bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Prospective Study of Aspirin Use and Prostate Cancer Risk by TMPRSS2:ERG Status
Authors: Stopsack Konrad H. , Gonzalez-Feliciano Amparo G. , Peisch Samuel F. , Downer Mary K. , Gage Riley A. , Finn Stephen , Lis Rosina T. , Graff Rebecca E. , Pettersson Andreas , Pernar Claire H. , Loda Massimo , Kantoff Philip W. , Ahearn Thomas U. , Mucci Lorelei A. 
Published: August 2018

Abstract
Background: In a case–control study, aspirin use was associated with a lower risk of a common prostate cancer molecular subtype, the TMPRSS2:ERG gene fusion. We sought to validate this finding in a prospective cohort.
Methods: In the Health Professionals Follow-up Study, 49,395 men reported on aspirin use on biennial questionnaires and were followed for prostate cancer incidence over 23 years. TMPRSS2:ERG status was assessed by IHC for presence of ERG on archival tumor specimens for 912 patients with prostate cancer, of whom 48% were ERG-positive.
Results: In multivariable models, we found no association between regular use of aspirin and risk of ERG-positive prostate cancer (HR, 1.02; 95% confidence interval, 0.85–1.23), nor any association with duration or frequency of aspirin use. In restricting to cases with either high Gleason grade or advanced stage disease, there remained no association with aspirin use.
Conclusions: Data from this prospective study with repeated assessments of aspirin use do not support the hypothesis that aspirin use is associated with a lower risk of ERG-positive prostate cancer.
Impact: Aspirin use is unlikely to lower the risk of this common molecular subtype of prostate cancer. However, there is emerging data supporting the role of other lifestyle and genetic factors underlying the development of the TMPRSS2:ERG fusion. Cancer Epidemiol Biomarkers Prev; 27(10); 1231–3. ©2018 AACR.
Methylomic Analysis of Ovarian Cancers Identifies Tumor-Specific Alterations Readily Detectable in Early Precursor Lesions
Authors: Pisanic Thomas R. , Cope Leslie M. , Lin Shiou-Fu , Yen Ting-Tai , Athamanolap Pornpat , Asaka Ryoichi , Nakayama Kentaro , Fader Amanda N. , Wang Tza-Huei , Shih Ie-Ming , Wang Tian-Li 
Published: August 2018

AbstractPurpose:High-grade serous ovarian carcinoma (HGSOC) typically remains undiagnosed until advanced stages when peritoneal dissemination has already occurred. Here, we sought to identify HGSOC-specific alterations in DNA methylation and assess their potential to provide sensitive and specific detection of HGSOC at its earliest stages.Experimental Design:MethylationEPIC genome-wide methylation analysis was performed on a discovery cohort comprising 23 HGSOC, 37 non-HGSOC malignant, and 36 histologically unremarkable gynecologic tissue samples. The resulting data were processed using selective bioinformatic criteria to identify regions of high-confidence HGSOC-specific differential methylation. Quantitative methylation-specific real-time PCR (qMSP) assays were then developed for 8 of the top-performing regions and analytically validated in a cohort of 90 tissue samples. Lastly, qMSP assays were used to assess and compare methylation in 30 laser-capture microdissected (LCM) fallopian tube epithelia samples obtained from cancer-free and serous tubal intraepithelial carcinoma (STIC) positive women.Results:Bioinformatic selection identified 91 regions of robust, HGSOC-specific hypermethylation, 23 of which exhibited an area under the receiver-operator curve (AUC) value ≥ 0.9 in the discovery cohort. Seven of 8 top-performing regions demonstrated AUC values between 0.838 and 0.968 when analytically validated by qMSP in a 90-patient cohort. A panel of the 3 top-performing genes (c17orf64, IRX2, and TUBB6) was able to perfectly discriminate HGSOC (AUC 1.0). Hypermethylation within these loci was found exclusively in LCM fallopian tube epithelia from women with STIC lesions, but not in cancer-free fallopian tubes.Conclusions:A panel of methylation biomarkers can be used to accurately identify HGSOC, even at precursor stages of the disease.
Validation of miR-31-3p Expression to Predict Cetuximab Efficacy When Used as First-Line Treatment in RAS Wild-Type Metastatic Colorectal Cancer
Authors: Laurent-Puig Pierre , Grisoni Marie-Lise , Heinemann Volker , Liebaert François , Neureiter Daniel , Jung Andreas , Montestruc François , Gaston-Mathe Yann , Thiébaut Raphaële , Stintzing Sebastian 
Published: August 2018

Abstract

Purpose:
MiR-31-3p expression has been shown to be associated with response to anti-EGFR therapy. We investigated the predictive role of this biomarker in the FIRE-3 study population, including its ability to differentiate outcomes between patients receiving anti-EGFR and anti-VEGF therapy.

Experimental Design:
MiR-31-3p expression was measured in primary tumors obtained from 340 patients with RAS WT mCRC enrolled in the FIRE-3 Trial. This included 164 patients randomized to receive FOLFIRI plus cetuximab (FOLFIRI+Cetux) and 176 to FOLFIRI plus bevacizumab (FOLFIRI+Beva). Patients were divided into subgroups defined by low or high miR-31-3p expression using a prespecified cut-off and by treatment arm. Analyses were performed to assess treatment efficacy by subgroup. Overall survival (OS) and progression-free survival (PFS) were analyzed using Kaplan–Meier curves and Cox regression models. Investigator-assessed objective response (iOR), early tumor shrinkage at 6 weeks (ETS), and centrally reviewed objective response (cOR) were analyzed using logistic regression models. The predictive value of miR-31-3p expression level was assessed through a treatment interaction test using multivariate models adjusted for potential confounding factors.

Results:
Low miR-31-3p expressers benefited from cetuximab compared with bevacizumab for PFS [HR, 0.74; 95% confidence interval (CI), 0.55–1.00; P = 0.05], OS (HR, 0.61; 95% CI, 0.41–0.88; P &lt; 0.01), iOR (OR, 4.0; 95% CI, 1.9–8.2; P &lt; 0.01), ETS (OR, 4.0; 95% CI, 2.1–7.7; P &lt; 0.01 and cOR (OR, 4.9; 95% CI, 2.3–10.5; P &lt; 0.01) in multivariate analyses. There was no difference in outcomes for high expressers between treatment arms. MiR-31-3p expression level was predictive of treatment effect for PFS (P = 0.03), OS (P = 0.05), iOR (P = 0.02), ETS (P = 0.04), and cOR (P &lt; 0.01).

Conclusions:
MiR-31-3p expression level was validated as a predictive biomarker of cetuximab therapy efficacy for patients with RAS WT mCRC.
Biochemical and Epigenetic Insights into L-2-Hydroxyglutarate, a Potential Therapeutic Target in Renal Cancer
Authors: Shelar Sandeep , Shim Eun-Hee , Brinkley Garrett J. , Kundu Anirban , Carobbio Francesca , Poston Tyler , Tan Jubilee , Parekh Vishwas , Benson Daniel , Crossman David K. , Buckhaults Phillip J. , Rakheja Dinesh , Kirkman Richard , Sato Yusuke , Ogawa Seishi , Dutta Shilpa , Velu Sadanandan E. , Emberley Ethan , Pan Alison , Chen Jason , Huang Tony , Absher Devin , Becker Anja , Kunick Conrad , Sudarshan Sunil 
Published: August 2018

Abstract

Purpose:
Elevation of L-2-hydroxylgutarate (L-2-HG) in renal cell carcinoma (RCC) is due in part to reduced expression of L-2-HG dehydrogenase (L2HGDH). However, the contribution of L-2-HG to renal carcinogenesis and insight into the biochemistry and targets of this small molecule remains to be elucidated.

Experimental Design:
Genetic and pharmacologic approaches to modulate L-2-HG levels were assessed for effects on in vitro and in vivo phenotypes. Metabolomics was used to dissect the biochemical mechanisms that promote L-2-HG accumulation in RCC cells. Transcriptomic analysis was utilized to identify relevant targets of L-2-HG. Finally, bioinformatic and metabolomic analyses were used to assess the L-2-HG/L2HGDH axis as a function of patient outcome and cancer progression.

Results:
L2HGDH suppresses both in vitro cell migration and in vivo tumor growth and these effects are mediated by L2HGDH's catalytic activity. Biochemical studies indicate that glutamine is the predominant carbon source for L-2-HG via the activity of malate dehydrogenase 2 (MDH2). Inhibition of the glutamine-MDH2 axis suppresses in vitro phenotypes in an L-2-HG–dependent manner. Moreover, in vivo growth of RCC cells with basal elevation of L-2-HG is suppressed by glutaminase inhibition. Transcriptomic and functional analyses demonstrate that the histone demethylase KDM6A is a target of L-2-HG in RCC. Finally, increased L-2-HG levels, L2HGDH copy loss, and lower L2HGDH expression are associated with tumor progression and/or worsened prognosis in patients with RCC.

Conclusions:
Collectively, our studies provide biochemical and mechanistic insight into the biology of this small molecule and provide new opportunities for treating L-2-HG–driven kidney cancers.
Comprehensive Genomic Profiling of Patient-matched Head and Neck Cancer Cells: A Preclinical Pipeline for Metastatic and Recurrent Disease
Authors: Nisa Lluís , Barras David , Medová Michaela , Aebersold Daniel M. , Medo Matúš , Poliaková Michaela , Koch Jonas , Bojaxhiu Beat , Eliçin Olgun , Dettmer Matthias S. , Angelino Paolo , Giger Roland , Borner Urs , Caversaccio Marco D. , Carey Thomas E. , Ho Liza , McKee Thomas A. , Delorenzi Mauro , Zimmer Yitzhak 
Published: August 2018

AbstractMetastases and tumor recurrence have a major prognostic impact in head and neck squamous cell carcinoma (HNSCC); however, cellular models that comprehensively characterize metastatic and recurrent HNSCC are lacking. To this end, we obtained genomic, transcriptomic, and copy number profiles of the UM-SCC cell line panel, encompassing patient-matched metastatic and recurrent cells. UM-SCC cells recapitulate the most prevalent genomic alterations described in HNSCC, featuring common TP53, PI3K, NOTCH, and Hippo pathway mutations. This analysis identified a novel F977Y kinase domain PIK3CA mutation exclusively present in a recurrent cell line (UM-SCC14B), potentially conferring resistance to PI3K inhibitors. Small proline-rich protein 2A (SPRR2A), a protein involved in epithelial homeostasis and invasion, was one of the most consistently downregulated transcripts in metastatic and recurrent UM-SCC cells. Assessment of SPRR2A protein expression in a clinical cohort of patients with HNSCC confirmed common SPRR2A downregulation in primary tumors (61.9% of cases) and lymph node metastases (31.3%), but not in normal tissue. High expression of SPRR2A in lymph node metastases was, along with nonoropharyngeal location of the primary tumor, an independent prognostic factor for regional disease recurrence after surgery and radiotherapy (HR 2.81; 95% CI, 1.16–6.79; P = 0.02). These results suggest that SPRR2A plays a dual role in invasion and therapeutic resistance in HNSCC, respectively through its downregulation and overexpression.Implications:The current study reveals translationally relevant mechanisms underlying metastasis and recurrence in HNSCC and represents an adjuvant tool for preclinical research in this disease setting. Underlining its discovery potential this approach identified a PIK3CA-resistant mutation as well as SPRR2A as possible theragnostic markers.
Polarization-Corrected Temperatures for 10-, 19-, 37-, and 89-GHz Passive Microwave Frequencies
Authors: Cecil Daniel J. , Chronis Themis 
Published: August 2018

AbstractCoefficients are derived for computing the polarization-corrected temperature (PCT) for 10-, 19-, 37- and 89-GHz (and similar) frequencies, with applicability to satellites in the Global Precipitation Measurement mission constellation and their predecessors. PCTs for 10- and 19-GHz frequencies have been nonexistent or seldom used in the past; developing those is the main goal of this study. For 37 and 89 GHz, other formulations of PCT have already become well established. We consider those frequencies here in order to test whether the large sample sizes that are readily available now would point to different formulations of PCT. The purpose of the PCT is to reduce the effects of surface emissivity differences in a scene and draw attention to ice scattering signals related to precipitation. In particular, our intention is to develop a PCT formula that minimizes the differences between land and water surfaces, so that signatures resulting from deep convection are not easily confused with water surfaces. The new formulations of PCT for 10- and 19-GHz measurements hold promise for identifying and investigating intense convection. Four examples are shown from relevant cases. The PCT for each frequency is effective at drawing attention to the most intense convection, and removing ambiguous signals that are related to underlying land or water surfaces. For 37 and 89 GHz, the older formulations of PCT from the literature yield generally similar values as ours, with the differences mainly being a few kelvins over oceans. An optimal formulation of PCT can depend on location and season; results are presented here separated by latitude and month.
Potential Cytochrome P450 Drug‐Drug Interactions among Pediatric Patients Undergoing Tonsillectomy
Authors: Faria John , Solverson Matthew , Faria Madlin , Benoit Margo , McCormick Michael 
Published: August 2018

ObjectiveTo evaluate the frequency of potential cytochrome P450 (CYP) drug‐drug interactions affecting opioid metabolism among children undergoing adenotonsillectomy.Study DesignCase series with chart review.SettingTertiary care children's hospital.Subjects and MethodsA retrospective review was conducted of 1000 patients undergoing adenotonsillectomy at Children's Hospital of Wisconsin. The discharge medication reconciliation form was reviewed. Each patient's list of medications was compared with various published sources to determine whether medications causing CYP inhibition or induction were present.ResultsThere were 157 unique medications with systemic absorption given postoperatively to this patient cohort. Eight percent of patients were on at least 5 medications after surgery other than their posttonsillectomy medication. The 5 most commonly prescribed medications were albuterol, cetirizine, fluticasone nasal spray, montelukast, and polyethylene glycol. Per a list of known CYP inducers and inhibitors published by the US Food and Drug Administration, 30 (3%) patients were on a medication that inhibited CYP3A4; 1 patient was on a CYP3A4 inducer, prednisone; and 46 (5%) patients were on a medication that inhibited CYP2D6.ConclusionsA small fraction of patients undergoing adenotonsillectomy are on medications that potentially alter the metabolism of opioid pain medications. Given the narrow therapeutic index of opioids and increased sensitivity to opioids among patients with obstructive sleep apnea, drug‐drug interactions need to be considered as they relate to whether an opioid is appropriate and at what dose.
A qualitative study of patient-centered goal-setting in geriatric rehabilitation: patient and professional perspectives
Authors: van Seben Rosanne , Smorenburg Susanne M , Buurman Bianca M 
Published: August 2018

Objective: To characterize how rehabilitation goals of older patients change over time and to explore professionals’ attitudes toward patient-centered goal-setting and their perspectives on rehabilitation goals. Design: Qualitative interview study. Setting: Three geriatric rehabilitation centers. Subjects: Ten patients (aged ⩾ 80), who had recently received inpatient geriatric rehabilitation, and seven professionals were purposively recruited. Methods: Semi-structured interviews. Patients were interviewed in the third or fourth week after discharge from inpatient rehabilitation, to reflect on their inpatient goals and to investigate long-term goals now that they were at home. A thematic analysis was performed. Results: During inpatient rehabilitation, participants’ main goals were regaining independence in self-care activities and going home. Post-discharge, patients were not at their baseline functioning level. Rehabilitation goals appeared to shift over time, and once at home, patients formulated more ambitious rehabilitation goals that were related to regaining full independence and being able to perform activities. Although professionals thought goal-setting together with the patient is important, they also stated that older individuals often are either unable to formulate goals or they set unrealistic ones. In addition, professionals indicated that goals have to be related to discharge criteria, such as performing basic self-care activities, and rehabilitation revolves around getting patients ready for discharge. Conclusion: During inpatient rehabilitation, patient goals are related to going home. After discharge, patients have ambitious goals, related to their premorbid functioning level. Rehabilitation services should distinguish between goals that are important while patients are inpatient and goals that are important after discharge.
Thyrotropin levels and severity of symptoms in migraine patients of tertiary headache center
Authors: Starikova Natalia L , Baidina Tatiana V , Kalashnikova Tatiana P 
Published: August 2018

Background The role of thyroid regulation in migraine is poorly understood, and data is contradictory. Objective To study the possible association of clinical features of migraine with patients’ thyroid function. Patients and methods One hundred and thirty migraine patients of a tertiary headache center took part in an open-label, cross-sectional comparative study. The Migraine Disability Assessment questionnaire, Spielberger State-Trait Anxiety Inventory, Beck Depression Inventory, Vanderbilt’s Questionnaire of Pain Management, Gothenburg Quality of Life Questionnaire and Migraine-Specific Quality of Life questionnaire were used. The effectiveness of the attacks’ therapy was assessed according to the Migraine Assessment of Current Therapy questionnaire. Levels of thyrotropine (thyroid stimulating hormone), thyroxine, and triiodothyronine were studied by standard immune chemiluminescent method using the Immulite-2000 set. Results An inverse correlation between levels of thyroid stimulating hormone in serum and duration of headache attacks was revealed. The effectiveness of abortive therapy for attacks showed a statistically significant positive correlation with thyroid stimulating hormone level. Quality of life measured by a general quality of life questionnaire, as well as the functional and social indices of a migraine-specific questionnaire, showed direct correlation with serum thyroid stimulating hormone. Conclusion These results show an association of a more severe clinical course of migraine with lower thyroid stimulating hormone levels.
Effects and mechanisms of differently cued and non-cued motor imagery in people with multiple sclerosis: A randomised controlled trial
Authors: Seebacher Barbara , Kuisma Raija , Glynn Angela , Berger Thomas 
Published: August 2018

Background: Walking impairment and fatigue are prevalent symptoms in people with multiple sclerosis (PwMS). Motor imagery (MI) with rhythmic auditory cueing improved walking in PwMS, but so far, the underlying mechanisms are not fully explored. Objective: This study investigated the effects and mechanisms of differently cued and non-cued MI on walking, fatigue and quality of life (QoL) in PwMS. Methods: A total of 60 PwMS with mild to moderate disability were randomised to music- and verbally cued MI (MVMI), music-cued MI (MMI) or MI. Participants practised cued or non-cued MI of walking for 17 minutes, six times per week for 4 weeks at home. Primary outcomes were walking speed (timed 25-foot walk) and walking distance (6-minute walk test). Results: A total of 59 participants completed the study. All interventions induced significant improvements in walking speed and distance, while MVMI was superior. After cued MI, fatigue and QoL significantly improved, with greatest changes seen after MVMI. All participants showed high MI ability. Post-intervention, sensorimotor synchronisation (SMS) was significantly more accurate after cued MI. Conclusion: All interventions significantly improved walking. MVMI was superior in improving walking, fatigue and QoL. Results suggest that MI and SMS were mechanisms of action.
Biomechanical study of optimum anchorage in dome-shaped high tibial osteotomy
Authors: Takahashi Toshiaki , Takahashi Manabu , Yamamoto Haruyasu , Miura Hiromasa 
Published: August 2018

Purpose: There has been no report to date on any biomechanical study regarding the strength of fixation at the osteotomy site in dome-shaped high tibial osteotomy (HTO). In this study, we evaluated the biomechanical strength of a spacer that we improved and determined the medial site of HTO. Methods: HTO correction angles of 15° and 20° were used in all experiments, which were performed on lower leg specimens from pigs ( n = 12). The osteotomy site was fixed by a locking plate and screws with a spacer. Compression (600 N/min until 1100 N) and extended cyclic loading (200 cycles at 1000–2000 N) were performed to compare initial displacements in HTO specimens with and without spacers. Results: The reduction ratios of displacement with and without spacers at HTO correction angles of 15° and 20° were 37% and 27%, respectively. No effect of the spacer at the correction angle of 15° was observed in the cyclic loading; however, the maximum displacement and amplitude were reduced with the spacer at the correction angle of 20°. Conclusions and clinical relevance: When the HTO correction angle is small, the effect of the spacer is uncertain. However, the spacer is effective at an HTO correction angle of 20°.
A carboxymethyl dextran-based polymeric conjugate as the antigen carrier for cancer immunotherapy
Authors: Shin Jung Min , Song Seok Ho , Vijayakameswara Rao N. , Lee Eun Sook , Ko Hyewon , Park Jae Hyung 
Published: August 2018

Abstract

Background
Antigen-specific cytotoxic T lymphocytes (CTLs), which eliminate target cells bearing antigenic peptides presented by surface major histocompatibility complex (MHC) class I molecules, play a key role in cancer immunotherapy. However, the majority of tumors are not immunologically rejected since they express self-antigens which are not recognized by CTLs as foreign. To foreignize these tumors for CTL-mediated immunological rejection, it is essential to develop carriers that can effectively deliver foreign antigens to cancer cells.

Methods
A polymeric conjugate, composed of a carboxymethyl dextran (CMD) as the backbone and ovalbumin (OVA) as a model foreign antigen, was prepared to investigate its potential as the antigen carrier for cancer immunotherapy.

Results
An in vitro cellular uptake study showed that the conjugate was successfully taken up by TC-1 cervical cancer cells. When CMD-OVA was systemically administered to tumor-bearing mice, the strong fluorescence signal was observed at the tumor site over the whole period of time period, suggesting high tumor targetability of the conjugate. Compared to free OVA, CMD-OVA induced significantly higher antigen presentation at the tumor site.

Conclusions
The CMD-OVA conjugate can effectively deliver the antigen to the tumor site, implying its high potential as the antigen carrier for cancer immunotherapy.