bluuebunny/crossref_metadata_2025_split huggingface dataset:
Transcriptomic and Protein Analysis of Small-cell Bladder Cancer (SCBC) Identifies Prognostic Biomarkers and DLL3 as a Relevant Therapeutic Target
Authors: Koshkin Vadim S. , Garcia Jorge A. , Reynolds Jordan , Elson Paul , Magi-Galluzzi Cristina , McKenney Jesse K. , Isse Kumiko , Bishop Evan , Saunders Laura R. , Balyimez Aysegul , Rashid Summya , Hu Ming , Stephenson Andrew J. , Fergany Amr F. , Lee Byron H. , Haber Georges-Pascal , Dowlati Afshin , Gilligan Timothy , Ornstein Moshe C. , Rini Brian I. , Abazeed Mohamed E. , Mian Omar Y. , Grivas Petros 
Published: October 2018

Abstract

Purpose:
Transcriptomic profiling can shed light on the biology of small-cell bladder cancer (SCBC), nominating biomarkers, and novel therapeutic targets.

Experimental Design:
Sixty-three patients with SCBC had small-cell histology confirmed and quantified by a genitourinary pathologist. Gene expression profiling was performed for 39 primary tumor samples, 1 metastatic sample, and 6 adjacent normal urothelium samples (46 total) from the same cohort. Protein levels of differentially expressed therapeutic targets, DLL3 and PDL1, and also CD56 and ASCL1, were confirmed by IHC. A SCBC PDX model was utilized to assess in vivo efficacy of DLL3-targeting antibody–drug conjugate (ADC).

Results:
Unsupervised hierarchical clustering of 46 samples produced 4 clusters that correlated with clinical phenotypes. Patients whose tumors had the most “normal-like” pattern of gene expression had longer overall survival (OS) compared with the other 3 clusters while patients with the most “metastasis-like” pattern had the shortest OS (P = 0.047). Expression of DLL3, PDL1, ASCL1, and CD56 was confirmed by IHC in 68%, 30%, 52%, and 81% of tissue samples, respectively. In a multivariate analysis, DLL3 protein expression on &gt;10% and CD56 expression on &gt;30% of tumor cells were both prognostic of shorter OS (P = 0.03 each). A DLL3-targeting ADC showed durable antitumor efficacy in a SCBC PDX model.

Conclusions:
Gene expression patterns in SCBC are associated with distinct clinical phenotypes ranging from more indolent to aggressive disease. Overexpression of DLL3 mRNA and protein is common in SCBC and correlates with shorter OS. A DLL3-targeted ADC demonstrated in vivo efficacy superior to chemotherapy in a PDX model of SCBC.
Patritumab with Cetuximab plus Platinum-Containing Therapy in Recurrent or Metastatic Squamous Cell Carcinoma of the Head and Neck: An Open-Label, Phase Ib Study
Authors: Dillon Magnus T. , Grove Lorna , Newbold Kate L. , Shaw Heather , Brown Nicholas F. , Mendell Jeanne , Chen Shuquan , Beckman Robert A. , Jennings Anne , Ricamara Marivic , Greenberg Jonathan , Forster Martin , Harrington Kevin J. 
Published: October 2018

Abstract

Purpose:
Patritumab plus cetuximab with platinum as first-line therapy for patients with recurrent and/or metastatic (R/M) squamous cell carcinoma of the head and neck (SCCHN) was evaluated for safety and to determine the recommended phase II combination dose.

Patients and Methods:
Patients aged ≥18 years with confirmed R/M SCCHN received intravenous patritumab (18 mg/kg loading dose; 9 mg/kg maintenance dose every 3 weeks) + cetuximab (400 mg/m2 loading dose; 250 mg/m2 maintenance dose weekly) + cisplatin (100 mg/m2 every 3 weeks) or carboplatin (AUC of 5) for six cycles or until toxicity, disease progression, or withdrawal. Primary endpoints were dose-limiting toxicities [DLT; grade ≥3 (21-day observation period)] and treatment-emergent adverse events (TEAE). Pharmacokinetics, human antihuman antibodies (HAHA), tumor response, progression-free survival (PFS), and overall survival (OS) were assessed.

Results:
Fifteen patients completed a median (range) of 8.7 (2.0–20.7) patritumab cycles. No DLTs were reported. Serious adverse events were reported in 9 patients (patritumab-related n = 4). TEAEs (N = 15 patients) led to patritumab interruption in 7 patients. Patritumab-related dose reductions were reported in 1 patient. Patritumab (18 mg/kg) pharmacokinetics (N = 15) showed mean (SD) AUC0–21d of 2,619 (560) μg/day/mL and maximum concentration of 499.9 (90.4) μg/mL. All patients were HAHA-negative at study end (single, transient low titer in 1 patient). Tumor response rate (complete plus partial response; N = 15) was 47%. Median (95% confidence interval) PFS and OS (N = 15) were 7.9 (3.7–9.7) and 13.5 (6.6–17.5) months, respectively.

Conclusions:
Patritumab (18 mg/kg loading dose, 9 mg/kg maintenance dose) plus cetuximab/platinum was tolerable, active in SCCHN, and selected as the phase II dose regimen.
Longer-term Lipid-lowering Drug Use and Risk of Incident and Fatal Prostate Cancer in Black and White Men in the ARIC Study
Authors: Mondul Alison M. , Joshu Corinne E. , Barber John R. , Prizment Anna E. , Bhavsar Nrupen A. , Selvin Elizabeth , Folsom Aaron R. , Platz Elizabeth A. 
Published: October 2018

Abstract
Lipid-lowering medications, particularly statins, may protect against aggressive prostate cancer. Fatal prostate cancer, the most clinically relevant outcome, remains understudied for this association. We prospectively studied lipid-lowering medication use and both incident and fatal prostate cancer in black and white men in the Atherosclerosis Risk in Communities (ARIC) study. A total of 6,518 men without cancer at visit 2 (1990–1992), the start of the statin era, were followed for prostate cancer incidence and death through 2012. Medication use was collected during study visits and telephone calls at up to nine time points during follow-up. Cox regression was used to estimate HR and 95% confidence intervals (CI) of total (white N = 541, black N = 259) and fatal (white N = 56, black N = 34) prostate cancer overall and by race. Lipid-lowering medication use was modeled as time-dependent current use or duration (never, &lt;10, and ≥10 years). By visit 4 (1996–1998), 21% of white and 11% of black men had used a lipid-lowering medication, mostly statins. There was a suggestion that current users were less likely to die from prostate cancer than nonusers (HR = 0.67, 95% CI = 0.42–1.07) after multivariable adjustment. We observed no statistically significant differences between black and white men. Current use was not associated with incident prostate cancer, although long-term use was statistically significantly inversely associated with incidence (HR = 0.68; 95% CI = 0.50–0.92). Long-term lipid-lowering medication use was associated with lower risk of prostate cancer. Current use was possibly associated with fatal prostate cancer.
Phage-Based Anti-HER2 Vaccination Can Circumvent Immune Tolerance against Breast Cancer
Authors: Bartolacci Caterina , Andreani Cristina , Curcio Claudia , Occhipinti Sergio , Massaccesi Luca , Giovarelli Mirella , Galeazzi Roberta , Iezzi Manuela , Tilio Martina , Gambini Valentina , Wang Junbiao , Marchini Cristina , Amici Augusto 
Published: October 2018

Abstract
Δ16HER2 is a splice variant of HER2 and defined as the transforming isoform in HER2-positive breast cancer. It has been shown that Δ16HER2 promotes breast cancer aggressiveness and drug resistance. In the present work, we used in silico modeling to identify structural differences between Δ16HER2 and the wild-type HER2 proteins. We then developed DNA vaccines specifically against the Δ16HER2 isoform and showed that these immunotherapies hampered carcinogenesis in a breast cancer transplantable model. However, the vaccines failed to elicit immune protection in Δ16HER2 transgenic mice because of tolerogenic mechanisms toward the human HER2 self-antigen, a scenario commonly seen in HER2+ patients. Thus, we engineered bacteriophages with immunogenic epitopes of Δ16HER2 exposed on their coat for use as anticancer vaccines. These phage-based vaccines were able to break immune tolerance, triggering a protective anti-Δ16HER2 humoral response. These findings provide a rationale for the use of phage-based anti-HER2/Δ16HER2 vaccination as a safe and efficacious immunotherapy against HER2-positive breast cancers.
Gut Microbial Product Predicts Cardiovascular Risk in Chronic Kidney Disease Patients
Authors: Jadoon Adil , Mathew Anna V. , Byun Jaeman , Gadegbeku Crystal A. , Gipson Debbie S. , Afshinnia Farsad , Pennathur Subramaniam ,   for the Michigan Kidney Translational Core CPROBE Investigator Group
Published: October 2018

<b><i>Background:</i></b> The gut microbiota is altered in patients with chronic kidney disease (CKD), and cardiovascular risk increases with progressive CKD. This study examined the potential link between short chain fatty acids (SCFAs), which are produced by the gut microbiota, and cardiovascular outcomes in patients with CKD. <b><i>Methods:</i></b> SCFAs were measured using a targeted liquid chromatography-mass spectrometry platform in baseline plasma samples from 214 patients with CKD enrolled in the Clinical Phenotyping Resource and Biobank Core; 81 patients with coronary artery disease (CAD) and 133 without CAD were randomly assigned to training and validation subsets. The primary outcome was a history of CAD and the secondary outcome was a composite history of cardiovascular disease (CVD) at enrollment. <b><i>Results:</i></b> We found significantly higher levels of the SCFA valerate among patients with CAD as compared with patients without CAD in the training set (<i>p</i> &#x3c; 0.001). The valerate concentrations were also significantly higher among subjects with composite outcomes of CVD compared to those without CVD (<i>p</i> = 0.006). These results were subsequently replicated in the validation set. Logistic regression analysis revealed a strong independent association between plasma valerate levels and CVD in both training and validation sets. When valerate was added to the base clinical model comprising of diabetes, hypertension, urinary protein-creatinine ratio, and estimated glomerular filtration rate, it increased the c-statistics for predicting CVD from 0.68 to 0.79 (<i>p</i> = 0.02) in the training set, an observation which was confirmed in the validation set. ­<b><i>Conclusion:</i></b> This study provides evidence for alterations in gut-microbiota-derived SCFAs with advancing CKD, demonstrates the association of higher plasma valerate levels with pre-existing CVD, and reveals areas for future exploration of cardiovascular risk in patients with CKD.
New species and synonymies in Hexoplonini Martins, 2006 (Coleoptera, Cerambycidae), with notes and new records on Cerambycinae Latreille, 1802
Authors: Nascimento Francisco Eriberto De Lima , Santos-Silva Antonio 
Published: October 2018

Glyptoscapus letiziae, a new species of Hexoplonini Martins, 2006, is described from Brazil (Minas Gerais). Glyptoscapus cicatricosus Aurivillius, 1899 and G. vanettii Martins, 1959 are synonymized with G. pallidulus (White, 1855). A key to species of Glyptoscapus is provided. New state records are presented for Thoracibidion io (Thomson, 1867) (Neoibidionini), Coleoxestia rafaeli Santos-Silva & Wappes, 2017 and C. denticornis (Gahan, 1892) (Cerambycini). The female of C. rafaeli is described for the first time.
A new species of Trichomyia (Diptera: Psychodidae: Trichomyiinae) and report of antennal sensilla in adult
Authors: Araújo Maíra Xavier , Bravo Freddy 
Published: October 2018

This paper describes and illustrates Trichomyia muiraquita Araújo & Bravo sp. nov. from the state of Amazonas, Brazil. Furthermore, with the aid of a scanning electron microscope and light microscope, we report for the first time the presence of two small sensilla in flagellomeres of the Trichomyia species.
Recombinase polymerase amplification assay for rapid detection of the root-knot nematode Meloidogyne enterolobii
Authors: Subbotin Sergei A. 
Published: October 2018

Summary
Rapid diagnosis tools for detection of root-knot nematodes play an important role in the disease control and eradication programme. Recombinase polymerase amplification (RPA) assays were developed targeting the IGS rRNA gene of the pacara earpod tree root-knot nematode, Meloidogyne enterolobii. The RPA assays using TwistAmp® Basic and TwistAmp® exo kits allowed detection of M. enterolobii from gall tissues and crude nematode extracts of all stages of target species without a DNA extraction step. The results of real-time RPA assays using a real-time fluorescent detection of a series of crude nematode extracts showed reliable detection with sensitivity of 1/10 of a second-stage juvenile in a RPA reaction tube after 15-20 min. The RPA assay provides affordable, simple, fast and sensitive detection of M. enterolobii.
Pneumatological Considerations for Christian-Muslim Peacebuilding Engagement
Authors: Anyanwu Uchenna D. 
Published: October 2018

Abstract
This essay explores the understanding of the Holy Spirit in Islam and his role in missio Dei from a Christian missiological perspective, and then argues for pneumatological considerations that Jesus’s followers can employ to promote Christian-Muslim peacebuilding engagement. It asserts that the task of reconciling all things belongs primarily to the domain of missio Dei and, consequently, that the Holy Spirit is the One who initiates and creates occasions and circumstances that birth enduring, holistic, and true peace. Armed with such understanding, peacebuilding enthusiasts who follow Jesus can engage in christo-pneumatological peacebuilding that entails the practice of faithful presence—dwelling with the “other” as the temple of the Holy Spirit, who glorifies the Son and the Father through the human participant in the missio Dei.
Insurance Status and Survival of Patients with Salivary Gland Cancer
Authors: Saraswathula Anirudh , Megwalu Uchechukwu C. 
Published: October 2018

ObjectivesTo evaluate the impact of insurance status on survival among patients with major salivary gland cancer.Study DesignRetrospective cohort study.SettingSEER program.Subjects and MethodsWe included patients aged <65 years diagnosed with major salivary gland cancers from 2007 to 2013. Those aged ≥65 years were excluded due to issues ascertaining insurance status. The independent variable was insurance status (insured, uninsured, or Medicaid); the primary outcome measure was overall survival (OS); and the secondary outcome measure was disease‐specific survival (DSS).ResultsCompared with insured patients, uninsured and Medicaid patients were more likely to present with stage III‐IV disease (uninsured: odds ratio [OR], 1.57; 95% CI, 1.09‐2.27; Medicaid: OR, 1.67; 95% CI, 1.27‐2.20) and with distant metastasis (uninsured: OR, 2.10; 95% CI, 1.18‐3.57; Medicaid: OR, 1.96; 95% CI, 1.25‐3.01) after adjusting for demographic and tumor variables. Uninsured and Medicaid patients also had worse OS (uninsured: hazard ratio [HR], 1.62; 95% CI, 1.14‐2.29; Medicaid: HR, 1.74; 95% CI, 1.33‐2.38) and DSS (uninsured: HR, 1.57; 95% CI, 1.08‐2.29; Medicaid: HR, 1.68; 95% CI, 1.25‐2.25) after adjusting for demographic and tumor variables. After further adjusting for treatment variables, only Medicaid status was significantly associated with worse OS (HR, 1.71; 95% CI, 1.30‐2.26) and DSS (HR, 1.65; 95% CI, 1.23‐2.23).ConclusionsInsurance status is associated with stage at presentation and survival among patients with salivary gland cancer.
Hypopharyngeal Cancer Treatment Delays: Benchmarks and Survival Association
Authors: Morse Elliot , Berson Elisa , Fujiwara Rance , Judson Benjamin , Mehra Saral 
Published: October 2018

ObjectiveTo characterize treatment delays in hypopharyngeal cancer, identify factors associated with delays, and associate delays with overall survival.Study DesignRetrospective cohort.SettingCommission on Cancer hospitals nationwide.Subjects and MethodsWe included patients in the National Cancer Database who were treated for hypopharyngeal cancer with primary radiation, concurrent chemoradiation, or induction chemotherapy and radiation. We identified median durations of diagnosis to treatment initiation (DTI), radiation treatment duration (RTD), and diagnosis to treatment end (DTE). We associated delays with patient, tumor, and treatment factors and overall survival via multivariable logistic and Cox proportional hazards regression, respectively.ResultsA total of 3850 patients treated with primary radiation or concurrent chemoradiation were included. Median durations of DTI, RTD, and DTE were 37, 52, and 92 days, respectively. Nonwhite race was associated with delays in DTI (odds ratio [OR] = 0.64; 95% CI, 0.51‐0.80; P <. 001) and DTE (OR = 0.60; 95% CI, 0.49‐0.75; P <. 001). Medicaid insurance was associated with delays in DTI (OR = 1.43; 95% CI, 1.07‐1.90; P =. 015), RTD (OR = 1.39; 95% CI, 1.06‐1.83; P =. 018), and DTE (OR = 1.48; 95% CI, 1.12‐1.97; P =. 007). Delays in RTD (hazard ratio [HR] = 1.24; 95% CI, 1.11‐1.37; P <. 001), not DTI (HR = 0.92; 95% CI, 0.82‐1.03; P =. 150) or DTE (HR = 1.01; 95% CI, 0.90‐1.15; P =. 825), were associated with impaired overall survival. We identified 922 patients who received induction chemotherapy. Delays in DTI, RTD, and DTE were not associated with overall survival in this cohort (HR = 1.10; 95% CI, 0.87‐1.39; P = 0.435; HR = 1.05; 95% CI, 0.83‐1.32; P = 0.686; HR = 1.11; 95% CI, 0.88‐1.41; P = 0.377, respectively).ConclusionsThe median durations identified can serve as national benchmarks. Delays during radiation are associated with impaired overall survival among patients treated with primary radiation or chemoradiation but not patients treated with induction chemotherapy.
Impact of Delay in Treatment Initiation on Overall Survival in Laryngeal Cancers
Authors: Kompelli Anvesh Reddy , Li Hong , Neskey David Michael 
Published: October 2018

ObjectiveDelayed treatment significantly affects survival in head and neck cancer, but defining delays for specific subsites remains controversial. The purpose of this study is to elicit the time point for delay in treatment initiation in all laryngeal cancers using a large cohort of patients within the National Cancer Database (NCDB).Study DesignA retrospective cohort study.SettingNCDB.Subjects and MethodsPatients with laryngeal cancer within the NCDB from 2006 to 2014 were identified. A recursive partition analysis (RPA) was performed to identify the time point at which delay contributed to increased hazard. Patients were stratified into 3 groups: no delay, at risk, and overtly delayed. Kaplan‐Meier method was used to compare overall survival of these cohorts. Multivariate logistic regression analysis was used to identify predictors of delay. A multivariate Cox regression model was used to identify the final covariates that significantly affect overall survival.ResultsRPA identified the threshold for delay becomes significant at 46 days and exceeds baseline hazard at 73 days. Delay beyond 73 days is associated with a 16.1‐month decrease in median survival (P <. 001). To ensure this was not due to any confounding variables, a subsequent Cox multivariate regression confirmed a significantly increased adjusted hazard ratio (HR) for patients who were at risk or delayed (adjusted HR [confidence interval], 1.09 [1.04‐1.15] and 1.26 [1.18‐1.35], respectively).ConclusionTreatment of laryngeal cancer requires a multidisciplinary approach, and coordinating this care can take time. Our study highlights that delay beyond 46 to 73 days significantly affects survival and identifies patients experiencing these delays.
Quantifying the angiogenesis of C6 glioma in rats based on CT quantitative parameters
Authors: Huang Xiaoyu , Liang Xiaohong , Zhang Qiaoying , Wang Dan , Liu Jianli , Zhang Lingyan , Zhou Junlin 
Published: October 2018

Background Glioma is the most common neoplasm that is neuroepithelial in nature. However, Spectral computed tomography (CT) has rarely been reported to detect angiogenesis in tumors. Purpose To investigate the value of multi-parameter spectral CT for the detection of angiogenesis in C6 glioma in rats. Material and Methods Fifteen male Wistar rats were seeded with C6 glioma cells in the right basal ganglia and spectral CT-enhanced scanning was performed at days 7, 10, and 14 after the C6 glioma cells were seeded. The spectral CT parameters were measured in three areas: the solid tumor; the peritumoral area; and the contralateral mirror area. After different periods of scanning, the rats’ brain tissue was stained with HE and CD105 immunohistochemical staining. Different periods of spectral CT quantitative parameters and pathological images were analyzed. Results The spectral CT parameter and CD105 among the solid tumor, peritumoral area, and contralateral mirror area were significantly different: monochromatic CT value (211.30 ± 34.67 HU, 119.16 ± 13.31 HU, and 55.59 ± 7.87 HU, P < 0.001); CD105 (16.14 ± 1.91, 6.79 ± 1.31, and 2.50 ± 0.51, P < 0.001); spectral curve slope (10.35 ± 1.89, 5.33 ± 0.87, 0.88 ± 0.26, P < 0.001); iodine (water) value (49.75 ± 9.02, 26.04 ± 4.32, 4.36 ± 1.18, P < 0.001). CD105 correlated strongly with the CT value at 65 keV (correlation coefficient r = 0.98, P < 0.001). Conclusion Multi-parameter spectral CT can reflect the formation of tumor angiogenesis in rat C6 glioma to a certain extent and can be used as an effective means to evaluate glioma.
A Randomized Study of Immunotherapy with Low-Dose Subcutaneous Interleukin-2 plus Melatonin Vs Chemotherapy with Cisplatin and Etoposide as First-Line Therapy for Advanced Non-Small Cell Lung Cancer
Authors: Lissoni Paolo , Meregalli Sofia , Fossati Vittorio , Paolorossi Franco , Barni Sandro , Tancini Gabriele , Frigerio Franco 
Published: October 2018

Aims and Background The theraputic role of chemotherapy in advanced non-small cell lung cancer (NSCLC) is controversial because of its potentially detrimental action on host anticancer defenses. On the contrary, IL-2 would seem to prolong survival time by improving the immune status, even though it is generally less effective in determining tumor regression in NSCLC. Our previous studies have suggested the possibility of increasing tumor sensitivity to IL-2 by concomitant administration of immunomodulating neurohormones, such as the pineal hormone melatonin (MLT). On this basis, a study was carried out to evaluate the efficacy of immunotherapy with low-dose IL-2 plus MLT versus chemotherapy in advanced NSCLC. Methods The study included 60 patients with locally advanced or metastatic NSCLC, who were randomized to receive immunotherapy or chemotherapy. The immunotherapy consisted of IL-2 (3 million IU/day subcutaneously for 6 days/week for 4 weeks) and MLT (40 mg/day orally every day, starting 7 days before IL-2); in nonprogressing patients, a second cycle was repeated after a 21-day rest period, then they underwent a maintenance period consisting of one week of therapy every month until progression. Chemotherapy consisted of cisplatin (20 mg/m2) and etoposide (100 mg/m2)/day intravenously for 3 days; cycles of chemotherapy were repeated every 21 days until progression. Results No complete response was obtained. A partial response was achieved in 7/29 patients treated with chemotherapy and in 6/31 patients receiving chemotherapy. The difference was not significant. In contrast, the mean progression-free period and the percentage survival at 1 year was significantly higher in patients treated with immunotherapy than in those treated with chemotherapy. Toxicity was substantially lower in patients receiving immunotherapy than in those given chemotherapy. Conclusions This randomized study showed that immunotherapy with low-dose IL-2 plus MLT is a better tolerated and more effective therapy in terms of survival time than chemotherapy containing cisplatin in patients affected by advanced NSCLC.