bluuebunny/crossref_metadata_2025 huggingface dataset:
Survival Outcomes of Primary Cutaneous T-Cell Lymphoma in Hiv-Infected Patients: A National Population-Based Study
Authors: Wang Jianhong , Liang Rong , Hao Caixia , Liu Xiangxiang , Zhang Na , Duan Xiaohui , Dong Hongjuan , Dong Baoxia , Gu Hongtao , Gao Guangxun , Zhang Tao , Bai Qingxian , Chen Xiequn
Published: January 2018

This study aimed to investigate clinical characteristics and survival outcomes of primary cutaneous T-cell lymphoma (CTCL) in HIV-infected and non-HIV-infected patients. All data were from the Surveillance, Epidemiology, and End Results program, 1973–2013, of the U.S. National Cancer Institute. Data of 318 HIV-infected patients and 1272 non-HIV-infected patients with primary CTCL were analyzed. Endpoints were overall survival and cancer-specific mortality. Independent variables included demographics, pre-existing malignancy, treatments, and environmental factors. Among 8823 patients with CTCL, 318 (3.60 per cent) were HIV-infected and 8505 (96.40 per cent) were not. 318 HIV-infected patients and 1272 non-HIV-infected patients selected by matching diagnosis dates were analyzed, including 941 (59.2 per cent) males and 649 (40.8 per cent) females with mean age 58.8 years. HIV-infected patients with CTCL had higher survival and significantly lower risk of overall mortality than non-HIV-infected patients (adjusted HR 0.37, 95 per cent CI 0.24 to 0.59, P<0.001). Non-HIV-infected, age and black race were significant risk factors for overall mortality. Age and race are independent risk factors for overall mortality in primary CTCL individuals, and HIV-infected status is an independent protective factor, suggesting that advanced antiretroviral therapy restores immunity and prolongs survival in HIV-infected patients with CTCL.
Variant in C-terminal region of intestinal alkaline phosphatase associated with benign familial hyperphosphatasaemia
Authors: Ishige Takayuki , Itoga Sakae , Utsuno Emi , Nishimura Motoi , Yoshikawa Masaharu , Kato Naoya , Matsushita Kazuyuki , Yokosuka Osamu , Nomura Fumio
Published: January 2018

Background

A genetic diagnosis has been rarely performed in benign familial hyperphosphatasaemia, and molecular mechanism largely remains unclear.

Objectives

We encountered a case with benign familial hyperphosphatasaemia of intestinal alkaline phosphatase (IAP). To elucidate the molecular mechanism, we performedALPIgene sequencing and in vitro protein expression analysis.

Methods

ALPIgene was sequenced by long-range PCR and massively parallel sequencing. The soluble and membrane-bound ALP activities of the cultured cell line, transfected with the wild-type or variant-typeALPIgene were analysed by a glycosylphosphatidylinositol (GPI)-cleaving assay.

Results

We identified a deletion–insertion variant in the C-terminal end of theALPIgene. This variant causes the attenuation of the hydrophobicity in GPI-anchor signal of IAP. An in vitro GPI-cleaving assay demonstrated that the membrane-bound IAP was greatly decreased, whereas the soluble IAP was increased, in the variant IAP.

Conclusions

The C-terminal variant inALPIcauses the benign familial hyperphosphatasaemia of IAP by the attenuation of the membrane-binding capability.
A false-carrier state for the c.579G>A mutation in the NCF1 gene in Ashkenazi Jews
Authors: De Boer Martin , Gavrieli Ronit , van Leeuwen Karin , Wolf Haike Reznik , Dushnitzki Maya , Bar-Yosef Yifaat , Bar-Ziv Anat , Behar Doron , Lipitz Shlomo , Miller Tal Elkan , Tool Anton T J , Kuijpers Taco W , van den Berg Timo K , Wolach Baruch , Roos Dirk , Pras Elon
Published: January 2018

Background

Mutations in the NCF1 gene that encodes p47phox, a subunit of the NADPH oxidase complex, cause chronic granulomatous disease (CGD). In Kavkazi Jews, a c.579G>A (p.Trp193Ter) mutation in NCF1 is frequently found, leading to CGD. The same mutation is found in about 1% of Ashkenazi Jews, although Ashkenazi CGD patients with this mutation have never been described.

Methods

We used Sanger sequencing, multiplex ligation-dependent probe amplification (MLPA), gene scan analysis and Ion Torrent Next Generation Sequencing for genetic analysis, and measured NADPH oxidase activity and p47phox expression.

Results

In an Ashkenazi couple expecting a baby, both parents were found to be heterozygotes for this mutation, as was the fetus. However, segregation analysis in the extended family was consistent with the fetus inheriting both carrier alleles from the parents. MLPA indicated four complete NCF1 genes in the fetus and three in each parent. Gene sequencing confirmed these results. Analysis of fetal leucocytes obtained by cordocentesis revealed substantial oxidase activity with three different assays, which was confirmed after birth. In six additional Ashkenazi carriers of the NCF1 c.579G>A mutation, we found five individuals with three complete NCF1 genes of which one was mutated (like the parents), and one individual with in addition a fusion gene of NCF1 with a pseudogene.

Conclusion

These results point to the existence of a ‘false-carrier’ state in Ashkenazi Jews and have wide implications regarding pre-pregnancy screening in this and other population groups.
Transcatheter and Doppler waveform correlation in transcatheter aortic valve replacement
Authors: Kalra Ankur , Makkar Raj R , Bhatt Deepak L , Khera Sahil , Kleiman Neal S , Reardon Michael J , Kern Morton J
Published: January 2018

Transcatheter aortic valve replacement (TAVR) has become the preferred therapy for treatment of severe aortic stenosis in patients at intermediate to high risk of perioperative mortality following surgical aortic valve replacement. Haemodynamic assessment is an integral part of the procedure, and it is crucial for the operator to have an in-depth understanding of the haemodynamic alterations that occur during balloon aortic valvuloplasty and transcatheter valve deployment. Comprehension of the haemodynamic tracings is also pivotal for early recognition of periprocedural complications. With expanding indications for TAVR, it is imperative for members of the structural heart team to have an in-depth, nuanced understanding of transcatheter haemodynamic waveforms and their correlation with echocardiographic Doppler waveforms that are obtained periprocedurally during TAVR. This review provides a collection of transcatheter haemodynamic tracings and their corresponding Doppler echocardiography correlates that are demonstrative of physiological alterations and pathological lesions (complications) that occur during TAVR.
Airflow limitation in people living with HIV and matched uninfected controls
Authors: Ronit Andreas , Lundgren Jens , Afzal Shoaib , Benfield Thomas , Roen Ashley , Mocroft Amanda , Gerstoft Jan , Nordestgaard Børge G , Vestbo Jørgen , Nielsen Susanne D
Published: January 2018

Introduction

Whether HIV influences pulmonary function remains controversial. We assessed dynamic pulmonary function in people living with HIV (PLWHIV) and uninfected controls.

Methods

A total of 1098 PLWHIV from the Copenhagen Co-morbidity in HIV infection study and 12 161 age-matched and sex-matched controls from the Copenhagen General Population Study were included. Lung function was assessed using FEV1and FVC, while airflow limitation was defined by the lower limit of normal (LLN) of FEV1/FVC and by FEV1/FVC<0.7 with FEV1predicted <80% (fixed). Logistic and linear regression models were used to determine the association between HIV and pulmonary function adjusting for potential confounders (including smoking and socioeconomic status).

Results

In predominantly white men with mean (SD) age of 50.6 (11.1) the prevalence of airflow limitation (LLN) was 10.6% (95% CI 8.9% to 12.6%) in PLWHIV and 10.6% (95% CI 10.0 to 11.1) in uninfected controls. The multivariable adjusted OR for airflow limitation defined by LLN for HIV was 0.97 (0.77–1.21, P<0.78) and 1.71 (1.34–2.16, P<0.0001) when defined by the fixed criteria. We found no evidence of interaction between HIV and cumulative smoking in these models (P interaction: 0.25 and 0.17 for LLN and fixed criteria, respectively). HIV was independently associated with 197 mL (152–242, P<0.0001) lower FEV1and 395 mL (344–447, P<0.0001) lower FVC, and 100 cells/mm3lower CD4 nadir was associated with 30 mL (7–52, P<0.01) lower FEV1and 51 mL (24–78, P<0.001) lower FVC.

Conclusion

HIV is a risk factor for concurrently decreased FEV1and FVC. This excess risk is not explained by smoking or socioeconomic status and may be mediated by prior immunodeficiency.

Trial registration number

NCT02382822.
Impacts of Canada’s minimum age for tobacco sales (MATS) laws on youth smoking behaviour, 2000–2014
Authors: Callaghan Russell Clarence , Sanches Marcos , Gatley Jodi , Cunningham James K , Chaiton Michael Oliver , Schwartz Robert , Bondy Susan , Benny Claire
Published: January 2018

Background

Recently, the US Institute of Medicine has proposed that raising the minimum age for tobacco purchasing/sales to 21 years would likely lead to reductions in smoking behavior among young people. Surprisingly few studies, however, have assessed the potential impacts of minimum-age tobacco restrictions on youth smoking.

Objective

To estimate the impacts of Canadian minimum age for tobacco sales (MATS) laws on youth smoking behaviour.

Design

A regression-discontinuity design, using seven merged cycles of the Canadian Community Health Survey, 2000–2014.

Participants

Survey respondents aged 14–22 years (n=98 320).

Exposure

Current Canadian MATS laws are 18 years in Alberta, Saskatchewan, Manitoba, Quebec, the Yukon and Northwest Territories, and 19 years of age in the rest of the country.

Main outcomes

Current, occasional and daily smoking status; smoking frequency and intensity; and average monthly cigarette consumption.

Results

In comparison to age groups slightly younger than the MATS, those just older had significant and abrupt increases immediately after the MATS in the prevalence of current smokers (absolute increase: 2.71%; 95% CI 0.70% to 4.80%; P=0.009) and daily smokers (absolute increase: 2.43%; 95% CI 0.74% to 4.12%; P=0.005). Average past-month cigarette consumption within age groups increased immediately following the MATS by 18% (95% CI 3% to 39%; P=0.02). There was no evidence of significant increases in smoking intensity for daily or occasional smokers after release from MATS restrictions.

Conclusion

The study provides relevant evidence supporting the effectiveness of Canadian MATS laws for limiting smoking among tobacco-restricted youth.
Impact of a negative emotional antitobacco mass media campaign on French smokers: a longitudinal study
Authors: Guignard Romain , Gallopel-Morvan Karine , Mons Ute , Hummel Karin , Nguyen-Thanh Viêt
Published: January 2018

Background

Mass media campaigns to encourage smoking cessation have been shown to be effective in a context of comprehensive tobacco control programme. The effectiveness of antismoking ads that evoke negative emotions remains unclear, in particular in countries with high smoking prevalence and among smokers with low perceived susceptibility, low self-efficacy or who are not users of smoking cessation services.

Objective

To evaluate short-term and long-term effects of a 1-month French national highly emotional media campaign, with a focus on these specific targets.

Design

A 6-month longitudinal survey by Internet. A sample of 3000 smokers were interviewed before the media campaign (T0). They were contacted again just after (T1) and 6 months after the campaign (T2).

Outcomes

Perceived susceptibility to the risks of smoking, self-efficacy to quit smoking, use of smoking cessation services (quitline and website) and 7-day quitting.

Methods

The analysis was carried out on 2241 individuals who answered at T1 and T2. Multiple logistic regressions were computed to test the association between the change in each outcome at T1 and T2 and the level of exposure based on self-reported recall.

Results

Self-reported recall was associated with an increase in perceived susceptibility and with use of cessation services. Campaign recall was also associated with higher 7-day quitting immediately after the campaign (OR=1.8 (1.0 to 3.2), P<0.05).

Conclusions

Fear-appeal mass media campaigns can be effective in encouraging cessation among smokers in a country with high smoking prevalence (France), but should be accompanied by convincing self-efficacy messages.
Cutaneous mast cell tumour and renal tubular adenocarcinoma in a Vietnamese potbellied pig
Authors: Williams Fred , Annetti Kendall , Nagy Dusty
Published: January 2018

The occurrence of neoplasia in pigs is relatively rare. Infrequent cases of cutaneous mast cell tumours have been reported, and there have been no reports of renal tubular adenocarcinomas in this species. The current communication describes an 18‐year‐old Vietnamese potbellied pig with renal and cutaneous mast cell tumours and a renal tubular adenocarcinoma. Grossly, there were fluid‐filled cysts in the kidneys and white‐tan nodules on the skin and in the renal parenchyma. Histopathology revealed focally extensive masses of round cells in the skin and kidney. Tryptase and c‐kit immunohistochemistry confirmed a diagnosis of mast cell tumour in cutaneous tissue. A second renal mass contained a dense cellular mass of erratically arranged tubules lined by layers of cuboidal epithelial cells, consistent with a renal tubular adenocarcinoma. These two types of neoplasia have rarely been reported in the literature alone and have never been reported concurrently in the same animal.
In vitro propagation and reintroduction of golden paintbrush (Castilleja levisecta), a critically imperilled plant species
Authors: Salama Ahmed , Shukla Mukund R. , Popova Elena , Fisk Nathan S. , Jones Maxwell P. , Saxena Praveen K.
Published: January 2018

Golden paintbrush (Castilleja levisecta Greenm.) is a hemiparasitic herbaceous perennial native to the Pacific Northwest of North America and is considered critically imperilled with only 11 populations remaining in the wild. The main objective of this study was to develop ex situ and in situ conservation through micropropagation and field plantings. In vitro cultures were initiated using nodal explants from two plants raised from seeds collected from a natural population. Shoots were then multiplied on Murashige and Skoog basal medium with 2.0 μmol L−1 6-benzylaminopurine (BA), 3.0 μmol L−1 kinetin (Kn), 2.2 g L−1 phytagel, and 3% sucrose. Explant position on source plants, culture vessel design, and application of different plant growth regulator levels for BA, Kn, and thiadiazuron (TDZ) were tested to optimize micropropagation protocols. Clones from the plants showed differences in plant height and number of nodes in response to various BA and TDZ concentrations. In vitro shoots were successfully rooted under ex vitro conditions using commercial rooting powder (0.8% indole-3-butyric acid) with an average of ∼17 roots per shoot and acclimatized in the greenhouse with 100% survival rate. Two-month-old plants were transferred to a Parks Canada restoration site at Fort Rodd Hill, Victoria, BC, with 7.5% survival. The use of micropropagation in combination with reintroduction efforts offers an excellent opportunity for conserving endangered plant biodiversity in vitro and facilitating in situ conservation efforts by providing plants for reintroduction.
Establishment of the First Well-differentiated Human Pancreatic Neuroendocrine Tumor Model
Authors: Benten Daniel , Behrang Yasmin , Unrau Ludmilla , Weissmann Victoria , Wolters-Eisfeld Gerrit , Burdak-Rothkamm Susanne , Stahl Felix R. , Anlauf Martin , Grabowski Patricia , Möbs Markus , Dieckhoff Jan , Sipos Bence , Fahl Martina , Eggers Corinna , Perez Daniel , Bockhorn Maximillian , Izbicki Jakob R. , Lohse Ansgar W. , Schrader Jörg
Published: January 2018

Clinical options for systemic therapy of neuroendocrine tumors (NET) are limited. Development of new drugs requires suitable representative in vitro and in vivo model systems. So far, the unavailability of a human model with a well-differentiated phenotype and typical growth characteristics has impaired preclinical research in NET. Herein, we establish and characterize a lymph node–derived cell line (NT-3) from a male patient with well-differentiated pancreatic NET. Neuroendocrine differentiation and tumor biology was compared with existing NET cell lines BON and QGP-1. In vivo growth was assessed in a xenograft mouse model. The neuroendocrine identity of NT-3 was verified by expression of multiple NET-specific markers, which were highly expressed in NT-3 compared with BON and QGP-1. In addition, NT-3 expressed and secreted insulin. Until now, this well-differentiated phenotype is stable since 58 passages. The proliferative labeling index, measured by Ki-67, of 14.6% ± 1.0% in NT-3 is akin to the original tumor (15%–20%), and was lower than in BON (80.6% ± 3.3%) and QGP-1 (82.6% ± 1.0%). NT-3 highly expressed somatostatin receptors (SSTRs: 1, 2, 3, and 5). Upon subcutaneous transplantation of NT-3 cells, recipient mice developed tumors with an efficient tumor take rate (94%) and growth rate (139% ± 13%) by 4 weeks. Importantly, morphology and neuroendocrine marker expression of xenograft tumors resembled the original human tumor.

Implications: High expression of somatostatin receptors and a well-differentiated phenotype as well as a slow growth rate qualify the new cell line as a relevant model to study neuroendocrine tumor biology and to develop new tumor treatments. Mol Cancer Res; 16(3); 496–507. ©2018 AACR.
Population-dependent Intron Retention and DNA Methylation in Breast Cancer
Authors: Kim Dongwook , Shivakumar Manu , Han Seonggyun , Sinclair Michael S. , Lee Young-Ji , Zheng Yonglan , Olopade Olufunmilayo I. , Kim Dokyoon , Lee Younghee
Published: January 2018

Regulation of gene expression by DNA methylation in gene promoter regions is well studied; however, the effects of methylation in the gene body (exons and introns) on gene expression are comparatively understudied. Recently, hypermethylation has been implicated in the inclusion of alternatively spliced exons; moreover, exon recognition can be enhanced by recruiting the methyl-CpG-binding protein (MeCP2) to hypermethylated sites. This study examines whether the methylation status of an intron is correlated with how frequently the intron is retained during splicing using DNA methylation and RNA sequencing data from breast cancer tissue specimens in The Cancer Genome Atlas. Interestingly, hypomethylation of introns is correlated with higher levels of intron expression in mRNA and the methylation level of an intron is inversely correlated with its retention in mRNA from the gene in which it is located. Furthermore, significant population differences were observed in the methylation level of retained introns. In African-American donors, retained introns were not only less methylated compared to European-American donors, but also were more highly expressed. This underscores the need for understanding epigenetic differences in populations and their correlation with breast cancer is an important step toward achieving personalized cancer care.

Implications: This research contributes to the understanding of how epigenetic markers in the gene body communicate with the transcriptional machinery to control transcript diversity and differential biological response to changes in methylation status could underlie some of the known, yet unexplained, disparities in certain breast cancer patient populations. Mol Cancer Res; 16(3); 461–9. ©2018 AACR.
Epigenetically Regulated Chromosome 14q32 miRNA Cluster Induces Metastasis and Predicts Poor Prognosis in Lung Adenocarcinoma Patients
Authors: González-Vallinas Margarita , Rodríguez-Paredes Manuel , Albrecht Marco , Sticht Carsten , Stichel Damian , Gutekunst Julian , Pitea Adriana , Sass Steffen , Sánchez-Rivera Francisco J. , Lorenzo-Bermejo Justo , Schmitt Jennifer , De La Torre Carolina , Warth Arne , Theis Fabian J. , Müller Nikola S. , Gretz Norbert , Muley Thomas , Meister Michael , Tschaharganeh Darjus F. , Schirmacher Peter , Matthäus Franziska , Breuhahn Kai
Published: January 2018

Most lung cancer deaths are related to metastases, which indicates the necessity of detecting and inhibiting tumor cell dissemination. Here, we aimed to identify miRNAs involved in metastasis of lung adenocarcinoma as prognostic biomarkers and therapeutic targets. To that end, lymph node metastasis–associated miRNAs were identified in The Cancer Genome Atlas lung adenocarcinoma patient cohort (sequencing data; n = 449) and subsequently validated by qRT-PCR in an independent clinical cohort (n = 108). Overexpression of miRNAs located on chromosome 14q32 was associated with metastasis in lung adenocarcinoma patients. Importantly, Kaplan–Meier analysis and log-rank test revealed that higher expression levels of individual 14q32 miRNAs (mir-539, mir-323b, and mir-487a) associated with worse disease-free survival of never-smoker patients. Epigenetic analysis including DNA methylation microarray data and bisulfite sequencing validation demonstrated that the induction of 14q32 cluster correlated with genomic hypomethylation of the 14q32 locus. CRISPR activation technology, applied for the first time to functionally study the increase of clustered miRNA levels in a coordinated manner, showed that simultaneous overexpression of 14q32 miRNAs promoted tumor cell migratory and invasive properties. Analysis of individual miRNAs by mimic transfection further illustrated that miR-323b-3p, miR-487a-3p, and miR-539-5p significantly contributed to the invasive phenotype through the indirect regulation of different target genes. In conclusion, overexpression of 14q32 miRNAs, associated with the respective genomic hypomethylation, promotes metastasis and correlates with poor patient prognosis in lung adenocarcinoma.

Implications: This study points to chromosome 14q32 miRNAs as promising targets to inhibit tumor cell dissemination and to predict patient prognosis in lung adenocarcinoma. Mol Cancer Res; 16(3); 390–402. ©2018 AACR.
Targeted AKT Inhibition in Prostate Cancer Cells and Spheroids Reduces Aerobic Glycolysis and Generation of Hyperpolarized [1-13C] Lactate
Authors: Tee Sui Seng , Suster Izabela , Truong Steven , Jeong Sangmoo , Eskandari Roozbeh , DiGialleonardo Valentina , Alvarez Julio A. , Aldeborgh Hannah N. , Keshari Kayvan R.
Published: January 2018

The PI3K/AKT/mTOR (PAM) signaling pathway is frequently mutated in prostate cancer. Specific AKT inhibitors are now in advanced clinical trials, and this study investigates the effect of MK2206, a non–ATP-competitive inhibitor, on the cellular metabolism of prostate cancer cells. We observed a reduction in cell motility and aerobic glycolysis in prostate cancer cells with treatment. These changes were not accompanied by a reduction in the ratio of high-energy phosphates or a change in total protein levels of enzymes and transporters involved in glycolysis. However, a decreased ratio of NAD+/NADH was observed, motivating the use of hyperpolarized magnetic resonance spectroscopy (HP-MRS) to detect treatment response. Spectroscopic experiments were performed on tumor spheroids, 3D structures that self-organize in the presence of an extracellular matrix. Treated spheroids showed decreased lactate production with on-target inhibition confirmed using IHC, demonstrating that HP-MRS can be used to probe treatment response in prostate cancer spheroids and can provide a biomarker for treatment response. Mol Cancer Res; 16(3); 453–60. ©2018 AACR.
Tumor Progression Is Mediated by Thymosin-β4 through a TGFβ/MRTF Signaling Axis
Authors: Morita Tsuyoshi , Hayashi Ken'ichiro
Published: January 2018

Although enhanced thymosin β4 (TMSB4X/Tβ4) expression is associated with tumor progression and metastasis, its tumor-promoting functions remain largely unknown. Here, it is demonstrated that TGFβ facilitates Tβ4 expression and leads to the activation of myocardin-related transcription factors (MRTF), which are coactivators of serum response factor (SRF) and regulate the expression of genes critical for the epithelial–mesenchymal transition (EMT) and tumor metastasis. In murine mammary gland cells (NMuMG), Tβ4 upregulation is required for full induction of a MRTF-regulated EMT gene expression program after TGFβ stimulation. Tβ4 levels are transcriptionally regulated via the novel cis-acting element AGACAAAG, which interacts with Smad and T-cell factor/lymphoid enhancer factor (TCF/LEF) to synergistically activate the Tβ4 promoter downstream of TGFβ. Murine skin melanoma cells (B16F0 and B16F1) also show the expression regulation of Tβ4 by Smad and TCF/LEF. Tβ4-knockout B16F1 (Tβ4 KO) clones show significantly diminished expression level of tumor-associated genes, which is regulated by the TGFβ/MRTFs pathway. In multiple human cancers, Tβ4 levels correlate positively with TGFβ1 and the tumor-associated gene expression levels through processes that respectively depend on TGFβ receptor 1 (TGFBR1) and MRTF expression. Kaplan–Meier survival analyses demonstrate that high Tβ4 expression associates with poor prognosis in an SRF expression–dependent manner in several cancers. In mice, Tβ4 KO clones show significantly decreased experimental metastatic potential; furthermore, ectopic expression of constitutively active MRTF-A fully restores the diminished metastatic activity. In conclusion, the TGFβ/Tβ4/MRTF/SRF pathway is critical for metastasis and tumor progression.

Implications: These findings define a molecular mechanism underlying a tumor-promoting function of thymosin β4 through activation of MRTF/SRF signaling. Mol Cancer Res; 16(5); 880–93. ©2018 AACR.
Novel Wearable Seismocardiography and Machine Learning Algorithms Can Assess Clinical Status of Heart Failure Patients
Authors: Inan Omer T. , Baran Pouyan Maziyar , Javaid Abdul Q. , Dowling Sean , Etemadi Mozziyar , Dorier Alexis , Heller J. Alex , Bicen A. Ozan , Roy Shuvo , De Marco Teresa , Klein Liviu
Published: January 2018

Background

Remote monitoring of patients with heart failure (HF) using wearable devices can allow patient-specific adjustments to treatments and thereby potentially reduce hospitalizations. We aimed to assess HF state using wearable measurements of electrical and mechanical aspects of cardiac function in the context of exercise.

Methods and Results

Patients with compensated (outpatient) and decompensated (hospitalized) HF were fitted with a wearable ECG and seismocardiogram sensing patch. Patients stood at rest for an initial recording, performed a 6-minute walk test, and then stood at rest for 5 minutes of recovery. The protocol was performed at the time of outpatient visit or at 2 time points (admission and discharge) during an HF hospitalization. To assess patient state, we devised a method based on comparing the similarity of the structure of seismocardiogram signals after exercise compared with rest using graph mining (graph similarity score). We found that graph similarity score can assess HF patient state and correlates to clinical improvement in 45 patients (13 decompensated, 32 compensated). A significant difference was found between the groups in the graph similarity score metric (44.4±4.9 [decompensated HF] versus 35.2±10.5 [compensated HF];
P
<0.001). In the 6 decompensated patients with longitudinal data, we found a significant change in graph similarity score from admission (decompensated) to discharge (compensated; 44±4.1 [admitted] versus 35±3.9 [discharged];
P
<0.05).

Conclusions

Wearable technologies recording cardiac function and machine learning algorithms can assess compensated and decompensated HF states by analyzing cardiac response to submaximal exercise. These techniques can be tested in the future to track the clinical status of outpatients with HF and their response to pharmacological interventions.
Hemoglobin, Albuminuria, and Kidney Function in Cardiovascular Risk: The ARIC (Atherosclerosis Risk in Communities) Study
Authors: Ishigami Junichi , Grams Morgan E. , Naik Rakhi P. , Caughey Melissa C. , Loehr Laura R. , Uchida Shinichi , Coresh Josef , Matsushita Kunihiro
Published: January 2018

Background

Reduced estimated glomerular filtration rate (
eGFR
) and elevated urinary albumin‐to‐creatinine ratio (
ACR
) individually increase risk of cardiovascular disease (
CVD
). We hypothesized that these associations are stronger among people with abnormal (both low and high) hemoglobin levels.

Methods and Results

Using 5801 participants with available hemoglobin measures of the ARIC (Atherosclerosis Risk in Community) study in 1996–1998, we explored the cross‐sectional association of
eGFR
and
ACR
with hemoglobin levels and their longitudinal associations with
CVD
(heart failure, coronary heart disease, and stroke) risk through 2013. At baseline, 8.8% had anemia (<13 g/dL in men and <12 g/dL in women) and 7.2% had high hemoglobin (≥16 g/dL in men and ≥15 g/dL in women). The adjusted prevalence ratio of anemia was 2.12 (95% confidence interval, 1.59–2.82) for
eGFR
30 to 59 compared with ≥90 mL/min per 1.73 m
2
and 1.45 (1.07–1.95) for
ACR
≥30 compared with <10 mg/g.
ACR
≥30 mg/g was also associated with high hemoglobin (prevalence ratio, 1.57 [1.12–2.19] compared with <10 mg/g). During follow‐up, there were 1069 incident
CVD
s among 5098
CVD
‐free participants at baseline. In multivariable Cox models, lower
eGFR
, higher
ACR
, and anemia were each independently associated with
CVD
risk, with the association of low
eGFR
being slightly stronger in anemia (
P
‐for‐interaction, 0.072). There was no hemoglobin‐
ACR
interaction; however, when
CVD
subtypes were analyzed separately, risk of coronary heart disease and stroke associated with high
ACR
was slightly stronger in high hemoglobin (
P
‐for‐interaction, 0.074).

Conclusions

Kidney function, albuminuria, and anemia were correlated and independently associated with
CVD
risk. Correlation and potential interaction for atherosclerotic
CVD
between albuminuria and high hemoglobin deserve further investigation.
Limited Accuracy of Administrative Data for the Identification and Classification of Adult Congenital Heart Disease
Authors: Khan Abigail , Ramsey Katrina , Ballard Cody , Armstrong Emily , Burchill Luke J , Menashe Victor , Pantely George , Broberg Craig S
Published: January 2018

Background

Administrative data sets utilize billing codes for research and quality assessment. Previous data suggest that such codes can accurately identify adults with congenital heart disease (
CHD
) in the cardiology clinic, but their use has yet to be validated in a larger population.

Methods and Results

All administrative codes from an entire health system were queried for a single year. Adults with a
CHD
diagnosis code (
International Classification of Diseases, Ninth Revision
, (
ICD‐9
) codes 745–747) defined the cohort. A previously validated hierarchical algorithm was used to identify diagnoses and classify patients. All charts were reviewed to determine a gold standard diagnosis, and comparisons were made to determine accuracy. Of 2399 individuals identified, 206 had no
CHD
by the algorithm or were deemed to have an uncertain diagnosis after provider review. Of the remaining 2193, only 1069 had a confirmed
CHD
diagnosis, yielding overall accuracy of 48.7% (95% confidence interval, 47–51%). When limited to those with moderate or complex disease (n=484), accuracy was 77% (95% confidence interval, 74–81%). Among those with
CHD
, misclassification occurred in 23%. The discriminative ability of the hierarchical algorithm (C statistic: 0.79; 95% confidence interval, 0.77–0.80) improved further with the addition of age, encounter type, and provider (C statistic: 0.89; 95% confidence interval, 0.88–0.90).

Conclusions

ICD
codes from an entire healthcare system were frequently erroneous in detecting and classifying
CHD
patients. Accuracy was higher for those with moderate or complex disease or when coupled with other data. These findings should be taken into account in future studies utilizing administrative data sets in
CHD
.
High‐Intensity Cigarette Smoking Is Associated With Incident Diabetes Mellitus In Black Adults: The Jackson Heart Study
Authors: White Wendy B. , Cain Loretta R. , Benjamin Emelia J. , DeFilippis Andrew P. , Blaha Michael J. , Wang Wei , Okhomina Victoria , Keith Rachel J. , Al Rifai Mahmoud , Kianoush Sina , Winniford Michael D. , Robertson Rose M. , Bhatnagar Aruni , Correa Adolfo , Hall Michael E.
Published: January 2018

Background

Previous reports on whether smoking is associated with insulin resistance and diabetes mellitus have yielded inconsistent findings. We aimed to evaluate the relationship between cigarette smoking and incident diabetes mellitus in the Jackson Heart Study.

Methods and Results

Jackson Heart Study participants enrolled at baseline without prevalent diabetes mellitus (n=2991) were classified by self‐report as current smokers, past smokers (smoked ≥400 cigarettes/life and no longer smoking), or never smokers. We quantified smoking intensity by number of cigarettes smoked daily; we considered ≥20 cigarettes per day (1 pack) “high‐intensity.” We defined diabetes mellitus as fasting glucose ≥126 mg/dL, hemoglobin A1c ≥6.5% or International Federation of Clinical Chemistry units HbA1c 48 mmol/mol, or use of diabetes mellitus medication. We estimated the adjusted associations of smoking status, intensity, and dose (pack‐years) with incident diabetes mellitus using Poisson regression models. At baseline there were 361 baseline current (1–10 cigarettes per day [n=242]; ≥20 [n=119]), 502 past, and 2128 never smokers. From Visit 1 to Visit 3 (mean 8.0±0.9 years), 479 participants developed incident diabetes mellitus. After adjustment for covariates, baseline current smokers who smoked less than a pack/d and past smokers had similar rates of incident diabetes mellitus compared with never smokers (incidence rate ratios 1.04, 95% confidence interval, 0.69–1.58 and 1.08, 95% confidence interval, 0.82–1.42, respectively). Baseline current high‐intensity smokers had a 79% (95% confidence interval, 1.14–2.81) higher incidence of diabetes mellitus compared with never smokers. Smoking dose (per 10 pack‐years) was also associated with a higher incidence of diabetes mellitus (incidence rate ratios 1.10, 95% confidence interval, 1.03–1.19) in adjusted models.

Conclusions

High‐intensity cigarette smoking and smoking pack‐years are associated with an increased risk of developing diabetes mellitus in blacks.
The Prototypical Majority Effect Under Social Influence
Authors: Koriat Asher , Adiv-Mashinsky Shiri , Undorf Monika , Schwarz Norbert
Published: January 2018

Majority views are reported with greater confidence and fluency than minority views, with the difference increasing with majority size. This Prototypical Majority Effect (PME) was attributed generally to conformity pressure, but Koriat et al. showed that it can arise from the processes underlying decision and confidence independent of social influence. Here we examined the PME under conditions that differ in social influence. In Experiment 1, a robust PME emerged in the absence of information about the majority views, but the provision sof that information increased the choice of the majority view and magnified the PME. In Experiment 2, a PME emerged in a minority-biased condition that misled participants to believe that the majority view was the minority view, but the PME was stronger in a majority-biased condition. The results were discussed in terms of a dual-process view: The PME observed under social influence may contain externally driven and internally driven components.
Thermoacoustic Lensing in Ultrasound Imaging of Nonechogenic Tissue During High-intensity Focused Ultrasound Exposure
Authors: Jahns Matthew , MacDougall Dan , Adamson Robert B. A.
Published: January 2018

We develop a ray-tracing theory to describe the effects of thermoacoustic lensing during high-intensity focused ultrasound (HIFU) on ultrasound images of reflectors lying distal to the HIFU focal region and discuss the application of thermal lensing effects to dose monitoring in HIFU therapy. By analyzing the effects of thermal and geometric delays of acoustic rays passing through a region of tissue undergoing localized heating, we show how the shape of a reflector distal to the heated region can be predicted and present experimental measurements in good agreement with the model. We also apply the model in reverse to estimate the thermal profile of a heated region based on a measured change in the shape of a distal reflector during HIFU delivery. As an example, we apply this technique to the measurements of thermal diffusion in porcine fat. An interesting aspect of the technique is that it can be applied to measure temperature in nonechogenic tissues as long as there is an observable reflector in the ultrasound images that is located distal to the region of localized heating.
“Either Everyone Was Guilty or Everyone Was Innocent”1: The Italian Power Elite, Neopatrimonialism, and the Importance of Social Relations
Authors: Doidge Mark
Published: January 2018

Rarely does the Byzantine world of football administration get exposed as clearly as during the 2006 calciopoli scandal. This scandal laid bare the interpersonal relationships of football administrators at the top three Italian men’s football clubs: Juventus, Inter, and AC Milan. This article draws on the media leaks that revealed the inner workings of those working within football to argue that the football clubs are pyramids of power for club presidents that allows them to operate within the Italian power elite. This is done through interpersonal clientelistic networks that operate within a neopatrimonial system. Theoretically, this article draws on four main concepts: C. Wright Mills’s concept of the Power Elite, Lomnitz’s model of “Pyramids of Power,” Eisenstadt’s notion of neopatrimonialism, and Mauss’s utilization of the gift. Power is exercised through quid pro quo relationships, with certain key individuals operating as brokers to the flow of favors throughout the network.
The Toxic Sublime: Landscape Photography and Data Visualization
Authors: Kane Carolyn
Published: January 2018

If the cliché about garbage – ‘Out of sight, out of mind’ – is true, its inverse, unfortunately, is not. Heaps and masses of garbage brought into direct view still somehow manage to escape acute recognition, let alone social responsibility or global political activism. This article investigates this trend as a growing problem between the human world and representation. Focusing on historical and contemporary landscape photography, the article questions whether data visualization trends, particularly those that attempt to visualize the post-industrial consumer landscape, help or hinder our capacity to understand our environment, and possibly even ecological endeavors. The article charts the history of photography’s landscape genre, mapping the contours of a shift from the classical ‘nature’ aesthetic, to an industrial, post-industrial, and eventually a mathematical aesthetic contingent on emergent techniques and data visualization in the attempt to depict ever amassing magnitudes of environmental despoliation.
Osteochondral Graft Size Is Significantly Associated With Increased Force and Decreased Chondrocyte Viability
Authors: Walczak Brian E. , Nies Matthew S. , Trask Darrin J. , Hetzel Scott , Roney Patrick J. , Squire Matthew W. , Baer Geoffrey S.
Published: January 2018

Background:

Insertion force has been shown to significantly reduce chondrocyte viability during osteochondral allograft transplantation. How graft size influences the required insertion force and chondrocyte viability has yet to be determined.

Hypothesis/Purpose:

The purpose was to characterize how graft size influences insertion force requirements and chondrocyte viability during osteochondral transplantation. The hypothesis was that larger grafts would require greater force and reduce chondrocyte viability.

Study Design:

Controlled laboratory study.

Methods:

Four graft sizes—15 × 5 mm, 15 × 10 mm, 25 × 5 mm, and 25 × 10 mm (diameter × depth)—were harvested from 13 thawed fresh-frozen human cadaveric distal femurs. Average, maximum, and cumulative force and number of impacts were recorded for 44 grafts by a surgical mallet embedded with a calibrated force sensor. In a separate experiment, fresh osteochondral tissues were subjected to mechanical loading. To capture a range of clinically important forces, categories were selected to correspond to impaction force data. Chondrocyte viability was assessed with confocal laser microscopy and live/dead staining.

Results:

Total force for all grafts averaged 4576 N. Median number of impacts for all grafts was 20 (range, 7-116). The mean number of impacts for 5-mm-deep grafts was 14.2 (95% CI, 10.8-18.6), as compared with 26.3 (95% CI, 19.9-34.4) for 10-mm-deep grafts ( P < .001). The mean cumulative force for 5-mm-deep grafts was 2128 N (95% CI, 1467-3087), as opposed to 4689 N (95% CI, 3232-6803) for 10-mm-deep grafts ( P = .001). For every 1 mm in graft depth, an average of 13.1% (95% CI, 6.2%-20.3%) more impacts are required when controlling for diameter and density ( P < .001). For every 1 mm in graft depth, the force required increases on average by 17.1% (95% CI, 7.7%-27.4%) when controlling for diameter and density ( P = .001). There was a significant reduction in chondrocyte viability for the forces required for graft thickness values >10 mm. Only forces associated with graft thickness <10 mm had chondrocyte viabilities consistently >70%.

Conclusion:

Insertion force increases significantly with increasing graft depth. Controlling for diameter and bone density, a 1-mm increase in graft depth is associated with 13.1% more impacts and 17.1% more force. Chondrocyte viability was significantly reduced to <70% at average forces associated with grafts thicker than 10 mm.

Clinical Relevance:

Based on the current data, graft depth is an important consideration for surgeons when sizing osteochondral allograft transplant for chondral lesions of the knee.
Sizing and modelling of stand-alone photovoltaic water pumping system for irrigation
Authors: Raghuwanshi Santosh Singh , Khare Vikas
Published: January 2018

The aim of this study is to calculate the size of the stand-alone solar photovoltaic generator and water pumping system for irrigation. In addition solar photovoltaic generator connects voltage source inverter to vector controlled induction motor-pump system. Perturb and observe method is used for harvesting maximum power of photovoltaic generator. The smooth-starting of motor-pump drive is achieved through the maximum power point tracking method. The operational performance of the solar-water-pump system is kept at 60 m head and supply daily average 35,000 L/day. In this paper result is validated by the comparison fuzzy logic controller and proportional-integral controller, driven by solar-motor-pump system. The results confirmed that fuzzy logic controller based pumping system gives more accurate results as compared to proportional-integral controller based motor-pump system. The fuzzy logic controller increases the accuracy and efficiency of the solar-water-pump system.
Reconstruction of Holocene hydroclimatic variability in subarctic treeline lakes using lake sediment grain-size end-members
Authors: Macumber Andrew L , Patterson R Timothy , Galloway Jennifer M , Falck Hendrik , Swindles Graeme T
Published: January 2018

Current climate trends are expected to result in the northward expansion of the subarctic treeline leading to changes in vegetation cover and permafrost distribution, as they did during the Holocene Climate Optimum when the treeline was 150 km north of its current position. The impacts of these changes on the region’s hydrology are still poorly understood. The grain-size distributions of treeline lake sediments provide an important proxy related to spring melt conditions that can be used to reconstruct hydroclimatic variability. End-member mixing analysis was used to model depositional end-members in 55 modern lake sediment samples and two sediment cores spanning the mid- to late Holocene collected from above and below the treeline in the central Northwest Territories, Canada. Cold climatic intervals (e.g. ‘Dark Ages Cold Period’, ‘Little Ice Age’) were characterised by an increase in the very coarse silt and the fine sand end-members. This was interpreted to be a response to degradation of vegetation cover and/or permafrost development. We observed increases in fine and coarse silt end-members during warmer climatic intervals (e.g. Medieval Climate Anomaly) and over the past c. 300 yr BP. This pattern is probably the result of extended melt seasons, with greater losses to evaporation and increased infiltration. The most pronounced palaeo-hydroclimatological change over the past c. 8000 yr BP was the abrupt increase in a very coarse silt end-member (mode = 50–200 µm) at c. 6300 yr BP. We interpreted the sedimentological change as an increase in winter precipitation and more energetic spring melt conditions, leading to the spring melt becoming the dominant lacustrine sediment delivery mechanism. These results place modern hydrological changes in a millennial context and show that analysis of temporal changes in the hydroclimatological system can provide insight into the future states of these sensitive subarctic ecosystems.
Adolescent Stress Treatment Study: A Cluster Randomized Trial
Authors: Lynch Stephanie , DeBlieck Conni , Summers Linda C. , Reinhardt Anita , Borges Wanda
Published: January 2018

High school students experience a variety of stressors. Mental health issues are critical to their health. The “Adolescent Stress Treatment (AST) Study: A Cluster Randomized Trial” compared the efficacy of two stress reduction devices, the EnergyPod™ and the SleepWing™. The EnergyPod™ is a device that provides a semiprivate acoustical and visual environment for rest, stress reduction, and sleep. The SleepWing™ is a smaller device offering similar benefits. High school students were offered the opportunity to participate in the AST study when they exhibited signs of agitation. The students completed the Profile of Mood States–Short Form (POMS-SF) pre- and postintervention. Total Mood Disturbance (TMD) was measured from the POMS-SF and significant improvement postintervention ( p < .001), regardless of intervention used. POMS-SF subscales were all significantly improved no matter which device was used. All participants in the study dramatically improved their mood after being in either therapeutic device.
Comparison of Two Weight-Based Desmopressin Dosing Strategies for Spontaneous Bleeding
Authors: Franquiz Miguel J. , Hines Michelle C. , Yeung Siu Yan Amy
Published: January 2018

Background: The pharmacokinetics and pharmacodynamics of desmopressin are appropriate for adjusted body weight–based dosing, particularly in obese patients. Objective: The objective of this study was to describe desmopressin dosing strategies, with emphasis on hemostatic outcomes among patients without preexisting bleeding disorders. Methods: This was a single-center, retrospective cohort study of patients who received intravenous weight-based desmopressin for a hemostatic indication. Demographics, comorbidities, treatment setting, indication, site of bleeding, and outcomes were collected from the medical record. Primary outcomes included need for procedural intervention to achieve hemostasis, transfusion requirement, and death. Association between desmopressin dose and outcome was evaluated using χ2 or Fischer’s exact tests and logistic and linear regression models. Multiple regression analysis was conducted to identify other predictors of outcome in the data set. Results: A total of 109 patients were included (n = 26, dose adjustment; n = 83, no dose adjustment). Baseline characteristics were well-matched between groups: mean (SD) age of 57.0 (13.5) years; mean (SD) Charlson Comorbidity Score of 6.5 (2.8); 37% were obese; 76% were critically ill; 81% were actively bleeding without differences in site of bleeding; and crude mortality was 39%. No differences in death, mean units of packed red blood cells transfused, or need for procedural hemostasis were observed between adjusted weight– and actual weight–based desmopressin dosing. Conclusions: When used adjunctively to blood product transfusion in actively bleeding patients, use of adjusted body weight–based desmopressin did not negatively affect clinical outcomes. More data are needed to confirm this dosing strategy.