Miracle-dz/UniFAR-FTUs huggingface dataset:
characterization of renal biomarkers for use in clinical trials: biomarker evaluation in healthy volunteers

Background: Several preclinical urinary biomarkers have been qualified and accepted by the health authorities (US Food and Drug Administration, European Medicines Agency, and Pharmaceuticals and Medical Devices Agency) for detecting drug-induced kidney injury during preclinical toxicologic testing. Validated human assays for many of these biomarkers have become commercially available, and this study was designed to characterize some of the novel clinical renal biomarkers. The objective of this study was to evaluate clinical renal biomarkers in a typical Phase I healthy volunteer population to determine confidence intervals (pilot reference intervals), intersubject and intrasubject variability, effects of food intake, effect of sex, and vendor assay comparisons. Methods: Spot urine samples from 20 male and 19 female healthy volunteers collected on multiple days were analyzed using single analyte and multiplex assays. The following analytes were measured: α -1-microglobulin, β -2-microglobulin, calbindin, clusterin, connective tissue growth factor, creatinine, cystatin C, glutathione S-transferase- α , kidney injury marker-1, microalbumin, N-acetyl- β -(D) glucosaminidase, neutrophil gelatinase-associated lipocalin, osteopontin, Tamm-Horsfall urinary glycoprotein, tissue inhibitor of metalloproteinase 1, trefoil factor 3, and vascular endothelial growth factor. Results: Confidence intervals were determined from the single analyte and multiplex assays. Intersubject and intrasubject variability ranged from 38% to 299% and from 29% to 82% for biomarker concentration, and from 24% to 331% and from 10% to 67% for biomarker concentration normalized to creatinine, respectively. There was no major effect of food intake or sex. Single analyte and multiplex assays correlated with r 2 $ 0.700 for five of six biomarkers when evaluating biomarker concentration, but for only two biomarkers when evaluating concentration normalized to creatinine. Conclusion: Confidence intervals as well as intersubject and intrasubject variability were determined for novel clinical renal biomarkers/assays, which should be considered for evaluation in the next steps of the qualification process. Notes: 1 Comparison between Central and Pacific Biomarker assays, both single analyte assays; 2 comparison between Pacific Biomarker (single analyte) and Rules Based Medicine (multiplex) assays.
Dissection of the host-pathogen interaction in human tuberculosis using a bioengineered 3-dimensional model

Cell biology differs between traditional cell culture and 3-dimensional (3-D) systems, and is modulated by the extracellular matrix. Experimentation in 3-D presents challenges, especially with virulent pathogens. Mycobacterium tuberculosis (Mtb) kills more humans than any other infection and is characterised by a spatially organised immune response and extracellular matrix remodelling. We developed a 3-D system incorporating virulent mycobacteria, primary human blood mononuclear cells and collagen–alginate matrix to dissect the host-pathogen interaction. Infection in 3-D led to greater cellular survival and permitted longitudinal analysis over 21 days. Key features of human tuberculosis develop, and extracellular matrix integrity favours the host over the pathogen. We optimised multiparameter readouts to study emerging therapeutic interventions: cytokine supplementation, host-directed therapy and immunoaugmentation. Each intervention modulates the host-pathogen interaction, but has both beneficial and harmful effects. This methodology has wide applicability to investigate infectious, inflammatory and neoplastic diseases and develop novel drug regimes and vaccination approaches. DOI: http://dx.doi. org/10.7554/eLife.21283. 001
exacerbation recovery patterns in newly diagnosed or maintenance treatment-naïve patients with COPD: secondary analyses of TICarI 1 trial data

Background: Little is known about the recovery patterns from acute exacerbations of chronic obstructive pulmonary disease (AECOPD) in newly diagnosed or maintenance treatment-naïve patients with COPD. This study describes the course of AECOPD in these patients at the time of treatment for the symptoms of acute respiratory tract infection (RTI). Methods: This study was a secondary analysis of data from a 12-week, randomized clinical trial (TICARI 1) testing the efficacy and safety of once-daily tiotropium 18 µ g maintenance therapy versus placebo in newly diagnosed or maintenance treatment-naïve COPD patients with acute RTI symptoms for # 7 days. Patients received standard care for AECOPD and RTI. Due to under-recruitment, the trial ended early and hence was underpowered to detect treatment differences. Data were pooled and exacerbation recovery patterns examined by using the EXAcerbation of Chronic Pulmonary Disease Tool (EXACT), forced expiratory volume in 1 second, rescue medication use, COPD Assessment Test™, Functional Assessment of Chronic Illness Therapy–Short Form, and Work Productivity and Activity Impairment Questionnaire: Respiratory Symptoms. Results: Of 140 patients, 73.6% had a prior COPD diagnosis without maintenance therapy; 80.0% had moderate-to-severe airflow obstruction. In addition to study drug, 40.0% were prescribed pharmacologic therapy (corticosteroids [34.3%], antibiotics [16.4%], and short-acting β 2 -adrenergic agonists [5.0%]) within ± 7 days of randomization. Over 12 weeks, 78.6% exhibited symptomatic recovery (EXACT score) in a median of 5.0 days. Across all patients, 49.3% recovered without relapse, 29.3% recovered and then relapsed, and 21.4% had persistent symptoms (recovery criteria unmet). Conclusion: A substantial portion of newly diagnosed or maintenance treatment-naïve patients with COPD experience relapse or persistent symptoms following a clinic visit for AECOPD with symptoms of RTI. Whether initiating maintenance therapy could improve outcomes and reduce exacerbation risk requires further study. originally designed to examine the efficacy and safety of once-daily tiotropium 18 µ g in this population. Symptomatic recovery was assessed using the EXAcerbation a 14-item completed by patients each evening, to assess the severity of breathlessness, cough, sputum, chest symptoms, sleep disturbance, feeling week or tired, and feeling worried or concerned. Over 12 weeks, 49.3% of patients recovered without a relapse, 29.3% recovered and subsequently relapsed, and 21.4% had persistent symptoms (ie, did not meet the recovery criteria). Results were consistent across health outcomes, including health status, dyspnea, activity limitation, and work productivity. The study findings suggest that a significant portion of newly diagnosed and treatment-naïve patients have difficulty recovering from an acute RTI. Further study of the short- and long-term effects of these events and the effectiveness of various treatment options is warranted.
Development of a composite outcome score for a complex intervention-measuring the impact of Community Health Workers Trials Sample

Development of a composite outcome score for a complex intervention measuring the impact of Community Health Workers Trials Sample doi:10.1186/s13063-015-0625-1 Hilary Watt (h.watt@imperial.ac.uk) Matthew Harris (m.harris@imperial.ac.uk) Jane Noyes (jane.noyes@bangor.ac.uk) Rhiannon Whitaker (Rhiannon@whitres.co.uk) Zoe Hoare (z.hoare@bangor.ac.uk) Rhiannon Tudor Edwards (r.t.edwards@bangor.ac.uk) Andy Haines (andy.haines@lshtm.ac.uk) Sample
Review of the national ambient air quality standards for particulate matter: Policy assessment of scientific and technical information. OAQPS staff paper. Final report

This staff evaluates and interprets the updated scientific and technical information that EPA staff believes is most relevant to the review of primary and secondary national ambient air quality standards for particulate matter (PM). This assessment is intended to bridge the gap between the scientific review in the 1996 criteria document and the judgements required of the Administrator in setting ambient air quality standards for PM.
Species of Concern within the Salish Sea Marine Ecosystem: changes from 2002 to 2008

Species of concern are native species, sub-species or ecologically significant units that warrant special attention to ensure their conservation. The number of species of concern within an ecosystem can be used as a crude measure of ecosystem health and it illustrates where cross-jurisdiction work is needed to recover declining species. Within the bi-national Puget Sound Georgia Basin marine ecosystem, an area also known as the Salish Sea, four jurisdictions assess which species require special initiatives to ensure protection and survival of the population: the Province of British Columbia, the State of Washington, the Canadian Federal Government, and the United States Federal Government. As of September 1, 2008, 64 species of concern were listed by one or more of these jurisdictions; one more than in 2006 when this list was last compiled and four more than in 2002 when this list was first compiled. Since 2006, three new species were added to the list and two were removed. Rougheye rockfish (Sebastes aleutianus) were listed as a species of special concern by the Canadian Federal Government as was the bluntnose sixgill shark (Hexanchus griseus). Additionally, Puget Sound steelhead (Oncorhynchus mykiss) were listed as threatened by the U.S. Federal Government. The shortspine thornyhead fish (Sebastolobus alascanus) changed from Canadian Federal Government candidate status to not-listed and was removed and two stocks of Pacific herring (Clupea pallasi) were consolidated into one due to removal of the Cherry Point stock from U.S. Federal Candidate status. Using unpublished estimates on species richness for the ecosystem, approximately 0.1% of invertebrates (3/3000), 13% of fishes (28/219), 18% of birds (23/128) and 45% (9/20) of mammals that utilize the Salish Sea marine waters are listed by one or more jurisdiction as species of concern. In light of projected increased population growth, on-going habitat modifications and expected climate change, the number of species of concern for this ecosystem is likely to increase if listing efforts remain consistent for all four jurisdictions. Increased and improved bi-national efforts to recover declining populations of species and recover this ecosystem are urgently needed to stop the insidious loss of species and ecosystem decay.
Stability Analysis of Impulsive Switched Time-Delay Systems With State-Dependent Impulses

This paper studies the stability for impulsive switched time-delay systems with state-dependent impulses. Since the impulses and the switches are not necessarily synchronous, we start from a stability analysis of impulsive switched time-delay systems with time-dependent impulses. Sufficient conditions are derived to guarantee the stability property, which extends the previous results for the synchronous switch and impulse case. For the state-dependent impulse case, using the B-equivalent method, impulsive switched time-delay systems with state-dependent impulses are transformed into impulsive switched time-delay systems with time-dependent impulses. The equivalence between the original system and the transformed system is established, and stability conditions are obtained for impulsive switched time-delay systems with state-dependent impulses. Finally, a numerical example is given to demonstrate the obtained results.
Molecular Expression of Bone Marrow Angiogenic Factors , Cell-Cell Adhesion Molecules and Matrix-MetalloProteinases in Plasmacellular Disorders : a Molecular Panel to İnvestigate Disease Progression

Citation: Rapanotti M.C. , Franceschini L. , Suarez Viguria T.M. , Ialongo C. , Fraboni D. , Cerretti R. , De Angelis G. , Pupo L. , Rizzo M. , Cantonetti M. , Postorino M. , Voso M.T, Lo-Coco F. Molecular expression of bone marrow angiogenic factors, cell-cell adhesion molecules and matrix-metallo-proteinases in plasmacellular disorders: a molecular panel to investigate disease progression. Mediterr J Hematol Infect Dis 2018, 10(1): e2018059, DOI: http://dx.doi. org/10.4084/MJHID.2018. 059
Evaluation of a Digital Consultation and Self-Care Advice Tool in Primary Care: A Multi-Methods Study

Digital services are often regarded as a solution to the growing demands on primary care services. Provision of a tool offering advice to support self-management as well as the ability to digitally consult with a General Practitioner (GP) has the potential to alleviate some of the pressure on primary care. This paper reports on a Phase II, 6-month evaluation of eConsult, a web-based triage and consultation system that was piloted across 11 GP practices across Scotland. Through a multi-method approach the evaluation explored eConsult use across practices, exposing both barriers and facilitators to its adoption. Findings suggest that expectations that eConsult would offer an additional and alternative method of accessing GP services were largely met. However, there is less certainty that it has fulfilled expectations of promoting self-help. In addition, low uptake meant that evaluation of current effectiveness was difficult for practices to quantify. The presence of an eConsult champion(s) within the practice was seen to be a significant factor in ensuring successful integration of the tool. A lack of patient and staff engagement, insufficient support and lack of protocols around processes were seen as barriers to its success.
Evaluation of office space utilisation in South African municipalities

Purpose: Office space planning requires design skills and space planning norms to ensure space efficient office areas allowing occupants to perform optimally. No specific space norms exist for South African municipalities. Municipal facilities are unique and fulfil many functions, challenging the application of space norms. This study was part of work commissioned by the Development Bank of South Africa (DBSA) to understand municipal office space use in preparing a guideline for future municipal office building funding applications. The study evaluated current South African municipal office space allocation, compared it to office space planning norms for South African organs of state and identified possible challenges to applying the said space planning norms to municipal office space planning.
(2017). The role of glycaemic and lipid risk factors in mediating the effect of BMI on coronary heart disease: A two-step, two-sample Mendelian randomization study.

Aims/hypothesis The extent to which effects of BMI on CHD are mediated by glycaemic and lipid risk factors is unclear. In this study we examined the effects of these traits using genetic evidence. Methods We used two-sample Mendelian randomisation to determine: (1) the causal effect of BMI on CHD (60,801 case vs 123,504 control participants), type 2 diabetes (34,840 case vs 114,981 control participants), fasting glucose ( n = 46,186), insulin ( n = 38,238), HbA 1c ( n = 46,368) and LDL-cholesterol, HDL-cholesterol and triacylglycerols ( n = 188,577); (2) the causal effects of glycaemic and lipids traits on CHD; and (3) the extent to which these traits mediate any effect of BMI on CHD. Results One SD higher BMI (~ 4.5 kg/m 2 ) was associated with higher risk of CHD (OR 1.45 [95% CI 1.27, 1.66]) and type 2 diabetes (1.96 [95% CI 1.35, higher levels of fasting glucose (0.07 mmol/l [95% CI 0.03, 0.11]), HbA 1c (0.05% fasting insulin (0.18 and triacylglycerols (0.20 lower ( − 0.23 SD [95% CI − 0.32, − 0.15]). There was no evidence for a causal relation between BMI and LDL-cholesterol. The causal associations of higher triacylglycerols, HbA 1c and diabetes risk with CHD risk remained after performing sensitivity analyses that considered different models of horizontal pleiotropy. The BMI – CHD effect reduced from 1.45 to 1.16 (95% CI 0.99, 1.36) and to 1.36 (95% CI 1.19, 1.57) with genetic adjustment for triacylglycerols or HbA 1c , respectively, and to 1.09 (95% CI 0.94, 1.27) with adjustment for both. Conclusions/interpretation Increased triacylglycerol levels and poor glycaemic control appear to mediate much of the effect of BMI on CHD.
abnormal intrinsic brain activities in stable patients with cOPD: a resting-state functional Mri study

Objective: The majority of previous neuroimaging studies have reported both structural and functional changes in COPD, whereas the intrinsic low-frequency oscillations changes and the relationship between the abnormal brain regions and the clinical performances remain unknown. The present study was conducted with the aim of evaluating the intrinsic brain activity in COPD patients using the amplitude of low-frequency ﬂuctuation (ALFF) method. Methods: All participants, including 19 stable patients with COPD and 20 normal controls (NCs) matched in age, sex, and education, underwent resting-state functional MRI scans and performed cognitive function tests and respiratory functions tests. The local spontaneous brain activity was examined using the voxel-wise ALFF. Pearson’s correlation analysis was used to investigate the relationships between the brain regions with altered ALFF signal values and the clinical features in COPD patients. Results: Compared with the NCs, COPD patients showed significantly lower cognitive function scores. Also, lower ALFF areas in the cluster of the posterior cingulate cortex (PCC) and precuneus, as well as a higher ALFF area in the brainstem were also found in COPD patients. The mean ALFF values in the PCC, precuneus, and brainstem showed high sensitivity and specificity in operating characteristic curves analysis, which might have the ability to distinguish COPD from NCs. Meanwhile, the mean signal values of the lower ALFF cluster displayed significant positive correlations with FEV 1 /FVC proportion and significant negative correlation with PaCO 2 ; the higher ALFF cluster showed significant positive correlation with FEV 1 proportion in COPD. Conclusion: According to the results of the present study, the COPD patients showed abnormal intrinsic brain activities in the precuneus, PCC, and brainstem, which might provide useful information to better understand the underlying pathophysiology of cognitive impairment.
Compositional profile of α / β-hydrolase fold proteins in mangrove soil metagenomes

Citation for published version (APA): Jiménez Avella, D. , Dini Andreote, F. , Ottoni, J. R. , de Oliveira, V. M. , van Elsas, J. D. , & Andreote, F. D. (2015). Compositional profile of α / β-hydrolase fold proteins in mangrove soil metagenomes: Prevalence of epoxide hydrolases and haloalkane dehalogenases in oil-contaminated sites. Microbial Biotechnology, 8(3), 604-613. https://doi.org/10.1111/1751-7915.12157
Review of antimicrobial use and considerations in the elderly population

: Pharmacologic management of infections in elderly patients presents multiple challenges to health care professionals due to variable pharmacokinetics, pharmacodynamics, and immune function. Age is a well-established risk factor for infection, but furthermore is a risk factor for prolonged length of hospital stay, increased incidence of complications, and significant and sustained decline in baseline functional status. In 2014, 46.2 million Americans were aged $ 65 years, accounting for 14.5% of the total population. By 2033, for the first time, the population of persons aged $ 65 years is projected to outnumber the people , 18 years of age. According to the National Ambulatory Medical Care Survey and the National Hospital Ambulatory Medical Care Survey, 154 million prescriptions for antimicrobials were estimated to have been written in doctors’ offices and emergency departments during a 1-year time period. In 2014, 266.1 million courses of antimicrobials were dispensed to outpatients by US community pharmacies. A study that evaluated 2007–2009 Medicare Part D data found that patients aged $ 65 years used more antimicrobials, at 1.10 per person per year, compared to 0.88 antimicrobials used per person per year in patients aged 0–64 years. With the abundance of antimicrobial prescriptions and the current growth in the number and proportion of older adults in the US, it is essential that health care providers understand appropriate antimicrobial pharmacotherapy in the elderly patient. This review focuses on the use and implications of antimicrobial agents in the elderly population. concentration of clarithromycin in the gastric mucous, while clarithromycin inhibits CYP 450 metabolism of omeprazole. Itraconazole capsules require an acidic environment for absorption. c when initiating voriconazole in a patient receiving omeprazole at a dose of 40 mg/day or greater reduce the dose of omeprazole by 50% 74 (while in vivo studies were performed with omeprazole, other proton pump inhibitors can also inhibit metabolism of voriconazole via CYP 450 enzymes CYP 2C9 and/or CYP 3A4). d There is no direct clinical evidence to confirm this interaction; however, the AUC of cefpodoxime has been shown to decrease by 40% when given with antacids such as aluminum/magnesium hydroxide and the histamine-2 receptor antagonist famotidine.
HEARTJNL225466 1943..1950

Background A low level of high-density lipoprotein cholesterol (HDL-C) is strongly associated with cardiovascular events. However, the significance of HDLC after statin therapy on the outcome of patients who have undergone percutaneous coronary intervention (PCI) with drug eluting stents (DES) is unclear. Objectives To investigate the significance of HDL-C after statin therapy on cardiovascular events in patients with coronary artery disease after DES implantation. Methods Patients who underwent PCI with DES from January 2004 to December 2009 were prospectively enrolled. The follow-up lipid panel of 2693 patients (median lab follow-up duration 225 days) who had continued using statins after PCI and who attained lowdensity lipoprotein cholesterol (LDL-C) <100 mg/dl was analysed. Major adverse cardiac events (MACE), including all-cause death, non-fatal myocardial infarction, and target vessel revascularisation according to follow-up HDL-C level (40 mg/dl for men or 50 mg/dl for women) were compared with the use of propensity scores matching. Results Median follow-up duration was 832 days. 1585 (58.9%) patients had low follow-up HDL-C and 1108 had high follow-up HDL-C. The low follow-up HDL-C group had significantly higher rates of MACE. Low follow-up HDL-C was a significant independent predictor of MACE (adjusted HR 1.404, 95% CI 1.111 to 1.774, p1⁄40.004). In further analysis with propensity scores matching, overall findings were consistent. Conclusions Raising HDL-C levels may be a subsequent goal after achieving target LDL-C levels in patients with