bluuebunny/crossref_metadata_2025_split huggingface dataset:
Nottingham Clinico-Pathological Response Index (NPRI) after Neoadjuvant Chemotherapy (Neo-ACT) Accurately Predicts Clinical Outcome in Locally Advanced Breast Cancer
Authors: Abdel-Fatah Tarek M. , Ball Graham , Lee Andrew H.S. , Pinder Sarah , MacMilan R. Douglas , Cornford Eleanor , Moseley Paul M. , Silverman Rafael , Price James , Latham Bruce , Palmer David , Chan Arlene , Ellis Ian O. , Chan Stephen Y.T. 
Published: December 2014

Abstract
Purpose: There is a need to identify more sensitive clinicopathologic criteria to assess the response to neoadjuvant chemotherapy (Neo-ACT) and guide subsequent adjuvant therapy.
Experimental Design: We performed a clinicopathologic assessment of 426 patients who had completed Neo-ACT for locally advanced breast cancer (LABC) with a median follow-up of 70 months. Patients were divided into a training set treated with anthracycline combination chemotherapy (n = 172); an internal validation set treated with anthracycline and taxane (n = 129); and an external validation set treated with anthracycline with or without taxane (n = 125).
Results: A multivariate Cox regression model demonstrated the absence of fibrosis, presence of lymphovascular invasion, increasing number of lymph node metastases, and administration of hormone therapy were significantly associated with short breast cancer–specific survival (BCSS) and disease-free survival (DFS); Ps &lt; 0.01, while reduction of tumor size was associated with DFS (P = 0.022). Nottingham Clinico-Pathological Response Indexes (NPRI) were calculated, and four prognostic groups (NPRI-PG) were identified. Patients in prognostic group 2 (NPRI-PG2) for BCSS (66 of 172; 38.4%) have the same prognosis as those who achieved pathologic complete response (pCR; NPRI-PG1; 15%). Receiver-operating characteristic (ROC) curves indicated that the NPRI outperformed the currently used prognostic factors and adding the NPRI improved their performance as a predictor for both BCSS (area under the curve [AUC], 0.88) and DFS (AUC, 0.87).
Conclusions: The NPRI predicts BCSS and DFS, with a higher sensitivity than pCR. The NPRI can also improve the sensitivity and specificity of clinicopathologic response as a study endpoint, for assessing response to Neo-ACT, and can serve as a valuable tool for the discovery of future predictive molecular markers. Clin Cancer Res; 21(5); 1052–62. ©2014 AACR.
Gene Expression Markers of Efficacy and Resistance to Cetuximab Treatment in Metastatic Colorectal Cancer: Results from CALGB 80203 (Alliance)
Authors: Cushman Stephanie M. , Jiang Chen , Hatch Ace J. , Shterev Ivo , Sibley Alexander B. , Niedzwiecki Donna , Venook Alan P. , Owzar Kouros , Hurwitz Herbert I. , Nixon Andrew B. 
Published: December 2014

Abstract
Purpose: Formalin-fixed, paraffin-embedded tumor samples from CALGB 80203 were analyzed for expression of EGFR axis–related genes to identify prognostic or predictive biomarkers for cetuximab treatment.
Patients and Methods: Patients (238 total) with first-line metastatic colorectal cancer (mCRC) were randomized to FOLFOX or FOLFIRI chemotherapy ± cetuximab. qRT-PCR analyses were conducted on tissues from 103 patients at baseline to measure gene expression levels of HER-related genes, including amphiregulin (AREG), betacellulin (BTC), NT5E (CD73), DUSP4, EGF, EGFR, epigen (EPGN), epiregulin (EREG), HBEGF, ERBB2 (HER2), ERBB3 (HER3), ERBB4 (HER4), PHLDA1, and TGFA. The interactions between expression levels and treatment with respect to progression-free survival (PFS) and overall survival (OS) were modeled using multiplicative Cox proportional hazards models.
Results: High tumor mRNA levels of HER2 [hazard ratio (HR), 0.64; P = 0.002] and EREG (HR, 0.89; P = 0.016) were prognostic markers associated with longer PFS across all patients. HER3 and CD73 expression levels were identified as potential predictive markers of benefit from cetuximab. In KRAS wild-type (WT) tumors, low HER3 expression was associated with longer OS from cetuximab treatment, whereas high HER3 expression was associated with shorter OS from cetuximab treatment (chemo + cetuximab: HR, 1.15; chemo-only: HR, 0.48; Pinteraction = 0.029). High CD73 expression was associated with longer PFS from cetuximab treatment in patients with KRAS-WT (chemo + cetuximab: HR, 0.91; chemo-only: HR, 1.57; Pinteraction = 0.026) and KRAS-mutant (Mut) tumors (chemo + cetuximab: HR, 0.80; chemo-only: HR, 1.29; P = 0.025).
Conclusions: Gene expression of HER3 and CD73 was identified as a potential predictive marker for cetuximab. These data implicate HER axis signaling and immune modulation as potential mechanisms of cetuximab action and sensitivity. Clin Cancer Res; 21(5); 1078–86. ©2014 AACR.
Interactions of Multitargeted Kinase Inhibitors and Nucleoside Drugs: Achilles Heel of Combination Therapy?
Authors: Damaraju Vijaya L. , Kuzma Michelle , Mowles Delores , Cass Carol E. , Sawyer Michael B. 
Published: December 2014

AbstractMultitargeted tyrosine kinase inhibitors (TKI) axitinib, pazopanib, and sunitinib are used to treat many solid tumors. Combination trials of TKIs with gemcitabine, a nucleoside anticancer drug, in pancreas, renal, lung, ovarian, and other malignancies resulted in little benefit to patients. TKI interactions with human nucleoside transporters (hNT) were studied by assessing inhibition of [3H]uridine uptake in yeast producing recombinant hNTs individually and in cultured human cancer cell lines. Axitinib, pazopanib, and sunitinib inhibited hENT1 at low micromolar concentrations. In A549, AsPC-1, and Caki-1 cells, [3H]uridine, [3H]thymidine, [3H]gemcitabine, and [3H]fluorothymidine (FLT) accumulation was blocked by all three TKIs. Pazopanib &gt; axitinib ≥ sunitinib inhibited hENT1 with IC50 values of 2, 7, and 29 μmol/L, respectively, leading to reduced intracellular gemcitabine and FLT accumulation. Pretreatment or cotreatment of Caki-1 cells with TKIs reduced cellular accumulation of [3H]nucleosides, suggesting that TKI scheduling with nucleoside drugs would influence cytotoxicity. In combination cytotoxicity experiments that compared sequential versus simultaneous addition of drugs in Caki-1 cells, cytotoxicity was greatest when gemcitabine was added before TKIs. In clinical settings, TKI inhibitor concentrations in tumor tissues are sufficient to inhibit hENT1 activity, thereby reducing nucleoside chemotherapy drug levels in cancer cells and reducing efficacy in combination schedules. An additional unwanted interaction may be reduced FLT uptake in tumor tissues that could lead to aberrant conclusions regarding tumor response. Mol Cancer Ther; 14(1); 236–45. ©2014 AACR.
DNA-Directed Polymerase Subunits Play a Vital Role in Human Telomeric Overhang Processing
Authors: Diotti Raffaella , Kalan Sampada , Matveyenko Anastasiya , Loayza Diego 
Published: December 2014

Abstract
Telomeres consist of TTAGGG repeats bound by the shelterin complex and end with a 3′ overhang. In humans, telomeres shorten at each cell division, unless telomerase (TERT) is expressed and able to add telomeric repeats. For effective telomere maintenance, the DNA strand complementary to that made by telomerase must be synthesized. Recent studies have discovered a link between different activities necessary to process telomeres in the S phase of the cell cycle to reform a proper overhang. Notably, the human CST complex (CTC1/STN1/TEN1), known to interact functionally with the polymerase complex (POLA/primase), was shown to be important for telomere processing. Here, focus was paid to the catalytic (POLA1/p180) and accessory (POLA2/p68) subunits of the polymerase, and their mechanistic roles at telomeres. We were able to detect p68 and p180 at telomeres in S-phase using chromatin immunoprecipitation. We could also show that the CST, shelterin, and polymerase complexes interact, revealing contacts occurring at telomeres. We found that the polymerase complex could associate with telomerase activity. Finally, depletion of p180 by siRNA led to increased overhang amounts at telomeres. These data support a model in which the polymerase complex is important for proper telomeric overhang processing through fill-in synthesis, during S phase. These results shed light on important events necessary for efficient telomere maintenance and protection.
Implications: This study describes the interplay between DNA replication components with proteins that associate with chromosome ends, and telomerase. These interactions are proposed to be important for the processing and protection of chromosome ends. Mol Cancer Res; 13(3); 402–10. ©2014 AACR.
Winter Climate Extremes over the Northeastern United States and Southeastern Canada and Teleconnections with Large-Scale Modes of Climate Variability*
Authors: Ning Liang , Bradley Raymond S. 
Published: December 2014

Abstract
The relationship between winter climate extremes across the northeastern United States and adjacent parts of Canada and some important modes of climate variability are examined to determine how these circulation patterns are related to extreme events. Linear correlations between 15 extreme climate indices related to winter daily precipitation, maximum and minimum temperature, and three dominant large-scale patterns of climate variability [the North Atlantic Oscillation (NAO), Pacific–North American (PNA) pattern, and El Niño–Southern Oscillation (ENSO)] were analyzed for the period 1950–99. The mechanisms behind these teleconnections are analyzed by applying composite analysis to the geopotential height, sea level pressure (SLP), moisture flux, and wind fields. Pressure anomalies and associated airflow patterns related with the different modes of climate variability explain the patterns of temperature and precipitation extremes across the region. The responses of the daily scale climate extremes to the seasonally averaged large-scale circulation patterns are achieved through shifts in the probability distributions.
Intrinsic Variability of Sea Level from Global Ocean Simulations: Spatiotemporal Scales
Authors: Sérazin Guillaume , Penduff Thierry , Grégorio Sandy , Barnier Bernard , Molines Jean-Marc , Terray Laurent 
Published: December 2014

AbstractIn high-resolution ocean general circulation models (OGCMs), as in process-oriented models, a substantial amount of interannual to decadal variability is generated spontaneously by oceanic nonlinearities: that is, without any variability in the atmospheric forcing at these time scales. The authors investigate the temporal and spatial scales at which this intrinsic oceanic variability has the strongest imprints on sea level anomalies (SLAs) using a ° global OGCM, by comparing a “hindcast” driven by the full range of atmospheric time scales with its counterpart forced by a repeated climatological atmospheric seasonal cycle. Outputs from both simulations are compared within distinct frequency–wavenumber bins. The fully forced hindcast is shown to reproduce the observed distribution and magnitude of low-frequency SLA variability very accurately. The small-scale (L < 6°) SLA variance is, at all time scales, barely sensitive to atmospheric variability and is almost entirely of intrinsic origin. The high-frequency (mesoscale) part and the low-frequency part of this small-scale variability have almost identical geographical distributions, supporting the hypothesis of a nonlinear temporal inverse cascade spontaneously transferring kinetic energy from high to low frequencies. The large-scale (L > 12°) low-frequency variability is mostly related to the atmospheric variability over most of the global ocean, but it is shown to remain largely intrinsic in three eddy-active regions: the Gulf Stream, Kuroshio, and Antarctic Circumpolar Current (ACC). Compared to its ¼° predecessor, the authors’ ° OGCM is shown to yield a stronger intrinsic SLA variability, at both mesoscale and low frequencies.
Spectral Kurtosis–Based Method for Weak Target Detection in Sea Clutter by Microwave Coherent Radar
Authors: Jin Yan , Chen Zezong , Fan Lingang , Zhao Chen 
Published: December 2014

AbstractA new method is proposed to detect small targets embedded in sea clutter for land-based microwave coherent radar using spectral kurtosis as a signature from radar data. It is executed according to the following procedures. First, the echoes of radar from each range gate are processed by the technique of short-time Fourier transform. Then, the kurtosis of each Doppler channel is estimated from the time–Doppler spectra. Last, the spectral kurtosis is compared to a threshold to determine whether a target exists. The proposed method is applied to measured datasets of different sea conditions from slight to moderate. The signal from a small boat is detected successfully. Furthermore, the detection performance of the proposed method is analyzed by the way of Monte Carlo simulation. It demonstrates that the spectral kurtosis–based detector works well for weak target detection when the target’s Doppler frequency is beyond the strong clutter region.
Performance investigation of liquid-to-air membrane energy exchanger under low solution/air heat capacity rates ratio conditions
Authors: Kassai Miklos , Simonson Carey J 
Published: December 2014

Liquid-to-air membrane energy exchanger is a novel membrane base energy exchanger, which allows both heat and moisture transfer between air and a salt solution. The heat and mass transfer performance of a single one is significantly dependent on two dimensionless parameters: number of heat transfer units and the ratio of heat capacity rates between solution flow and air flow (Cr*). The performance of liquid-to-air membrane energy exchanger under high Cr* (i.e. Cr* ≥ 1) has been comprehensively investigated experimentally and numerically in previous research. In this study, the effectiveness of a small-scale liquid-to-air membrane energy exchanger under low Cr* conditions (i.e. Cr* < 1) is experimentally tested. Good agreement between the experimental and numerical results is achieved under low Cr* cases. Practical application: The ideal energy exchanger is one that can transfer both heat and moisture because during hot and humid conditions such an exchanger is capable of transferring up to four times as much energy as an exchanger that can transfer sensible heat only. It is beneficial if the exchanger can transfer heat and moisture also between remote supply and exhaust airstreams, as this may minimize the ducting required and reduces contaminant transfer from one airstream to the other. This is very important for applications such as hospitals, laboratories, and manufacturing facilities, where slight cross contamination can cause serious health effects.
Comparison of 4D CT, Ultrasonography, and 99mTc Sestamibi SPECT/CT in Localizing Single‐Gland Primary Hyperparathyroidism
Authors: Suh Yong Joon , Choi June Young , Kim Su‐jin , Chun In Kook , Yun Tae Jin , Lee Kyu Eun , Kim Ji‐hoon , Cheon Gi Jeong , Youn Yeo‐Kyu 
Published: December 2014

ObjectiveThe present study was designed to evaluate 4D computerized tomography (CT) as a means of localizing abnormal parathyroid glands in primary hyperparathyroidism (HPT).Study DesignCase series with expertized image review.SettingTertiary care hospital.Subjects and MethodsA total of 38 patients were recruited for study, all of whom had undergone focused parathyroidectomy for single‐lesion primary HPT between June 2011 and September 2013. In each patient, 3 imaging procedures were performed: cervical ultrasonography (US), 99mTc‐sestamibi SPECT/CT (SeS), and 4D CT. Collective imaging data were blindly reviewed and compared.Results4D CT outperformed US and SeS in terms of sensitivity (P =. 27), specificity (P =. 01), positive predictive value (PPV) (P <. 01), negative predictive value (NPV) (P =. 19), and accuracy (P <. 01). In 7.9% (3/38) of patients, 4D CT provided specific anatomic information that was unaffordable by US and SeS. Localization by 4D CT correlated with tissue parathyroid hormone level (P =. 02), maximum diameter (P =. 01), and volume (P <. 01) of abnormal parathyroid glands.Conclusion4D CT proved helpful in localizing target parathyroid glands of primary HPT that were missed by traditional imaging.
Effects of whole body vibration on pain, stiffness and physical functions in patients with knee osteoarthritis: a systematic review and meta-analysis
Authors: Wang Pu , Yang Xiaotian , Yang Yonghong , Yang Lin , Zhou Yujing , Liu Chuan , Reinhardt Jan D , He Chengqi 
Published: December 2014

Objective: To assess the effects of whole body vibration for pain, stiffness and physical functions in patients with knee osteoarthritis. Data sources: We searched the Cochrane Central Register of Controlled Trials, MEDLINE, Physiotherapy Evidence Database (PEDro) and EMBASE (up to October 2014) to identify relevant randomized controlled trials. The outcome measures were pain, stiffness and physical functions. Review methods: Two investigators identified eligible studies and extracted data independently. The PEDro score was used to evaluate the methodological quality of the selected studies. Standard mean differences (SMDs) and 95% confidence intervals (CIs) were calculated, and heterogeneity was assessed using the I2 test. Results: A total of five randomized controlled trials involving 170 patients with knee osteoarthritis met the inclusion criteria. Only four studies involving 144 patients were deemed to be good quality trials (PEDro score = 6–7). Meta-analysis revealed that whole body vibration has a signiﬁcant treatment effect in Western Ontario and McMaster Universities index physical function score (SMD = −0.72 points, 95% CI = −1.14 to −0.30, P = 0.0008), 12 weeks whole body vibration improved the 6-minute walk test (SMD 1.15 m, 95% CI 0.50 to 1.80, P = 0.0006) and balance (SMD = −0.78 points, 95% CI −1.40 to −0.16, P = 0.01). Whole body vibration was not associated with a signiﬁcant reduction in Western Ontario and McMaster Universities index pain and stiffness score. Conclusion: Eight-week and 12-week whole body vibration is beneficial for improving physical functions in patients with knee osteoarthritis and could be included in rehabilitation programs.
Change in physiological variables in the last 2 weeks of life: An observational study of hospital in-patients with cancer
Authors: Taylor Paul , Crouch Simon , Howell Debra A , Dowding Dawn W , Johnson Miriam J 
Published: December 2014

Background: Recognising dying remains a difficult clinical skill which has gained increasing importance in the United Kingdom since the Neuberger review. Clinical and research methods exist to aid recognition of dying but do not exhibit the level of accuracy required for such an important decision. Aim: To explore change in key clinical parameters as cancer patients near the end of life. Design: This is a retrospective cohort study of terminally ill patients. Data were collected from hospital case-notes. Case-note data were analysed using multilevel modelling to explore absolute values and rates of change of given variables. Setting/participants: Hospital in-patients who died from solid-tumour malignancies within a 3-month period in 2009 formed the cohort. The setting was an acute hospital trust in the North of England. Results: A total of 15,337 data points from the case-notes of 102 patients were analysed. There was a clinically and statistically significant deterioration in respiratory function and renal function over the last 2 weeks of life. Heart rate and serum sodium also changed but did not vary greatly from normal limits. White cell parameters, haemoglobin and albumin showed evidence for change over longer periods. Conclusion: Results demonstrate statistically and clinically significant change in routinely measured respiratory and renal function variables during the final 2 weeks of life in people dying with cancer. Although useful in acute early warning scores, in a terminally ill patient, relative haemodynamic stability should not be interpreted as reassuring. Further work is needed to understand how these findings apply to the individual or inform other prognostic work.
Adapting to domiciliary non-invasive ventilation in chronic obstructive pulmonary disease: A qualitative interview study
Authors: Gale Nicola K , Jawad Maryam , Dave Chirag , Turner Alice M 
Published: December 2014

Background: Domiciliary non-invasive ventilation may be used in palliative care of patients with chronic obstructive pulmonary disease, although there is uncertainty regarding effect on quality of life. Aim: Explore experiences of domiciliary non-invasive ventilation in chronic obstructive pulmonary disease, to understand decision-making processes and improve future palliative care. Design: Qualitative interview study, based on constructivist grounded theory, and using the framework method for data management and analysis. Participants: 20 chronic obstructive pulmonary disease patients, 4 carers and 15 healthcare professionals. Results: Most patients had very severe chronic obstructive pulmonary disease. Data were categorised into four domains – clinical, technical, socio-economic and experiential. Healthcare professionals felt uncertain regarding clinical evidence, emphasising social support and tolerance as deciding factors in non-invasive ventilation use. Conversely, patients reported symptomatic benefit, which generally outweighed negative experiences and led to continued use. Healthcare professionals felt that patients chose to be on non-invasive ventilation; however, most patients felt that they had no choice as healthcare professionals recommended non-invasive ventilation or their poor health mandated it. Conclusions: Our study identifies ‘adapting to non-invasive ventilation’ as the central process enabling long-term use in palliative care, although the way in which this is approached by healthcare professionals and patients does not always converge. We present ideas emerging from the data on potential interventions to improve patient experience and adaptation.
Bacterial loads of Ureaplasma parvum contribute to the development of inflammatory responses in the male urethra
Authors: Deguchi Takashi , Shimada Yasushi , Horie Kengo , Mizutani Kohsuke , Seike Kensaku , Tsuchiya Tomohiro , Yokoi Shigeaki , Yasuda Mitsuru , Ito Shin 
Published: December 2014

Ureaplasma parvum, which has been recognised as a coloniser in the male urethra, is detected in some men with non-gonococcal urethritis. In this study, we quantified the 16 S rRNA genes of U. parvum by a real-time polymerase chain reaction-based assay in first-voided urine from 15 symptomatic and 38 asymptomatic men who were positive only for U. parvum. We also determined the leukocyte counts by automated quantitative urine particle analysis in their first-voided urine. Positive correlations were observed between copies of the 16 S rRNA genes of U. parvum/ml and the leukocyte counts/µl in first-voided urine ( p = 0.0019). The loads of ≥104 copies of the 16 S rRNA gene/ml, corresponding to ≥5 × 103 cells of U. parvum/ml, were significantly associated with the presence of ≥12.5 leukocytes/µl in first-voided urine that might document the presence of inflammatory responses in the urethra. However, a large portion of the subjects (83.0%) had bacterial loads of <5 × 103 cells of U. parvum/ml, and 79.5% of them showed <12.5 leukocytes/µl. The ambiguity of the pathogenic role of U. parvum in non-gonococcal urethritis could, in part, be due to its low bacterial loads, which might not give rise to inflammatory responses in the male urethra.