bluuebunny/crossref_metadata_2025_split huggingface dataset:
Enhancement of Nab-Paclitaxel Antitumor Activity through Addition of Multitargeting Antiangiogenic Agents in Experimental Pancreatic Cancer
Authors: Awasthi Niranjan , Zhang Changhua , Schwarz Anna M. , Hinz Stefan , Schwarz Margaret A. , Schwarz Roderich E. 
Published: March 2014

Abstract
Nanoparticle albumin–bound paclitaxel (nab-paclitaxel, NPT) has recently shown efficacy in pancreatic ductal adenocarcinoma (PDAC). Targeting tumor angiogenesis is a sensible combination therapeutic strategy for cancer, including PDAC. We tested the hypothesis that NPT response in PDAC can be enhanced by the mechanistically different antiangiogenic agents bevacizumab (Bev) or sunitinib (Su), despite its inherently increased tumor penetration and drug delivery. Compared with controls (19 days), median animal survival was increased after NPT therapy (32 days, a 68% increase, P = 0.0008); other regimens with enhanced survival were NPT+Bev (38 days, a 100% increase, P = 0.0004), NPT+Su (37 days, a 95% increase, P = 0.0004), and NPT+Bev+Su (49 days, a 158% increase, P = 0.0001) but not bevacizumab, sunitinib, or Bev+Su therapy. Relative to controls (100 ± 22.8), percentage net local tumor growth was 28.2 ± 23.4 with NPT, 55.6 ± 18 (Bev), 38.8 ± 30.2 (Su), 11 ± 7.2 (Bev+Su), 32.8 ± 29.2 (NPT+Bev), 6.6 ± 10.4 (NPT+Su), and 13.8 ± 12.5 (NPT+Bev+Su). Therapeutic effects on intratumoral proliferation, apoptosis, microvessel density, and stromal density corresponded with tumor growth inhibition data. In AsPC-1 PDAC cells, NPT IC50 was reduced &gt;6-fold by the addition of sunitinib (IC25) but not by bevacizumab. In human umbilical vein endothelial cells (HUVEC), NPT IC50 (82 nmol/L) was decreased to 41 nmol/L by bevacizumab and to 63 nmol/L by sunitinib. In fibroblast WI-38 cells, NPT IC50 (7.2 μmol/L) was decreased to 7.8 nmol/L by sunitinib, but not by bevacizumab. These findings suggest that the effects of one of the most active cytotoxic agents against PDAC, NPT, can be enhanced with antiangiogenic agents, which clinically could relate to greater responses and improved antitumor results. Mol Cancer Ther; 13(5); 1032–43. ©2014 AACR.
Identification of Transmembrane Protein 98 as a Novel Chemoresistance-Conferring Gene in Hepatocellular Carcinoma
Authors: Ng Kevin Tak-Pan , Lo Chung Mau , Guo Dong Yong , Qi Xiang , Li Chang Xian , Geng Wei , Liu Xiao Bing , Ling Chang Chun , Ma Yuen Yuen , Yeung Wai Ho , Shao Yan , Poon Ronnie Tung-Ping , Fan Sheung Tat , Man Kwan 
Published: March 2014

AbstractChemoresistance is one of the major obstacles in systemic chemotherapy and targeted therapy for patients with advanced hepatocellular carcinoma. To identify novel chemoresistance-associated targets in hepatocellular carcinoma, chemoresistant hepatocellular carcinoma cell lines were established. By comparing the global gene expression profiles between chemoresistant and chemosensitive cell lines, eight novel chemoresistance-associated genes were identified to be significantly associated with the commonly augmented chemoresistance of hepatocellular carcinoma cells. One upregulated candidate named transmembrane protein 98 (TMEM98) was found to be overexpressed in 80 of 118 (67.80%) of patients with hepatocellular carcinoma. TMEM98 mRNA in tumor tissues was significantly higher than nontumor tissues of patients with hepatocellular carcinoma (P &lt; 0.0001). Upregulation of TMEM98 was significantly correlated with advanced tumor stage (P = 0.048), high incidence of early tumor recurrence (P = 0.005), poor overall survival (P = 0.029), and poor disease-free survival (P = 0.011) of patients with hepatocellular carcinoma after hepatectomy. Importantly, upregulation of TMEM98 mRNA in patients with hepatocellular carcinoma who received transarterial chemoembolization (TACE) treatment was significantly higher than in patients without TACE treatment (P = 0.046). Moreover, patients with poor response to TACE treatment had higher degree of TMEM98 upregulation than the responsive patients. In vitro and in vivo studies showed that suppression of TMEM98 in chemoresistant hepatocellular carcinoma cells restored their chemosensitivity, while forced overexpression of TMEM98 enhanced their chemoresistance. The mechanism of TMEM98 in conferring chemoresistance of hepatocellular carcinoma might be possibly through activation of the AKT pathway and deactivation of p53. In conclusion, we identified a panel of novel common chemoresistance-associated genes and demonstrated that TMEM98 is a chemoresistance-conferring gene in hepatocellular carcinoma. Mol Cancer Ther; 13(5); 1285–97. ©2014 AACR.
Characterization of the Novel and Specific PI3Kα Inhibitor NVP-BYL719 and Development of the Patient Stratification Strategy for Clinical Trials
Authors: Fritsch Christine , Huang Alan , Chatenay-Rivauday Christian , Schnell Christian , Reddy Anupama , Liu Manway , Kauffmann Audrey , Guthy Daniel , Erdmann Dirk , De Pover Alain , Furet Pascal , Gao Hui , Ferretti Stephane , Wang Youzhen , Trappe Joerg , Brachmann Saskia M. , Maira Sauveur-Michel , Wilson Christopher , Boehm Markus , Garcia-Echeverria Carlos , Chene Patrick , Wiesmann Marion , Cozens Robert , Lehar Joseph , Schlegel Robert , Caravatti Giorgio , Hofmann Francesco , Sellers William R. 
Published: March 2014

AbstractSomatic PIK3CA mutations are frequently found in solid tumors, raising the hypothesis that selective inhibition of PI3Kα may have robust efficacy in PIK3CA-mutant cancers while sparing patients the side-effects associated with broader inhibition of the class I phosphoinositide 3-kinase (PI3K) family. Here, we report the biologic properties of the 2-aminothiazole derivative NVP-BYL719, a selective inhibitor of PI3Kα and its most common oncogenic mutant forms. The compound selectivity combined with excellent drug-like properties translates to dose- and time-dependent inhibition of PI3Kα signaling in vivo, resulting in robust therapeutic efficacy and tolerability in PIK3CA-dependent tumors. Novel targeted therapeutics such as NVP-BYL719, designed to modulate aberrant functions elicited by cancer-specific genetic alterations upon which the disease depends, require well-defined patient stratification strategies in order to maximize their therapeutic impact and benefit for the patients. Here, we also describe the application of the Cancer Cell Line Encyclopedia as a preclinical platform to refine the patient stratification strategy for NVP-BYL719 and found that PIK3CA mutation was the foremost positive predictor of sensitivity while revealing additional positive and negative associations such as PIK3CA amplification and PTEN mutation, respectively. These patient selection determinants are being assayed in the ongoing NVP-BYL719 clinical trials. Mol Cancer Ther; 13(5); 1117–29. ©2014 AACR.
Long-Term Follow-Up After Catheter Ablation of Paroxysmal Atrial Fibrillation
Authors: Takigawa Masateru , Takahashi Atsushi , Kuwahara Taishi , Okubo Kenji , Takahashi Yoshihide , Watari Yuji , Takagi Katsumasa , Fujino Tadashi , Kimura Shigeki , Hikita Hiroyuki , Tomita Makoto , Hirao Kenzo , Isobe Mitsuaki 
Published: March 2014

Background—
Although catheter ablation (CA) is a standard treatment for atrial fibrillation (AF), its long-term efficacy remains unclear. This study aimed to elucidate the incidences of AF recurrence and of progression from paroxysmal to persistent AF, after CA, in patients with paroxysmal AF.

Methods and Results—

We examined the incidence of AF recurrence and AF progression in 1220 consecutive patients (mean age, 61 years), with symptomatic paroxysmal AF, undergoing CA, based on extensive pulmonary vein isolation and focal ablation for nonpulmonary vein foci. AF recurrence–free survival probabilities at 5 years were 59.4% after the initial CA and 81.1% after the final CA (average, 1.3 procedures). During a median follow-up period of 47.9 (range, 5.3–123.3) months after the initial CA, AF progressed from paroxysmal to persistent in 15 (1.2%) patients (0.3%/y). The duration of AF history (hazard ratio [HR], 1.03;
P
<0.0001), number of ineffective antiarrhythmics (HR, 1.09;
P
=0.005), and left atrial diameter indexed by the body surface area (HR, 1.05;
P
=0.001) were significant predictors of AF recurrence. Patient age (HR, 1.12;
P
=0.0001) and left atrial diameter indexed by the body surface area (HR, 1.26;
P
=0.0006) were significantly associated with AF progression. Patients aged ≤65 years and with a left atrial diameter indexed by the body surface area of ≤24.0 mm/m
2
did not develop AF progression for ≤10 years after the initial CA.

Conclusions—
Although the long-term follow-up revealed the effect of CA on preventing AF recurrence, repeated CA sessions might be required. The rate of progression from paroxysmal to persistent AF was 0.3%/y.
Impact of Cardiac Resynchronization Therapy on Hospitalizations in the Resynchronization-Defibrillation for Ambulatory Heart Failure Trial
Authors: Gillis Anne M , Kerr Charles R. , Philippon François , Newton Gary , Talajic Mario , Froeschl Michael , Froeschl Sandra , Swiggum Elizabeth , Yetisir Elizabeth , Wells George A. , Tang Anthony S. 
Published: March 2014

Background—
This study reports the impact of cardiac resynchronization therapy (CRT) on hospitalizations in patients randomized to implantable cardioverter-defibrillator (ICD) or ICD-CRT in the Resynchronization-Defibrillation for Ambulatory Heart Failure Trial (RAFT).

Methods and Results—

Hospitalization rates and lengths of hospital stay were compared between the 2 groups. At the 18-month follow-up, the numbers of patients hospitalized for any cause were similar in the ICD (n=351, 38.8%) and ICD-CRT (n=331, 30.0%) groups. The number of patients hospitalized for heart failure was significantly lower in the ICD-CRT (n=101, 11.3%) compared with the ICD (n=141, 15.6%;
P
=0.003) group. The number of patients hospitalized for a device-related indication was similar in the ICD-CRT group (n=147, 16.4%) and ICD group (n=126, 13.9%;
P
=0.148). The total number of hospitalizations for any cause (n=1448 versus n=1553;
P
=0.042), any cardiovascular cause (n=667 versus n=790;
P
=0.017), and any heart failure cause (n=385 versus n=505;
P
<0.0001) was significantly lower in ICD-CRT group compared with the ICD group, whereas the number of hospitalizations for device-related causes was significantly higher in the ICD-CRT group compared with the ICD group (246 versus 159;
P
<0.001). Although the reduction in hospitalizations for heart failure in the CRT-ICD group was offset by an increased number of hospitalizations for device-related indications, the length of hospital stay for any cause was significantly shorter in the ICD-CRT group (8.83±13.30 days) compared with the ICD group (9.59±14.40 days;
P
=0.005).

Conclusion—
ICD-CRT therapy significantly reduces hospitalizations and total days in hospital in patients with New York Heart Association class II/III heart failure compared with ICD therapy despite increased admissions for device-related indications.

Clinical Trial Registration—

URL:
http://www.clinicaltrials.gov
. Unique identifier: NCT00251251.
A modified iterative algorithm for the (Hermitian) reflexive solution of the generalized Sylvester matrix equation
Authors: Beik Fatemeh Panjeh Ali 
Published: March 2014

Recently, Ramadan et al. have focused on the following matrix equation: [Formula: see text] and propounded two gradient-based iterative algorithms for solving the above matrix equation over reflexive and Hermitian reflexive matrices, respectively. In this paper, we develop two new iterative algorithms based on a two-dimensional projection technique for solving the mentioned matrix equation over reflexive and Hermitian reflexive matrices. The performance of our proposed algorithms is collated with the gradient-based iterative algorithms. It is both theoretically and experimentally demonstrated that the approaches handled surpass the offered algorithms in the earlier referred work in solving the mentioned matrix equation over reflexive and Hermitian reflexive matrices. In addition, it is briefly discussed that a one-dimensional projection technique can accelerate the speed of convergence of the gradient-based iterative algorithm for solving general coupled Sylvester matrix equations over reflexive matrices without assuming the restriction of the existence of a unique solution.
Off-pump versus on-pump revascularization in females: a meta-analysis of observational studies
Authors: Attaran S , Harling L , Ashrafian H , Moscarelli M , Casula R , Anderson J , Punjabi P , Athanasiou T 
Published: March 2014

Background: Coronary revascularization in female patients presents several challenges, including smaller target vessels and smaller conduits. Furthermore, late presentation and more co-morbidities than males may increase complication rates. The aim of this study was to assess whether off-pump coronary artery bypass (OPCAB) improves outcomes when compared to on-pump coronary artery bypass (ONCAB) in the female population. Methods: A systematic literature review identified six observational studies, incorporating 23313 patients (n=9596 OPCAB, 13717 ONCAB). These were meta-analyzed using random effects modeling. Heterogeneity, subgroup analysis, quality scoring and publication bias were assessed. The primary endpoints were 30-day mortality and major cardiac, respiratory and renal complications. Secondary endpoints were the number of grafts per patient. Results: No statistically significant difference was observed in 30-day mortality between the OPCAB and ONCAB groups (4.8% vs. 0.7%; OR 0.96; 95%CI [0.41, 2.24], p=0.92). Significant inter-study heterogeneity was also present (I2=94%) and was not explained by study size or quality. Peri-operative myocardial infarction (OR 0.65; 95%CI [0.51, 0.84], p=0.0009) was significantly lower with OPCAB without significant heterogeneity; however, OPCAB did not significantly alter other morbidity outcomes. OPCAB was associated with a trend towards fewer grafts per patient than ONCAB. Conclusions: OPCAB is a safe alternative to ONCAB in the surgical revascularisation of female patients and may reduce post-operative myocardial infarction (MI). However, this does not translate into a reduction in 30-day mortality and OPCAB does not significantly improve other cardiovascular, renal or neurological outcomes. Late outcome data remains lacking and a well-structured, randomized trial is required to answer vital questions regarding the effect of OPCAB on women in the long-term.
Mid-term clinical outcomes and morphological changes after endovascular aneurysm repair of inflammatory abdominal aortic aneurysms: a single-center experience
Authors: Lee Seung Hyun , Won Jong Yun , Lee Do Yun , Kim Il Jung , Lee Shin Jae , Kim Man Deuk , Park Sung Il , Lee Kwang Hun , Ko Young Guk , Choi Dong-Hoon , Kim Eun-Kyung 
Published: March 2014

Background: Endovascular aneurysm repair (EVAR) has been suggested as treatment for inflammatory abdominal aortic aneurysms (IAAA), but the actual clinical and radiological outcomes need to be evaluated. Purpose: To report morphological changes in EVAR of IAAAs. Material and Methods: Ten male patients (mean age, 67 years; range, 54–78 years) with IAAA were treated with EVAR using endovascular stent-grafts between March 2001 and January 2012. We retrospectively compared computed tomography angiography (CTA) images taken immediately (30 days after the EVAR), short-term (up to 1 year), and mid-term (beyond 1 year) to CTA images taken before the EVAR. Clinical success was defined as successful deployment of the stent-graft without a type I or III endoleak. Morphologic responses of IAAA to EVAR were reviewed by measuring the changes in aneurysm sac maximum diameter (mm), periaortic fibrosis (PAF) thickness (mm), and PAF enhancement (Hounsfield units [HU] on delayed CTA) on serial images. Results: Ten IAAA patients treated with EVAR were followed for a mean of 42 months (range, 7–129 months). No aneurysm-related deaths were observed during the follow-up of 10 patients. Primary clinical success was achieved in seven patients, assisted primary clinical success in one patient, and secondary clinical success in two patients. Aneurysm sac maximum diameter decreased in all patients (mean percentage reduction of 7.6%, 8.5%, and 17.3% in immediate, short-term, and mid-term follow-up CTA, respectively). PAF thickness decreased in eight patients (10.4%, 16.8%, and 27.2% regression upon follow-up). PAF enhancement decreased in nine patients and increased in one patient (mean percentage decrease of 13.0%, 27.3%, and 40.8% upon follow-up). Conclusion: Treatment of IAAA with EVAR was effective and reduced aneurysmal sac diameter and the extent of PAF with acceptable morbidity.
Monoenergetic extrapolation of cardiac dual energy CT for artifact reduction
Authors: Secchi Francesco , De Cecco Carlo Nicola , Spearman James Vance , Silverman Justin Robert , Ebersberger Ullrich , Sardanelli Francesco , Schoepf U Joseph 
Published: March 2014

Background Monoenergetic extrapolation of cardiac dual-energy computed tomography (DECT) could be useful in artifact reduction in clinical practice. Purpose To evaluate the potential of monoenergetic extrapolation of cardiac DECT data for reducing artifacts from metal and high iodine contrast concentration. Material and Methods With IRB approval and in HIPAA compliance, 35 patients (22 men, 61 ± 12 years) underwent cardiac DECT with dual-source CT (100 kVp and 140 kVp). Contrast material injection protocols were adapted to the patient’s weight using non-ionic low-osmolar 370 mgI/mL iopromide. Datasets were transferred to a stand-alone workstation and dedicated monoenergetic analysis software was used for postprocessing. Reconstructions with the following five photon energies were generated: 40 keV, 60 keV, 80 keV, 100 keV, and 120 keV. Artifact severity was graded on a 5-point Likert scale (0, massive artifact; 5, absence of artifact). The size of artifact and image noise (expressed as HU) in anatomic structures adjacent to the artifact were measured. Quantitative and subjective image quality was compared using Friedman and Wilcoxon tests. Results We observed artifacts arising from densely concentrated contrast material in the superior vena cava (SVC) in 18 patients, from sternal wires in 14, from bypass clips in eight, and from coronary artery stents in seven. Artifact size in monoenergetic reconstructions from 40 to 120 keV decreased from 21.3 to 19 mm for the SVC ( P < 0.001), from 8.4 to 2.6 mm for sternal wires ( P < 0.001), from 6.4 to 2.2 mm for bypass clips ( P < 0.001), and from 5.9 to 2.7 mm for stents ( P < 0.001), respectively. The quality score changed from 0.2 to 3.8 for the SVC ( P < 0.001), from 0.1 to 4 for sternal wires ( P < 0.001), from 0 to 3.9 for bypass clips ( P < 0.001), and from 0 to 3.9 for stents ( P < 0.001). Lowest noise in adjacent structures was found at 80 keV for the SVC (39.1 HU), for sternal wires (33.3), for bypass clips (26.9), and for stents (33.9). Conclusion A significant reduction of high-attenuation artifacts can be achieved by use of higher monoenergetic energy levels with cardiac DECT. However, image noise in anatomic structures affected by artifacts is lowest at 80 keV, which suggests an evaluation approach that makes use of multiple energy levels for a complete diagnosis.
Performance and comparison of self-reported STI symptoms among high-risk populations – MSM, sex workers, persons living with HIV/AIDS – in El Salvador
Authors: Shah Neha S , Kim Evelyn , de Maria Hernández Ayala Flor , Guardado Escobar Maria Elena , Nieto Ana Isabel , Kim Andrea A , Paz-Bailey Gabriela 
Published: March 2014

Summary Resource-limited countries have limited laboratory capability and rely on syndromic management to diagnose sexually transmitted infections (STIs). We aimed to estimate the sensitivity, specificity and positive predictive value (PPV) of STI syndromic management when used as a screening method within a study setting. Men who have sex with men (MSM), female sex workers (FSWs) and people living with HIV/AIDS (PLWHA) participated in a behavioural surveillance study. Data were obtained on demographics, sexual behaviours, STI history and service utilisation. Biological specimens were tested for genital inflammatory infections ( Neisseria gonorrhoeae [GC], Chlamydia trachomatis [CT], Mycoplasma genitalium [MG], Trichomonas vaginalis [TV]) and genital ulcerative infection (syphilis and Herpes simplex virus-2). There was a high prevalence of Herpes simplex virus-2 (MSM 48.1%, FSW 82.0% and PLWHA 84.4%). Most participants reported no ulcerative symptoms and the majority of men reported no inflammatory symptoms. Sensitivity and PPV were poor for inflammatory infections among PLWHA and MSM. Sensitivity in FSWs for inflammatory infections was 75%. For ulcerative infections, sensitivity was poor, but specificity and PPV were high. Reliance on self-reported symptoms may not be an effective screening strategy for these populations. STI prevention studies should focus on symptom recognition and consider routine screening and referral for high-risk populations.
Prediction of In-Season Shoulder Injury From Preseason Testing in Division I Collegiate Football Players
Authors: Pontillo Marisa , Spinelli Bryan A. , Sennett Brian J. 
Published: March 2014

Background: Collegiate football is a high-demand sport in which shoulder injuries are common. Research has described the incidence of these injuries, with little focus on causative factors or injury prevention. Hypothesis: Football athletes who score lower on preseason strength and functional testing are more likely to sustain an in-season shoulder injury. Study Design: Prospective, cohort study. Level of Evidence: Level 2. Methods: Twenty-six collegiate football players underwent preseason testing with a rotational profile for shoulder range of motion, isometric strength of the rotator cuff at 90° elevation and external rotation in the 90/90 position, fatigue testing (prone-Y, scaption, and standing cable press), and the Closed Kinetic Chain Upper Extremity Stability Test (CKCUEST). Data collected postseason included the type of shoulder injury and the side injured. Logistic regression was used to determine if the testing measures predicted injury, and a receiver operating characteristic curve was constructed to examine the relationship of CKCUEST to injury. Results: Six athletes sustained shoulder injuries during the season. Predictor variables could significantly predict whether that player would sustain an injury during the season for both the right and left shoulders ( P < 0.05). The variables that were significantly correlated with injury of the right side were forward elevation strength, prone-Y to fatigue, and the CKCUEST ( P < 0.05); on the left, only the CKCUEST was significant ( P < 0.05). The area under the receiver operating characteristic curve for the CKCUEST was 0.86 (ϵ = 0.87, P = 0.01). Using a score of 21 touches, the CKCUEST had a sensitivity of 0.83, a specificity of 0.79, and an odds ratio of 18.75 in determining whether a player sustained a shoulder injury. Conclusion: For this sample, the combination of preseason strength, fatigue, and functional testing was able to identify football players who would sustain a shoulder injury during the season. Clinical Relevance: Using a battery of strength, fatigue, and functional testing may be helpful in identifying football players during preseason who are at a higher risk for sustaining a shoulder injury. This information can be used to optimize preseason testing and implementation of injury prevention programs.