bluuebunny/crossref_metadata_2025 huggingface dataset:
Virtual patient simulation to improve nurses’ relational skills in a continuing education context: A convergent mixed-methods study
Authors: Rouleau Geneviève , Gagnon Marie-Pierre , Côté José , Richard Lauralie , Chicoine Gabrielle , Pelletier Jérôme
Published: November 2020

Background: Some nurses may feel ill-equipped to support people living with HIV who do not optimally adhere to their antiretroviral therapy. In response, to enhance the relational skills nurses require in situations of non-adherence, we developed a virtual patient simulation that features an HIV-positive man struggling to adhere to his therapy. The simulation is informed by a strengths-based nursing approach, motivational interviewing, and adult learning theories This study aimed to assess nurses’ perception of simulation’s acceptability. Specific objectives were: to measure the simulation design elements, its role in supporting practice, its quality and technology acceptance, and the achievement of learning objectives; to explore nurses’ learning experience.Methods: We conducted a convergent mixed methods study by combining a quantitative pre-experimental, one-group post-test design and a qualitative exploratory study. We used convenience and snowball sampling approaches to select Canadian registered nurses (n=49). who self-reported as having basic computer literacy skills. Participants completed an online sociodemographic questionnaire, consulted the simulation, and filled out an online post-test survey. Descriptive statistics (mean, SD, median, interquartile range) were used to present quantitative findings. From the 27 participants who completed the simulation and post-test survey, five participated in a focus group to explore their learning experience. The discussion transcript was subjected to thematic analysis. At the final stage of the study, we used a comparison strategy for integrating the quantitative and qualitative results.Results: Nurses perceived the simulation to be highly acceptable. They rated the global system quality and the technology acceptance with high scores. They reported having enjoyed the simulation and recommended other providers use it. Four qualitative themes were identified: motivations to engage in the simulation-based research; learning in a realistic, immersive, and non-judgmental environment; perceived utility of the simulation; and perceived difficulty in engaging in the simulation-based research.Conclusions: The simulation contributed to knowledge and skills development on motivational interviewing and enhanced nurses’ self-confidence in applying relational skills. Simulation holds the potential to change practice, as nurses become more self-reflective and aware of the impact of their relational skills on patient care. Relational skills are fundamental to high-quality nursing care.Trial registration: ISRCTN18243005, retrospectively registered on July 3 2020.
A DNA Methylation-based Test for Esophageal Cancer Detection
Authors: Salta Sofia , Macedo-Silva Catarina , Miranda-Gonçalves Vera , Lopes Nair , Gigliano Davide , Guimarães Rita , Farinha Mónica , Sousa Olga , Henrique Rui , Jeronimo Carmen
Published: November 2020

Background: Esophageal cancer (ECa) is the 7th most incident cancer and the 6th leading cause of cancer-related death. Most patients are diagnosed with locally advanced or metastatic disease, enduring poor survival. Biomarkers enabling early cancer detection may improve patient management, treatment effectiveness, and survival, are urgently needed. In this context, epigenetic-based biomarkers such as DNA methylation are potential candidates. Methods: Herein, we sought to identify and validate DNA methylation-based biomarkers for early detection and prediction of response to therapy in ECa patients. Promoter methylation levels were assessed in a series of treatment-naïve ECa, post-neoadjuvant treatment ECa, and normal esophagus tissues, using quantitative methylation-specific PCR for COL14A1, GPX3, and ZNF569. Results: ZNF569 methylation (ZNF569me) levels significantly differed between ECa and normal samples (p<0.001). Moreover, COL14A1 methylation (COL14A1me) and GPX3 methylation (GPX3me) levels discriminated adenocarcinomas and squamous cell carcinomas, respectively, from normal samples (p=0.002 and p=0.009, respectively). COL14A1me & ZNF569me accurately identified adenocarcinomas (82.29%) whereas GPX3me & ZNF569me identified squamous cell carcinomas with 81.73% accuracy. Furthermore, ZNF569me and GPX3me levels significantly differed between normal and pre-treated ECa. Conclusion: The biomarker potential of a specific panel of methylated genes for ECa was confirmed. These might prove useful for early detection and might allow for the identification of minimal residual disease after adjuvant therapy.
Molecular characterization and serodiagnostic potential of two serpin proteins in Psoroptes cuniculi
Authors: Gu Xiaobin , Chen Yuhang , Zhang Chongyang , Xie Yue , Shen Nengxing , Wang Ce , Zhou Xuan , Yang Guangyou , He Ran , Peng Xuerong , Yang Deying , He Zhi , Zhong Zhijun
Published: November 2020

Background: Psoroptes cuniculi is a global common ectoparasite of wild and domestic rabbits and causes an economically devastating loss and serious welfare issues of commercial rabbit husbandry. Serine proteinase inhibitor (serpin) is present in almost all organisms that are involved in host-pathogen interactions, inflammatory responses, and reproductive development, etc. However, the research on P. cuniculi serpins is still limited.Methods: In this study, two serpin genes of P. cuniculi (Pso c 27 and PsoSP2 cDNAs) were cloned, and the molecular characterization was analyzed. The transcriptional profiles and tissue localization of these two serpins in P. cuniculi were investigated by quantitative real-time PCR and immunohistochemistry, respectively. The potential function of recombinant Pso c 27 and PsoSP2 (rPso c 27and rPsoSP2) in the serodiagnosis of P. cuniculi infestation in rabbits were evaluated by indirect enzyme-linked immunosorbent assay (iELISA). Results: Both of the 523 residue Pso c 27 and the 240 residue PsoSP2 proteins contained typical serpin domains and signatures. Both Pso c 27and PsoSP2 cDNAs expressed throughout the life-cycle, more specifically, significantly higher expression in female mites than the larva, nymph, and male mites (Pso c 27, F(3, 8) = 1935.953, P < 0.0001; PsoSP2, F(3, 8) = 660.669, P < 0.0001). The native Pso c 27 and PsoSP2 localized in ovary and mouthpart of adult female mites, respectively. Compared to rPsoSP2, the rPso c 27 displayed better diagnostic efficiency with higher values of sensitivity, specificity and the area under the receiver operating characteristic curve (AUC) (rPso c 27 vs rPsoSP2: 96.0 vs 90.0%; 90.91 vs 78.18%; 0.988 vs 0.964, respectively). Moreover, the rPso c 27 showed seropositive in 80% rabbits as early as the 2 weeks post-infestation (p.i.), prior to visible clinical signs and microscopy-positive of skin scrapings. Conclusions: These results suggested that these two serpins may play essential roles in reproductive development, serum-feeding, and pathogenicity of P. cuniculi. Compared to PsoSP2, Pso c 27 appeared as a potential antigen for serodiagnosis of P. cuniculi infestation in rabbits, especially at the early stage of infestation.
Plant nutrient quality impacts survival and reproductive fitness of the dengue vector Aedes aegypti
Authors: Nyasembe Vincent Odhiambo , Tchouassi David Poumo , Muturi Martha Njeri , Pirk Christian W. W. , Sole Catherine L. , Torto Baldwyn
Published: November 2020

Background: In a recent study using DNA barcoding, we identified the plants fed upon by four Afro-tropical mosquito species that vector dengue, malaria, and Rift Valley fever. Herein, we have expanded on this study by investigating the role of three of the plants Pithecellobium dulce (Fabaceae), Leonotis nepetifolia (Lamiaceae), and Opuntia ficus-indica (Cactaceae) on survival, fecundity, and egg viability of the dengue vector Aedes aegypti. Methods: We tested these effects using females that received a) an initial three rations of bloodmeal, and b) received no bloodmeal at all. Two controls were included; age-matched females fed on glucose solution with or without initial bloodmeal, and those fed exclusively on bloodmeal. Data was collected daily over a 30-day period. The amino acid content of Ae. aegypti guts and the amino acid content of their respective diets was detected by coupled liquid chromatography – mass spectrometry.Results: Females fed on P. dulce and exclusive bloodmeal had a shorter survival than those fed on glucose. On the other hand, females fed on L. nepetifolia survived longer than those fed exclusively on bloodmeal, whereas those fed on O. ficus-indica had the shortest survival time. With initial bloodmeal, females fed on L. nepetifolia laid 1.6-fold more eggs while those fed on the other diets laid fewer eggs, compared to those fed exclusively on bloodmeal. Hatching rates of the eggs laid varied with the diet. Mass spectroscopic analysis of gut contents of mosquitoes exposed to the different diets showed qualitative and quantitative differences in their amino acid levels. Conclusion: Our findings highlight the central role of plant nutrients in the reproductive fitness of dengue vectors which may impact their disease transmission potential.
Mitophagy Promotes Sorafenib Resistance through Hypoxia-Inducible ATAD3A Dependent Axis
Authors: Wu Hong , Wang Tao , Liu Yiqiang , Li Xin , Xu Senlin , Wu Changtao , Zou Hongbo , Cao Mianfu , Jin Guoxiang , Lang Jinyi , Wang Bin , Liu Baohua , Luo Xiaolin , Xu Chuan
Published: November 2020

Background: The identification of novel targets for recovering sorafenib resistance is pivotal for Hepatocellular carcinoma (HCC) patients. Mitophagy is the programmed degradation of mitochondria, and is likely involved in drug resistance of cancer cells. Here, we identified hyperactivated mitophagy is essential for sorafenib resistance, and the mitophagy core regulator gene ATAD3A (ATPase family AAA domain containing 3A) was down regulated in hypoxia induced resistant HCC cells. Blocking mitophagy may restore the sorafenib sensitivity of these cells and provide a new treatment strategy for HCC patients. Methods: Hypoxia induced sorafenib resistant cancer cells were established by culturing under 1% O 2 with increasing drug treatment. RNA sequencing was conducted in transfecting LM3 cells with sh-ATAD3A lentivirus. Subsequent mechanistic studies were performed in HCC cell lines by manipulating ATAD3A expression isogenically where we evaluated drug sensitivity, molecular signaling events. In vivo study, we investigated the combined treatment effect of sorafenib and miR-210-5P antagomir. Results: We found a hyperactivated mitophagy regulating by ATAD3A-PINK/PARKIN axis in hypoxia induced sorafenib resistant HCC cells. Gain- and loss- of ATAD3A were related to hypoxia-induced mitophagy and sorafenib resistance. In addition, ATAD3A is a functional target of miR-210-5p and its oncogenic functions are likely mediated by increased miR-210-5P expression. miR-210-5P was upregulated under hypoxia and participated in regulating sorafenib resistance. In vivo xenograft assay showed that miR-210-5P antagomir combined with sorafenib abrogated the tumorigenic effect of ATAD3A down-regulation in mice. Conclusions: Loss of ATAD3A hyperactivates mitophagy which is a core event in hypoxia induced sorafenib resistance in HCC cells. Targeting miR-210-5P-ATAD3A axis is a novel therapeutic target for sorafenib-resistant HCC. Keywords: Mitophagy, ATAD3A, Hypoxia, Sorafenib resistance
Isolating the Energetic and Mechanical Consequences of Imposed Reductions in Ankle and Knee Flexion during Gait.
Authors: McCain Emily , Libera Theresa , Berno Matthew , Sawicki Gregory , Saul Katherine , Lewek Michael
Published: November 2020

Background: Weakness of ankle and knee musculature following injury or disorder results in reduced joint motion associated with metabolically expensive gait compensations to enable limb support and advancement. However, neuromechanical coupling between the ankle and knee make it difficult to discern independent roles of these restrictions in joint motion on compensatory mechanics and metabolic penalties.Methods: We sought to determine relative impacts of ankle and knee impairment on compensatory gait strategies and energetic outcomes using an unimpaired cohort (N=15) with imposed unilateral joint range of motion restrictions as a surrogate for reduced motion resulting from gait pathology. Participants walked on a dual-belt instrumented treadmill at 0.8 m s-1 using a 3D printed ankle stay and a knee brace to systematically limit ankle motion (restricted-ank), knee motion (restricted-knee), and ankle and knee motion (restricted-a+k) simultaneously. In addition, participants walked without any ankle or knee bracing (control) and with knee bracing worn but unrestricted (braced).Results: When ankle motion was restricted (restricted-ank, restricted-a+k) we observed decreased peak propulsion relative to the braced condition on the restricted limb. Reduced knee motion (restricted-knee, restricted-a+k) increased restricted limb circumduction relative to the restricted-ank condition through ipsilateral hip hiking. Interestingly, restricted limb average positive hip power increased in the restricted-ank condition but decreased in the restricted-a+k and restricted-knee conditions, suggesting that locking the knee impeded hip compensation. As expected, reduced ankle motion, either without (restricted-ank) or in addition to knee restriction (restricted-a+k) yielded significant increase in net metabolic rate when compared with the braced condition. Furthermore, the relative increase in metabolic cost was significantly larger with restricted-a+k when compared to restricted-knee condition.Conclusions: Our methods allowed for the reproduction of asymmetric gait characteristics including reduced propulsive symmetry and increased circumduction. The metabolic consequences bolster the potential energetic benefit of targeting ankle function during rehabilitation.
Laboratory and microcosm experiments reveal contrasted adaptive responses to ammonia and water mineralisation in aquatic stages of the sibling species Anopheles gambiae (sensu stricto) and Anopheles coluzzii 
Authors: AKPODIETE NWAMAKA OLUCHUKWU , TRIPET FREDERIC
Published: November 2020

Background: The sibling species of the malaria mosquito, Anopheles gambiae (sensu stricto) and Anopheles coluzzii co-exist in many parts of West Africa and are thought to have recently diverged through a process of ecological speciation with gene flow. Divergent larval ecological adaptations, resulting in Genotype × Environment (G × E) interactions have been proposed as important drivers of speciation in these species. In West Africa, An. coluzzii tends to be associated with permanent man-made larval habitats such as irrigated rice fields which are typically more eutrophic and mineral and ammonia-rich than the temporary rain pools exploited by An. gambiae (s.s.) Methods: To highlight G × E interactions at the larval stage and their possible role in ecological speciation of these species, we first investigated the effect of exposure to ammonium hydroxide and water mineralisation on larval developmental success. Mosquito larvae were exposed to two water sources and increasing ammonia concentrations in small containers until adult emergence. In a second experiment, larval developmental success was compared across 2 contrasted microcosms to highlight G × E interactions under conditions like those found in the natural environment. Results: The first experiment revealed significant G × E interactions in developmental success and phenotypic quality for both species in response to increasing ammonia concentrations and water mineralisation. The An. coluzzii strain outperformed the An. gambiae (s.s.) strain under limited conditions that were closer to more eutrophic habitats. The second experiment revealed divergent crisscrossing reaction norms in the developmental success of the sibling species in the two contrasted larval environments. As expected, An. coluzzii had higher emergence rates in the rice paddy environment with emerging adults of superior phenotypic quality compared to An. gambiae (s.s.), and vice versa in the rain puddle environment.Conclusions: Evidence for such G × E interactions lends support to the hypothesis that divergent larval adaptations to the environmental conditions found in man-made habitats such as rice-fields in An. coluzzii may have been an important driver of its ecological speciation.
Roquin1 inhibits the proliferation of breast cancer cells by inducing G1/S cell cycle arrest via selectively destabilizing the mRNAs of cell cycle–promoting genes
Authors: Lu Wenbao , Zhou Meicen , Wang Bing , Liu Xueting , Li Bingwei
Published: November 2020

Background: Dysregulation of cell cycle progression is one of the common features of human cancer cells, however, its mechanism remains unclear. This study aims to clarify the role and the underlying mechanisms of Roquin1 in cell cycle arrest induction in breast cancer. Methods: Public cancer databases were analyzed to identify the expression pattern of Roquin1 in human breast cancers and the significant association with patient survival. Quantitative real-time PCR and western blots were performed to detect the expression of Roquin1 in breast cancer samples and cell lines. Cell counting, MTT assay, flow cytometry, and in vivo study were conducted to investigate the effects of Roquin1 on cell proliferation, cell cycle progression and tumor progression. RNA-sequencing was applied to identify the differential genes and pathways regulated by Roquin1. RNA immunoprecipitation assay, luciferase reporter assay, mRNA half-life detection, RNA affinity binding assay, and RIP-ChIP were used to explore the molecular mechanisms of Roquin1. Results: We showed that Roquin1 expression in breast cancer tissues and cell lines was inhibited, and the reduction in Roquin1 expression was associated with poor overall survival and relapse free survival of patients with breast cancer. Roquin1 overexpression inhibited breast cancer cell proliferation and induced G1/S cell cycle arrest without causing significant apoptosis. In contrast, knockdown of Roquin1 promoted breast cancer cell growth and cycle progression. Moreover, in vivo induction of Roquin1 by adenovirus significantly suppressed breast tumor growth and metastasis. Mechanistically, Roquin1 selectively destabilizing cell cycle–promoting genes, including Cyclin D1, Cyclin E1, cyclin dependent kinase 6 (CDK6) and minichromosome maintenance 2 (MCM2) through targeting the stem–loop structure in the 3’untranslated region (3’UTR) of mRNAs via its ROQ domain, leading to the downregulation of cell cycle–promoting mRNAs. Conclusions: Our findings demonstrated that Roquin1 was a novel breast tumor suppressor and could induce G1/S cell cycle arrest by selectively downregulating the expression of cell cycle–promoting genes, which might as a potential molecular target for breast cancer treatment.
Patterns of flea infestation in rodents and insectivores from intensified agro-ecosystems, NW Spain
Authors: Herrero-Cófreces Silvia , Flechoso Manuel Fabio , Rodríguez-Pastor Ruth , Luque-Larena Juan José , Mougeot Francois
Published: November 2020

Background: Fleas frequently infest small mammals and play important vectoring roles in the epidemiology of (re)emerging zoonotic disease. Rodent outbreaks in intensified agro-ecosystems of NW Spain have been recently linked to periodic zoonotic disease spillover to local human populations. Obtaining qualitative and quantitative information about the composition and structure of the whole flea and small mammal host coexisting communities is paramount to understand disease transmission cycles and to dilucidate the disease-vectoring role of flea species. The aims of this research were to: i) characterise and quantify the flea community parasiting a small mammal guild in intensive farmlands in NW Spain, and ii) determine and evaluate patterns of co-infection and the variables that may influence parasitological parameters.Methods: We conducted a large scale survey stratified by season and habitat of fleas parasitizing the small mammal host guild. We report on the prevalence, mean intensity, and mean abundance of flea species parasitizing Microtus arvalis, Apodemus sylvaticus, Mus spretus and Crocidura russula. We also report on aggregation patterns (variance-to-mean ratio and Discrepancy index), co-infection of hosts by different flea species (Fager Index), and used Generalized Linear Mixed Models to study flea parameter variation according to season, habitat and host sex. Results: Three flea species dominated the system: Ctenophthalmus apertus gilcolladoi, Leptopsylla taschenbergi and Nosopsyllus fasciatus. Results showed a high aggregation pattern of fleas in all hosts. All host species in the guild shared C. a. gilcolladoi and N. fasciatus, but L. taschenbergi mainly parasitized mice (M. spretus and A. sylvaticus). We found significant male-biased infestation patterns in mice, seasonal variations in flea abundances for all rodent hosts (M. arvalis, M. spretus and A. sylvaticus), and relatively lower infestation values for voles inhabiting alfalfas. Simultaneous co-infections occurred in a third of all hosts, and N. fasciatus was the commonest flea co-infecting small mammal hosts. Conclusions: The generalist N. fasciatus and C. a. gilcolladoi dominated the flea community, and a high percentage of co-infections with both species occurred within the small mammal guild. Nosopsyllus fasciatus may show higher competence of inter-specific transmission, and future research should unravel its role in the circulation of rodent-borne zoonoses.
Value of AFP and PIVKA-II in diagnosis of HBV-related hepatocellular carcinoma and prediction of vascular invasion and tumor differentiation
Authors: Si Yuan-quan , Wang Xiu-Qin , Fan Gang , Wang Chang-Yin , Zheng Yuan-Wen , Song Xie , Pan Cui-Cui , Chu Fu-Lu , Liu Zhan-Feng , Lu Bing-Ru , Lu Zhi-Ming
Published: November 2020

Background: To explore the value of alpha fetoprotein (AFP) and protein induced by vitamin K absence or antagonist-II (PIVKA-II) in diagnosis of HBV-related hepatocellular carcinoma (HCC) and their relationship with vascular invasion, tumor differentiation and size. Methods: A total of 433 participants were enrolled in this study including 266 cases with HBV-related HCC, 87 cases with HBV DNA positive benign liver disease and 80 healthy individuals. Then we explored the correlation between AFP, PIVKA-II serum level and several pathological features such as vascular invasion, tumor differentiation and size. The value of these two markers used singly or jointly in diagnosing HBV-related HCC was evaluated by receiver operating characteristic (ROC) curve. The ROC curve was also plotted to identify AFP, PIVKA-II serum cut-off values that would best distinguish HBV-related HCC patients with and without vascular invasion.Results: The level of AFP and PIVKA-II in HBV-related HCC group was significantly higher (Z was 7.428, 11.243 respectively, all P<0.01). When AFP and PIVKA-II were used as the individual tumor marker, the areas under the ROC curve (AUC) of HBV-related HCC diagnosis were 0.765 (95% CI, 0.713～0.8170) for AFP, 0.901 (95% CI, 0.868～0.935) for PIVKA-II, and 0.917 (95% CI, 0.886～0.948) for AFP and PIVKA-II simultaneously. The serum levels of AFP and PIVKA-II were positively correlated with tumor differentiation and size. High AFP and PIVKA-II expression was signiﬁcantly associated with the presence of vascular invasion (P was 0.007 and 0.014 respectively). The AFP level >64.4ng/ml or PIVKA-II level >957.61mAU/ml was the best critical value to predict the presence of vascular invasion. Conclusion: Our results validate that AFP and PIVKA-II play a significant role in the diagnosis of HBV-related HCC. The diagnostic value of AFP and PIVKA-II combined detection or single assay of PIVKA-II is higher than that of separate assay of AFP. Moreover, their concentration has important clinical value in judging tumor size, tumor cell differentiation and vascular invasion.
Clinicopathologic Characteristics and Surgical Outcome of Synthetic Fiber Conjunctival Granuloma
Authors: Chen Zhang , Wang Tianyang , Pan Qintuo , Zhang Zhaoliang , Zhang Zongduan
Published: November 2020

Background: Until recently, synthetic fiber conjunctival granuloma (SFCG) is rarely reported and has been poorly understood. Our study was to explore the clinical features, histopathologic characteristics, surgical outcomes, and prognosis of SFCG after surgical excision. Methods: Retrospective review of clinical findings, histopathological and immunohistochemical studies identified 18 cases of SFCG. Specimens were routinely processed and stained with H&E. Immunohistochemical stains for GMS, PAS, CD68 and CK-pan were also performed.Results: Eighteen patients with an average age of 9.3±6.6 years had a tender white to red mass on the conjunctiva. All the lesions were completely removed, and none of the patients relapsed. Histologically, all of the specimens revealed inflammatory granulation tissues with a large number of inflammatory cells infiltration and the presence of synthetic fibers. Immunohistochemical stains were positive for CD68, CK, GMS and PAS. Conclusions: Synthetic fiber conjunctival granuloma is an uncommon lesion with foreign body sensation caused by inoculation of synthetic exogenous materials. These lesions are mostly unilateral and occur in the inferior conjunctival fornix. SFCGs are characterized by a large number of inflammatory cells infiltration and the presence of synthetic fibers. Surgical excision followed by topical corticosteroids has been clinically proven to be effective.
FLT-PET for the assessment of systemic sarcoidosis including cardiac and CNS involvement: A prospective study with comparison to FDG-PET
Authors: Martineau Patrick , Pelletier-Galarneau Matthieu , Juneau Daniel , Leung Eugene , Nery Pablo , deKemp Rob , Beanlands Rob , Birnie David
Published: November 2020

BACKGROUND:FDG’s biodistribution limits the evaluation of cardiac sarcoidosis (CS) and neurosarcoidosis (NS). While protocols for cardiac suppression exist, they can be inconvenient for patients and lead to incomplete cardiac suppression in many cases. Furthermore, FDG PET is limited in the detection of neurosarcoidosis due to an inability to suppress high level of physiological uptake within the brain. FLT has been shown to accumulate in sarcoidosis lesions and this tracer lacks significant physiological myocardial and brain uptake, suggesting that this tracer may be useful for the assessment of sarcoidosis, including CS and NS, without the need for patient preparation. This prospective pilot study examined the performance of FLT vs FDG PET for systemic sarcoidosis, including cardiac and neural involvement.MATERIALS AND METHODS:14 subjects with sarcoidosis were prospectively recruited and imaged with FDG- and FLT-PET. Two blinded, experienced readers independently reviewed the FLT-PET and FDG-PET images. Lesion distribution was compared between FLT and FDG. Agreement between FLT- and FDG-PET was determined using Cohen’s kappa and the intra-class correlation coefficient. Inter-observer variability of FLT and FDG-PET was assessed.RESULTS:12 subjects had CS as per Heart Rhythm Society criteria and 1 had NS. FLT-PET was positive in 12 (86%), and FDG-PET in 11 (79%), with cardiac uptake present in 6 (50%) and 7 (58%) of subjects with CS, respectively. The subject with NS demonstrated uptake on both FLT and FDG-PET, with more lesions on FLT. There were no significant differences in the anatomical distribution of lesions between FLT and FDG. SUVs were significantly (p<0.001) higher for FDG than FLT (5.8 ± 3.0 vs 2.3 ± 1.1, respectively), but not (p=0.90) after adjusting for blood pool activity (2.8 ± 1.4 vs 2.8 ± 1.1, respectively). Agreement between FLT- and FDG-PET was good to excellent for the diagnosis of sarcoidosis, lung involvement, CS, and NS (κ = 0.76, 0.69, 0.86, and 1.0, respectively). Inter-observer agreement for FLT was excellent for diagnosing sarcoidosis, CS and NS (κ = 0.81, 0.85, and 1.0, respectively) and comparable to that of FDG.CONCLUSIONS:FLT-PET may be useful for the assessment of systemic sarcoidosis, as well as cardiac and neural involvement.
Effectiveness of chiropractic manipulation versus sham manipulation for recurrent headaches in children aged 7-14 years. A randomised clinical trial
Authors: Lynge Susanne , Dissing Kristina Boe , Vach Werner , Christensen Henrik Wulf , Hestbaek Lise
Published: November 2020

Background To investigate the effectiveness of chiropractic spinal manipulation versus sham manipulation in children aged 7-14 with recurrent headaches.Methods Design: A two-arm, single-blind, superiority randomised controlled trial.Setting: One chiropractic clinic and one paediatric specialty practice in Denmark Participants: 199 children aged 7 to 14 years, who experienced at least one episode of headache per week for the previous 6 months and with at least one musculoskeletal dysfunction identified. Interventions: All participants and parents received standard oral and written advice to reduce headaches. In addition, children in the active treatment group received chiropractic spinal manipulation and children in the control group received sham manipulation for a period of 4 months. Number and frequency of treatments were based on the chiropractor’s individual evaluation in the active treatment group, and the children in the control group received approximately eight visits during the treatment period.Primary outcome measures: ‘Number of days with headache’, ‘pain intensity’ and ‘medication’ were reported weekly by text messages, and global perceived effect by text message after 4 months. A planned fixed sequence strategy based on an initial outcome data analysis was used to prioritize outcomes. ‘Number of days with headache’ and ‘pain intensity’ were chosen as equally important outcomes of highest priority, followed by global perceived effect and medication. The significance level for the first two outcomes was fixed to 0.025 to take multiplicity into account.Results Chiropractic spinal manipulation resulted in significantly fewer days with headaches (reduction of 0.81 vs. 0.41, p=0.019, NNT=7 for 20% improvement) and better global perceived effect (dichotomized into improved/not improved, OR=2.8 (95% CI: 1.5-5.3), NNT=5) compared with a sham manipulation procedure. There was no difference between groups for pain intensity during headache episodes. Due to methodological shortcomings, no conclusions could be drawn about medication use.Conclusions Chiropractic spinal manipulation resulted in fewer headaches and higher global perceived effect, with only minor side effects. It did not lower the intensity of the headaches.Since the treatment is easily applicable, of low cost and minor side effects, chiropractic spinal manipulation might be considered as a valuable treatment option for children with recurrent headaches.Trial registration ClinicalTrials.gov, identifier NCT02684916, registered 02/18/2016 – retrospectively registered. https://clinicaltrials.gov/ct2/show/NCT02684916
Cardiovascular and Renal Outcomes with SGLT-2 Inhibitors versus GLP-1 Receptor Agonists in Patients with Type 2 Diabetes Mellitus and Chronic Kidney Disease: A Systematic Review and Network Meta-analysis
Authors: Yamada Takayuki , Wakabayashi Mako , Bhalla Abhinav , Chopra Nitin , Miyashita Hirotaka , Mikami Takahisa , Ueyama Hiroki , Fujisaki Tomohiro , Saigusa Yusuke , Yamaji Takahiro , Azushima Kengo , Urate Shingo , Suzuki Toru , Abe Eriko , Wakui Hiromichi , Tamura Kouichi
Published: November 2020

BackgroundEmerging evidence suggests that sodium-glucose cotransporter-2 (SGLT-2) inhibitors and glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are associated with decreased risk of cardiovascular and renal events in type 2 diabetes mellitus (DM) patients. However, no study to date has compared the effect of SGLT-2 inhibitors with that of GLP-1 RAs in type 2 DM patients with chronic kidney disease (CKD). We herein investigated the benefits of SGLT-2 inhibitors and GLP-1 RAs in CKD patients.MethodsWe performed a systematic literature search through October 2020. We selected randomized control trials that compared the risk of major adverse cardiovascular events (MACE) and a composite of renal outcomes. We performed a network meta-analysis to compare SGLT-2 inhibitors with GLP-1 RA indirectly. Risk ratios (RRs) with corresponding 95% confidence interval (CI) were synthesized.ResultsThirteen studies were selected with a total of 24,887 patients. SGLT-2 inhibitors led to a risk reduction in MACE and renal events (RR [95 %CI]; 0.86 [0.74-0.99] and 0.68 [0.62-0.75], respectively). However, GLP-1 RAs did not reduce cardiovascular and renal risk (RR 0.91 [0.79-1.05] and 0.91 [0.81-1.02], respectively). Compared to GLP-1 RAs, SGLT-2 inhibitors did not demonstrate a significant difference in MACE (RR 0.9 [0.75-1.08]), while SGLT-2 inhibitors were associated with. a lower risk of renal events compared to GLP-1 RAs (RR 0.75 [0.64-0.87]). A sensitivity analysis revealed that GLP-1 analogues significantly decreased MACE than placebo (RR 0.81 [0.68-0.97]), while exendin-4 analogues did not (RR 1.03 [0.86-1.23]).ConclusionsIn patients with type 2 DM and CKD, SGLT-2 inhibitors were associated with a decreased risk of cardiovascular and renal events, but GLP-1 RAs were not. SGLT-2 inhibitors significantly decreased the risk of renal events compared to GLP-1 RAs. Among GLP-1 RAs, GLP-1 analogues showed a positive impact, while exendin-4 analogues did not.
A comparison of the demographics, injury patterns and outcome data for patients injured in motor vehicle collisions who are trapped compared to patients who are not trapped
Authors: Nutbeam Tim , Fenwick Rob , Smith Jason , Bouamra Omar , Wallis Lee , Stassen Willem
Published: November 2020

Background Motor vehicle collisions (MVCs) are a common cause of major trauma and death. Following an MVC, up to 40% of patients will be trapped in their vehicle. Extrication methods are focused on the prevention of secondary spinal injury through movement minimisation and mitigation. This approach is time consuming and patients may have time-critical injuries. The purpose of this study is to describe the outcomes and injuries of those trapped following an MVC: this will help guide meaningful patient-focused interventions and future extrication strategies.Methods We undertook a retrospective database study using the Trauma Audit and Research Network database. Patients were included if they were admitted to an English hospital following an MVC from 2012-2018. Patients were excluded when their outcomes were not known or if they were secondary transfers. Results This analysis identified 426,135 cases of which 63,625 patients were included: 6983 trapped and 56,642 not trapped. Trapped patients had a higher mortality (8.9% vs 5.0%, p<0.001). Spinal cord injuries were rare (0.29% of all extrications) but frequently (50.1%) associated with other severe injuries. Spinal cord injuries were more common in patients who were not trapped (p<0.001). Injury Severity Score (ISS) was higher in the trapped group 18 (IQR 10-29) vs 13 (IQR 9-22). Trapped patients had more deranged physiology with lower blood pressures, lower oxygen saturations and lower Glasgow comas Scale, GCS (all p<0.001). Trapped patients had more significant injuries of the head chest, abdomen and spine (all p<0.001) and an increased rate of pelvic injures with significant blood loss, blood loss from other areas or tension pneumothorax (all p<0.001). Conclusion Trapped patients are more likely to die than those who are not trapped. The frequency of spinal cord injuries is low, accounting for <0.3% of all patients extricated. Patients who are trapped are more likely to have time-critical injuries requiring intervention. Extrication takes time and when considering the frequency, type and severity of injuries reported here, the benefit of movement minimisation may be outweighed by the additional time taken. Improved extrication strategies should be developed which are evidence-based and allow for the expedient management of other life-threatening injuries.
WNT4 secreted by tumor tissues promotes tumor progression in colorectal cancer by activation of the Wnt/β-catenin signalling pathway
Authors: Yang Dongmei , Li Qing , Shang Renduo , Yao Liwen , Wu Lianlian , Zhang Mengjiao , Zhang Lihui , Xu Ming , Lu Zihua , Zhou Jie , Huang Li , Huang Xiaodong , Cheng Du , Yang Yanning , Yu Honggang
Published: November 2020

Background: Wingless and Int-related protein (Wnt) ligands are aberrantly expressed in patients with colorectal cancer (CRC). However, the aberrant level of Wnt ligands in serum have not been explored. Here, we aimed to identify the levels of WNT4 in serum and explored its oncogenic role in CRC Methods: The Oncomine database was used to analyze the relationship between WNT4 and the prognosis of CRC. ELISA was performed to measure WNT4 levels in serum and conditioned medium from fresh CRC tissues and adjacent normal tissues. Western blot and immunohistochemistry were carried out to measure the expression of WNT4 in human CRC tissues and adjacent normal tissues. The migration and invasion of CRC cells were determined by trans-well assay, and the effects of WNT4 on CRC invasion and metastasis in vivo were verified by tumor xenograft in nude mice. Cancer-associated fibroblasts (CAFs) and angiogenesis in subcutaneous nodules were detected by immunofluorescence (IF). In addition, the suspended spheres formation and tube formation assay were performed to explore the effects of WNT4 on CAFs and angiogenesis respectively. Results: WNT4 was significantly upregulated in serum of CRC patients, and CRC tissues were identified as an important source of elevated WNT4 levels in CRC patients. Interestingly, elevated levels of WNT4 in serum were downregulated after tumor resection. Furthermore, we found that WNT4 contributed to epithelial-to-mesenchymal transition (EMT) and activated fibroblasts by activating the WNT4/β-catenin pathway in vitro and in vivo. Moreover, angiogenesis was induced via the WNT4/β-catenin/Ang2 pathway. Those effects could be reversed by ICG-001, a β-catenin/TCF inhibitor. Conclusion: Our findings indicated that serum levels of WNT4 may be a potential biomarker for CRC. WNT4 secreted by colorectal cancer tissues promote the progression of CRC by inducing EMT, activate fibroblasts and promote angiogenesis through the canonical Wnt/β-catenin signalling pathway.
Differential response of digesta- and mucosa-associated intestinal microbiota to dietary black soldier fly (Hermetia illucens) larvae meal in seawater phase Atlantic salmon (Salmo salar)
Authors: Li Yanxian , Bruni Leonardo , Jaramillo-Torres Alexander , Gajardo Karina , Kortner Trond M. , Krogdahl Åshild
Published: November 2020

Background: Intestinal digesta is commonly used for studying responses of microbiota to dietary shifts, yet evidence is accumulating that it represents an incomplete view of the intestinal microbiota. The present work aims to investigate the differences between digesta- and mucosa-associated intestinal microbiota in Atlantic salmon (Salmo salar) and how they may respond differently to dietary perturbations. In a 16-week seawater feeding trial, Atlantic salmon were fed either a commercially-relevant reference diet or an insect meal diet containing ~15% black soldier fly (Hermetia illucens) larvae meal. The digesta- and mucosa-associated distal intestinal microbiota were profiled by 16S rRNA gene sequencing. Results: Regardless of diet, we observed substantial differences between digesta- and mucosa-associated intestinal microbiota. Microbial richness and diversity were much higher in the digesta than the mucosa. The insect meal diet altered the distal intestinal microbiota resulting in higher microbial richness and diversity. The diet effect, however, depended on the sample origin. Digesta-associated intestinal microbiota showed more pronounced changes than the mucosa-associated microbiota. Multivariate association analyses identified two mucosa-enriched taxa, Brevinema andersonii and Spirochaetaceae, associated with the expression of genes related to immune responses and barrier function in the distal intestine, respectively. Conclusions: Our data show that salmon intestinal digesta and mucosa harbor microbial communities with clear differences. Mucosa-associated intestinal microbiota seems more resilient to variations in the diet composition than digesta-associated intestinal microbiota. To fully unveil the response of intestinal microbiota to dietary changes, concurrent profiling of digesta- and mucosa-associated intestinal microbiota is recommended whenever feasible.
Inhibition of Ref(2)P, the Drosophila homologue of p62/SQSTM1, increases lifespan and leads to motor function decline
Authors: Hurley Emily P. , Staveley Brian Ernest
Published: November 2020

Objective: Sequestosome 1 (p62/SQSTM1) is a multifunctional scaffold/adaptor protein encoded by the p62/SQSTM1 gene with function in cellular homeostasis. Mutations in the p62/SQSTM1 gene have been known to be associated with patients with Amyotrophic Lateral Sclerosis (ALS), Frontotemporal Dementia (FTD), and Parkinson Disease (PD). The aim of the present study was to create a novel model of human neurogenerative disease in Drosophila melanogaster by altering the expression of Ref(2)P, the Drosophila orthologue of the human p62/SQSTM1 gene. Ref(2)P expression was altered in all neurons, the dopaminergic neurons and in the motor neurons, with longevity and locomotor function assessed over time.Results: Inhibition of Ref(2)P resulted in a significantly increased median lifespan in the motor neurons, followed by a severe decline in motor skills. Inhibition of Ref(2)P in the dopaminergic neurons resulted in a significant, but minimal increase in median lifespan, accompanied by a drastic decline in locomotor function. Inhibition of Ref(2)P in the ddc-Gal4-expressing neurons resulted in a significant increase in median lifespan, while dramatically reducing motor function.
Integrated analyses of miRNA and mRNA profiles in leukocytes and serums in traditional Chinese medicine (TCM)-defined Pi-qi-deficiency syndrome and Pi-wei damp-heat syndrome resulting from chronic atrophic gastritis
Authors: You Leiming , Zhang Shen , Li Ting’an , Sang Xiaopu , Li Kunyu , Wang Wei , Gao Xinhui , Wu Jiarui , Huang Guangrui , Wang Ting , Xu Anlong
Published: November 2020

Background: To investigate the microRNA (miRNA)-gene interactions underlying leukocyte functions and characteristics, especially the potential serum biomarkers, implicated in the traditional Chinese medicine (TCM)-defined Pi-qi-deficiency syndrome (PQDS) and Pi-wei damp-heat syndrome (PDHS) resulting from chronic atrophic gastritis (CAG). Methods: Using RNA/miRNA-sequencing approach, compared with healthy control population, we identified the PDHS- or PQDS-specific miRNAs and genes in leukocytes or serums, especially the Zheng (syndrome)-specific miRNA-gene interactions, and further decoded their functions and pathways. Results: Despite being the TCM-defined Zhengs resulting from the same disease of CAG, the Zheng-specific genes and miRNAs were not same. The PDHS-specific leukocyte genes were mainly involved in defense and immune responses, including NOD-like receptor signaling and several synapses-related pathways. The expression upregulation of PDHS-specific genes enriched in the neutrophil degranulation pathway, indicated the enhanced leukocyte degranulation activation. The PQDS-specific genes in leukocytes were implicated in inflammatory response, extracellular matrix (ECM) organization and collagen catabolism. They could be enriched in MAPK and IL17 signaling and helper T cell differentiation pathways, especially the pathways associated with cell-to-cell adhesion/junction and communication such as cell adhesion molecules, ECM organization and ECM-receptor interaction, probably contributing to the characteristics and functions of leukocytes. Also, the experimentally-supported miRNA-gene interactions, concerned with COL4A2, COL26A1, SPP1 and PROCR, were implicated in the regulation of pathways related to cell-to-cell adhesion/junction and communication, suggesting the potential roles of the PQDS-specific miRNA-gene interactions for the characteristic and functional changes of leukocytes. Interestingly, the PQDS-specific miRNAs in the serums and the corresponding leukocytes, seemed to have the common roles in contributing to the characteristics and functions of leukocytes. Importantly, the hsa-miR-122-5p could be a potential biomarker, capable of being contained and carried in plasma exosomes and much higher expression in both the leukocytes and corresponding serums in the CAG patients with PQDS rather than PDHS. Conclusions: These results may provide new insights into the characteristic and functional changes of leukocytes in the two Zhengs, PDHS and PQDS, especially the miRNA-mediated gene regulation underlying leukocyte characteristics and functions, with potential leukocyte and serum biomarkers for future application in integrative medicine.Trial registration: ClinicalTrials.gov, NCT02915393. Registered on September 17, 2016.
Rhizosphere community selection reveals bacteria associated with reduced root disease 
Authors: Paulitz Timothy , Yin Chuntao , Vargas Juan M. Casa , Schlatter Daniel C. , Hagerty Christina H. , Hulbert Scot H.
Published: November 2020

Background: Microbes benefit plants by increasing nutrient availability, producing plant growth hormones, and protecting against pathogens. However, it is largely unknown how plants change root microbial communities. Results: In this study, we used a multi-cycle selection system and infection by the soilborne fungal pathogen Rhizoctonia solani AG8 (hereafter AG8) to examine how plants impact the rhizosphere bacterial community and recruit beneficial microorganisms to suppress soilborne fungal pathogens and promote plant growth. Successive plantings dramatically enhanced disease suppression on susceptible wheat cultivars to AG8 in the greenhouse. Accordingly, analysis of the rhizosphere soil microbial community using deep sequencing of 16S rRNA genes revealed distinct bacterial community profiles assembled over successive wheat plantings. Moreover, the cluster of bacterial communities formed from the AG8-infected rhizosphere was distinct from those without AG8 infection. Interestingly, the bacterial communities from the rhizosphere with the lowest wheat root disease gradually separated from those with the worst wheat root disease over planting cycles. Successive monocultures and application of AG8 increased the abundance of some bacterial genera which have potential antagonistic activities, such as Chitinophaga, Pseudomonas, Chryseobacterium, and Flavobacterium, and a group of plant growth-promoting (PGP) and nitrogen-fixing microbes, including Pedobacter, Variovorax, and Rhizobium. Furthermore, 47 bacteria isolates belong to 35 species were isolated. Among them, eleven and five exhibited antagonistic activities to AG8 and Rhizoctonia oryzae in vitro, respectively. Notably, Janthinobacterium displayed broad antagonism against the soilborne pathogens Pythium ultimum, AG8, and R. oryzae in vitro, and disease suppressive activity to AG8 in soil. Conclusions: Our results demonstrated that successive wheat plantings and pathogen infection can shape the rhizosphere microbial communities and specifically accumulate a group of beneficial microbes. Our findings suggest that soil community selection may offer the potential for addressing agronomic concerns associated with plant diseases and crop productivity.