bluuebunny/crossref_metadata_2025_split huggingface dataset:
Hyperphosphatemia is required for initiation but not propagation of kidney failure-induced calcific aortic valve disease
Authors: Shuvy Mony , Abedat Suzan , Eliaz Ran , Abu-Rmeileh Israa , Abu-Snieneh Asmahan , Ben-Dov Iddo Z. , Meir Karen , Pereg David , Beeri Ronen , Lotan Chaim 
Published: August 2019

High serum levels of phosphate are associated with uremia-induced calcific aortic valve disease (CAVD). However, it is not clear whether hyperphosphatemia is required in all phases of the process. Our aim was to determine the effects of phosphate and phosphate depletion at different phases of valve disease. The experimental design consisted of administering a uremia-inducing diet, with or without phosphate enrichment, to rats for 7 wk. Forty-two rats were fed with a phosphate-enriched uremic regimen that caused renal insufficiency and hyperphosphatemia. Another 42 rats were fed with a phosphate-depleted uremic regimen, which induces similar severity of renal insufficiency, but without its related mineral disorder. Aortic valves were evaluated at several points during the time of diet administration. In the second part, additional 54 rats were fed a phosphate-enriched diet for various time periods and were then switched to a phosphate-depleted diet to complete 7 wk of uremic diet. Osteoblast-like phenotype, inflammation, and eventually valve calcification were observed only in rats that were fed with a phosphate-enriched regimen. Significant valve calcification was observed only in rats that were fed a phosphate-enriched diet for at least 4 wk. Valve calcification was observed only when the switch to a phosphate-depleted regimen occurred after osteoblast markers and activation of Akt and ERK intracellular signaling pathways had already been found in the valve. Phosphate is essential for the initiation of the calcification process. However, when osteoblast markers are already expressed in valve tissue, phosphate depletion will not halt the disease. NEW & NOTEWORTHY High serum levels of phosphate are associated with uremia-induced calcific aortic valve disease. However, it is not clear whether hyperphosphatemia is required in all phases of the process. Our aim was to determine the effects of phosphate and phosphate depletion at different phases of valve disease. Our findings indicated that phosphate is essential for the initiation of the process that includes macrophage accumulation and osteoblast phenotype. Furthermore, hyperphosphatemia is dispensable beyond a certain phase of the process, a point of “no return” after which phosphate depletion does not prevent calcification. This point is relatively early in the course of calcification, when no calcification is apparent, but the inflammation, osteoblast markers, and activation of ERK and Akt pathways have already been identified. Our findings emphasize the complexity of the calcification process and suggest that different mediators might be required during different phases and that the role of phosphate precedes the actual calcification.
Association between Alcohol Consumption and Survival in Colorectal Cancer: A Meta-analysis
Authors: Kim Youngyo , Je Youjin , Giovannucci Edward L. 
Published: August 2019

Abstract

Background:
Although an association between alcohol consumption and risk of colorectal cancer is well established, little is known about the association between alcohol consumption and colorectal cancer survival. We conducted a meta-analysis of prospective cohort studies to quantitatively assess this association.

Methods:
Data searches were performed using PubMed and ISI Web of Science databases through December 2018. We estimated pooled RRs with 95% confidence intervals (CI) using random-effects models.

Results:
Twelve studies with 32,846 patients with colorectal cancer were included in the meta-analysis. Compared with no alcohol consumption, light (RR = 0.87; 95% CI, 0.81–0.94) and moderate (RR = 0.92; 95% CI, 0.85–1.00) prediagnostic alcohol consumption were associated with lower risk of all-cause mortality. Light prediagnostic alcohol consumption was associated with lower risk of colorectal cancer–specific mortality (RR = 0.87; 95% CI, 0.78–0.98). However, heavy prediagnostic alcohol consumption was not significantly associated with colorectal cancer survival. In a dose–response analysis, a nonlinear association between prediagnostic alcohol consumption and all-cause mortality was observed (Pnonlinearity = 0.0025), showing the reduction in RR at &lt;30 g/day of alcohol consumption. By type of alcohol, wine consumption was associated with lower risk of mortality from all-causes and colorectal cancer, but a positive association was observed between moderate liquor consumption and all-cause mortality. There was no association between postdiagnostic alcohol consumption and colorectal cancer survival.

Conclusions:
Light and moderate prediagnostic alcohol consumption were associated with better survival in colorectal cancer.

Impact:
Our findings suggest that light and moderate alcohol consumption may be associated with better survival in colorectal cancer, but further studies are warranted.
Calcium Channel Blockers and Risk of Lymphedema among Breast Cancer Patients: Nested Case–Control Study
Authors: Stolarz Amanda J. , Lakkad Mrinmayee , Klimberg V. Suzanne , Painter Jacob T. 
Published: August 2019

Abstract

Background:
To assess the risk of lymphedema associated with the use of calcium channel blockers (CCB) among breast cancer patients.

Methods:
A nested case–control study of adult female breast cancer patients receiving an antihypertensive agent was conducted using administrative claims data between 2007 and 2015. Cases were patients with lymphedema who were matched to 5 controls based on nest entry date (±180 days), age (±5 years), number of hypertensive drug classes, Charlson Comorbidity Index (CCI), thiazide exposure, and insurance type. Exposure to CCBs and covariates was identified in the 180-day period prior to event date. Conditional logistic regression was used to assess the impact of exposure among cases and controls.

Results:
A total of 717 cases and 1,681 matched controls were identified. After matching on baseline characteristics, mastectomy (7.8% vs. 4.8%; P = 0.0039), exposure to radiotherapy (27.1% vs. 21.7%; P = 0.0046), taxane-based chemotherapy (11.7% vs. 7.4%; P = 0.0007), anthracycline-based chemotherapy (6.0% vs. 3.6%; P = 0.0073), CCB use (28.3% vs. 23.3%; P = 0.0087), and CCI (19.8% vs. 12.7%; P &lt; 0.0001; score of 4 or above) were all higher in cases during the 180 days prior to the event date. In the adjusted analysis, CCB exposure was significantly associated with increased risk of lymphedema (OR = 1.320; 95% confidence interval, 1.003–1.737).

Conclusions:
CCB use was significantly associated with the development of lymphedema in breast cancer patients.

Impact:
CCBs should be avoided or used with caution in breast cancer patients to reduce the risk for developing lymphedema.
The Genomic Landscape of Merkel Cell Carcinoma and Clinicogenomic Biomarkers of Response to Immune Checkpoint Inhibitor Therapy
Authors: Knepper Todd C. , Montesion Meagan , Russell Jeffery S. , Sokol Ethan S. , Frampton Garrett M. , Miller Vincent A. , Albacker Lee A. , McLeod Howard L. , Eroglu Zeynep , Khushalani Nikhil I. , Sondak Vernon K. , Messina Jane L. , Schell Michael J. , DeCaprio James A. , Tsai Kenneth Y. , Brohl Andrew S. 
Published: August 2019

Abstract

Purpose:
Merkel cell carcinoma (MCC) is a rare, aggressive cutaneous malignancy, which has demonstrated sensitivity to immune checkpoint inhibitor therapy. Here, we perform the largest genomics study in MCC to date to characterize the molecular landscape and evaluate for clinical and molecular correlates to immune checkpoint inhibitor response.

Experimental Design:
Comprehensive molecular profiling was performed on 317 tumors from patients with MCC, including the evaluation of oncogenic mutations, tumor mutational burden (TMB), mutational signatures, and the Merkel cell polyomavirus (MCPyV). For a subset of 57 patients, a retrospective analysis was conducted to evaluate for clinical and molecular correlates to immune checkpoint inhibitor response and disease survival.

Results:
Genomic analyses revealed a bimodal distribution in TMB, with 2 molecularly distinct subgroups. Ninety-four percent (n = 110) of TMB-high specimens exhibited an ultraviolet light (UV) mutational signature. MCPyV genomic DNA sequences were not identified in any TMB-high cases (0/117), but were in 63% (110/175) of TMB-low cases. For 36 evaluable patients treated with checkpoint inhibitors, the overall response rate was 44% and response correlated with survival at time of review (100% vs. 20%, P &lt; 0.001). Response rate was 50% in TMB-high/UV-driven and 41% in TMB-low/MCPyV-positive tumors (P = 0.63). Response rate was significantly correlated with line of therapy: 75% in first-line, 39% in second-line, and 18% in third-line or beyond (P = 0.0066). PD-1, but not PD-L1, expression was associated with immunotherapy response (77% vs. 21%, P = 0.00598, for PD-1 positive and negative, respectively).

Conclusions:
We provide a comprehensive genomic landscape of MCC and demonstrate clinicogenomic associates of immunotherapy response.
Scented Candles as an Unrecognized Factor that Increases the Risk of Bladder Cancer; Is There Enough Evidence to Raise a Red Flag?
Authors: Adamowicz Jan , Juszczak Kajetan , Poletajew Slawomir , Van Breda Shane Vontelin , Pokrywczynska Marta , Drewa Tomasz 
Published: August 2019

Abstract
The causes of bladder cancer are not yet fully uncovered, however the research has identified a number of factors that may increase the risk of developing this cancer. The chemical carcinogenesis of bladder cancer due to chronic exposure to aromatic hydrocarbons has been well-established. The identification of this correlation led to an improvement of safety measures in chemical industry and a gradual decrease of bladder cancer cases among workers. Nevertheless, in the majority of bladder cancer cases, the specific cause of the disease still can't be specified. It makes the question of unrecognized factors associated with bladder cancer development even more relevant. Taking under consideration known chemical carcinogenesis of bladder cancer, this minireview takes under investigation the possible link between using scented candles and a risk of bladder cancer development. Burning scented candles contain many of the substances that are associated with a bladder cancer. Furthermore the scented candles are not only very popular but also widely available on the market, with limited quality regulations and unspecified raw materials determining a spectrum of potentially dangerous substances emitted during burning.
Ripple-AT Study
Authors: Luther Vishal , Agarwal Sharad , Chow Anthony , Koa-Wing Michael , Cortez-Dias Nuno , Carpinteiro Luís , de Sousa João , Balasubramaniam Richard , Farwell David , Jamil-Copley Shahnaz , Srinivasan Neil , Abbas Hakam , Mason James , Jones Nikki , Katritsis George , Lim Phang Boon , Peters Nicholas S. , Qureshi Norman , Whinnett Zachary , Linton Nick W.F. , Kanagaratnam Prapa 
Published: August 2019

Background:
Ripple mapping (RM) is an alternative approach to activation mapping of atrial tachycardia (AT) that avoids electrogram annotation. We tested whether RM is superior to conventional annotation based local activation time (LAT) mapping for AT diagnosis in a randomized and multicenter study.

Methods:
Patients with AT were randomized to either RM or LAT mapping using the CARTO3v4 CONFIDENSE system. Operators determined the diagnosis using the assigned 3D mapping arm alone, before being permitted a single confirmatory entrainment manuever if needed. A planned ablation lesion set was defined. The primary end point was AT termination with delivery of the planned ablation lesion set. The inability to terminate AT with this first lesion set, the use of more than one entrainment manuever, or the need to crossover to the other mapping arm was defined as failure to achieve the primary end point.

Results:

One hundred five patients from 7 centers were recruited with 22 patients excluded due to premature AT termination, noninducibility or left atrial appendage thrombus. Eighty-three patients (pts; RM=42, LAT=41) completed mapping and ablation within the 2 groups of similar characteristics (RM versus LAT: prior ablation or cardiac surgery n=35 [83%] versus n=35 [85%],
P
=0.80). The primary end point occurred in 38/42 pts (90%) in the RM group and 29/41pts (71%) in the LAT group (
P
=0.045). This was achieved without any entrainment in 31/42 pts (74%) with RM and 18/41 pts (44%) with LAT (
P
=0.01). Of those patients who failed to achieve the primary end point, AT termination was achieved in 9/12 pts (75%) in the LAT group following crossover to RM with entrainment, but 0/4 pts (0%) in the RM group crossing over to LAT mapping with entrainment (
P
=0.04).

Conclusions:
RM is superior to LAT mapping on the CARTO3v4 CONFIDENSE system in guiding ablation to terminate AT with the first lesion set and with reduced entrainment to assist diagnosis.

Clinical Trials Registration:

https://www.clinicaltrials.gov
. Unique identifier: NCT02451995.
Low‐Cost Fetal Magnetocardiography: A Comparison of Superconducting Quantum Interference Device and Optically Pumped Magnetometers
Authors: Strand Sarah , Lutter William , Strasburger Janette F. , Shah Vishal , Baffa Oswaldo , Wakai Ronald T. 
Published: August 2019

Background

Fetal magnetocardiography (
fMCG
) is a highly effective technique for evaluation of fetuses with life‐threatening arrhythmia, but its dissemination has been constrained by the high cost and complexity of Superconducting Quantum Interference Device (SQUID) instrumentation. Optically pumped magnetometers (
OPM
s) are a promising new technology that can replace
SQUID
s for many applications. This study compares the performance of an
fMCG
system, utilizing
OPM
s operating in a person‐sized magnetic shield, to that of a conventional
fMCG
system, utilizing
SQUID
magnetometers operating in a magnetically shielded room.

Methods and Results

fMCG
recordings were made in 24 subjects using the
SQUID
system with the mother lying supine in a magnetically shielded room and the
OPM
system with the mother lying prone in a person‐sized, cylindrical shield. Signal‐to‐noise ratios of the
OPM
and
SQUID
recordings were not statistically different and were adequate for diagnostic purposes with both technologies. Although the environmental noise was higher using the small open‐ended shield, this was offset by the higher signal amplitude achieved with prone positioning, which reduced the distance between the fetus and sensors and improved patient comfort. In several subjects,
fMCG
provided a differential diagnosis that was more precise and/or definitive than was possible with echocardiography alone.

Conclusions

The
OPM
‐based system was portable, improved patient comfort, and performed as well as the
SQUID
‐based system at a small fraction of the cost. Electrophysiological assessment of fetal rhythm is now practical and will have a major impact on management of fetuses with long
QT
syndrome and other life‐threatening arrhythmias.
Circulating DNAs, a Marker of Neutrophil Extracellular Traposis and Cancer-Related Stroke
Authors: Bang Oh Young , Chung Jong-Won , Cho Yeon Hee , Oh Mi Jeong , Seo Woo-Keun , Kim Gyeong-Moon , Ahn Myung-Ju 
Published: August 2019

Background and Purpose—
The role of circulating neutrophil extracellular traps (NETs) in cancer-related stroke is unknown.

Methods—
We conducted a prospective cohort study to test whether NETs are increased in cancer-related stroke and whether elevated NETs levels are associated with coagulopathy, assessed using D-dimer levels (≥2 μg/mL). Plasma DNA and nucleosome were assessed as NET-specific biomarkers.

Results—

In total, 138 patients were recruited; 38 patients had cancer-related stroke (active cancer and acute cryptogenic embolic stroke), 33 patients were healthy-controls, 27 patients were cancer-controls (active cancer but no stroke), and 40 patients were stroke-controls (acute ischemic stroke but no cancer). Plasma DNA and nucleosome levels were significantly elevated in cancer-related stroke patients than in healthy-controls (
P
<0.05). These levels were correlated with the D-dimer levels (
P
<0.01). In multiple regression analyses, increased plasma DNA levels were associated with cancer-related stroke (odds ratio=11.65 for highest quartile; 95% CI, 3.199–42.46) and D-dimer levels of ≥2 μg/mL (odds ratio=19.09 for highest quartile; 95% CI, 4.143–87.95) after adjusting for possible confounders.

Conclusions—
Increased circulating DNA levels were associated with cancer-related stroke, suggesting that NETosis is one of the molecular mechanisms of cancer-related stroke. Further long-term follow-up studies in large cohorts are needed to confirm the role of NET-specific biomarkers.
Mitigating Batrachochytrium salamandrivorans in Europe
Authors: Thomas Valarie , Wang Yu , Van Rooij Pascale , Verbrugghe Elin , Baláž Vojtech , Bosch Jaime , Cunningham Andrew A. , Fisher Matthew C. , Garner Trenton W.J. , Gilbert Maarten J. , Grasselli Elena , Kinet Thierry , Laudelout Arnaud , Lötters Stefan , Loyau Adeline , Miaud Claude , Salvidio Sebastiano , Schmeller Dirk S. , Schmidt Benedikt R. , Spitzen-van der Sluijs Annemarieke , Steinfartz Sebastian , Veith Michael , Vences Miguel , Wagner Norman , Canessa Stefano , Martel An , Pasmans Frank 
Published: August 2019

Abstract
The infectious chytrid fungus Batrachochytrium salamandrivorans (Bsal) has been responsible for severe population declines of salamander populations in Europe. Serious population declines and loss of urodelan diversity may occur if appropriate action is not taken to mitigate against the further spread and impact of Bsal. We provide an overview of several potential mitigation methods, and describe their possible advantages and limitations. We conclude that long-term, context-dependent, multi-faceted approaches are needed to successfully mitigate adverse effects of Bsal, and that these approaches should be initiated pre-arrival of the pathogen. The establishment of ex situ assurance colonies, or management units, for species threatened with extinction, should be considered as soon as possible. While ex situ conservation and preventive measures aimed at improving biosecurity by limiting amphibian trade may be implemented quickly, major challenges that lie ahead are in designing in situ disease containment and mitigation post-arrival and in increasing public awareness.
Index of Non-tariff Measures: A Study of the EU Textile and Garment Market
Authors: Chattopadhyay Sudeshna 
Published: August 2019

The post-WTO period has witnessed a rapid increase in growth of non-tariff measures (NTMs). As a result, quantification of NTMs has emerged as an important policy question. Quantification of NTMs is often challenging as these measures, in most cases, do not have direct numerical measurements. Hence, proxies have to be constructed. The present article proposes a methodology which uses time series information on legislation related to NTMs to construct comprehensive indices of NTMs. The incidence of NTMs is very high in the textile and garments (T&G) sector in the EU, which is also an important destination of India’s textile and garments exports. Hence, the EU textile and garments sector is selected as a case study. Separate NTM indices are constructed for the German and rest of the EU market, and the effects of these indices on the flow of India’s T&G exports are explored. JEL Codes: F13, F18
Children and handwashing: Developing a resource to promote health and well-being in low and middle income countries
Authors: Crosby Sapphire , Laird Katie , Younie Sarah 
Published: August 2019

Objective: Using a participatory action research (PAR) model, this paper reports on findings from a mixed-methods study which aimed to discover whether specifically developed health education resources ( A Germ’s Journey) aid children’s understanding of health-hygiene principles, and how these findings can inform the future development of culturally relevant resources to teach children in low- and middle-income countries about the association between bacteria, handwashing and disease. Design: Educational health-hygiene workshops were conducted at 13 case study sites ( n = 651) in collaboration with local organisations in Ahmedabad, India. During Phase 1 of the study, children’s and teacher–trainer workshops were conducted using UK resources. Following suggestions from local teachers, a Gujarati book was co-created and in Phase 2, workshops (using the Gujarati book) were delivered. Methods: Data were collected from children using quasi-experimental methods, using pre-workshop questions, follow-up questions, observations and baseline and post-workshop assessments. Data were collected from teachers using questionnaires. Results: Following teacher–trainer workshops during Phase 1 of the study, 100% of teachers stated that they would use the resources with their pupils in the future. Two months after participating in the workshops, 60%–73% of children knew how germs can cause illness, and 76%–80% knew how to remove germs from hands. When assessed during Phase 2 of the study, 54% of children scored higher after the intervention, showing an increased understanding of microbiology after using the resources. Conclusion: The results indicate that children had an improved understanding of the causes of bacterial disease and the health implications of not using adequate health-hygiene practices. Recommendations for the future development of resources include the use of a PAR model of research, co-creation with end users, and working alongside local organisations and participants in order to access ‘hard-to-reach’ areas.
Invisible hemolysis in serum samples interferes in NSE measurement
Authors: Mastroianni Antonio , Panella Rossella , Morelli Daniele 
Published: August 2019

Introduction: The accuracy of serum neuron-specific enolase (NSE) measurements is critical, particularly in neurologic diseases and cancer. NSE measurements are compromised by slight, even invisible, hemolysis, which can produce apparently higher NSE levels, leading to inappropriate clinical decisions. In this article, we describe this issue and propose a solution for avoiding incorrect results. Methods: Twenty blood samples from donors with NSE values that were within the reference interval were considered. Experimental hemolysis was induced in vitro to examine the relationship between the degree of hemolysis and the increase in serum NSE. The data were then subjected to statistical analysis. Results: There was excellent correlation ( r2 0.953) between the degree of hemolysis and the rise in NSE concentration. Each hemolysis unit (equal to 1 mg/dL of free hemoglobin) corresponded to a mean value of 0.29 ± 0.09 ng/mL NSE that was released from red blood cells. Conclusion: The hemolysis index must be measured in every sample with no evident hemolysis before assaying it for NSE. Moreover, if the degree of hemolysis is between 5 and 30 units, the increase in NSE (from 1.5 to 9.0 ng/mL) must be calculated, and the laboratory results should be appended with comments that suggest the approximate rise in NSE.