bluuebunny/crossref_metadata_2025_split huggingface dataset:
Exploring mechanisms of action in clinical trials of complex surgical interventions using mediation analysis
Authors: Sharples Linda , Papachristofi Olympia , Rex Saleema , Landau Sabine 
Published: August 2020

Background: Surgical interventions allow for tailoring of treatment to individual patients and implementation may vary with surgeon and healthcare provider. In addition, in clinical trials assessing two competing surgical interventions, the treatments may be accompanied by co-interventions. Aims: This study explores the use of causal mediation analysis to (1) delineate the treatment effect that results directly from the surgical intervention under study and the indirect effect acting through a co-intervention and (2) to evaluate the benefit of the surgical intervention if either everybody in the trial population received the co-intervention or nobody received it. Methods: Within a counterfactual framework, relevant direct and indirect effects of a surgical intervention are estimated and adjusted for confounding via parametric regression models, for the situation where both mediator and outcome are binary, with baseline stratification factors included as fixed effects and surgeons as random intercepts. The causal difference in probability of a successful outcome (estimand of interest) is calculated using Monte Carlo simulation with bootstrapping for confidence intervals. Packages for estimation within standard statistical software are reviewed briefly. A step by step application of methods is illustrated using the Amaze randomised trial of ablation as an adjunct to cardiac surgery in patients with irregular heart rhythm, with a co-intervention (removal of the left atrial appendage) administered to a subset of participants at the surgeon’s discretion. The primary outcome was return to normal heart rhythm at one year post surgery. Results: In Amaze, 17% (95% confidence interval: 6%, 28%) more patients in the active arm had a successful outcome, but there was a large difference between active and control arms in the proportion of patients who received the co-intervention (55% and 30%, respectively). Causal mediation analysis suggested that around 1% of the treatment effect was attributable to the co-intervention (16% natural direct effect). The controlled direct effect ranged from 18% (6%, 30%) if the co-intervention were mandated, to 14% (2%, 25%) if it were prohibited. Including age as a moderator of the mediation effects showed that the natural direct effect of ablation appeared to decrease with age. Conclusions: Causal mediation analysis is a useful quantitative tool to explore mediating effects of co-interventions in surgical trials. In Amaze, investigators could be reassured that the effect of the active treatment, not explainable by differential use of the co-intervention, was significant across analyses.
Antenatal haemoglobinopathy screening – Experiences of a large Australian Centre
Authors: Ai Sylvia , Cliffe Corrina , Kidson-Gerber Giselle 
Published: August 2020

Background Antenatal screening is vital to identifying couples at risk of having children with a clinically significant haemoglobinopathy. In Australia, immigration is increasing carrier incidence. Methods A retrospective analysis was performed of full blood count, high-performance liquid chromatography and haemoglobin electrophoresis of women and their partners who underwent antenatal haemoglobinopathy screening over three years at a major NSW laboratory. Genetic testing results were included where available. Results One thousand six hundred and twenty-eight women and 729 male partners were screened at a median gestation of 14 weeks. 8.2% of women had a clinically significant result, with a median 16-day interval to partner testing. In 35% of couples screened simultaneously, the partner did not require testing. Genetic confirmatory testing was performed in 65% of high risk couples. Conclusion There was a significant delay to antenatal haemoglobinopathy screening for mothers, limiting time for genetic diagnosis, prenatal diagnosis and management of affected pregnancies. Screening should be performed earlier. Simultaneous couple testing is not cost-effective.
Impact of Two Different Reference Measurement Procedures on Apparent System Accuracy of 18 CE-Marked Current-Generation Blood Glucose Monitoring Systems
Authors: Freckmann Guido , Baumstark Annette , Jendrike Nina , Mende Jochen , Schauer Sebastian , Link Manuela , Pleus Stefan , Haug Cornelia 
Published: August 2020

Background: Measurement accuracy has been assessed for many different blood glucose monitoring systems (BGMS) over the years by different study groups. However, the choice of the comparison measurement procedure may impact the apparent level of accuracy found in such studies. Materials and Methods: Measurement accuracy of 18 different BGMS was assessed in a setting based on ISO 15197 using two different comparison methods in parallel: a glucose oxidase (GOD)-based and a hexokinase (HK)-based method. Accuracy limits of ISO 15197 were applied, and additional analyses were performed, including bias, linear regression, and mean absolute relative difference (MARD) to assess the impact of possible differences between comparison methods on the apparent level of accuracy. Results: While ≈80% of BGMS met the accuracy criteria of ISO 15197 when compared with the respective manufacturers’ reference measurement procedure, only two-thirds did so against both comparison methods. The mean relative bias ranged from −6.6% to +5.7% for the analysis against the GOD-based method and from −11.1% to +1.3% for the analysis against the HK-based method, whereas MARD results ranged from 3.7% to 9.8% and from 2.3% to 10.5%, respectively. Results of regression analysis showed slopes between 0.85 and 1.08 (GOD-based method) and between 0.81 and 1.01 (HK-based method). Conclusions: The results of this study indicate that there are systematic differences between the reference measurement procedures used for BGMS calibration as well as for system accuracy assessment. Because of the potential impact on therapy of patients with diabetes resulting from these differences, further steps toward harmonization of the measurement procedures’ results are important.
Intraarticular Corticosteroids for Hip Osteoarthritis: A Review
Authors: Choueiri Magda , Chevalier Xavier , Eymard Florent 
Published: August 2020

Introduction Hip osteoarthritis is a prevalent condition responsible for important pain and disability. Most available guidelines for nonsurgical management of hip osteoarthritis recommend a combination of nonpharmacological and pharmacological treatment modalities. Intraarticular corticosteroid injections have been used for decades, although evidence is quite scarce, and many controversies remain. Methods This article reviews the available literature from Medline and Embase and discusses the evidence for intraarticular corticosteroid injections in hip osteoarthritis, where only 5 randomized controlled trials were found in the literature. These are analyzed in this article, which also aims to explain the main characteristics and features of glucocorticoids, along with their contraindications and potential adverse effects. Results Available randomized controlled trials show that intraarticular corticosteroid injections provide pain relief and functional improvement in hip osteoarthritis. This efficacy has not been shown with intraarticular hyaluronic acid injections. Conclusion This review shows that intraarticular corticosteroid injections are efficacious in hip osteoarthritis and that this benefit can last up to 12 weeks.
A cut above? Inferior vena cava resection without reconstruction: a dual-centre experience
Authors: Noël Jonathan P , Tang Sarah Yu Weng , Muhammad Nana Aishatu Liman , Nicol David , Kockelbergh Roger C 
Published: August 2020

Objectives: To evaluate outcomes in our patients undergoing inferior vena cava (IVC) resection without reconstruction, as part of an adrenal/renal cell cancer (RCC) operation. Methods: British Association of Urological Surgeons (BAUS) Data and Audit System records were obtained for two operating surgeons, each at geographically separate urological cancer centres. Retrospectively reviewed case notes of patients who had undergone IVC resection without reconstruction as part of an adrenal/RCC operation, assessing operative parameters, length of stay, complications and follow-up status. Results: A total of Twenty-eight patients (20 right-sided tumours, 8 left sided) underwent IVC resection without reconstruction in May 2013–February 2017. No perioperative or early deaths occurred. Fourteen patients (50%) had complications: sepsis; pneumonia; congestive cardiac failure; acute kidney injury; symptomatic peripheral deep venous thrombosis; splenectomy; and significant chyle leak. At a median follow-up of 21 months (range 1–55 months) six patients (21.4%) have died and two patients (7.1%) progressed to metastatic disease, giving a 71.4% progression-free survival in this series. Conclusions: This case series illustrates our experience of IVC resection without reconstruction as an acceptably safe procedure. This should be considered as an alternative to graft reconstruction, particularly as minimal invasive approaches are being adopted. Level of Evidence: 3
Successful treatment of a rare Cowper’s bulbourethral gland syringocele in an adult with endoscopic laser deroofing using a rigid ureteroscope
Authors: Patel Sheena , Rai Jaskarn 
Published: August 2020

Cystic dilatation of Cowper’s glands, also known as a syringocele, is a well-known condition of childhood, with increased recognition as a rare presentation of urinary tract symptoms in adults. Surgical techniques for its treatment vary, with several described in the literature. However, consensus on optimal treatment is unclear. We present a rare case of a Cowper’s gland syringocele successfully treated with laser deroofing with a previously undescribed method using a rigid ureteroscope, and we also review techniques in the literature. Level of evidence: Level 5.
Increased lipid metabolism impairs NK cell function and mediates adaptation to the lymphoma environment
Authors: Kobayashi Takumi , Lam Pui Yeng , Jiang Hui , Bednarska Karolina , Gloury Renee , Murigneux Valentine , Tay Joshua , Jacquelot Nicolas , Li Rui , Tuong Zewen Kelvin , Leggatt Graham R. , Gandhi Maher K. , Hill Michelle M. , Belz Gabrielle T. , Ngo Shyuan , Kallies Axel , Mattarollo Stephen R. 
Published: August 2020

Abstract
Natural killer (NK) cells play critical roles in protection against hematological malignancies but can acquire a dysfunctional state, which limits antitumor immunity. However, the underlying reasons for this impaired NK cell function remain to be uncovered. We found that NK cells in aggressive B-cell lymphoma underwent substantial transcriptional reprogramming associated with increased lipid metabolism, including elevated expression of the transcriptional regulator peroxisome activator receptor-γ (PPAR-γ). Exposure to fatty acids in the lymphoma environment potently suppressed NK cell effector response and cellular metabolism. NK cells from both diffuse large B-cell lymphoma patients and Eµ-myc B-cell lymphoma-bearing mice displayed reduced interferon-γ (IFN-γ) production. Activation of PPAR-γ partially restored mitochondrial membrane potential and IFN-γ production. Overall, our data indicate that increased lipid metabolism, while impairing their function, is a functional adaptation of NK cells to the fatty-acid rich lymphoma environment.
Specific functions of Exostosin-like 3 (EXTL3) gene products
Authors: Yamada Shuhei 
Published: August 2020

AbstractExostosin-like 3 (EXTL3) encodes the glycosyltransferases responsible for the biosynthesis of the backbone structure of heparan sulfate (HS), a sulfated polysaccharide that is ubiquitously distributed on the animal cell surface and in the extracellular matrix. A lack of EXTL3 reduces HS levels and causes embryonic lethality, indicating its indispensable role in the biosynthesis of HS. EXTL3 has also been identified as a receptor molecule for regenerating islet-derived (REG) protein ligands, which have been shown to stimulate islet β-cell growth. REG proteins also play roles in keratinocyte proliferation and/or differentiation, tissue regeneration and immune defenses in the gut as well as neurite outgrowth in the central nervous system. Compared with the established function of EXTL3 as a glycosyltransferase in HS biosynthesis, the REG-receptor function of EXTL3 is not conclusive. Genetic diseases caused by biallelic mutations in the EXTL3 gene were recently reported to result in a neuro-immuno-skeletal dysplasia syndrome. EXTL3 is a key molecule for the biosynthesis of HS and may be involved in the signal transduction of REG proteins.
Comparative genomic analysis of Flavobacteriaceae: insights into carbohydrate metabolism, gliding motility and secondary metabolite biosynthesis
Authors: Gavriilidou Asimenia , Gutleben Johanna , Versluis Dennis , Forgiarini Francesca , van Passel Mark W. J. , Ingham Colin J. , Smidt Hauke , Sipkema Detmer 
Published: August 2020

AbstractBackgroundMembers of the bacterial familyFlavobacteriaceaeare widely distributed in the marine environment and often found associated with algae, fish, detritus or marine invertebrates. Yet, little is known about the characteristics that drive their ubiquity in diverse ecological niches. Here, we provide an overview of functional traits common to taxonomically diverse members of the familyFlavobacteriaceaefrom different environmental sources, with a focus on the Marine clade. We include seven newly sequenced marine sponge-derived strains that were also tested for gliding motility and antimicrobial activity.ResultsComparative genomics revealed that genome similarities appeared to be correlated to 16S rRNA gene- and genome-based phylogeny, while differences were mostly associated with nutrient acquisition, such as carbohydrate metabolism and gliding motility. The high frequency and diversity of genes encoding polymer-degrading enzymes, often arranged in polysaccharide utilization loci (PULs), support the capacity of marineFlavobacteriaceaeto utilize diverse carbon sources. Homologs of gliding proteins were widespread among all studiedFlavobacteriaceaein contrast to members of other phyla, highlighting the particular presence of this feature within theBacteroidetes. Notably, not all bacteria predicted to glide formed spreading colonies. Genome mining uncovered a diverse secondary metabolite biosynthesis arsenal ofFlavobacteriaceaewith high prevalence of gene clusters encoding pathways for the production of antimicrobial, antioxidant and cytotoxic compounds. Antimicrobial activity tests showed, however, that the phenotype differed from the genome-derived predictions for the seven tested strains.ConclusionsOur study elucidates the functional repertoire of marineFlavobacteriaceaeand highlights the need to combine genomic and experimental data while using the appropriate stimuli to unlock their uncharted metabolic potential.
Enterohaemorrhagic Escherichia coli activates nitrate respiration to benefit from the inflammatory response for initiation of microcolony-formation
Authors: Nada Risa , Ebihara Shinya , Yen Hilo , Tobe Toru 
Published: August 2020

Abstract
Background
For successful colonization, enterohaemorrhagic Escherichia coli (EHEC) injects virulence factors, called effectors, into target cells through the type three secretion system (T3SS), which is composed of a needle and basal body. Under anaerobic conditions, the T3SS machinery remains immature and does not have a needle structure. However, activation of nitrate respiration enhances the completion of the T3SS machinery. Because nitric oxide released by the host inflammatory response increases nitrate concentration, we sought to determine the effect of the inflammatory response on initiation of EHEC microcolony-formation.

Results
The colony-forming capacity was increased in accordance with the increase of nitrate in the medium. The addition of the nitric oxide-producing agent NOR-4 also enhanced the adherence capacity, which was dependent on nitrate reductase encoded by the narGHJI genes. Culture supernatant of epithelial cells, which was stimulated by a cytokine mixture, enhanced the colony-forming capacity of wild-type EHEC but not of the narGHJI mutant. Finally, colony formation by wild-type EHEC on epithelial cells, which were preincubated with heat-killed bacteria, was higher than the narGHJI mutant, and this effect was abolished by aminoguanidine hydrochloride, which is an iNOS (inducible nitric oxide synthase) inhibitor.

Conclusions
These results indicate that the inflammatory response enhances EHEC adherence by increasing nitrate concentration.
Hydrogen sulphide alleviates iron deficiency by promoting iron availability and plant hormone levels in Glycine max seedlings
Authors: Chen Juan , Zhang Ni-Na , Pan Qing , Lin Xue-Yuan , Shangguan Zhouping , Zhang Jian-Hua , Wei Ge-Hong 
Published: August 2020

Abstract
Background
Hydrogen sulphide (H2S) is involved in regulating physiological processes in plants. We investigated how H2S ameliorates iron (Fe) deficiency in soybean (Glycine max L.) seedlings. Multidisciplinary approaches including physiological, biochemical and molecular, and transcriptome methods were used to investigate the H2S role in regulating Fe availability in soybean seedlings.

Results
Our results showed that H2S completely prevented leaf interveinal chlorosis and caused an increase in soybean seedling biomass under Fe deficiency conditions. Moreover, H2S decreased the amount of root-bound apoplastic Fe and increased the Fe content in leaves and roots by regulating the ferric-chelate reductase (FCR) activities and Fe homeostasis- and sulphur metabolism-related gene expression levels, thereby promoting photosynthesis in soybean seedlings. In addition, H2S changed the plant hormone concentrations by modulating plant hormone-related gene expression abundances in soybean seedlings grown in Fe-deficient solution. Furthermore, organic acid biosynthesis and related genes expression also played a vital role in modulating the H2S-mediated alleviation of Fe deficiency in soybean seedlings.

Conclusion
Our results indicated that Fe deficiency was alleviated by H2S through enhancement of Fe acquisition and assimilation, thereby regulating plant hormones and organic acid synthesis in plants.
Psychological characteristics and associations between living kidney transplantation recipients and biologically related or unrelated donors
Authors: Lee Yujin , Park Hyewon , Jee Hee-Jung , Lee Heon-Jeong , Gwon Jun Gyo , Min Hyeonjin , Jung Cheol Woong , Kim Myung-Gyu , Cho Chul-Hyun 
Published: August 2020

Abstract
Background
Although recipients and donors in living kidney transplantation experience psychological distress—including depression and anxiety—during the pre-operative period, very few studies have evaluated the related psychological reactions. This study aimed to determine the characteristics and correlations of the mood states and personality of recipients and donors (genetically related and unrelated) of living kidney transplantations.

Methods
A total of 66 pairs of living donors and recipients were enrolled from April 2008 to June 2019 in this study, of whom 53 eligible pairs of living donors and recipients were included in the retrospective analysis of their psychological assessments in the pre-transplantation states. While participants’ personality patterns were assessed using the Minnesota Multiphasic Personality Inventory-2 (MMPI-2), mood states were evaluated via both the State-Trait Anxiety Inventory (STAI) and The Center for Epidemiologic Studies Depression Scale (CES-D). Statistical analysis was performed using paired t-tests and Spearman’s correlation analyses.

Results
The recipient group showed significantly higher scores for Hypochondriasis (t = − 4.49, p = .0001), Depression (t = − 3.36, p = .0015), and Hysteria (t = − 3.30, p = .0018) of MMPI-2 and CES-D (t = − 3.93, p = .0003) than the donor group. The biologically unrelated recipient group reported higher scores of Hypochondriasis (t = − 3.37, p = .003) and Depression (t = − 2.86, p = 0.0098) than the unrelated donor group. Higher scores for Hypochondriasis (t = − 3.00, p = 0.0054) and CES-D (t = − 3.53, p = .0014) were found in the related recipient group. A positive association was found for Hypomania (r = .40, p = .003) of MMPI-2, STAI-S (r = .36, p = .009), and CES-D (r = .36, p = .008) between the recipient and donor groups.

Conclusions
Recipients suffered from a higher level of depression and somatic concerns than donors before living kidney transplantation. Psychological problems like depression and anxiety can occur in both living kidney transplantation donors and recipients. This study suggests that clinicians must pay attention to mood states not only in recipients but also in donors because of emotional contagion.
Establishment of age group classification for risk stratification in glioma patients
Authors: Lin Zhiying , Yang Runwei , Li Kaishu , Yi Guozhong , Li Zhiyong , Guo Jinglin , Zhang Zhou , Junxiang Peng , Liu Yawei , Qi Songtao , Huang Guanglong 
Published: August 2020

Abstract
Background
Age is associated with the prognosis of glioma patients, but there is no uniform standard of age-group classification to evaluate the prognosis of glioma patients. In this study, we aimed to establish an age group classification for risk stratification in glioma patients.

Methods
1502 patients diagnosed with gliomas at Nanfang Hospital between 2000 and 2018 were enrolled. The WHO grade of glioma was used as a dependent variable to evaluate the effect of age on risk stratification. The evaluation model was established by logistic regression, and the Akaike information criterion (AIC) value of the model was used to determine the optimal cutoff points for age-classification. The differences in gender, WHO grade, pathological subtype, tumor cell differentiation, tumor size, tumor location, and molecular markers between different age groups were analyzed. The molecular markers included GFAP, EMA, MGMT, P53, NeuN, Oligo2, EGFR, VEGF, IDH1, Ki-67, PR, CD3, H3K27M, TS, and 1p/19q status.

Results
The proportion of men with glioma was higher than that of women with glioma (58.3% vs 41.7%). Analysis of age showed that appropriate classifications of age group were 0–14 years old (pediatric group), 15–47 years old (youth group), 48–63 years old (middle-aged group), and ≥ 64 years old (elderly group).The proportions of glioblastoma and large tumor size (4–6 cm) increased with age (p = 0.000, p = 0.018, respectively). Analysis of the pathological molecular markers across the four age groups showed that the proportion of patients with larger than 10% area of Ki-67 expression or positive PR expression increased with age (p = 0.000, p = 0.017, respectively).

Conclusions
Appropriate classifications of the age group for risk stratification are 0–14 years old (pediatric group), 15–47 years old (young group), 48–63 years old (middle age group) and ≥ 64 years old (elderly group). This age group classification is effective in evaluating the risk of glioblastoma in glioma patients.