX3 axis. In conclusion, we identified that lncRNAs participate in various malignant behaviors in OS. We also proved that LINC01614 could function as competing endogenous RNAs and promote the proliferation, invasion, and metastasis of OS cells, and thus acts as a novel prognostic marker for OS in clinic.
Mining TCGA Data for Key Biomarkers Related to Immune Microenvironment in Endometrial Carcinoma by Immune Score and Weighted Correlation Network Analysis
Authors: Guo Chengbin , Tang Yuqin , Zhang Yongqiang , Li Gen
Published: December 2020

Background: Endometrial cancer (EC) is one of the most lethal gynecological cancer in women. It is imperative to identify the potential immune microenvironment-related biomarkers associated with the prognosis for EC. Methods: RNA-seq data and related clinical information of EC patients were derived from The Cancer Genome Atlas (TCGA). The immune score of each EC sample was obtained by ESTIMATE algorithm. Weighted gene co-expression network analysis (WCGNA) was used to identify the interesting module and potential key genes concerning the immune score. Further, the expression patterns of the key genes were verified via the GEPIA database. Last, CIBERSORT was used to evaluate the relative abundances of 22 immune cell types in EC. Results: Immune scores were significantly associated with tumor grade and histology of EC, and high immune scores may exert a protective influence on the survival outcome for EC. WCGNA indicated that the black module was significantly correlated with the immune score in EC. Function analysis revealed it mainly involved in those terms related to immune regulation and inflammatory response. Moreover, 11 key genes were identified from the black module, validated by the GEPIA database, and revealed strong correlations with infiltration levels of multiple immune cell types, as was the prognosis of EC. Conclusion: In our study, 11 key genes showed abnormal expressions and strong correlations with immune cell infiltration in EC, most of which were significantly associated with the prognosis of EC. These findings made them promising therapeutic targets for the treatment of EC.
Systemic Immune-Inflammation Index Predicts Prognosis of Patients With Esophageal Squamous Cell Carcinoma Undergoing Radical Radiotherapy: A Propensity Score-Matched Analysis
Authors: Zhao Yan , Shen Wen-Bin , Song Chun-Yang , Xu Jin-Rui , Li Shu-Guang , Deng Wen-Zhao , Li Juan , Zhu Shu-Chai
Published: December 2020

BackgroundThe systemic immune-inflammation index (SII) was recently investigated as a prognostic predictor in several kinds of solid tumors, including esophageal squamous cell carcinoma (ESCC) after esophagectomy. However, just few studies regarding SII in patients with ESCC undergoing radical radiotherapy are available. In addition, there has been hardly any report investigating the change trend of SII during radiotherapy. The aim of this study was to identify the prognostic value of SII in ESCC patients undergoing radical radiotherapy. MethodsWe retrospectively reviewed 303 ESCC patients undergoing radical radiotherapy. The change trend of SII was assessed by the box plot and curve fitting method. The time-dependent receiver operating characteristics was used to determine the optimal cutoff value of the SII. The association between SII and survival was determined by Kaplan-Meier method and Cox regression model. Propensity score matching (PSM) was applied to imbalance the baseline characteristics. ResultsHigh SII was associated with poor overall survival (OS) and progression-free survival (PFS) in patients with ESCC undergoing radical radiotherapy. Multivariate analysis showed that SII was a significant predictor for OS and PFS, whether before or after PSM. In addition, SII displayed an exponential increase trend during radiotherapy. The change of SII was also associated with OS and PFS. Conclusions﻿The SII is a significant and independent predictor for OS and PFS of ESCC patients undergoing radical radiotherapy. Based on simple and inexpensive standard laboratory measurements, SII can be a promising marker for ESCC patients.
Molecular Cytogenetic Characterization and Fusarium Head Blight of Five Wheat Thinopyrum Intermedium Partial Amphiploids
Authors: Wang Hui , Cheng Shuwei , Shi Yue , Zhang Shuxin , Yan Wei , Song Weifu , Yang Xuefeng , Song Qingjie , Jang Bo , Qi Xiaoyue , Li Xinling , Friebe Bernd , Zhang Yanming
Published: December 2020

Background: Partial amphiploids created by crossing octoploid tritelytrigia and Thinopyrum intermedium are important intermediates in wheat breeding because of their resistance to major wheat diseases. We examined the chromosome compositions of five wheat Th. intermedium partial amphiploids using GISH and multicolor FISH. Results: The result revealed that five lines had 10 14 J genome chromosomes from Th. intermedium and 42 common wheat chromosomes, using the J genomic DNA from Th. bessarabicum and the oligo probes pAs1 1 , pAs1 3 , AFA 4 , GAA ) 10, and pSc119.2 1 . Five lines resembled the parent Ganmai 8 but had better protein contents. P rotein contents of t wo lines HS2 2 and HS2 5 were up to more than 20%. Evaluation of Fusarium head blight (FHB) resistance revealed that the percent of symptomatic spikelets (PSS) of these lines were below 30%. Lines HS2 2, HS2 4, HS2 5, and HS2 16 were less than 20%. Line HS2 5 with 14 J genome chromosomes from Th. intermedium showed the best disease resistance, with PSS values of 10.8% and 16.6% in 2016 and 2017, respectively. Conclusions: New wheat Th. intermedium amphiploids with the J genome chromosomes were identified and can be considered as a valuable source of FHB resistance in wheat breeding.
A Placental Trisomy 2 Detected by NIPT Evolved in a Fetal Small Supernumerary Marker Chromosome (sSMC).
Authors: Domaradzka Justyna Anna , Deperas Marta , Obersztyn Ewa , Kucińska-Chahwan Anna , Brison Nathalie , Bogaert Kris Van Den , Roszkowski Tomasz , Kędzior Marta , Bartnik-Głaska Magdalena , Łuszczek Alicja , Jakubów-Durska Krystyna , Vermeesch Joris Robert , Nowakowska Beata Anna
Published: December 2020

Background: Non-invasive prenatal testing (NIPT) is known to be more sensitive and more specific for common aneuploidy as well as sex determination at an early pregnancy compared to traditional biochemical and sonographic screening. However, recently the widespread use of the NIPT caused a neglecting of the limitations of this technology. Case presentation: The 38-year-old woman underwent amniocentesis because of a high risk of trisomy 2 revealed by the genome-wide Non-Invasive Prenatal Test (NIPT). The invasive prenatal diagnosis revealed the mosaicism for a small supernumerary marker chromosome sSMC derived from chromosome 2. Interphase fluorescence in situ hybridization (FISH) on uncultured amniocytes revealed three signals of centromere 2 in 30% of the cells. GTG-banded metaphases revealed abnormal karyotype (47,XX,+mar[21]/46,XX[19]) and was confirmed by array comparative genomic hybridization (aCGH). Cytogenetic analyses (FISH, aCGH, karyotype) on fetal skin biopsies were performed and confirmed the genomic gain of the centromeric region of chromosome 2. In the placenta, three cell lines were detected: a normal cell line, a cell line with trisomy 2 and a third one with only the sSMC.Conclusion: Whole-genome Non-Invasive Prenatal Testing allows not only the identification of common fetal trisomies but also diagnosis of rare chromosomal abnormalities. Especially in such cases, it is extremely important to perform not only NIPT verification on a sample of material other than trophoblast, but also to apply appropriate research methods. Such conduct allows detailed analysis of the detected aberration, thus appropriate clinical validity.
Metabolically Healthy Obese Children and the Role of the Gut Microbiota
Authors: Yuan Xin , Chen Ruimin , McCormick Kenneth L. , Zhang Ying , Lin Xiangquan , Yang Xiaohong
Published: December 2020

Background The term “metabolically healthy obese (MHO)” denotes a hale and salutary status, yet this connotation has not been validated in children, and may, in fact, be a misnomer. As pertains to obesity, the gut microbiota has garnered attention as conceivably a nosogenic or, on the other hand, protective participator.Objective This study explored the characteristics of the fecal microbiota of obese Chinese children and adolescents of disparate metabolic status, and the associations between their gut microbiota and circulating proinflammatory factors, such as IL-6 and TNF-α, and a cytokine up-regulator and mediator, leptin. Results Based on weight and metabolic status, the 86 Chinese children (ages 5-15 years) were divided into three groups: metabolically healthy obese (MHO, n=42), metabolic unhealthy obesity (MUO, n=23), and healthy normal weight controls (Con, n=21). In the MUO subjects, the phylum Tenericutes, as well as the alpha and beta diversity, were significantly reduced compared with the controls. Furthermore, Phylum Synergistetes and genus Bacteroides were more prevalent in the MHO population compared with controls. For the MHO subgroup, Spearman’s correlation analysis revealed that serum IL-6 positively correlated with genus Paraprevotella, and leptin correlated positively with genus Phascolarctobacterium and negatively with genus Dialister (all p<0.05).Conclusion Dysbiosis of gut microsystem prevails in the MHO cohort, and the abundance of some metabolism-related bacteria associates with the degree of circulating inflammatory compounds. As for a role in the etiology or facilitation of obesity- or perhaps vice versa- this childhood microbial imbalance awaits long-term, longitudinal investigation.
Single-cell Transcriptomic Analysis of Eutopic Endometrium and Ectopic Lesions of Adenomyosis
Authors: Liu Zhiyong , Sun Zhonghua , Liu Hongyun , Niu Weipin , Wang Xin , Liang Na , Wang Xin , Wang Yanfei , Shi Yaxin , Xu Li , Shi Wei
Published: December 2020

Background: Adenomyosis (AM) is a common benign chronic gynaecological disorder; however, the precise pathogenesis of adenomyosis is still poorly understood. Single-cell RNA sequencing (scRNA-seq) can uncover rare subpopulations, explore genetic and functional heterogeneity, and reveal the uniqueness of each cell. It provides us a new approach to reveal biological issues from a more detailed and microscopic perspective. Here, we utilize this revolutionary technology to identify the changes of gene expression patterns between ectopic lesions and the eutopic endometrium at the single-cell level and explore a potential novel pathogenesis of AM.Methods: A control endometrium (sample with leiomyoma excluding endometrial disorders, n=1), eutopic endometrium and ectopic lesion (from a patient with adenomyosis, n=1) samples were analysed by scRNA-seq, and additional leiomyoma (n=3) and adenomyosis (n=3) samples were used to confirm colocalization and vasculogenic mimicry (VM) formation. Protein colocalization was visualized by immunofluorescence, and CD34-periodic acid-Schiff (PAS) double staining was used to assess the formation of VM.Results: The scRNA-seq results suggest that cancer-, cell motility- and inflammation- (CMI) associated terms, cell proliferation and angiogenesis play important roles in the progression of AM. Moreover, the colocalization of EPCAM and PECAM1 increased significantly in the ectopic endometrium group (P < 0.05), cell subpopulation with high copy number variation (CNV) levels possessing tumour-like features existed in the ectopic lesion sample, and VNN1- and EPCAM-positive cell subcluster displayed active cell motility in endometrial epithelial cells. Furthermore, the epithelial cells transformed to endothelial cells with the obvious accumulation of vasculogenic mimicry formations (positively stained with PAS but not CD34, P < 0.05) in ectopic lesions.Conclusions: In the present study, our results support the theory of adenomyosis derived from the invasion and migration of the endometrium. Moreover, cell subcluster with high CNV level and tumour-associated characteristics is identified. Furthermore, epithelial-endothelial transition (EET) and the formation of VM in tumours, the latter of which facilitates the blood supply and plays an important role in maintaining cell growth, were also confirmed to occur in AM. These results indicated that the inhibition of EET and VM formation may be a potential strategy for AM management.
Identification of a Potent Antagonist of Smoothened in Hedgehog Signaling
Authors: Fan Junwan , Li Haowen , Zhao Zichen , Kuang Lun , He Wenyan , Wang Yongjun , Cheng Steven Y. , Chen Wei
Published: December 2020

Background Hedgehog signaling is essential to the regulation of embryonic development, tissue homeostasis, and stem cell self-renewal, making it a prime target for developing cancer therapeutics. Given the close link between aberrant Hedgehog signaling and cancers, many small molecular compounds have been developed to inhibit this pathway for treating cancer and several of such compounds have been approved by FDA (GDC-0449 and LDE-225). As we known, acquired drug resistance is the main obstacle of first generation of Smoothened inhibitors. Therefore, new Smoothened inhibitors that could inhibit wild-type and mutant receptors are essential for refractory cancers. ResultsWe established the Smoothened β arrestin 2 GFP high throughput screening platform based on the mechanistic discovery of Hedgehog signaling pathway, and discovered several active small molecules targeting Smoothened including 0025A 0025A. Here we show that 0025A can block the translocation of β arrestin 2 GFP to Smoothened , displace Bodipycyclopamine binding to wild type Smoothened or mutant Smoothened D473H and reduce the expression of Gli upon Hedgehog stimulation. In addition, we reveal that 0025A can effectively suppress hair follicle morphogenesis and hair growth in mice. Conclusions Thus, our results demonstrate that 0025A is a potent antagonist targeting Smoothened wild-type and mutant type and mutant receptors in the Hreceptors signaling pathway and may provide a new new therapy for refractory cancers.
K-Seq, An Affordable, Reliable, and Open Klenow NGS-Based Genotyping Technology
Authors: Ziarsolo Peio , Hasing Tomas , Hilario Rebeca , Garcia-Carpintero Victor , Blanca Jose , Bombarely Aureliano , Canizares Joaquin
Published: December 2020

Background K-seq, a new genotyping methodology based on the amplification of genomic regions using two steps of Klenow amplification with short oligonucleotides, followed by standard PCR and Illumina sequencing, is presented. The protocol was accompanied by software developed to aid with primer set design.Results As the first examples, K-seq in species as diverse as tomato, dog and wheat was developed. K-seq provided genetic distances similar to those based on WGS in dogs. Experiments comparing K-seq and GBS in tomato showed similar genetic results, although K-seq had the advantage of finding more SNPs for the same number of Illumina reads. The technology reproducibility was tested with two independent runs of the tomato samples, and the correlation coefficient of the SNP coverages between samples was 0.8 and the genotype match was above 94%. K-seq also proved to be useful in polyploid species. The wheat samples generated specific markers for all subgenomes, and the SNPs generated from the diploid ancestors were located in the expected subgenome with accuracies greater than 80%.Conclusion K-seq is an open, patent-unencumbered, easy-to-set-up, cost-effective and reliable technology ready to be used by any molecular biology laboratory without special equipment in many genetic studies.
Full-Length Transcriptome Sequences by A Combination of Sequencing Platforms Applied to Isoflavonoid and Triterpenoid Saponin Biosynthesis of Astragalus Mongholicus Bunge
Authors: Yin Minzhen , Chu Shanshan , Shan Tingyu , Zha Liangping , Peng Huasheng
Published: December 2020

Background: Astragalus mongholicus Bunge is an important medicinal plant and has been used in traditional Chinese medicine for a long history, which is rich in isoflavonoids and triterpenoid saponins. Although these active constituents in A. mongholicus have been discovered for a long time, the molecular genetic basis of the isoflavonoid and triterpenoid saponin biosynthesis pathways is virtually unknown due to the lack of a reference genome. The combination of next-generation sequencing (NGS) and single-molecule real-time (SMRT) sequencing to analyze genes involved in the biosynthetic pathways of secondary metabolites in medicinal plants has been widely recognized.Results: In this study, NGS, SMRT sequencing, and targeted compounds were combined to investigate the association between isoflavonoids and triterpenoid saponins and gene expression in roots, stems and leaves of A. mongholicus. A total of four main isoflavonoids and four astragalosides (belong to triterpenoid saponins) were measured, and 44 differentially expressed genes (DEGs) of nine gene families, 44 DEGs of 16 gene families that encode for enzymes involved in isoflavonoid and triterpenoid saponin biosynthesis were identified, separately. Additionally, transcription factors (TFs) associated with isoflavonoid and triterpenoid saponin biosynthesis were analyzed, including 72 MYBs, 53 bHLHs, 64 AP2-EREBPs and 11 bZIPs. The above transcripts exhibit different expression trends in different organs.Conclusions: Our study provides important genetic information for the essential genes of isoflavonoid and triterpenoid saponin biosynthesis in A. mongholicus, and provides a basis for developing its medicinal value.
No association of serum sTREM2 and MRI-based brain volume in elderly people living in a rural community: a 7-year follow-up study
Authors: Orihashi Ryuzo , Mizoguchi Yoshito , Imamura Yoshiomi , Yamada Shigeto , Monji Akira
Published: December 2020

BackgroundThis study aimed to investigate the association between serum levels of soluble triggering receptor expressed on myeloid cells 2 (sTREM2), a soluble form of an innate immune receptor expressed on the microglia, and brain volume in elderly people.MethodsThe survey was conducted twice in Kurokawa-cho, Imari, Saga Prefecture, Japan, among people aged 65 years and older. We collected data from 596 residents. Serum sTREM2 level measurements, brain MRI, Mini-Mental State Examination (MMSE), and Clinical Dementia Rating (CDR) were performed at Time 1 (2009–2011). Follow-up brain MRI, MMSE, and CDR were performed at Time 2 (2016–2017). The interval between Time 1 and Time 2 was approximately 7 years. Sixty-nine participants (16 men, mean age 72.69 ± 3.18 years; 53 women, mean age 72.68 ± 4.64 years) completed this study. We analyzed the correlation between serum sTREM2 levels (Time 1) and brain volume (Time 1, Time 2, and Time 1–Time 2 difference) using voxel-based morphometry implemented with Statistical Parametric Mapping.ResultsParticipants in this study had lower MMSE and CDR scores 7 years after the baseline evaluation. However, analyses at the cluster level by applying multiple comparison corrections (family wise error; P < 0.05) showed no correlation between serum sTREM2 levels and volume of different brain regions, either cross-sectional or longitudinal. ConclusionsSerum sTREM2 level could not serve as an immune biomarker of aging-related volume changes in brain regions closely related to cognitive function in elderly people aged 65 years and above.
Diagnostic Value of Apparent Diffusion Coefficient Maps for the Differentiation of Brain Metastases from Lung cancer
Authors: Mueller Sebastian Johannes , Khadhraoui Eya , Neef Nicole , Ernst Marielle-Sophie , Riedel Christian Heiner
Published: December 2020

Background: Brain metastases are particularly common in patients with small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC), with NSCLC showing a more aggressive clinical course and lower chemo- and radio sensitivity compared to SCLC. Early adequate therapy is highly desirable and depends on a reliable classification of tumor type. The apparent diffusion coefficient is a noninvasive neuroimaging marker with the potential to differentiate between major histological subtypes. Here we determine the sensitivity and specificity of the apparent diffusion coefficient to distinguish between NSCLC and SCLC.Methods: We enrolled all NSCLC and SCLC patients diagnosed between 2008 and 2019 at the University Medical Center Göttingen. Cranial MR scans were visually inspected for brain metastases and the ratio of the apparent diffusion coefficient (ADC) was calculated by dividing the ADC measured within the solid part of a metastasis by a reference ADC extracted from an equivalent region in unaffected tissue on the contralateral hemisphere.Results: Out of 411 enrolled patients, we detected 129 patients (83 NSCLC, 46 SCLC) with sufficiently large brain metastases with histologically classified lung cancer and no hemorrhage. We analyzed 185 brain metastases, 84 of SCLC and 101 of NSCLC. SCLC brain metastases showed an ADC ratio of 0.68 ± 0.12 SD, and NSCLC brain metastases showed an ADC ratio of 1.47 ± 0.31 SD. Receiver operating curve statistics differentiated brain metastases of NSCLC from SCLC with an area under the curve of 0.99 and a 95% CI of 0.98 to 1, p < 0.001. Youden's J cut-point is 0.97 at a sensitivity of 0.989 and a specificity of 0.988. Conclusions: In patients with lung cancer and brain metastases with solid tumor parts, ADC ratio enables an ad hoc differentiation of SCLC and NSCLC, easily achieved during routine neuroradiological examination. Non-invasive MR imaging enables an early-individualized management of brain metastases from lung cancer.Trial registration: The study was registered in the German Clinical Trials Register (DRKS00023016).
How Central Support Built Capacity to Deliver a Health Promoting Intervention for Older Adults
Authors: Gould Joanie Sims , McKay Heather , Franke Thea
Published: December 2020

Background: A number of conceptual frameworks guide implementation and scale-up of evidence based (health promoting) interventions (EBIs). However, few studies delve into these frameworks to describe aspects of the delivery system--such as capacity building--that support successful scale-up. A standardized approach to capacity building is needed to develop new strategies and transfer successful strategies to new settings. Therefore, our objectives were to describe: (1) implementation strategies adopted by the central support system to build practitioners’ capacity to implement and scale-up a health promoting intervention (Choose to Move (CTM)), and (2) elements within capacity building strategies deemed essential to effectively implement CTM in diverse community contexts.Methods:﻿ CTM is a flexible, scalable, community-based health promoting physical activity (PA) and social connectedness intervention for older adults. In 2018-2020, eight health and social service societies, rural or remote municipalities, or community based organizations delivered CTM programs (n=22) that served older adults (n=322). We conducted in depth interviews with delivery partners (n=23), and a focus group with the central support system (n= 4) to assess key elements within capacity building strategies.Results: Capacity building strategies that delivery partners adopted were site selection/marketing, training, tools, technical assistance, peer networking, assessment and feedback. Essential elements that emerged within capacity building strategies were: a support system champion, activity coach skills, self efficacy and confidence; interactive assistance to answer questions and clarify materials. Key elements of central support that emerged were helping organizations-- adapt and tailor the EBI, leverage resources and strategies, maintain fidelity to the EBI, develop partnerships, train and monitor, learn from peers, increase awareness of older adult needs, increase PA programs for older adults and inform future organizational practices and processes. Central support provided a sounding board to organizations and were more successful if they were familiar with delivery partner resources and values, created buy-in and planned ahead.Conclusion: There is a key role for capacity building under the stewardship of central support units to promote implementation success. More clearly described capacity-building strategies that are designed and delivered to support implementation and scale-up would serve to advance the field, in future.
Care to Quit: A Stepped Wedge Cluster Randomised Controlled Trial to Implement Best Practice Smoking Cessation Care in Cancer Centres
Authors: Paul Christine L , Warren Graham , Vinod Shalini , Meiser Bettina , Stone Emily , Barker Daniel , White Kate , McLennan James , Day Fiona , McCarter Kristen , McEnallay Melissa , Tait Jordan , Canfell Karen , Weber Marianne , Segan Catherine
Published: December 2020

BackgroundCigarette smoking in people with cancer is associated with negative treatment related outcomes including increased treatment toxicity and complications, medication side effects, decreased performance status and morbidity. Evidence based smoking cessation care is not routinely provided to patients with cancer. The purpose of this study is to determine the effectiveness of a smoking cessation implementation intervention on abstinence from smoking in people diagnosed with cancer.MethodsA stepped wedge cluster randomized design will be used. All sites begin in the control condition providing treatment as usual. In a randomly generated order, sites will move to the intervention condition. Based on the Theoretical Domains Framework, implementation of Care to Quit will include i) building the capability and motivation of a critical mass of key clinical staff and identifying champions; and ii) identifying and implementing cessation care models/pathways. 2160 patients with cancer (diagnosed in the prior six months), aged 18+, who report recent combustible tobacco use (past 90 days or in the 30 days prior to cancer diagnosis) and are accessing anti-cancer therapy, will be recruited at nine sites. Assessments will be conducted at baseline and 7-month follow-up. The primary outcome will be 6-month abstinence from smoking. Secondary outcomes include biochemical verification of abstinence from smoking, duration of quit attempts, tobacco consumption, nicotine dependence, variables, provision and receipt of smoking cessation care, mental health and quality of life and cost effectiveness of the intervention. DiscussionThis study will implement best practice smoking cessation care in cancer centres and has the potential for wide dissemination. Trial registrationThe trial is registered with ANZCTR (www.anzctr.org.au): ACTRN (submitted, awaiting approval due to ANZCTR delays) prior to the accrual of the first participant and will be updated regularly as per registry guidelines.
Association Between Physical Activity Level and Cardiovascular Risk Factors in Adolescents Living with Type 1 Diabetes: A Cross-sectional Study
Authors: Wu Nana , Bredin Shannon , Jamnik Veronica , Koehle Michael , Guan Yanfei , Shellington Erin , Li Yongfeng , Li Jun , Warburton Darren
Published: December 2020

Background: Type 1 diabetes (T1D) is associated with a high risk of cardiovascular disease (CVD) and an increased rate of premature mortality from CVD. Regular physical activity can improve overall health and wellbeing and plays an important role in primary and secondary prevention of CVD. Methods: This cross-sectional study assessed cardiovascular risk factors, physical activity, and fitness (and their associations) in young individuals living with T1D and healthy controls. Primary outcomes included blood pressure, lipid profiles, and physical activity (accelerometry). We included a total of 48 individuals living with T1D and 19 healthy controls, aged 12 to 17 years. Statistical differences between groups were determined with chi-square, independent-samples t-tests or analysis of covariance. The associations between aerobic fitness, daily physical activity variables and cardiovascular risk factors were assessed with univariate and multivariate linear regression analysis.Results: In comparison to healthy controls, youth living with T1D showed higher levels of total cholesterol (4.03 ± 0.81 vs. 3.14 ± 0.67 mmol·L-1, p = 0.001), low-density lipoprotein cholesterol (LDL-C) (2.31 ± 0.72 vs. 1.74 ± 0.38 mmol·L-1, p = 0.035), and triglycerides (0.89 ± 0.31 vs. 0.60 ± 0.40 mmol·L-1 p = 0.012), and lower maximal oxygen power (VO2max) (35.48 ± 8.72 vs. 44.43 ± 8.29 mL·kg-1·min-1, p = 0.003), total physical activity counts (346.87 ± 101.97 vs. 451.01 ± 133.52 counts·min-1, p = 0.004), metabolic equivalents (METs) (2.09 ± 0.41 vs. 2.41 ± 0.60 METs, p = 0.033), moderate to vigorous intensity physical activity (MVPA), and the percentage of time spent in MVPA. The level of HDL-C was positively associated with METs (β = 0.29, p = 0.030, model R2 = 0.17), and the level of triglycerides was negatively associated with physical activity counts (β = -0.001, p = 0.018, model R2 = 0.205) and METs (β = -0.359, p = 0.015, model R2 = 0.208) in persons living with T1D. Conclusions:Youth with T1D, despite their young age and short duration of diabetes, present early signs of CVD risk, as well as low physical activity levels and cardiorespiratory fitness compared to healthy controls. Regular physical activity is associated with a beneficial cardiovascular profile in T1D, including improvements in lipid profile. Thus, physical activity participation should be widely promoted in youth living with T1D.
Intubation is Safe in Respiratory Failure Associated with Septic Shock: An Observational Study
Authors: Yang Ting , Shen Yongchun , Park John G. , Schulte Phillip J , Hanson Andrew C , Herasevich Vitaly , Dong Yue , Bauer Philippe R
Published: December 2020

BackgroundAcute respiratory failure associated with sepsis contributes to higher in-hospital mortality. Intubation and invasive mechanical ventilation is a common rescue procedure. However, the 2016 International Guidelines for Management of Sepsis and Septic Shock does not provide any recommendation on indication nor timing of intubation. Timely intubation may improve outcome. The decision to intubate those patients is often hampered by the fear of further hemodynamic deterioration following intubation. MethodsThis study aimed at evaluating the impact of timely intubation on outcome in sepsis associated respiratory failure. We conducted an ancillary analysis of a prospective registry od adult ICU patients with septic shock admitted to the medical ICU in a tertiary medical center, between April 30th, 2014 and December 31st, 2017. All cases of sepsis with lactate >4 mmol/L, mean arterial pressure <65 mmHg, or vasopressor use after 30 mL/kg fluid boluses and suspected or confirmed infection. Patients who remained hospitalized at 24 hours following sepsis onset were separated into intubated and non-intubated groups. The primary outcome was hospital mortality. Univariate and multivariable analyses were used, adjusted for admission characteristics and stabilization of shock within 6 hours. In a secondary analysis, time-dependent propensity score matching was used to match intubated and non-intubated patients.ResultsWe identified 345 (33%) patients intubated within 24 hours and 707 (67%) not intubated. Intubated patients were younger, transferred more often from an outside facility, had higher severity of illness scores, more lung infection, achieved blood pressure goals more often but less often lactate normalization within 6 hours. The crude in-hospital mortality was higher, 89 (26%) vs. 82 (12%), p<0.001, as were ICU mortality, and ICU and hospital length of stay. After adjustment, intubation showed no effect on hospital mortality but fewer hospital-free days through day 28. After 1:1 propensity score matching, there was no difference in hospital mortality, but fewer hospital-free days in the intubated group. ConclusionsIntubation within 24 hours of sepsis onset was safe and not associated with hospital mortality, but was associated with less 28-day hospital-free days. Intubation should not be discouraged in appropriate patients with septic shock.
Enhancing health care professionals’ knowledge of childhood sexual abuse through self-assessment: A realist review
Authors: Adisa Olumide , Allen Katherine , Tyrrell Katie
Published: December 2020

Background

Healthcare professionals (HCPs) are well-placed to facilitate disclosures by child sexual abuse/exploitation (CSA/E) survivors and promote timely access to specialist support. However, research with HCPs shows that many are reluctant to enquire about abuse and feel underprepared to deal with disclosures. Self-assessment offers a participatory approach that may be employed as part of a suite of educational interventions to increase HCP knowledge and confidence. As a complex intervention involving multiple steps and actors, its effectiveness is contingent on organisational contexts. Realist reviews offer a theory-driven and contextually sensitive approach for understanding the mechanisms of change that generate specific outcomes, enabling reviewers to identify generalisable insights on how and why programmes work.
Methods

We adopted a realist approach to answer the following questions: how are CSA/E self-assessment tools currently being used by HCPs, what does ‘good practice’ in the use of such tools look like, under what circumstances are existing tools effective, and why? Guided by Pawson’s 5 stages, we conducted a realist review of abuse-related self-assessment tools for HCPs. Following preliminary scoping of the literature, we developed an initial programme theory which informed our search strategy and theoretical framework.
Results

25 items met criteria for data extraction, and relevant contexts (C), mechanisms (M) and outcomes (O) were identified and mapped. Eight of these were included in the final synthesis. We identified two key ‘families’ of abuse-related self-assessment for healthcare contexts: PREMIS, a validated survey instrument to assess HCP knowledge, confidence and practice in relation to domestic violence and abuse (DVA); Trauma-informed practice/care (TIP/C) organisational self-assessment protocols. Two revised programme theories were formulated: 1. Individual self-assessment can promote organisational accountability 2. Organisational self-assessment can increase the coherence and sustainability of changes in practice.
Conclusions

Our review contributes to the evidence base on improving healthcare responses to CSA/E survivors, illustrating that self-assessment tools or protocols specifically designed to improve HCP responses to adult survivors of CSA/E remain under-developed and under-studied. Refined programme theories developed during synthesis regarding DVA and TIP/C related tools or protocols suggest areas for CSA/E-specific future research with stakeholders and service users.
Risk Factors of Pancreatitis after Percutaneous Transhepatic Biliary Stent Implantation in Patients with Distal Malignant Biliary Obstruction
Authors: Jia Nan , Chang Zhihui , Liu Zhaoyu
Published: December 2020

Purpose Percutaneous transhepatic biliary stent implantation (PTBS) has been widely used in the treatment of malignant obstructive jaundice (MBO)，which is an effective palliative therapy. The goal of the research was to explore the risk factors of postoperative pancreatitis in patients who had received PTBS.Materials and Methods This study retrospectively included 248 patients with distal malignant biliary obstruction (DMBO) who received PTBS from 2014 to 2019. The risk factors of postoperative pancreatitis such as clinical characteristics, laboratory and stent variables were evaluated by logistic regression analysis.Results Pancreatitis occurred in 51 (20%) patients, all of whom were mild pancreatitis. Multivariate analysis showed that stent implantation across the duodenal papilla, preoperative (within 3 days) administration of proton pump inhibitors (PPIs) were independent risk factors that related to pancreatitis (OR =13.242, 95% CI: 1.729–101.405; P = 0.013; OR =2.113, 95% CI: 1.024–4.36; P = 0.043, respectively), while preoperative administration of antibiotics was a protective factor (OR =0.466, 95% CI: 0.226–0.961; P = 0.039).Conclusion Patients with DMBO who underwent PTBS across the duodenal papilla were more likely to developing postoperative pancreatitis. Preoperative (within 3 days) administration of PPIs was also an independent risk factor for postoperative pancreatitis. Furthermore, preoperative administration of antibiotics may lower the risk of pancreatitis.
Correlation of [18F] FDG-PET/CT with dosimetry data: recurrence pattern after radiotherapy for head and neck carcinoma
Authors: Pisani Carla , Vigna Luca , Mastroleo Federico , Loi Gianfranco , Amisano Valentina , Masini Laura , Deantonio Letizia , Valletti Paolo Aluffi , Sacchetti Gian Mauro , Krengli Marco
Published: December 2020

ObjectiveTo analyze the pattern of failure in relation to pre-treatment [18F] FDG-PET/CT uptake in head and neck squamous cell carcinoma (HNSCC) patients treated with definitive radio-chemotherapy (RT-CHT).Methods and MaterialsFrom 2012 to 2016, 87 HNSCC patients treated with definitive RT-CHT, with intensity modulated radiation therapy with simultaneous integrated boost (IMRT-SIB), underwent pre-treatment [18F] FDG-PET/CT (PETpre), and MRI/CT for radiotherapy (RT) planning purposes. Patients with local recurrence, received [18F] FDG-PET/CT, (PETrec) at the time of the discovery of recurrence. In these patients, the biological target volume (BTV), BTVpre and BTVrec were segmented on PET images by means of an adaptive thresholding algorithm. The overlapping volume between BTVpre and BTVrec (BTVpre&rec) was generated and the dose coverage of BTVrec and BTVpre&rec was checked on the planning CT using the D99 and D95 dose metrics. The recurrent volume was defined as: ‘‘In-Field (IF)’’, ‘‘Extending Outside the Field (EOF)’’ or ‘‘Out-of-Field (OF)’’ if D95 was respectively equal or higher than 95%, D95 was between 95% and 20% or the D95 was less than 20% of prescribed dose.ResultsWe found 10/87 patients (11.5%) who had recurrence at primary site. Mean BTVpre was 13.1 cc (4.6-37.4 cc), while the mean BTVrec was 4.3 cc (1.1-12.7 cc). Two recurrences resulted 100% inside BTVpre, 4 recurrences were mostly inside (61%-91%) and 4 recurrences were marginal to BTVpre (33-1%). At dosimetric analysis, six recurrences (60%) were IF, 3 (30%) EOF and one (10%) OF. The mean D99 of the overlapping volumes BTVpre&rec was 68.1Gy (66.5-69.2 Gy), considering a prescription dose of 70 Gy to the planning target volume (PTV). ConclusionOur study shows that the recurrence may originate from the volume with the highest FDG-signal. Results support the hypothesis that an intensification of the dose on these volumes could be helpful to prevent local relapse.
Comparison of Diaphragmatic Paralysis, Respiratory Function and Postoperative Pain After Interscalene Brachial Plexus Block With a Reduction Dose of Levobupivacaine 0.25% 10 ml Versus 20 ml Undergoing Arthroscopic Shoulder Surgery: Study Protocol for the Randomized, Controlled and Double-blinded REDOLEV Study.
Authors: Oliver-Fornies Pablo , Lahuerta Pablo Ortega , Gomez Roberto Gomez , Pellicer Inmaculada Gonzalo , Gutierrez Leticia Oliden , Cabeza Jose Vinuales , Ligorit Lucia Gallego , Melgar Carlos Edgardo Orellana
Published: December 2020

Background: Arthroscopic shoulder surgery involves dynamic and severe postoperative pain. Interscalene brachial plexus block provides adequate analgesia, but the spread of local anaesthetics administered causes a phrenic nerve block that entrains a nonnegligible incidence of hemidiaphragmatic paralysis acute.The main objective of this trial is to compare the hemidiaphragmatic paralysis after interscalene brachial plexus block in arthroscopic shoulder surgery, between a standard volume (20 ml) and a low volume (10 ml) of 0.25% levobupivacaine.Methods: This is a comparative, prospective, single-center, double-blind, two-arm randomized controlled trial. Forty-eight patients will be included. The primary end-point is to determine the hemidiaphragmatic paralysis incidence diagnosed by the diaphragmatic thickness ratio in ultrasound. The secondary endpoints are as follows: (1) hemidiaphragmatic paralysis incidence diagnosed by forced vital capacity and (2) forced expiratory volume at 1 second decrease in spirometry; (3) hemidiaphragmatic paralysis incidence diagnosed by using diaphragmatic excursion decrease in ultrasound; (4) postoperative pain regarding 24-hour morphine intravenous total consumption and (5) time to first analgesic consumption of patient-controlled analgesia pump; and (6) postoperative harm between the two trial arms.Discussion: This trial would demonstrate that low-volume interscalene brachial plexus block decreases hemidiaphragmatic paralysis in arthroscopic shoulder surgery by using spirometry and ultrasound and would not provide inferior postoperative analgesia according to opioid requirements of postoperative patient-controlled analgesia in comparison to the standard volume used in current practice.Trial registration: EudraCT and Spanish Trial Register (REec) registration number: 2019-003855-12 (Registered on 07 January 2020). ClinicalTrials.gov identification number: NCT04385966 (Retrospectively registered on 08 May 2020). Ethics Committee approval: EC19/093 (18 Dic 2019).
Impact of Sofosbuvir and Daclastavir on Health-related Quality of Life in Patients Co-infected With Hepatitis C and Human Immunodeficiency Virus
Authors: Yunihastuti Evy , Amelia Fhadilla , Hapsari Arini Ika , Wicaksana Bramantya , Natali Veritea , Widhani Alvina , Sulaiman Andri Sanityoso , Karjadi Teguh Harjono
Published: December 2020

BackgroundWe conducted a real-life study of health-related quality of life (HRQoL) transformation before and 12 weeks after sofosbuvir and daclatasvir therapy in HCV/HIV co-infected patients. Factors related to the significant changes of each HRQoL domain were also evaluated.MethodsA prospective study was performed in the HIV integrated clinic at Cipto Mangunkusumo Hospital, Jakarta. HCV/HIV co-infected patients who started sofosbuvir and daclatasvir from government free DAA program in 2017-2019. WHOQoL-HIV BREF and RAND SF-36 questionnaires were recorded at baseline and post-treatment week 12. Results145 patients with mean age of 37.8 years (SD=4.2) were included in the analysis. Most of patients were male (89%), previous IVDU (89%), active smoker (50.4%) and non-cirrhosis (80%). SVR12 was achieved in 95.5% of patients. Sofosbuvir and daclatasvir treatments showed positive impacts on 4 domains of WHOQoL-HIV BREF and 3 domains of SF-36. Predicting factors of significant increase in each domain were: male and normal body mass index (BMI) for level of independence (RR 4.01,95% CI 1.09-14.74 and 4.80,95% CI 1.79-12.81); higher HCV-RNA for overall perception of QoL (RR 0.42,95% CI 0.18-0.94); non-smoking status for overall perception of health (RR 0.32,95% CI 0.15-0.66); male and fibrosis stage 0-1 for general health (6.21,95% CI 1.69-22.88 and 2.86,95% CI 1.16-7.00). Spiritual/personal belief decline was predicted by non-smoking status (RR 0.49,95% CI 0.24-0.98). Treatment success was not associated with any changes of HR-QoL.ConclusionsHCV/HIV co-infected patients were successfully treated with sofosbuvir and daclatasvir and experienced improvement of HRQoL 12 weeks after treatment completion.