bluuebunny/crossref_metadata_2025_split huggingface dataset:
Biomarkers of Exposure among U.S. Adult Cigar Smokers: Population Assessment of Tobacco and Health (PATH) Study Wave 1 (2013–2014)
Authors: Chang Cindy M. , Rostron Brian L. , Chang Joanne T. , Corey Catherine G. , Kimmel Heather L. , Sosnoff Connie S. , Goniewicz Maciej L. , Edwards Kathryn C. , Hatsukami Dorothy K. , Wang Yuesong , Del Valle-Pinero Arseima Y. , Yang Maocheng , Travers Mark J. , Arnstein Stephen , Taylor Kristie , Conway Kevin , Ambrose Bridget K. , Borek Nicolette , Hyland Andrew , Wang Lanqing , Blount Benjamin C. , van Bemmel Dana M. 
Published: February 2019

Abstract

Background:
Given the diverse cigar market and limited data on biomarker patterns by cigar type, we compared biomarkers of nicotine and tobacco toxicants among cigar smokers and other groups.

Methods:
Using Wave 1 urinary biomarker data from 5,604 adults in the Population Assessment of Tobacco and Health (PATH) Study, we compared geometric mean concentrations among cigar-only smokers (all cigars and separately for traditional, cigarillo, and filtered cigars), cigarette-only smokers, dual cigar/cigarette smokers, and never users of tobacco. We calculated geometric mean ratios comparing groups with never users adjusting for sex, age, race/ethnicity, education and creatinine.

Results:
Some day cigar-only smokers had lower biomarker concentrations than every day cigar-only smokers, but higher than never users. Every day cigar-only smokers (n = 61) had lower TNE-2 (cotinine+trans-3′-hydroxycotinine) compared to every day cigarette-only (n = 2217; P &lt; 0.0001) and dual cigar/cigarette smokers (n = 601; P &lt; 0.0001). Several biomarkers, including NNAL (NNK metabolite) and CYMA (metabolite of acrylonitrile), were comparable in these groups. In exploratory analyses, every day filtered cigar-only (n = 7) smokers had higher biomarker concentrations compared with every day traditional cigar-only smokers (n = 12) and cigarillo-only smokers (n = 24). Every day smokers of each cigar type were similar to exclusive cigarette smokers. For some biomarkers, particularly for every day filtered cigar-only smokers, concentrations were higher.

Conclusions:
For some biomarkers, every day cigar-only smokers were comparable with every day cigarette-only smokers. Exploratory analyses suggest that biomarkers vary by cigar type with every day filtered cigar-only smokers having the highest concentrations.

Impact:
High exposure to harmful constituents among cigar smokers is a continuing health issue.
Ligand-binding Domain–activating Mutations of ESR1 Rewire Cellular Metabolism of Breast Cancer Cells
Authors: Zinger Lotem , Merenbakh-Lamin Keren , Klein Anat , Elazar Adi , Journo Shani , Boldes Tomer , Pasmanik-Chor Metsada , Spitzer Avishay , Rubinek Tami , Wolf Ido 
Published: February 2019

Abstract

Purpose:
Mutations in the ligand-binding domain (LBD) of estrogen receptor α (ER) confer constitutive transcriptional activity and resistance to endocrine therapies in patients with breast cancer. Accumulating clinical data suggest adverse outcome for patients harboring tumors expressing these mutations. We aimed to elucidate mechanisms conferring this aggressive phenotype.

Experimental Design:
Cells constitutively expressing physiologic levels of ER-harboring activating LBD mutations were generated and characterized for viability, invasiveness, and tumor formation in vivo. Gene expression profile was studied using microarray and RNAseq technologies. Metabolic properties of the cells were assessed using global metabolite screen and direct measurement of metabolic activity.

Results:
Cells expressing mutated ER showed increased proliferation, migration, and in vivo tumorigenicity compared with cells expressing the wild-type ER (WT-ER), even in the presence of estrogen. Expression of the mutated ER was associated with upregulation of genes involved in invasion and metastases, as well as elevation of genes associated with tumor cell metabolism. Indeed, a metabolic examination revealed four distinct metabolic profiles: WT-ER–expressing cells either untreated or estrogen treated and mutated ER–expressing cells either untreated or estrogen treated. Pathway analyses indicated elevated tricarboxylic acid cycle activity of 537S-ER–expressing cells. Thus, while WT-ER cells were mostly glucose-dependent, 537S-ER were not addicted to glucose and were able to utilize glutamine as an alternative carbon source.

Conclusions:
Taken together, these data indicate estrogen-independent rewiring of breast cancer cell metabolism by LBD-activating mutations. These unique metabolic activities may serve as a potential vulnerability and aid in the development of novel treatment strategies to overcome endocrine resistance.
Establishment and Characterization of Four Novel Thyroid Cancer Cell Lines and PDX Models Expressing the RET/PTC1 Rearrangement, BRAFV600E, or RASQ61R as Drivers
Authors: Schweppe Rebecca E. , Pozdeyev Nikita , Pike Laura A. , Korch Christopher , Zhou Qiong , Sams Sharon B. , Sharma Vibha , Pugazhenthi Umarani , Raeburn Christopher , Albuja-Cruz Maria B. , Reigan Philip , LaBarbera Daniel V. , Landa Iñigo , Knauf Jeffrey A. , Fagin James A. , Haugen Bryan R. 
Published: February 2019

Abstract

Cancer cell lines are critical models to study tumor progression and response to therapy. In 2008, we showed that approximately 50% of thyroid cancer cell lines were redundant or not of thyroid cancer origin. We therefore generated new authenticated thyroid cancer cell lines and patient-derived xenograft (PDX) models using in vitro and feeder cell approaches, and characterized these models in vitro and in vivo. We developed four thyroid cancer cell lines, two derived from 2 different patients with papillary thyroid cancer (PTC) pleural effusions, CUTC5, and CUTC48; one derived from a patient with anaplastic thyroid cancer (ATC), CUTC60; and one derived from a patient with follicular thyroid cancer (FTC), CUTC61. One PDX model (CUTC60-PDX) was also developed. Short tandem repeat (STR) genotyping showed that each cell line and PDX is unique and match the original patient tissue. The CUTC5 and CUTC60 cells harbor the BRAF (V600E) mutation, the CUTC48 cell line expresses the RET/PTC1 rearrangement, and the CUTC61 cells have the HRAS (Q61R) mutation. Moderate to high levels of PAX8 and variable levels of NKX2-1 were detected in each cell line and PDX. The CUTC5 and CUTC60 cell lines form tumors in orthotopic and flank xenograft mouse models.

Implications:
We have developed the second RET/PTC1-expressing PTC-derived cell line in existence, which is a major advance in studying RET signaling. We have further linked all cell lines to the originating patients, providing a set of novel, authenticated thyroid cancer cell lines and PDX models to study advanced thyroid cancer.
Inflammation and Aortic Pulse Wave Velocity: A Multicenter Longitudinal Study in Patients With Inflammatory Bowel Disease
Authors: Zanoli Luca , Ozturk Kadir , Cappello Maria , Inserra Gaetano , Geraci Giulio , Tuttolomondo Antonio , Torres Daniele , Pinto Antonio , Duminuco Andrea , Riguccio Gaia , Aykan Musa B. , Mulé Giuseppe , Cottone Santina , Perna Alessandra F. , Laurent Stephane , Fatuzzo Pasquale , Castellino Pietro , Boutouyrie Pierre 
Published: February 2019

Background

Inflammatory bowel disease (
IBD
) is characterized by a low prevalence of traditional risk factors, an increased aortic pulse‐wave velocity (
aPWV
), and an excess of cardiovascular events. We have previously hypothesized that the cardiovascular risk excess reported in these patients could be explained by chronic inflammation. Here, we tested the hypothesis that chronic inflammation is responsible for the increased
aPWV
previously reported in
IBD
patients and that anti‐TNFa (anti‐tumor necrosis factor‐alpha) therapy reduce
aPWV
in these patients.

Methods and Results

This was a multicenter longitudinal study. We enrolled 334 patients: 82 patients with ulcerative colitis, 85 patients with Crohn disease, and 167 healthy control subjects matched for age, sex, and mean blood pressure, from 3 centers in Europe, and followed them for 4 years (range, 2.5–5.7 years). At baseline,
IBD
patients had higher
aPWV
than controls.
IBD
patients in remission and those treated with anti–TNFa during follow‐up experienced an aortic destiffening, whereas
aPWV
increased in those with active disease and those treated with salicylates (
P
=0.01). Disease duration (
P
=0.02) was associated with aortic stiffening as was, in patients with ulcerative colitis, high‐sensitivity C‐reactive protein during follow‐up (
P
=0.02). All these results were confirmed after adjustment for major confounders. Finally, the duration of anti–TNFa therapy was not associated with the magnitude of the reduction in
aPWV
at the end of follow‐up (
P
=0.85).

Conclusions

Long‐term anti–TNFa therapy reduces
aPWV
, an established surrogate measure of cardiovascular risk, in patients with
IBD
. This suggests that effective control of inflammation may reduce cardiovascular risk in these patients.
Association of Diabetes Mellitus Status and Glycemic Control With Secondary Prevention Medication Adherence After Acute Myocardial Infarction
Authors: Adamek Kylie E. , Ramadurai Deepa , Gunzburger Elise , Plomondon Mary E. , Ho P. Michael , Raghavan Sridharan 
Published: February 2019

Background

Cardioprotective medication adherence can mitigate the risk of recurrent cardiovascular events and mortality after acute myocardial infarction (
AMI
). We examined the associations of diabetes mellitus status and glycemic control with cardioprotective medication adherence after
AMI
.

Methods and Results

We performed a retrospective observational cohort study of 14 517
US
veterans who were hospitalized for their first
AMI
between 2011 and 2014 and prescribed a beta‐blocker, 3‐hydroxy‐3‐methyl‐glutaryl‐CoA‐reductase inhibitor, and angiotensin‐converting enzyme inhibitor or angiotensin receptor blocker. The primary exposure was a diagnosis of type 2 diabetes mellitus; in diabetes mellitus patients, hemoglobin A1c (HbA1c) was a secondary exposure. The primary outcome was 1‐year adherence to all 3 medication classes, defined as proportion of days covered ≥0.8, assessed using adjusted risk differences and multivariable Poisson regression. Of 14 517 patients (mean age, 66.3 years; 98% male), 52% had diabetes mellitus; 9%, 31%, 24%, 15%, and 21% had HbA1c <6%, 6% to 6.9%, 7% to 7.9%, 8% to 8.9%, and ≥9%, respectively. Diabetes mellitus patients were more likely to be adherent to all 3 drug classes than those without diabetes mellitus (adjusted difference in adherence, 2.1% [0.5, 3.7]). Relative to those with HbA1c 6% to 6.9%, medication adherence declined with increasing HbA1c (risk ratio of achieving proportion of days covered ≥0.8, 0.99 [0.94, 1.04], 0.93 [0.87, 0.99], 0.82 [0.77, 0.88] for HbA1c 7–7.9%, 8–8.9%, and ≥9%, respectively).

Conclusions

Although diabetes mellitus status had a minor positive impact on cardioprotective medication adherence after
AMI
, glycemic control at the time of
AMI
may help identify diabetes mellitus patients at risk of medication nonadherence who may benefit from adherence interventions after
AMI
.
Peripheral neutrophil CD64 index combined with complement, CRP, WBC count and B cells improves the ability of diagnosing bacterial infection in SLE
Authors: Feng M , Zhang S L , Liang Z J , Wang Y L , Zhao X C , Gao C , Guo H , Luo J 
Published: February 2019

Objective To investigate the diagnostic role of complement C3, complement C4, C-reactive protein (CRP), procalcitonin (PCT), white blood cell count (WBC), neutrophil CD64 (nCD64) index, lymphocyte subsets and their combination in differentiating bacterial infection from disease relapse in systemic lupus erythematosus (SLE). Methods The above biomarkers in 36 hospitalized SLE patients with bacterial infection and 45 with lupus flare without infection were retrospectively studied. Bacterial infection was proven by positive cultures or typical clinical symptoms and signs combined with positive response to antibiotics. Lupus flare was defined as three points greater than their previous SLE disease activity index score. The diagnostic value for bacterial infection was evaluated by the areas under the receiver operating characteristic curves (AUC) and a novel bioscore system combining multiple biomarkers. Results Increased CRP ( p = 0.049), WBC ( p = 0.028) and nCD64 index ( p = 0.034) were observed in the infected group and C3 ( p = 0.001), C4 ( p = 0.016) and B cells levels ( p = 0.010) were significantly reduced. The AUC for the above six biomarkers had no significant difference. Interestingly, the combination of nCD64 index, CRP, WBC, C3 and C4 improved significantly the diagnostic potential of SLE infection (AUC 0.783 (interquartile range 0.672, 0.871), p < 0.001; sensitivity 85.29% specificity 62.50%). In the bioscore system including the above six biomarkers, the bacterial infection rate in patients with bioscore ≤2, 3, 4, 5 and 6 were 0.00, 39.29, 59.10, 61.54 and 100.00%, respectively. Conclusion The combination of nCD64 index, C3, C4, CRP, WBC and B cells in a bioscore is useful to diagnose bacterial infection in SLE.
Early predictors of epilepsy and subsequent relapse in children with acute disseminated encephalomyelitis
Authors: Rossor Thomas , Benetou Christina , Wright Sukhvir , Duignan Sophie , Lascelles Karine , Robinson Robert , Das Krishna , Ciccarelli Olga , Wassmer Evangeline , Hemingway Cheryl , Lim Ming , Hacohen Yael 
Published: February 2019

Objective: To identify predictors of epilepsy and clinical relapses in children presenting with acute disseminated encephalomyelitis (ADEM). Methods: Children presenting with ADEM between 2005 and 2017 and tested clinically for MOG-Ab were identified from three tertiary paediatric neurology centres in the United Kingdom. Patients were followed up for a median of 6 years (range, 1–16 years). Results: A total of 74 children were studied (38 females; median age at first presentation: 4.5 years (range, 1.4–16 years)). MOG-Ab was positive in 50/74 (67.6%) of cases, and 27 (54%) of MOG-Ab positive children presented with a neurological relapse over time. MOG-Ab was more frequently positive in the relapsing group than in the monophasic group (27/31 vs 23/43; odds ratio 5.9 (95% CI: 1.8–19.7); p = 0.002). 16/74 (22%) children had seizures during the acute presentation with ADEM and 12/74 (16.2%) patients were diagnosed with post-ADEM epilepsy. The diagnosis of post-ADEM epilepsy was more frequently observed in children with relapsing disease than monophasic disease (10/31 vs 2/43; odds ratio 9.8 (95% confidence interval (CI): 2.0–48.7); p = 0.003), in children who had positive intrathecal oligoclonal bands than those with negative bands (4/7 vs 4/30; odds ratio 8.7 (95% CI: 1.4–54.0); p = 0.027) and in children who had positive MOG-Ab than negative MOG-Ab cases (11/12 vs 39/62; odds ratio 6.5 (95% CI:0.8–53.6); p = 0.051). Conclusion: A higher relapse rate and a greater risk of post-ADEM epilepsy in children with MOG-Ab-associated disease may indicate a chronic disease with immune-mediated seizures in these children.
Apathy as a herald of cognitive changes in multiple sclerosis: A 2-year follow-up study
Authors: Raimo Simona , Spitaleri Daniele , Trojano Luigi , Santangelo Gabriella 
Published: February 2019

Background: Behavioral symptoms, such as apathy and depression, are common in multiple sclerosis (MS) but their relationship with cognitive and clinical characteristics often remains underinvestigated and not monitored over time. Objective: The aim of this study was to assess the evolution of cognitive profile of patients affected by MS in relation to apathy and depression using a 2-year follow-up study. Methods: Two years after the first assessment, 100 of 125 MS patients were re-evaluated on a comprehensive neuropsychological battery, and on specific scales for assessment of apathy (Apathy Evaluation Scale—Self-reported) and depression (Hamilton Depression Rating Scale). Results: After 2 years (T1), we found a relatively consistent prevalence of apathy (about 40%) and a reduction in prevalence of depression (from 44% to 30%). Higher level of apathy at baseline predicted the progressive cognitive changes at follow-up; and patients with apathy without depression (“pure” apathy) than patients without apathy had poorer performance on the interference task of the Stroop test assessing inhibitory control. Conclusion: The present results suggested that apathy in MS was associated with more severe executive dysfunctions (in particular cognitive control). Apathy rather than depression predicted cognitive impairment in MS over time.
White-matter-nulled MPRAGE at 7T reveals thalamic lesions and atrophy of specific thalamic nuclei in multiple sclerosis
Authors: Planche Vincent , Su Jason H , Mournet Sandy , Saranathan Manojkumar , Dousset Vincent , Han May , Rutt Brian K , Tourdias Thomas 
Published: February 2019

Background: Investigating the degeneration of specific thalamic nuclei in multiple sclerosis (MS) remains challenging. Methods: White-matter-nulled (WMn) MPRAGE, MP-FLAIR, and standard T1-weighted magnetic resonance imaging (MRI) were performed on MS patients ( n = 15) and matched controls ( n = 12). Thalamic lesions were counted in individual sequences and lesion contrast-to-noise ratio (CNR) was measured. Volumes of 12 thalamic nuclei were measured using an automatic segmentation pipeline specifically developed for WMn-MPRAGE. Results: WMn-MPRAGE showed more thalamic MS lesions ( n = 35 in 9 out of 15 patients) than MP-FLAIR ( n = 25) and standard T1 ( n = 23), which was associated with significant improvement of CNR ( p < 0.0001). MS patients had whole thalamus atrophy ( p = 0.003) with lower volumes found for the anteroventral ( p < 0.001), the pulvinar ( p < 0.0001), and the habenular ( p = 0.004) nuclei. Conclusion: WMn-MPRAGE and automatic thalamic segmentation can highlight thalamic MS lesions and measure patterns of focal thalamic atrophy.
Metformin decreases the risk of sudden sensorineural hearing loss in patients with diabetes mellitus: A 14-year follow-up study
Authors: Chen Hsin-Chien , Chung Chi-Hsiang , Lu Chieh-Hua , Chien Wu-Chien 
Published: February 2019

Background: The risk of sudden sensorineural hearing loss associated with metformin use in patients with diabetes mellitus has not been fully examined. Study design: It is a retrospective matched-cohort study. Subjects and methods: We examined the medical records of patients with diabetes mellitus over 18 years old in Taiwan’s National Health Insurance Research Database for the period between 1 January 2000 and 31 December 2013, to establish matched cohorts (14,109 with and 42,327 without metformin use) at a ratio of 1:3 by sex, age and index year. Results: We used a Cox regression hazard model to identify risk factors of sudden sensorineural hearing loss during 14 years of follow-up, and the results indicate that a significantly lower percentage of diabetes mellitus patients with metformin use ( p = 0.033) developed sudden sensorineural hearing loss compared with those without metformin use (0.21%, 29/14,109 vs 0.32%, 136/42,327). After adjustment for age and other variables [adjusted hazard ratio: 0.630 (95% confidence interval: 0.422–0.941, p = 0.024)], this study also demonstrated that metformin use appeared to reduce the risk of developing sudden sensorineural hearing loss. Conclusion: This study demonstrated an association between metformin use and lower incidence of sudden sensorineural hearing loss among patients with diabetes mellitus.
Creating person-centred support for people with intellectual disabilities at the end of life: An Australian qualitative study of unmet needs and strategies
Authors: McNamara Beverley , Same Anne , Rosenwax Lorna 
Published: February 2019

Background: People with intellectual disabilities at the end of life are at risk of receiving inadequate and inequitable end-of-life care. This study explores their unmet needs, opportunities for person-centred care and experiences of health service use. Methods: Qualitative interviews with 26 experienced health professionals and carers were used to explore their patients’ and residents’ unmet needs and end-of-life care options and to outline strategies to support them. Results: A range of challenges and unmet needs experienced by people with intellectual disabilities are presented in themes: (1) accommodation setting at the end of life: dying ‘at home’; (2) personal factors and networks: a circle of support; (3) end-of-life medical care and decision-making. Strategies to facilitate good end-of-life care and a model of care are presented. Conclusions: Well-prepared and collaborative disability and health service workforces are needed, together with flexible and adequate end-of-life funding to ensure compassionate and person-centred care.
Glycaemic profile in the second and third trimesters of normal pregnancy compared to non-pregnant adult females
Authors: Nigam Aruna , Varun Neha , Sharma Sumedha , Munjal YP , Prakash Anupam 
Published: February 2019

Aim To assess the glycaemic profile and glycaemic variation in the second and third trimesters of normal pregnancies. Methodology Healthy pregnant women aged 19–35 years between 24 and 36 weeks of gestation were recruited for ambulatory glucose profile monitoring. A total of 18 women in the second trimester, 15 women in the third trimester and 9 healthy non-pregnant women were recruited providing, respectively, 205 days (19,680 data points), 147 days (14,112 data points) and 100 days (9,600 data points) for analysis. Results Mean blood glucose level was 20.2% lower in the second trimester and 10.6% lower in the third trimester than non-pregnant women (p < 0.001). In pregnancy, it took 15 to 20 minutes more to reach peak postprandial blood glucose levels compared to non-pregnant women (p = 0.003). Glycaemic variability was more in the third trimester (p < 0.001). Conclusion There is tight blood sugar control along with lower mean blood glucose in healthy pregnant women compared to non-pregnant women. Despite this tight glycaemic control, glycaemic variability is higher during pregnancy.