bluuebunny/crossref_metadata_2025_split huggingface dataset:
Temporal analysis of determinants for respiratory emergency department visits in a large German hospital
Authors: Krefis Anne Caroline , Fischereit Jana , Hoffmann Peter , Pinnschmidt Hans , Sorbe Christina , Augustin Matthias , Augustin Jobst 
Published: November 2018

IntroductionAssociations between air pollutants, meteorological conditions and respiratory diseases have been extensively shown. The aim of this study was to investigate associations between daily meteorological data, data on air pollution and emergency department (ED) visits depending on the day of the week, season and year (study period from 2013 to 2015).MethodsHighly correlated environmental data entered a categorical principal components analysis (CATPCA). We analysed cross-correlation functions between the time series of the respective daily environmental factors and daily ED visits. Time lags with peak correlations of environmental variables obtained by the CATPCA on ED visits together with day of the week, year, running day (linear, quadratic and cubic), season and interaction terms entered the univariate analysis of variance (UNIANOVA) model.ResultsThe analyses demonstrated main effects on ED visits for the day of the week with highest admission rates on Mondays (B=10.69; ƞ2=0.333; p<0.001). A significant time trend could be observed showing increasing numbers of ED visits per each year (p<0.001). The variable ‘running day’ (linear, quadratic and cubic) indicated a significant non-linear effect over time. The variable season showed significant results with winter, spring and summer recording fewer ED visits compared with the reference season autumn. Environmental variables showed no direct associations with respiratory ED visits.DiscussionED visits were significantly associated with temporal variables. Our data did not show direct associations between environmental variables and ED visits.In times of rapid urbanisation, increases in respiratory diseases, temperature and air pollution, our analyses can help focus future studies and enhance strategies to reduce increasing numbers of respiratory diseases and ED visits. Because the potential costs of medical care in hospitals can be high compared with physicians, public health recommendations for reducing the increasing ED visits should be promoted and evaluated.
Early diagnosis of progressive multifocal leucoencephalopathy: longitudinal lesion evolution
Authors: Scarpazza Cristina , Signori Alessio , Prosperini Luca , Sormani Maria Pia , Cosottini Mirco , Capra Ruggero , Gerevini Simonetta 
Published: November 2018

ObjectiveEarly diagnosis of natalizumab-related progressive multifocal leucoencephalopathy (NTZ-PML) in multiple sclerosis has been deemed a major priority by the regulatory agencies but has yet to become a reality. The current paper aims to: (1) investigate whether patients with NTZ-PML pass through a prolonged presymptomatic phase with MRI abnormalities, (2) estimate the longitudinal PML lesion volume increase during the presymptomatic phase and (3) estimate the presymptomatic phase length and its impact on therapy duration as a risk stratification parameter.MethodsAll Italian patients who developed NTZ-PML between 2009 and 2018 were included. The data of patients with available prediagnostic MRI were analysed (n=41). Detailed clinical and neuroradiological information was available for each participant.Results(1) PML lesions were detectable in the presymptomatic phase in 32/41 (78%) patients; (ii) the lesion volume increased by 62.8 % for each month spent in the prediagnostic phase; (3) the prediagnostic phase length was 150.8±74.9 days; (4) PML MRI features were detectable before the 24th month of therapy in 31.7 % of patients in our cohort.ConclusionsConsidering the latency of PML clinical manifestation, the presymptomatic phase length supports the usefulness of MRI surveillance every 3–4  months. Early diagnosis could prompt a better outcome for patients due to the relationship between lesion volume and JC virus infection. The insight from this study might also have an impact on risk stratification algorithms, as therapy duration as a parameter of stratification appears to need reassessment.
More than three passes of stent retriever is an independent predictor of parenchymal hematoma in acute ischemic stroke
Authors: Bourcier Romain , Saleme Suzana , Labreuche Julien , Mazighi Mikael , Fahed Robert , Blanc Raphael , Gory Benjamin , Kyheng Maeva , Marnat Gaultier , Bracard Serge , Desal Hubert , Consoli Arturo , Piotin Michel , Lapergue Bertrand 
Published: November 2018

IntroductionDespite successful recanalization with mechanical thrombectomy (MT) for acute anterior ischemic stroke (AAIS), the number of passes may impact clinical outcome.We analyzed the impact of more than three MT passes (>3) in a trial that evaluated contact aspiration (CA) versus stent retriever (SR) as the first-line technique in AAIS.MethodsWe included patients with mTICI 2b/3 recanalization after MT for isolated intracranial occlusions. The primary outcome was the percentage of patients with a 90-day modified Rankin Scale (mRS)≤2. Secondary outcomes included overall distribution of 90-day mRS, parenchymal hematoma on 24 hours' brain imaging (PH), and 90-day mortality.ResultsAmong the 281 patients included and even after adjustment on time to recanalization, significantly more patients with >3 passes had PH than patients with ≤3 passes in multivariate analysis (adjusted OR, 3.62; 95% CI, 1.55 to 8.44). When the analyses were stratified according to CA vs. SR, patients with >3 passes had a stronger risk of PH than patients with ≤3 passes, only in the SR first-line-treated group (adjusted OR, 9.24; 95% CI, 2.65 to 32.13) and not in the CA first-line-treated group (adjusted RR, 1.73; 95% CI, 0.57 to 5.19). A negative association of borderline significance (P=0.07) between >3 passes and favorable outcome was observed only in SR first-line-treated patients (adjusted OR, 0.33; 95% CI, 0.09 to 1.11).ConclusionsAfter three passes of SR and unlike for three passes of CA, there is an increased risk of PH and a trend toward a worse clinical outcome.
Pre-test characteristics of unstable angina patients with obstructive coronary artery disease confirmed by coronary angiography
Authors: Fladseth Kristina , Kristensen Andreas , Mannsverk Jan , Trovik Thor , Schirmer Henrik 
Published: November 2018

ObjectivePatients referred for acute coronary angiography (CAG) with unstable angina (UA) have low mortality and low rate of obstructive coronary artery disease (CAD). Better pre-test selection criteria are warranted. We aimed to assess the current guidelines against other clinical variables as predictors of obstructive CAD in patients with UA referred for acute CAG.MethodsFrom 2005 to 2012, all CAGs performed at the University Hospital of North Norway, the sole provider of CAG in the region, were recorded in a registry. We included 979 admissions of UA and retrospectively collected data regarding presenting clinical parameters from patient hospital records. Obstructive CAD was defined as ≥50% stenosis and considered prognostically significant if found in the left main stem, proximal LAD or all three main coronary arteries. Characteristics were analysed by logistic regression analysis. A score was developed using ORs from significant factors in a multivariable model.ResultsThe overall rate of obstructive CAD was 45%, and the rate of prognostically significant CAD was 11%. The risk criteria recommended in American College of Cardiology/American Heart Association and European Society of Cardiology guidelines had an area under the curve (AUC) of 0.58. Adding clinical information increased the AUC to 0.77 (95% CI 0.74 to 0.80). Applying the derived score, we found that 56% (n=546) of patients had a score of <13, which was associated with a negative predictive value of 95% for prognostic significant CAD.ConclusionsThe current results suggest that CAG may be postponed or cancelled in more than half of patients with UA by improving pre-test selection criteria with the addition of clinical parameters to current guidelines.
Obesity paradox on outcome in atrial fibrillation maintained even considering the prognostic influence of biomarkers: insights from the ARISTOTLE trial
Authors: Sandhu Roopinder K , Ezekowitz Justin A , Hijazi Ziad , Westerbergh Johan , Aulin Julia , Alexander John H , Granger Christopher B , Halvorsen Sigrun , Hanna Michael S , Lopes Renato D , Siegbahn Agneta , Wallentin Lars 
Published: November 2018

ObjectiveWe investigated the association between obesity and biomarkers indicating cardiac or renal dysfunction or inflammation and their interaction with obesity and outcomes.MethodsA total of 14 753 patients in the Apixaban for Reduction In STroke and Other ThromboemboLic Events in Atrial Fibrillation (ARISTOTLE) trial provided plasma samples at randomisation to apixaban or warfarin. Median follow-up was 1.9 years. Body Mass Index (BMI) was measured at baseline and categorised as normal, 18.5–25  kg/m2; overweight, >25 to <30 kg/m2; and obese, ≥30 kg/m2. We analysed the biomarkers high-sensitivity C reactive protein (hs-CRP), interleukin 6 (IL-6), growth differentiation factor-15 (GDF-15), troponin T and N-terminal B-type natriuretic peptide (NT-pro-BNP). Outcomes included stroke/systemic embolism (SE), myocardial infarction (MI), composite (stroke/SE, MI, or all-cause mortality), all-cause and cardiac mortality, and major bleeding.ResultsCompared with normal BMI, obese patients had significantly higher levels of hs-CRP and IL-6 and lower levels of GDF-15, troponin T and NT-pro-BNP. In multivariable analyses, higher compared with normal BMI was associated with a lower risk of all-cause mortality (overweight: HR 0.73 (95% CI 0.63 to 0.86); obese: 0.67 (0.56 to 0.80), p<0.0001), cardiac death (overweight: HR 0.74 (95% CI 0.60 to 0.93); obese: 0.71 (0.56 to 0.92), p=0.01) and composite endpoint (overweight: 0.80 (0.70 to 0.92); obese: 0.72 (0.62 to 0.84), p<0.0001).ConclusionsRegardless of biomarkers indicating inflammation or cardiac or renal dysfunction, obesity was independently associated with an improved survival in anticoagulated patients with AF.Trial registration numberNCT00412984.
Multiple biomarker panel to screen for severe aortic stenosis: results from the CASABLANCA study
Authors: Elmariah Sammy , McCarthy Cian , Ibrahim Nasrien , Furman Deborah , Mukai Renata , Magaret Craig , Rhyne Rhonda , Barnes Grady , van Kimmenade Roland R J , Januzzi James L 
Published: November 2018

ObjectiveSevere aortic valve stenosis (AS) develops via insidious processes and can be challenging to correctly diagnose. We sought to develop a circulating biomarker panel to identify patients with severe AS.MethodsWe enrolled study participants undergoing coronary or peripheral angiography for a variety of cardiovascular diseases at a single academic medical centre. A panel of 109 proteins were measured in blood obtained at the time of the procedure. Statistical learning methods were used to identify biomarkers and clinical parameters that associate with severe AS. A diagnostic model incorporating clinical and biomarker results was developed and evaluated using Monte Carlo cross-validation.ResultsOf 1244 subjects (age 66.4±11.5  years, 28.7% female), 80 (6.4%) had severe AS (defined as aortic valve area (AVA) <1.0  cm2). A final model included age, N-terminal pro-B-type natriuretic peptide, von Willebrand factor and fetuin-A. The model had good discrimination for severe AS (OR=5.9, 95% CI 3.5 to 10.1, p<0.001) with an area under the curve of 0.76 insample and 0.74 with cross-validation. A diagnostic score was generated. Higher prevalence of severe AS was noted in those with higher scores, such that 1.6% of those with a score of 1 had severe AS compared with 15.3% with a score of 5 (p<0.001), and score values were inversely correlated with AVA (r=−0.35; p<0.001). At optimal model cut-off, we found 76% sensitivity, 65% specificity, 13% positive predictive value and 98% negative predictive value.ConclusionsWe describe a novel, multiple biomarker approach for diagnostic evaluation of severe AS.Trial registration numberNCT00842868.
The Geikie Archive at Haslemere Museum: family and professional material
Authors: Betterton John 
Published: November 2018

Abstract
The family history of Sir Archibald Geikie (1835–1924) is examined with reference to his immediate family and descendants, including much previously unpublished documentary archival material preserved at the Haslemere Educational Museum. The lives of Archibald's children are also examined. This account includes previously unpublished images of the Geikie family and gives new insights into aspects of Archibald Geikie's character through the memories of his grandson, Derick Jacob Behrens (1917–2004). Geikie's continued academic life after his retirement from the Geological Survey is discussed in relation to that institution.
Exercise-induced calf muscle hyperemia: quantitative mapping with low-dose dynamic contrast enhanced magnetic resonance imaging
Authors: Zhang Jeff L. , Layec Gwenael , Hanrahan Christopher , Conlin Christopher C. , Hart Corey , Hu Nan , Khor Lillian , Mueller Michelle , Lee Vivian S. 
Published: November 2018

Peripheral artery disease (PAD) in the lower extremities often leads to intermittent claudication. In the present study, we proposed a low-dose DCE MRI protocol for quantifying calf muscle perfusion stimulated with plantar flexion and multiple new metrics for interpreting perfusion maps, including the ratio of gastrocnemius over soleus perfusion (G/S; for assessing the vascular redistribution between the two muscles) and muscle perfusion normalized by whole body perfusion (for quantifying the muscle’s active hyperemia). Twenty-eight human subjects participated in this Institutional Review Board-approved study, with 10 healthy subjects ( group A) for assessing interday reproducibility and 8 healthy subjects ( group B) for exploring the relationship between plantar-flexion load and induced muscle perfusion. In a pilot group of five elderly healthy subjects and five patients with PAD ( group C), we proposed a protocol that measured perfusion for a low-intensity exercise and for an exhaustion exercise in a single MRI session. In group A, perfusion estimates for calf muscles were highly reproducible, with correlation coefficients of 0.90–0.93. In group B, gastrocnemius perfusion increased linearly with the exercise workload ( P < 0.05). With the low-intensity exercise, patients with PAD in group C showed substantially lower gastrocnemius perfusion compared with elderly healthy subjects [43.4 (SD 23.5) vs. 106.7 (SD 73.2) ml·min−1·100 g−1]. With exhaustion exercise, G/S [1.0 (SD 0.4)] for patients with PAD was lower than both its low-intensity level [1.9 (SD 1.3)] and the level in elderly healthy subjects [2.7 (SD 2.1)]. In conclusion, the proposed MRI protocol and the new metrics are feasible for quantifying exercise-induced muscle hyperemia, a promising functional test of PAD.NEW & NOTEWORTHY To quantitatively map exercise-induced hyperemia in calf muscles, we proposed a high-resolution MRI method shown to be highly reproducible and sensitive to exercise load. With the use of low contrast, it is feasible to measure calf muscle hyperemia for both low-intensity and exhaustion exercises in a single MRI session. The newly proposed metrics for interpreting perfusion maps are promising for quantifying intermuscle vascular redistribution or a muscle’s active hyperemia.
T-cell–Secreted TNFα Induces Emergency Myelopoiesis and Myeloid-Derived Suppressor Cell Differentiation in Cancer
Authors: Al Sayed Mohamad F. , Amrein Michael A. , Bührer Elias D. , Huguenin Anne-Laure , Radpour Ramin , Riether Carsten , Ochsenbein Adrian F. 
Published: November 2018

AbstractHematopoiesis in patients with cancer is characterized by reduced production of red blood cells and an increase in myelopoiesis, which contributes to the immunosuppressive environment in cancer. Some tumors produce growth factors that directly stimulate myelopoiesis such as G-CSF or GM-CSF. However, for a majority of tumors that do not directly secrete hematopoietic growth factors, the mechanisms involved in the activation of myelopoiesis are poorly characterized. In this study, we document in different murine tumor models activated hematopoiesis with increased proliferation of long-term and short-term hematopoietic stem cells and myeloid progenitor cells. As a consequence, the frequency of myeloid-derived suppressor cells and its ratio to CD8+ T cells increased in tumor-bearing mice. Activation of hematopoiesis and myeloid differentiation in tumor-bearing mice was induced by TNFα, which was mainly secreted by activated CD4+ T cells. Therefore, the activated adaptive immune system in cancer induces emergency myelopoiesis and immunosuppression.Significance:These findings characterize a regulatory circuit linking activated T cells to suppression of tumor-specific immune responses, providing a conceptual advance in the understanding of emergency-hematopoiesis in cancer and opening new targets for therapeutic approaches.
Loss of TRIM29 Alters Keratin Distribution to Promote Cell Invasion in Squamous Cell Carcinoma
Authors: Yanagi Teruki , Watanabe Masashi , Hata Hiroo , Kitamura Shinya , Imafuku Keisuke , Yanagi Hiroko , Homma Akihiro , Wang Lei , Takahashi Hidehisa , Shimizu Hiroshi , Hatakeyama Shigetsugu 
Published: November 2018

Abstract

TRIM29 (tripartite motif-containing protein 29) is a TRIM family protein that has been implicated in breast, colorectal, and pancreatic cancers. However, its role in stratified squamous epithelial cells and tumors has not been elucidated. Here, we investigate the expression of TRIM29 in cutaneous head and neck squamous cell carcinomas (SCC) and its functions in the tumorigenesis of such cancers. TRIM29 expression was lower in malignant SCC lesions than in adjacent normal epithelial tissue or benign tumors. Lower expression of TRIM29 was associated with higher SCC invasiveness. Primary tumors of cutaneous SCC showed aberrant hypermethylation of TRIM29. Depletion of TRIM29 increased cancer cell migration and invasion; conversely, overexpression of TRIM29 suppressed these. Comprehensive proteomics and immunoprecipitation analyses identified keratins and keratin-interacting protein FAM83H as TRIM29 interactors. Knockdown of TRIM29 led to ectopic keratin localization of keratinocytes. In primary tumors, lower TRIM29 expression correlated with the altered expression of keratins. Our findings reveal an unexpected role for TRIM29 in regulating the distribution of keratins, as well as in the migration and invasion of SCC. They also suggest that the TRIM29–keratin axis could serve as a diagnostic and prognostic marker in stratified epithelial tumors and may provide a target for SCC therapeutics.

Significance:
These findings identify TRIM29 as a novel diagnostic and prognostic marker in stratified epithelial tissues.
Adipokines Deregulate Cellular Communication via Epigenetic Repression of Gap Junction Loci in Obese Endometrial Cancer
Authors: Polusani Srikanth R. , Huang Yi-Wen , Huang Guangcun , Chen Chun-Wei , Wang Chiou-Miin , Lin Li-Ling , Osmulski Pawel , Lucio Nicholas D. , Liu Lu , Hsu Ya-Ting , Zhou Yufan , Lin Chun-Lin , Aguilera-Barrantes Irene , Valente Philip T. , Kost Edward R. , Chen Chun-Liang , Shim Eun Yong , Lee Sang Eun , Ruan Jianhua , Gaczynska Maria E. , Yan Pearlly , Goodfellow Paul J. , Mutch David G. , Jin Victor X. , Nicholson Bruce J. , Huang Tim H.-M. , Kirma Nameer B. 
Published: November 2018

Abstract

Emerging evidence indicates that adipose stromal cells (ASC) are recruited to enhance cancer development. In this study, we examined the role these adipocyte progenitors play relating to intercellular communication in obesity-associated endometrial cancer. This is particularly relevant given that gap junctions have been implicated in tumor suppression. Examining the effects of ASCs on the transcriptome of endometrial epithelial cells (EEC) in an in vitro coculture system revealed transcriptional repression of GJA1 (encoding the gap junction protein Cx43) and other genes related to intercellular communication. This repression was recapitulated in an obesity mouse model of endometrial cancer. Furthermore, inhibition of plasminogen activator inhibitor 1 (PAI-1), which was the most abundant ASC adipokine, led to reversal of cellular distribution associated with the GJA1 repression profile, suggesting that PAI-1 may mediate actions of ASC on transcriptional regulation in EEC. In an endometrial cancer cohort (n = 141), DNA hypermethylation of GJA1 and related loci TJP2 and PRKCA was observed in primary endometrial endometrioid tumors and was associated with obesity. Pharmacologic reversal of DNA methylation enhanced gap-junction intercellular communication and cell–cell interactions in vitro. Restoring Cx43 expression in endometrial cancer cells reduced cellular migration; conversely, depletion of Cx43 increased cell migration in immortalized normal EEC. Our data suggest that persistent repression by ASC adipokines leads to promoter hypermethylation of GJA1 and related genes in the endometrium, triggering long-term silencing of these loci in endometrial tumors of obese patients.

Significance:
Studies reveal that adipose-derived stem cells in endometrial cancer pathogenesis influence epigenetic repression of gap junction loci, which suggests targeting of gap junction activity as a preventive strategy for obesity-associated endometrial cancer.
VCAM-1–targeted MRI Enables Detection of Brain Micrometastases from Different Primary Tumors
Authors: Cheng Vinton W.T. , Soto Manuel Sarmiento , Khrapitchev Alexandre A. , Perez-Balderas Francisco , Zakaria Rasheed , Jenkinson Michael D. , Middleton Mark R. , Sibson Nicola R. 
Published: November 2018

Abstract

Purpose:
A major issue for the effective treatment of brain metastasis is the late stage of diagnosis with existing clinical tools. The aim of this study was to evaluate the potential of vascular cell adhesion molecule 1 (VCAM-1)-targeted MRI for early detection of brain micrometastases in mouse models across multiple primary tumor types.
Experimental Design: Xenograft models of brain micrometastasis for human breast carcinoma (MDA231Br-GFP), lung adenocarcinoma (SEBTA-001), and melanoma (H1_DL2) were established via intracardiac injection in mice. Animals (n = 5–6/group) were injected intravenously with VCAM-1–targeted microparticles of iron oxide (VCAM-MPIO) and, subsequently, underwent T2*-weighted MRI. Control groups of naïve mice injected with VCAM-MPIO and tumor-bearing mice injected with nontargeting IgG-MPIO were included.

Results:
All models showed disseminated micrometastases in the brain, together with endothelial VCAM-1 upregulation across the time course. T2*-weighted MRI of all tumor-bearing mice injected with VCAM-MPIO showed significantly more signal hypointensities (P &lt; 0.001; two-sided) than control cohorts, despite a lack of blood–brain barrier (BBB) impairment. Specific MPIO binding to VCAM-1–positive tumor-associated vessels was confirmed histologically. VCAM-1 expression was demonstrated in human brain metastasis samples, across all three primary tumor types.

Conclusions:
VCAM-1–targeted MRI enables the detection of brain micrometastases from the three primary tumor types known to cause the majority of clinical cases. These findings represent an important step forward in the development of a broadly applicable and clinically relevant imaging technique for early diagnosis of brain metastasis, with significant implications for improved patient survival.