bluuebunny/crossref_metadata_2025_split huggingface dataset:
Patient-reported sleep disturbance in advanced cancer: frequency, predictors and screening performance of the Edmonton Symptom Assessment System sleep item
Authors: Yennurajalingam Sriram , Balachandran Dave , Pedraza Cardozo Sandra L , Berg Elyssa A , Chisholm Gary B , Reddy Akhila , DeLa Cruz Vera , Williams Janet L , Bruera Eduardo 
Published: October 2015

AimsSleep Disturbance (SD) is a severe debilitating symptom in advanced cancer patients (ACP). However, routine screening of SD is uncommon. The primary aim of this study was to determine the optimal cutoff score for SD screening for Edmonton Symptom Assessment system (ESAS) sleep item using Pittsburgh Sleep Quality Index (PSQI) as a gold standard. We also determined the frequency of SD, obstructive sleep apnea symptoms (OSA) and restless leg syndrome (RLS) and factors associated with SD.MethodsWe prospectively surveyed 180 consecutive ACP. Patients completed validated assessment for symptoms. We determined epidemiological performance, receiver operating characteristics, and correlations of SD.ResultsSD according to PSQI was diagnosed in 112/180 (62%), and median (IQR) ESAS sleep was 5 (2-7). ESAS sleep ≥ 4 had a sensitivity of 74% and 80%, and specificity of 71% and 64% in the training and validation samples, respectively for screening of SD. The frequency of OSA was 61%; RLS was 38%. ESAS sleep was associated [r, p-value] with PSQI (0.61, <0.0001), pain (0.4, <0.0001); fatigue (0.35, <0.0001); depression (0.20, 0.006); anxiety (0.385, <0.0001); drowsiness (0.385, <0.0001), shortness of breath (0.24, <0.0014); anorexia (0.32, <0.0001), well-being (0.36, <0.0001). Multivariate analysis found well-being (OR per point 1.34, p=0.0003), pain (OR 1.21, p<0.0037), dyspnea (OR 1.16, p=0.027), and OSA (OR 0.31, P=0.003) as independent predictors of SD. There was no association between SD and survival.ConclusionsSD is frequent and ESAS SD item ≥ 4 has good sensitivity for SD screening.
Tertiary lymphoid structures: prognostic significance and relationship with tumour-infiltrating lymphocytes in triple-negative breast cancer
Authors: Lee Hee Jin , Park In Ah , Song In Hye , Shin Su-Jin , Kim Joo Young , Yu Jong Han , Gong Gyungyub 
Published: October 2015

BackgroundTumour-infiltrating lymphocytes (TILs) have a strong prognostic significance, particularly in triple-negative breast cancer (TNBC). One important source of TILs in breast cancer is tertiary lymphoid structures (TLSs).ObjectiveTo carry out a histological analysis of surgically resected TNBC to identify the location of TLSs, the relationship between TLSs and TILs and their prognostic significance in TNBC.MethodsWe retrospectively analysed 769 patients with TNBC.ResultsTILs were defined as the percentage of stroma of invasive carcinoma infiltrated by lymphocytes. TLSs were mainly present within adjacent terminal duct lobular units and around in situ components. TNBC with higher levels of TILs showed a higher nuclear grade, lower lymphovascular invasion, less accompanying in situ component, a homogeneous growth pattern, necrosis in invasive areas, low levels of tumour stroma, high levels of peritumoral lymphocytic infiltration and moderate to abundant TLSs in adjacent tissue. TILs, the degree of peritumoral lymphocytic infiltration and adjacent TLSs were prognostic factors for disease-free and overall survival. Although the TIL level did not have a prognostic value in stage I, it added significant prognostic information for stages II and III. Conversely, patients with high levels of TILs did not show prognostic differences according to the pTNM stage. Patients with high levels of TILs (>60%) and moderate to abundant TLSs had significantly better disease-free survival than those with high levels of TILs but none or few TLSs.ConclusionsTLSs are frequently present in TNBC and are closely associated with TILs. TILs provide additional prognostic information in patients with TNBC with a higher pTNM stage.
The significance of tectonism in the glaciations of Greece
Authors: Bathrellos George D. , Skilodimou Hariklia D. , Maroukian Hampik 
Published: October 2015

Abstract

Glaciers were common features in the highlands of Greece during the Middle to Late Pleistocene glacial periods and cirques are characteristic landforms of mountain glaciation. This study examined the cirques of Greece and the role of tectonic uplift in determining their altitude across the country, from Mount Olympus to the Peloponnesus and Crete. An inventory of 227 Middle to Late Pleistocene age limestone cirques was compiled. The number and total area of the cirques decreased from northern mainland Greece (Macedonia, Epirus) to the south (the Peloponnesus, Crete) and on moving to higher elevations. Continued tectonic uplift of the Olympus massif, the Peloponnesus and Crete has led to altitudinal changes in cirques in every subsequent ice age. The formation of cirques at lower elevations during Marine Isotope Stage 12 suggests extreme climatic conditions. On Mount Olympus, the mean elevation of cirques was estimated to have increased by
c.
450 m since Marine Isotope Stage 12; in the northern and southern Peloponnesus the elevation increased by
c.
500 m and 190 m, respectively, and in Crete by
c.
400 m. The cirques have uplifted at approximately the same rate in northern Greece, but at different rates in southern Greece during this period.
Plasticity beyond Cancer Cells and the “Immunosuppressive Switch”
Authors: Granot Zvi , Fridlender Zvi G. 
Published: October 2015

Abstract
Tumor initiation, growth, and metastatic progression are complex processes that, in order to be successful, require extraordinary cellular plasticity. Accordingly, tumor cell plasticity and how it affects disease progression have been studied extensively. However, as our understanding of the tumor microenvironment deepens, we are confronted with the notion that functional plasticity in the context of cancer is not limited to tumor cells alone but is also commonly seen in normal stromal cells of the microenvironment, and specifically in immune cells. Here, we review the functional plasticity these cells exhibit in the context of cancer, highlighting the role of circulating and tumor-associated neutrophils. We further discuss how this plasticity supports or limits tumor progression, inducing an “immunosuppressive switch” to promote further tumor growth and development. Cancer Res; 75(21); 4441–5. ©2015 AACR.
Tetracycline Antibiotics Impair Mitochondrial Function and Its Experimental Use Confounds Research
Authors: Chatzispyrou Iliana A. , Held Ntsiki M. , Mouchiroud Laurent , Auwerx Johan , Houtkooper Riekelt H. 
Published: October 2015

Abstract
Tetracyclines, a class of antibiotics that target bacterial translation, are commonly used in research for inducible gene expression using Tet-ON/Tet-OFF systems. However, such tetracycline-inducible systems carry a risk. Given that mitochondria have a “bacterial” ancestry, these antibiotics also target mitochondrial translation and impair mitochondrial function. Indeed, treatment with doxycycline—a tetracycline derivative—disturbs mitochondrial proteostasis and metabolic activity, and induces widespread gene-expression changes. Together, this affects physiology in well-established model systems ranging from cultured cells to simple organisms and to mice and plants. These changes are observed with doxycycline doses that are widely used to regulate gene expression. In light of these findings, and bearing in mind the conserved role of mitochondria in metabolism and whole organism homeostasis, we caution against the use of tetracyclines in experimental approaches. The use of newly developed tetracycline-based systems that are more sensitive could be an alternative; however, even if no overt mitochondrial toxicity is detected, widespread changes in gene expression may sensitize cells to the intended tetracycline-controlled loss or gain of function, thereby introducing a “two-hit model.” This is highly relevant for cancer research, as mitochondrial metabolism holds a central position in the reallocation of nutrients for biomass production known as the Warburg effect. Cancer Res; 75(21); 4446–9. ©2015 AACR.
The Colony-Stimulating Factor 3 Receptor T640N Mutation Is Oncogenic, Sensitive to JAK Inhibition, and Mimics T618I
Authors: Maxson Julia E. , Luty Samuel B. , MacManiman Jason D. , Paik Jason C. , Gotlib Jason , Greenberg Peter , Bahamadi Swaleh , Savage Samantha L. , Abel Melissa L. , Eide Christopher A. , Loriaux Marc M. , Stevens Emily A. , Tyner Jeffrey W. 
Published: October 2015

Abstract
Purpose: Colony-stimulating factor 3 receptor (CSF3R) mutations have been identified in the majority of chronic neutrophilic leukemia (CNL) and a smaller percentage of atypical chronic myeloid leukemia (aCML) cases. Although CSF3R point mutations (e.g., T618I) are emerging as key players in CNL/aCML, the significance of rarer CSF3R mutations is unknown. In this study, we assess the importance of the CSF3R T640N mutation as a marker of CNL/aCML and potential therapeutic target.
Experimental Design: Sanger sequencing of leukemia samples was performed to identify CSF3R mutations in CNL and aCML. The oncogenicity of the CSF3R T640N mutation relative to the T618I mutation was assessed by cytokine independent growth assays and by mouse bone marrow transplant. Receptor dimerization and O-glycosylation of the mutants was assessed by Western blot, and JAK inhibitor sensitivity was assessed by colony assay.
Results: Here, we identify a CSF3R T640N mutation in two patients with CNL/aCML, one of whom was originally diagnosed with MDS and acquired the T640N mutation upon evolution of disease to aCML. The T640N mutation is oncogenic in cellular transformation assays and an in vivo mouse bone marrow transplantation model. It exhibits many similar phenotypic features to T618I, including ligand independence and altered patterns of O-glycosylation—despite the transmembrane location of T640 preventing access by GalNAc transferase enzymes. Cells transformed by the T640N mutation are sensitive to JAK kinase inhibition to a similar degree as cells transformed by CSF3R T618I.
Conclusions: Because of its similarities to CSF3R T618I, the T640N mutation likely has diagnostic and therapeutic relevance in CNL/aCML. Clin Cancer Res; 22(3); 757–64. ©2015 AACR.
Global Hypomethylation (LINE-1) and Gene-Specific Hypermethylation (GSTP1) on Initial Negative Prostate Biopsy as Markers of Prostate Cancer on a Rebiopsy
Authors: Zelic Renata , Fiano Valentina , Zugna Daniela , Grasso Chiara , Delsedime Luisa , Daniele Lorenzo , Galliano Diego , Pettersson Andreas , Gillio-Tos Anna , Merletti Franco , Richiardi Lorenzo 
Published: October 2015

Abstract
Purpose: Men at risk of missed prostate cancer on a negative biopsy often undergo a rebiopsy. We evaluated whether global hypomethylation, measured through LINE-1 methylation, and GSTP1 hypermethylation on a negative biopsy are associated with subsequent prostate cancer diagnosis.
Experimental Design: We performed a case–control study nested in an unselected series of 737 men who received at least two prostate biopsies at least three months apart at the Molinette Hospital (Turin, Italy). Two pathology wards were included for replication purposes. The study included 67 cases and 62 controls in Ward 1 and 62 cases and 66 controls in Ward 2. We used pyrosequencing to analyze LINE-1 and GSTP1 methylation in the negative biopsies. Odds ratios (OR) of prostate cancer diagnosis were estimated using conditional logistic regression.
Results: After mutual adjustment, GSTP1 hypermethylation was associated with an OR of prostate cancer diagnosis of 5.1 (95% confidence interval: 1.7–14.9) in Ward 1 and 2.0 (0.8–5.3) in Ward 2, whereas an association was suggested only for low LINE-1 methylation levels (&lt;70% vs. 70%–74%) with an OR of 2.1 (0.5–9.1) in Ward 1 and 1.6 (0.4–6.1) in Ward 2. When the two wards were combined the association was stronger for tumors with Gleason score ≥4+3 [GSTP1 hypermethylation: 9.2 (2.0–43.1); LINE-1 (&lt;70% vs. 70%–74%): 9.2 (1.4–59.3)]. GSTP-1 alone improved the predictive capability of the model (P = 0.007).
Conclusions: GSTP1 hypermethylation on a negative biopsy is associated with the risk of prostate cancer on a rebiopsy, especially of high-grade prostate cancer. Consistent results were found only for extremely low LINE-1 methylation levels. Clin Cancer Res; 22(4); 984–92. ©2015 AACR.
Enzymatically Modified Low‐Density Lipoprotein Is Present in All Stages of Aortic Valve Sclerosis: Implications for Pathogenesis of the Disease
Authors: Twardowski Laura , Cheng Fei , Michaelsen Jens , Winter Stefan , Hofmann Ute , Schaeffeler Elke , Müller Simon , Sonnenberg Maike , Steuer Kristin , Ott German , Schwab Matthias , Franke Ulrich F. W. , Torzewski Michael 
Published: October 2015

Background

We have demonstrated previously that enzymatically degraded low‐density lipoprotein (
eLDL
) is an essential causative component for the initiation of atherosclerosis. Here, we investigated the different stages of human aortic valve sclerosis for the presence of
eLDL
and effectors of the innate immune system, as well as the interaction of
eLDL
with isolated valvular interstitial cells/myofibroblasts to discover possible pathways leading to aortic valve sclerosis.

Methods and Results

Human aortic valvular tissue was obtained from 68 patients undergoing valve replacement surgery. Patients were classified into 3 groups (mild, moderate, or severe aortic valve sclerosis), and clinical data for statistical analysis were gathered from all patients. Immunohistochemical staining demonstrated extensive extracellular deposits of
eLDL
throughout all grades of aortic valve sclerosis. Complementary analysis of lipid composition revealed higher concentrations of the decisive components of
eLDL
(ie, unesterified cholesterol and linoleic acid) compared with internal control tissues. Further, the complement component C3d and terminal complement complexes colocalized with
eLDL
compatible with the proposal that subendothelially deposited
eLDL
is enzymatically transformed into a complement activator at early stages of valvular cusp lesion development. Gene expression profiles of proteases and complement components corroborated by immunohistochemistry demonstrated an upregulation of the protease cathepsin D (a possible candidate for
LDL
degradation to
eLDL
) and the complement inhibitor
CD
55. Surprisingly, substantial C‐reactive protein expression was not observed before grade 2 aortic valve sclerosis as investigated with microarray analysis, reverse transcription–polymerase chain reaction analysis, and immunohistochemistry. Finally, we demonstrated cellular uptake of
eLDL
by valvular interstitial cells/myofibroblasts.

Conclusions
The present study is a startup of a hypothesis on the pathogenesis of aortic valve sclerosis declaring extracellular lipoprotein modification, subsequent complement activation, and cellular uptake by valvular interstitial cells/myofibroblasts as integral players.
Differences Among Cardiologists in Rates of Positive Coronary Angiograms
Authors: Wasfy Jason H. , Hidrue Michael K. , Yeh Robert W. , Armstrong Katrina , Dec G. William , Pomerantsev Eugene V. , Fifer Michael A. , Ferris Timothy G. 
Published: October 2015

Background
Understanding the sources of variation for high‐cost services has the potential to improve both patient outcomes and value in health care delivery. Nationally, the overall diagnostic yield of coronary angiography is relatively low, suggesting overutilization. Understanding how individual cardiologists request catheterization may suggest opportunities for improving quality and value. We aimed to assess and explain variation in positive angiograms among referring cardiologists.

Methods and Results

We identified all cases of diagnostic coronary angiography at Massachusetts General Hospital from January 1, 2012, to June 30, 2013. We excluded angiograms for acute coronary syndrome. For each angiogram, we identified clinical features of the patients and characteristics of the requesting cardiologists. We also identified angiogram positivity, defined as at least 1 epicardial coronary stenosis ≥50% luminal narrowing. We then constructed a series of mixed‐effects logistic regression models to analyze predictors of positive coronary angiograms. We assessed variation by physician in the models with median odds ratios. Over this time period, 5015 angiograms were identified. We excluded angiograms ordered by cardiologists requesting <10 angiograms. Among the remaining 2925 angiograms, 1450 (49.6%) were positive. Significant predictors of positive angiograms included age, male patients, and peripheral arterial disease. After adjustment for clinical variables only, the median odds ratio was 1.23 (95%
CI
1.0–1.36), consistent with only borderline clinical variation after adjustment. In the full clinical and nonclinical model, the median odds ratio was 1.07 (95%
CI
1.07–1.20), also consistent with clinically insignificant variation.

Conclusions
Substantial variation exists among requesting cardiologists with respect to positive and negative coronary angiograms. After adjustment for clinical variables, there was only borderline clinically significant variation. These results emphasize the importance of risk adjustment in reporting related to quality and value.
Metacommunication in social play: the meaning of aggression-like elements is modified by play face in Hanuman langurs (Semnopithecus entellus)
Authors: Špinka Marek , Palečková Marie , Řeháková Milada 
Published: October 2015

The metacommunication hypothesis asserts that some elements of play behaviour are associated with play elements borrowed from aggression and interpret these aggression-like elements as playful. Using data from free living Hanuman langurs (Semnopithecus entellus), we tested three predictions that follow from the metacommunication hypothesis: (i) aggression-like elements (ALEs) abbreviate play bouts; (ii) candidate signal elements are sequentially associated with ALEs; (iii) associations of candidate signal elements with ALEs prolong play bouts. Play face and five other candidate signal elements were evaluated in relation to nine ALEs. We confirmed all three predictions for play face, albeit only if the play face and/or the ALEs occurred at the start of the play bout. The other candidate elements were not associated with ALEs. We conclude that play face fulfils the metacommunicatory function in Hanuman langur play bouts, while other play specific elements may serve other signal or non-signal functions.
Diagnosis of Pediatric Foreign Body Ingestion
Authors: Sink Jacquelyn R. , Kitsko Dennis J. , Mehta Deepak K. , Georg Matthew W. , Simons Jeffrey P. 
Published: October 2015

Objectives: (1) To describe clinical and radiologic findings in patients with esophageal foreign bodies. (2) To examine the sensitivity and specificity of history, physical examination, and radiologic studies in children with suspected foreign body ingestion. Methods: A retrospective cohort study was performed evaluating all children who underwent esophagoscopy for suspected foreign body ingestion at our institution from 2006 to 2013. Results: Five hundred forty-three patients were included (54% male). Average age was 4.7 years (SD = 4.1 years). Foreign bodies were identified on esophagoscopy in 497 cases (92%). Ingestion was witnessed in 23% of cases. Most common presenting symptoms were choking/gagging (49%), vomiting (47%), and dysphagia/odynophagia (42%). Most patients with foreign bodies had a normal exam (76%). Most foreign bodies were radiopaque (83%). In 59% of patients with normal chest radiographs, a foreign body was present. Sensitivity and specificity of 1 or more findings on history, physical examination, and imaging were 99% and 0%, 21% and 76%, and 83% and 100%, respectively. Conclusions: Most patients with esophageal foreign bodies are symptomatic. Although many patients will have a normal physical examination, an abnormal exam should increase suspicion for a foreign body. Most esophageal foreign bodies are radiopaque, but a normal chest radiograph cannot rule out a foreign body.
Prevalence of hypertension and associated risk factors in Chinese Jing compared with Mulao populations
Authors: Xie Rui-Bin , Liao Pei-Juan , Yin Rui-Xing , Hu Xi-Jiang , Huang Jian , Wei Dai-Xun , Li Hui , Huang Feng , Yao Li-Mei , Pan Shang-Ling , Yang De-Zhai , Lin Wei-Xiong 
Published: October 2015

Objective * These authors contributed equally to this work. At present, they work at the Hezhou People’s Hospital, Hezhou, China. To retrospectively compare differences in the prevalence of hypertension and associated risk factors between the Chinese Jing and Mulao populations. Methods Subjects of Jing and Mulao ethnicities were surveyed using stratified randomized sampling. Demography, diet and lifestyle data were collected using standardized questionnaires. Several anthropometric parameters, blood pressure (BP) levels and serum lipid concentrations were obtained. Results Data from 915 Jing and 911 Mulao subjects aged ≥35 years were included. Diastolic BP levels and prevalence of hypertension were lower, but prevalence of isolated systolic hypertension was higher, in the Jing compared with the Mulao population. Prevalence of hypertension in the age 60–69 years, body mass index (BMI) > 24 kg/m2, and smoker subgroups was lower in the Jing compared with the Mulao populations. Prevalence of hypertension correlated with age, cigarette smoking, triglyceride level, waist circumference, sodium intake and total dietary fibre in the Jing population; hypertension prevalence also correlated with age, triglyceride level, BMI, total fat, sodium intake and total dietary fibre in the Mulao population (unconditional logistic regression analyses). Conclusions Prevalence of hypertension and associated risk factors were different between the two ethnic minorities, which might result from the combined effects of differences in their geographic, dietary, lifestyle, and genetic backgrounds.
Risk factors for breast cancer in women residing in urban and rural areas of eastern China
Authors: Wang Feng , Yu LiXiang , Wang Fei , Liu LiYuan , Guo MingMing , Gao DeZong , Zhang Qiang , Li YuYang , Li Liang , Fu QinYe , Yu ZhiGang 
Published: October 2015

Objective To investigate breast cancer risk factors in Chinese women residing in urban and rural areas of eastern China using a large-scale cross-sectional survey. Methods In this multistage, stratified cluster sampling epidemiological survey, information on demographic characteristics, diet and lifestyle variables were gathered using a carefully designed questionnaire. Multivariate logistic regression analysis and subgroup analyses of the data were performed, including separate analyses of data from women residing in urban and rural areas. Results A total of 122 058 women were included in the survey. Age, body mass index, number of miscarriages, family history of breast cancer and menopausal status were found to be risk factors for breast cancer, while the consumption of soya bean products was a protective factor. Among women residing in urban areas, high or moderate intake of soya bean products and red meat were protective factors. Among women residing in rural areas, obesity and a high intake of milk were identified as risk factors for breast cancer, while a moderate intake of soya bean products was a protective factor. Conclusions This type of data is crucial for understanding the risk factors for breast cancer and could facilitate the development and targeting of effective intervention strategies, with the ultimate aim of breast cancer prevention.