Advanced Electrodes for Solid Acid Fuel Cells by Platinum Deposition on CsH_(2)PO_4

We demonstrate cathodes for solid acid fuel cells fabricated by vapor deposition of platinum from the metalorganic precursor Pt(acac)_2 on the solid acid CsH_(2)PO_4 at 210 °C. A network of platinum nanoparticles with diameters of 2−4 nm serves as both the oxygen reduction catalyst and the electronic conductor in the electrode. Electrodes with a platinum content of 1.75 mg/cm^2 are more active for oxygen reduction than previously reported electrodes with a platinum content of 7.5 mg/cm^2. Electrodes containing <1.75 mg/cm^2 of platinum show significantly reduced catalytic activity and increased ohmic resistance indicative of a highly discontinuous catalytic-electronic platinum network

Volumetric growth rates of meningioma and its correlation with histological diagnosis and clinical outcome: a systematic review.

INTRODUCTION: Tumour growth has been used to successfully predict progression-free survival in low-grade glioma. This systematic review sought to establish the evidence base regarding the correlation of volumetric growth rates with histological diagnosis and potential to predict clinical outcome in patients with meningioma. METHODS: This systematic review was conducted according to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. Databases were searched for full text English articles analysing volumetric growth rates in patients with a meningioma. RESULTS: Four retrospective cohort studies were accepted, demonstrating limited evidence of significantly different tumour doubling rates and shapes of growth curves between benign and atypical meningiomas. Heterogeneity of patient characteristics and timing of volumetric assessment, both pre- and post-operatively, limited pooled analysis of the data. No studies performed statistical analysis to demonstrate the clinical utility of growth rates in predicting clinical outcome. CONCLUSION: This systematic review provides limited evidence in support of the use of volumetric growth rates in meningioma to predict histological diagnosis and clinical outcome to guide future monitoring and treatment

The effect of preconditioning with high-intensity training on tissue levels of G-CSF, its receptor and C-kit after an acute myocardial infarction in male rats

Background: Exercise training is known as a practical way to increase cardioprotection against stress, and it seems that stem cell recruitment is one of its mechanisms. The purpose of the present study was to investigate the effect of preconditioning with High-intensity interval training (HIIT) on tissue levels of G-CSF, its receptor and C-Kit following acute myocardial infarction in male rats. Methods: Twenty Male Wistar rats were randomly divided into 4 groups of control, MI, HIIT, and HIIT+MI. Training groups performed 2 weeks of high intensity interval training in 4 sections. The first section consisted training in 3 days and 2 sessions in each day (4 � 2 min with 35-40 m/min and 3 � 2 min with 25-30 m/min between high intervals. The second part included 2 days of training (4 � 2 min with 40 to 45 m/min and 3 � 2 min with 28 to 32 m /min). The third part was performed in 3 days with one more repetition. The fourth section consisted 2 days of training and with one more repetition compared to section 3. For induction of myocardial infarction, subcutaneous injection of isoprenaline was used. CK, total CK, LDH, and troponin T were measured in serum and G-CSF, G-CSFR and C-Kit proteins were measured by the Western Blot method in the heart tissue. Results: The results of this study showed that enzymes of CK, total CK, LDH, troponin T had a significant increase in both MI and HIIT+MI groups compared to the other two groups (P < 0.001) and these indices in the MI group were significantly higher than the HIIT+MI group. Also, the results demonstrated that G-CSF, G-CSFR and C-Kit protein expression in the heart tissue significantly increased after MI. As well as, 2 weeks of HIIT training significantly increased G-CSF and C-kit in the training group compared to the control group, but the training caused that these proteins does not increase in HIIT+MI group as much as MI group. Conclusions: Along with other protective pathways, high intensity interval training can increase cardioprotection and decrease heart injuries through the increase in G-CSF, G-CSFR and C-kit level. © 2020 The Author(s)

Inclusion of Premenopausal Women in Breast Cancer Clinical Trials

BACKGROUND: Patients with premenopausal breast cancer (PMBC) have been historically excluded from some clinical trials because of the limitations of using endocrine therapy (ET) in this population. We analyzed breast cancer randomized clinical trials (RCTs) to determine the rates of and factors associated with inclusion of PMBC patients to provide a benchmark for PMBC inclusion in RCTs moving forward. METHODS: Using ClinicalTrials.Gov, we identified breast cancer phase III RCTs and extracted inclusion criteria and patient enrollment information. Multiple binary logistic regression modeling was used to assess trial-related factors that were associated with PMBC patient inclusion. RESULTS: Of 170 breast cancer RCTs identified, 131 (77.1%) included PMBC patients. Sixty-five (38.2%) trials analyzed patients with hormone-receptor-positive (HR+) and HER2-negative (HER2-) breast cancer, of which 31 (47.7%) allowed for enrollment of PMBC patients. Lower rates of PMBC inclusion were seen in trials that studied HR+/HER2-patients (47.7% PMBC inclusion in HR+/HER2-trials vs. 94.3% in non-HR+/HER2-trials, aOR 0.07 [95% CI: 0.02-0.19], p \u3c 0.001) and in trials that randomized or mandated ET (44.4% in ET trials vs. 83.2% in non-ET trials, aOR 0.21 [95% CI: 0.10-0.83], p = 0.02). Trials studying chemotherapy (CT) were associated with inclusion of PMBC patients (100% in CT trials vs. 70.5% in non-CT trials, a OR 14.02 [95% CI: 1.54-127.91], p = 0.01). All surgical and radiation therapy clinical trials allowed for the inclusion of PMBC patients in their eligibility criteria. CONCLUSIONS: Breast cancer clinical trials should carefully select their enrollment criteria and consider inclusion of premenopausal patients when appropriate

Incidence of Primary End Point Changes Among Active Cancer Phase 3 Randomized Clinical Trials

IMPORTANCE: Primary end point (PEP) changes to an active clinical trial raise questions regarding trial quality and the risk of outcome reporting bias. It is unknown how the frequency and transparency of the reported changes depend on reporting method and whether the PEP changes are associated with trial positivity (ie, the trial met the prespecified statistical threshold for PEP positivity). OBJECTIVES: To assess the frequency of reported PEP changes in oncology randomized clinical trials (RCTs) and whether these changes are associated with trial positivity. DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional study used publicly available data for complete oncology phase 3 RCTs registered in ClinicalTrials.gov from inception through February 2020. MAIN OUTCOMES AND MEASURES: The main outcome was change between the initial PEP and the final reported PEP, assessed using 3 methods: (1) history of tracked changes on ClinicalTrials.gov, (2) self-reported changes noted in the article, and (3) changes reported within the protocol, including all available protocol documents. Logistic regression analyses were performed to evaluate whether PEP changes were associated with US Food and Drug Administration approval or trial positivity. RESULTS: Of 755 included trials, 145 (19.2%) had PEP changes found by at least 1 of the 3 detection methods. Of the 145 trials with PEP changes, 102 (70.3%) did not have PEP changes disclosed within the manuscript. There was significant variability in rates of PEP detection by each method (χ2 = 72.1; P \u3c .001). Across all methods, PEP changes were detected at higher rates when multiple versions of the protocol (47 of 148 [31.8%]) were available compared with 1 version (22 of 134 [16.4%]) or no protocol (76 of 473 [16.1%]) (χ2 = 18.7; P \u3c .001). Multivariable analysis demonstrated that PEP changes were associated with trial positivity (odds ratio, 1.86; 95% CI, 1.25-2.82; P = .003). CONCLUSIONS AND RELEVANCE: This cross-sectional study revealed substantial rates of PEP changes among active RCTs; PEP changes were markedly underreported in published articles and mostly occurred after reported study completion dates. Significant discrepancies in the rate of detected PEP changes call into question the role of increased protocol transparency and completeness in identifying key changes occurring in active trials

HPV-Related Anal Cancer Is Associated With Changes in the Anorectal Microbiome During Cancer Development

BACKGROUND: Squamous cell carcinoma of the anus (SCCA) is a rare gastrointestinal cancer. Factors associated with progression of HPV infection to anal dysplasia and cancer are unclear and screening guidelines and approaches for anal dysplasia are less clear than for cervical dysplasia. One potential contributing factor is the anorectal microbiome. In this study, we aimed to identify differences in anal microbiome composition in the settings of HPV infection, anal dysplasia, and anal cancer in this rare disease. METHODS: Patients were enrolled in two prospective studies. Patients with anal dysplasia were part of a cross-sectional cohort that enrolled women with high-grade lower genital tract dysplasia. Anorectal tumor swabs were prospectively collected from patients with biopsy-confirmed locally advanced SCCA prior to receiving standard-of-care chemoradiotherapy (CRT). Patients with high-grade lower genital tract dysplasia without anal dysplasia were considered high-risk (HR Normal). 16S V4 rRNA Microbiome sequencing was performed for anal swabs. Alpha and Beta Diversity and composition were compared for HR Normal, anal dysplasia, and anal cancer. RESULTS: 60 patients with high-grade lower genital tract dysplasia were initially enrolled. Seven patients had concurrent anal dysplasia and 44 patients were considered HR Normal. Anorectal swabs from 21 patients with localized SCCA were included, sequenced, and analyzed in the study. Analysis of weighted and unweighted UniFrac distances demonstrated significant differences in microbial community composition between anal cancer and HR normal (p CONCLUSION: Although alpha diversity was similar between HR Normal, dysplasia and cancer patients, composition differed significantly between the three groups. Increased anorecta

A map of transcriptional heterogeneity and regulatory variation in human microglia.

Microglia, the tissue-resident macrophages of the central nervous system (CNS), play critical roles in immune defense, development and homeostasis. However, isolating microglia from humans in large numbers is challenging. Here, we profiled gene expression variation in primary human microglia isolated from 141 patients undergoing neurosurgery. Using single-cell and bulk RNA sequencing, we identify how age, sex and clinical pathology influence microglia gene expression and which genetic variants have microglia-specific functions using expression quantitative trait loci (eQTL) mapping. We follow up one of our findings using a human induced pluripotent stem cell-based macrophage model to fine-map a candidate causal variant for Alzheimer's disease at the BIN1 locus. Our study provides a population-scale transcriptional map of a critically important cell for human CNS development and disease

Rs1888747 polymorphism in the FRMD3 gene, gene and protein expression: Role in diabetic kidney disease

© 2016 Buffon et al. Background: We carried out a case-control study in patients with type 2 diabetes mellitus (T2DM) to evaluate the association between seven single nucleotide polymorphisms (SNPs) previously described to be linked to diabetic kidney disease (DKD) in type 1 diabetes mellitus (T1DM). Additionally, we evaluated gene and protein expression related to the polymorphism associated with DKD. Methods: The association study included 1098 T2DM patients (718 with DKD and 380 without DKD). Out of the 13 polymorphisms associated with DKD in a previous study with T1DM, seven were chosen for evaluation in this sample: rs1888747, rs9521445, rs39075, rs451041, rs1041466, rs1411766 and rs6492208. The expression study included 91 patients who underwent nephrectomy. Gene expression was assessed by RT-qPCR and protein expression in kidney samples was quantified by western blot and it localization by immunohistochemistry. Results: The C/C genotype of rs1888747 SNP was associated with protection for DKD (OR = 0.6, 95 % CI 0.3-0.9; P = 0.022). None of the other SNPs were associated with DKD. rs1888747 is located near FRMD3 gene. Therefore, FRMD3 gene and protein expression were evaluated in human kidney tissue according to rs1888747 genotypes. Gene and protein expression were similar in subjects homozygous for the C allele and in those carrying the G allele. Conclusions: Replication of the association between rs1888747 SNP and DKD in a different population suggests that this link is not the result of chance. rs1888747 SNP is located at the FRMD3 gene, which is expressed in human kidney. Therefore, this gene is a candidate gene for DKD. However, in this study, no rs1888747 genotype or specific allele effect on gene and/or protein expression of the FRMD3 gene was demonstrated

Smurfs, cyborgs and changelings: prospects of human enhancement retrospected

This article stems from the impression of being condemned to late and moralizing reactions in regard to advances\ud in the life sciences.We suggest a return to a speculative\ud and theoretical approach in posing the question(s) of the limit of possible thinking of the enhanced human. This return allows for the possibility to show, not just inductively, but “clearly and distinctly,” the specific justifications and lines of reasoning of anthropocentric prejudice or species narcissism. It also enables us to move freely and precisely along the limits of thinking the\ud human/non-human. In this way, we hope to put forward a few\ud markers or guideposts that would further the debate about\ud notions of human enhancement