bluuebunny/crossref_metadata_2025_split huggingface dataset:
Towards the Clinical utility of CFD for assessment of intracranial aneurysm rupture – a systematic review and novel parameter-ranking tool
Authors: Liang Li , Steinman David A , Brina Olivier , Chnafa Christophe , Cancelliere Nicole M , Pereira Vitor M 
Published: October 2018

BackgroundIntracranial aneurysms (IAs) are vascular dilations on cerebral vessels that affect between 1%–5% of the general population, and can cause life-threatening intracranial hemorrhage when ruptured. Computational fluid dynamics (CFD) has emerged as a promising tool to study IAs in recent years, particularly for rupture risk assessment. However, despite dozens of studies, CFD is still far from clinical use due to large variations and frequent contradictions in hemodynamic results between studies.PurposeTo identify key gaps in the field of CFD for the study of IA rupture, and to devise a novel tool to rank parameters based on potential clinical utility.MethodsA Pubmed search identified 231 CFD studies for IAs. Forty-six studies fit our inclusion criteria, with a total of 2791 aneurysms. For included studies, study type, boundary conditions, solver resolutions, parameter definitions, geometric and hemodynamic parameters used, and results found were recorded.Data synthesisAspect ratio, aneurysm size, low wall shear stress area, average wall shear stress, and size ratio were the parameters that correlate most strongly with IA rupture.LimitationsSignificant differences in parameter definitions, solver spatial and temporal resolutions, number of cycles between studies as well as frequently missing information such as inlet flow rates were identified. A greater emphasis on prospective studies is also needed.ConclusionsOur recommendations will help increase standardization and bridge the gaps in the CFD community, and expedite the process of making CFD clinically useful in guiding the treatment of IAs.
Childhood and adult exposure to secondhand tobacco smoke and cardiac structure and function: results from Echo-SOL
Authors: Burroughs Peña Melissa Suzanne , Swett Katrina , Kaplan Robert C , Perreira Krista , Daviglus Martha , Kansal Mayank M , Cai Jianwen , Giachello Aida L , Gellman Marc D , Velazquez Eric J , Rodriguez Carlos J 
Published: October 2018

ObjectiveTo describe the relationship of household secondhand smoke (SHS) exposure and cardiac structure and function.MethodsParticipants (n=1069; 68 % female; age 45–74 years) without history of tobacco use, coronary artery disease or severe valvular disease were included. Past childhood (starting at age <13 years), adolescent/adult and current exposure to household SHS was assessed. Survey linear regression analyses were used to model the relationship of SHS exposure and echocardiographic measures of cardiac structure and function, adjusting for covariates (age, sex, study site, alcohol use, physical activity and education).ResultsSHS exposure in childhood only was associated with reduced E/A velocity ratio (β=−0.06 (SE 0.02), p=0.008). SHS exposure in adolescence/adult only was associated with increased left ventricular ejection fraction (LVEF) (1.2 (0.6), p=0.04), left atrial volume index (1.7 (0.8), p=0.04) and decreased isovolumic relaxation time (−0.003 (0.002), p=0.03). SHS exposure in childhood and adolescence/adult was associated with worse left ventricular global longitudinal strain (LVGLS) (two-chamber) (0.8 (0.4), p= 0.049). Compared with individuals who do not live with a tobacco smoker, individuals who currently live with at least one tobacco smoker had reduced LVEF (−1.4 (0.6), p=0.02), LVGLS (average) (0.9 (0.40), p=0.03), medial E′ velocity (−0.5 (0.2), p=0.01), E/A ratio (−0.09 (0.03), p=0.003) and right ventricular fractional area change (−0.02 (0.01), p=0.01) with increased isovolumic relaxation time (0.006 (0.003), p=0.04).ConclusionsPast and current household exposure to SHS was associated with abnormalities in cardiac systolic and diastolic function. Reducing household SHS exposure may be an opportunity for cardiac dysfunction prevention to reduce the risk of future clinical heart failure.
Effect of sildenafil (Revatio) on postcardiac surgery acute kidney injury: a randomised, placebo-controlled clinical trial: the REVAKI-2 trial protocol
Authors: Aujla Hardeep , Kumar Tracy , Woźniak Marcin , Dott William , Sullo Nikol , Joel-David Lathishia , Morris Thomas , Brookes Cassandra , Barber Shaun , Murphy Gavin James 
Published: October 2018

IntroductionAcute kidney injury (AKI) is a common and severe complication of cardiac surgery. The administration of pharmacological renoprotective agents during the perioperative period could prevent or reduce the severity of AKI and improve clinical outcomes. Experimental studies suggest that sildenafil may have therapeutic potential for the prevention of AKI. This trial will test the hypothesis that postoperative AKI will be reduced in cardiac surgery patients if they receive sildenafil compared with placebo.Methods and analysisAdult cardiac surgery patients 18 years of age or above undergoing cardiac surgery with cardiopulmonary bypass and cardioplegic arrest at a single tertiary cardiac centre in the UK will be randomised in a 1:1 ratio to receive either sildenafil or placebo. The primary outcome is serum creatinine concentration measured at preoperation and daily for up to 7 days postoperatively. Secondary outcomes will include measures of inflammation, organ injury, volumes of blood transfused and resource use. Allocation concealment, internet-based randomisation stratified by operation type, and blinding of outcome assessors will reduce the risk of bias. A sample size of 112 patients will have a 90% power to detect a mean difference of 10 μmol/L for serum creatinine values between treatment and placebo control groups with an alpha value of 0.05.Ethics and disseminationThe trial protocol was approved by a UK ethics committee (reference 15/YH/0489). The trial findings will be disseminated in scientific journals and meetings.Trial registration numberISRCTN18386427.
Antibiotic therapy for pelvic inflammatory disease: an abridged version of a Cochrane systematic review and meta-analysis of randomised controlled trials
Authors: Savaris Ricardo F , Fuhrich Daniele G , Duarte Rui V , Franik Sebastian , Ross Jonathan D C 
Published: October 2018

Objective
To assess the effectiveness and safety of antibiotic regimens used to treat pelvic inflammatory disease (PID).

Design
This is a systematic review and meta-analysis of randomised controlled trials (RCTs). Risk of bias was assessed using the criteria outlined in the Cochrane guidelines. Quality of evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation.

Data sources
Eight electronic databases were searched from date of inception up to July 2016. Database searches were complemented by screening of reference lists of relevant studies, trial registers, conference proceeding abstracts and grey literature.

Eligibility criteria
RCTs comparing the use of antibiotics with placebo or other antibiotics for the treatment of PID in women of reproductive age, either as inpatient or outpatient treatment.

Results
We included 37 RCTs (6348 women). The quality of evidence ranged from very low to high, the main limitations being serious risk of bias (due to poor reporting of study methods and lack of blinding), serious inconsistency and serious imprecision. There was no clear evidence of a difference in the rates of cure for mild-moderate or for severe PID for the comparisons of azithromycin versus doxycycline, quinolone versus cephalosporin, nitroimidazole versus no use of nitroimidazole, clindamycin plus aminoglycoside versus quinolone, or clindamycin plus aminoglycoside versus cephalosporin. No clear evidence of a difference between regimens in antibiotic-related adverse events leading to discontinuation of therapy was observed.

Conclusions
We found no conclusive evidence that one regimen of antibiotics was safer or more effective than any other for the treatment of PID, and there was no clear evidence for the use of nitroimidazoles (metronidazole) compared with the use of other drugs with activity against anaerobes. More evidence is needed to assess treatments for women with PID, particularly comparing regimens with or without the addition of nitroimidazoles and the efficacy of azithromycin compared with doxycycline.
Trichomonas vaginalis
and HIV infection acquisition: a systematic review and meta-analysis
Authors: Masha Simon Chengo , Cools Piet , Sanders Eduard J , Vaneechoutte Mario , Crucitti Tania 
Published: October 2018

Objectives
Trichomoniasis is the most prevalent curable STI globally, with the highest incidence and prevalence in sub-Saharan Africa (sSA). STIs have largely been associated with an increase in HIV acquisition. Our objective was to assess the existing literature available in English regarding the association of Trichomoniasis and HIV-1 acquisition.

Methods

The review protocol was registered at the International Prospective Register of Systematic Reviews (PROSPERO) under number CRD42018082702. We searched MEDLINE, Embase and Scopus databases to collect articles measuring the association of
Trichomonas vaginalis
infection and HIV acquisition and performed a meta-analysis and qualitative synthesis of the literature.

Results

We identified 1806 unduplicated citations, of which 18 papers and 1 conference abstract were eligible for inclusion in the review after applying our inclusion and exclusion criteria. All the studies included in the systematic review had been carried out in sSA. The articles reported various measures of effects, namely: HRs, rate ratios, risk ratios and ORs. In a meta-analysis restricted to 11 studies reporting HR, individuals infected with
T. vaginalis
were 1.5 times more likely to acquire HIV compared with individuals not infected with
T. vaginalis
(95% CI 1.3 to 1.7; p<0.001).

Conclusions

T. vaginalis
is an important factor in HIV acquisition especially in sSA where the prevalence
of
both
T. vaginalis
and HIV-1 are high. This systematic review and meta-analysis confirms the evidence that infection with
T. vaginalis
augments HIV acquisition with 50%. Diagnosis and treatment of
T. vaginalis
infection in both high-risk and low-risk individuals may be a potential tool to reduce new HIV infections.

Trial registration number
CRD42018082702
Diabetes mellitus attenuates the pressure response against hypotensive stress by impairing the sympathetic regulation of the baroreflex afferent arc
Authors: Kamada Kazuhiro , Saku Keita , Tohyama Takeshi , Kawada Toru , Mannoji Hiroshi , Abe Kiyokazu , Nishikawa Takuya , Sunagawa Genya , Kishi Takuya , Sunagawa Kenji , Tsutsui Hiroyuki 
Published: October 2018

Patients with diabetes mellitus (DM) often show arterial pressure (AP) lability associated with cardiovascular autonomic neuropathy. Because the arterial baroreflex tightly regulates AP via sympathetic nerve activity (SNA), we investigated the systematic baroreflex function, considering the control theory in DM by open-loop analysis. We used Zucker diabetic fatty (ZDF) rats as a type 2 DM model. Under general anesthesia, we isolated the carotid sinuses from the systemic circulation, changed intracarotid sinus pressure (CSP), and recorded SNA and AP responses. We compared CSP-AP (total loop), CSP-SNA (afferent arc), and SNA-AP (efferent arc) relationships between ZDF lean ( n = 8) and ZDF fatty rats ( n = 6). Although the total loop gain of baroreflex (ΔAP/ΔCSP) at the operating point did not differ between the two groups, the average gain in the lower CSP range was markedly reduced in ZDF fatty rats (0.03 ± 0.01 vs. 0.87 ± 0.10 mmHg/mmHg, P < 0.001). The afferent arc showed the same trend as the total loop, with a response threshold of 139.8 ± 1.0 mmHg in ZDF fatty rats. There were no significant differences in the gain of efferent arc between the two groups. Simulation experiments indicated a markedly higher AP fall and lower total loop gain of baroreflex in ZDF fatty rats than in ZDF lean rats against hypotensive stress because the efferent arc intersected with the afferent arc in the SNA unresponsive range. Thus, we concluded that impaired baroreflex sympathetic regulation in the lower AP range attenuates the pressure response against hypotensive stress and may partially contribute to AP lability in DM. NEW & NOTEWORTHY In this study, we investigated the open-loop baroreflex function, considering the control theory in type 2 diabetes mellitus model rats to address the systematic mechanism of arterial pressure (AP) lability in diabetes mellitus. The unresponsiveness of baroreflex sympathetic regulation in the lower AP range was observed in type 2 diabetic rats. It may attenuate the baroreflex pressure-stabilizing function and induce greater AP fall against hypotensive stress.
IL-13 promotes in vivo neonatal cardiomyocyte cell cycle activity and heart regeneration
Authors: Wodsedalek Dylan J. , Paddock Samantha J. , Wan Tina C. , Auchampach John A. , Kenarsary Aria , Tsaih Shirng-Wern , Flister Michael J. , O’Meara Caitlin C. 
Published: October 2018

There is great interest in identifying signaling mechanisms by which cardiomyocytes (CMs) can enter the cell cycle and promote endogenous cardiac repair. We have previously demonstrated that IL-13 stimulated cell cycle activity of neonatal CMs in vitro. However, the signaling events that occur downstream of IL-13 in CMs and the role of IL-13 in CM proliferation and regeneration in vivo have not been explored. Here, we tested the role of IL-13 in promoting neonatal CM cell cycle activity and heart regeneration in vivo and investigated the signaling pathway(s) downstream of IL-13 specifically in CMs. Compared with control, CMs from neonatal IL-13 knockout (IL-13−/−) mice showed decreased proliferative markers and coincident upregulation of the hypertrophic marker brain natriuretic peptide ( Nppb) and increased CM nuclear size. After apical resection in anesthetized newborn mice, heart regeneration was significantly impaired in IL-13−/− mice compared with wild-type mice. Administration of recombinant IL-13 reversed these phenotypes by increasing CM proliferation markers and decreasing Nppb expression. RNA sequencing on primary neonatal CMs treated with IL-13 revealed activation of gene networks regulated by ERK1/2 and Akt. Western blot confirmed strong phosphorylation of ERK1/2 and Akt in both neonatal and adult cultured CMs in response to IL-13. Our data demonstrated a role for endogenous IL-13 in neonatal CM cell cycle and heart regeneration. ERK1/2 and Akt signaling are important pathways known to promote CM proliferation and protect against apoptosis, respectively; thus, targeting IL-13 transmembrane receptor signaling or administering recombinant IL-13 may be therapeutic approaches for activating proregenerative and survival pathways in the heart. NEW & NOTEWORTHY Here, we demonstrate, for the first time, that IL-13 is involved in neonatal cardiomyocyte cell cycle activity and heart regeneration in vivo. Prior work has shown that IL-13 promotes cardiomyocyte cell cycle activity in vitro; however, the signaling pathways were unknown. We used RNA sequencing to identify the signaling pathways activated downstream of IL-13 in cardiomyocytes and found that ERK1/2 and Akt signaling was activated in response to IL-13.
Folic Acid and Vitamin B12 Supplementation and the Risk of Cancer: Long-term Follow-up of the B Vitamins for the Prevention of Osteoporotic Fractures (B-PROOF) Trial
Authors: Oliai Araghi Sadaf , Kiefte-de Jong Jessica C. , van Dijk Suzanne C. , Swart Karin M.A. , van Laarhoven Hanneke W. , van Schoor Natasja M. , de Groot Lisette C.P.G.M. , Lemmens Valery , Stricker Bruno H. , Uitterlinden André G. , van der Velde Nathalie 
Published: October 2018

Abstract

Background:
Folic acid and vitamin B12 play key roles in one-carbon metabolism. Disruption of one-carbon metabolism may be involved in the risk of cancer. Our aim was to assess the long-term effect of supplementation with both folic acid and vitamin B12 on the incidence of overall cancer and on colorectal cancer in the B Vitamins for the Prevention of Osteoporotic Fractures (B-PROOF) trial.

Methods:
Long-term follow-up of B-PROOF trial participants (N = 2,524), a multicenter, double-blind randomized placebo-controlled trial designed to assess the effect of 2 to 3 years daily supplementation with folic acid (400 μg) and vitamin B12 (500 μg) versus placebo on fracture incidence. Information on cancer incidence was obtained from the Netherlands cancer registry (Integraal Kankercentrum Nederland), using the International Statistical Classification of Disease (ICD-10) codes C00–C97 for all cancers (except C44 for skin cancer), and C18–C20 for colorectal cancer.

Results:
Allocation to B vitamins was associated with a higher risk of overall cancer [171 (13.6%) vs. 143 (11.3%); HR 1.25; 95% confidence interval (CI), 1.00–1.53, P = 0.05]. B vitamins were significantly associated with a higher risk of colorectal cancer [43(3.4%) vs. 25(2.0%); HR 1.77; 95% CI, 1.08–2.90, P = 0.02].

Conclusions:
Folic acid and vitamin B12 supplementation was associated with an increased risk of colorectal cancer.

Impact:
Our findings suggest that folic acid and vitamin B12 supplementation may increase the risk of colorectal cancer. Further confirmation in larger studies and in meta-analyses combining both folic acid and vitamin B12 are needed to evaluate whether folic acid and vitamin B12 supplementation should be limited to patients with a known indication, such as a proven deficiency.
Accuracy of a Novel Histoplasmosis Enzyme Immunoassay to Evaluate Suspicious Lung Nodules
Authors: Deppen Stephen A. , Massion Pierre P. , Blume Jeffrey , Walker Ronald C. , Antic Sanja , Chen Heidi , Durkin Michele M. , Wheat L. Joseph , Grogan Eric L. 
Published: October 2018

Abstract

Background:
Granulomas caused by infectious lung diseases present as indeterminate pulmonary nodules (IPNs) on radiography. Newly available serum enzyme immunoassay (EIA) for histoplasmosis has not been studied for the evaluation of IPNs. We investigated serum biomarkers of histoplasmosis antibodies as an indication of benign disease in IPNs from a highly endemic region.

Methods:
A total of 152 serum samples from patients presenting with pulmonary nodules ≤30 mm in maximum diameter were analyzed for histoplasmosis antibodies by immunodiffusion and EIA IgG and IgM tests. Serology and FDG-PET/CT scan diagnostic test characteristics were estimated and compared.

Results:
Cancer prevalence was 55% (n = 83). Thirty-nine (26%) individuals were positive for IgG histoplasmosis antibodies. Twelve samples were IgM antibody positive. Immunodiffusion serology was similar to IgM antibody results with 13 positive tests. Diagnostic likelihood ratios for benign disease were 0.62, 0.33, and 0.28 for FDG-PET/CT, IgG, and IgM antibodies, respectively. When both IgG and IgM were positive (n = 8), no nodules were cancerous and six were FDG-PET/CT avid.

Conclusions:
A positive EIA test for both IgM and IgG strongly suggested histoplasmosis etiology and benign granuloma for 12% of benign nodules arising from a highly endemic region. Presence of either IgG or IgM histoplasma antibodies was associated with benign disease. The EIA test was more sensitive in assessing histoplasma exposure than immunodiffusion serology.

Impact:
A new CLIA-certified histoplasmosis antibody EIA test measures histoplasmosis exposure, offers a possible alternative clinical diagnosis for benign IPNs, and may improve IPN evaluation while avoiding harmful invasive biopsies.
STAT3 Inhibition Combined with CpG Immunostimulation Activates Antitumor Immunity to Eradicate Genetically Distinct Castration-Resistant Prostate Cancers
Authors: Moreira Dayson , Adamus Tomasz , Zhao Xingli , Su Yu-Lin , Zhang Zhuoran , White Seok Voon , Swiderski Piotr , Lu Xin , DePinho Ronald A. , Pal Sumanta K. , Kortylewski Marcin 
Published: October 2018

Abstract

Purpose:
Prostate cancers show remarkable resistance to emerging immunotherapies, partly due to tolerogenic STAT3 signaling in tumor-associated myeloid cells. Here, we describe a novel strategy combining STAT3 inhibition with Toll-like Receptor 9 (TLR9) stimulation to unleash immune response against prostate cancers regardless of the genetic background.

Experimental Design:
We developed and validated a conjugate of the STAT3 antisense oligonucleotide (ASO) tethered to immunostimulatory TLR9 agonist (CpG oligonucleotide) to improve targeting of human and mouse prostate cancer and myeloid immune cells, such as myeloid-derived suppressor cells (MDSC).

Results:
CpG-STAT3ASO conjugates showed improved biodistribution and potency of STAT3 knockdown in target cells in vitro and in vivo. Systemic administration of CpG-STAT3ASO (5 mg/kg) eradicated bone-localized, Ras/Myc-driven, and Ptenpc−/−Smad4pc−/−Trp53c−/− prostate tumors in the majority of treated mice. These antitumor effects were primarily immune-mediated and correlated with an increased ratio of CD8+ to regulatory T cells and reduced pSTAT3+/PD-L1+ MDSCs. Both innate and adaptive immunity contributed to systemic antitumor responses as verified by the depletion of Gr1+ myeloid cells and CD8+ and CD4+ T cells, respectively. Importantly, only the bifunctional CpG-STAT3ASO, but not control CpG oligonucleotides, STAT3ASO alone, or the coinjection of both oligonucleotides, succeeded in recruiting neutrophils and CD8+ T cells into tumors. Thus, the concurrence of TLR9 activation with STAT3 inhibition in the same cellular compartment is indispensable for overcoming tumor immune tolerance and effective antitumor immunity against prostate cancer.

Conclusions:
The bifunctional, immunostimulatory, and tolerance-breaking design of CpG-STAT3ASO offers a blueprint for the development of effective and safer oligonucleotide strategies for treatment of immunologically “cold” human cancers.
Dialysate Calcium Concentration below 3.0 mEq/L Is Not Associated with Improved Outcomes in the Japanese Dialysis Outcomes and Practice Patterns Study
Authors: Iseki Kunitoshi , Henn Lisa L. , Nomura Takanobu , Kanda Eiichiro , Tsuruya Kazuhiko , Hirakata Hideki , Port Friedrich K. , Pisoni Ronald L. , Tentori Francesca , Robinson Bruce M. 
Published: October 2018

<b><i>Background:</i></b> Abnormal chronic kidney disease-mineral and bone disorder (CKD-MBD) markers have been associated with adverse outcomes in hemodialysis (HD) patients. Dialysate calcium concentration (D-Ca) likely influences serum calcium and phosphorus levels. Optimal D-Ca level remains unclear. We hypothesized that higher D-Ca is associated with cardiovascular events and mortality among Japanese HD patients. <b><i>Methods:</i></b> Enrollment data of chronic HD patients in the prospective observational study JDOPPS, phases 1–5 (1999–2015), provided exposures and covariates. All-cause mortality, non-arrhythmic cardiovascular events (NonAR-CVE), or their composites were analyzed by D-Ca, and divided into 2.5, 2.75, and 3.0 mEq/L. To minimize confounding by indication, analyses were restricted to facilities in which at least 90% of patients received the same D-Ca prescription. Association of D-Ca level with outcomes was evaluated in Cox models stratified by phase and accounting for facility clustering. Covariates describing patient demographics, comorbidities, laboratory values, CKD-MBD therapy, and facility attributes provided adjustment. <b><i>Results:</i></b> Of 9,201 patients included, 25.0% had D-Ca of 2.5 mEq/L; 6.8% D-Ca 2.75; and 68.2% D-Ca 3.0. Median follow-up time was 2.03 years. D-Ca was not associated with all-cause mortality, with hazards ratios for 2.5 vs. 3.0 mEq/L of 0.90 and 95% CI (0.73–1.11), nor with other outcomes. One effect modification occurred, protective for lower D-Ca on NonAR-CVE in the absence of cardiovascular comorbidities (<i>p</i> = 0.032), although corresponding D-Ca effects were not significant after multiple comparisons adjustment (<i>p</i> = 0.261 [D-Ca 2.5] and 0.125 [D-Ca 2.75]). <b><i>Conclusion:</i></b> Lowering D-Ca level below 3.0 mEq/L seems not to have a meaningful effect on patient outcomes.