bluuebunny/crossref_metadata_2025_split huggingface dataset:
Parallel genetic divergence among coastal–marine ecotype pairs of European anchovy explained by differential introgression after secondary contact
Authors: Le Moan A. , Gagnaire P.‐A. , Bonhomme F. 
Published: March 2016

AbstractEcophenotypic differentiation among replicate ecotype pairs within a species complex is often attributed to independent outcomes of parallel divergence driven by adaptation to similar environmental contrasts. However, the extent to which parallel phenotypic and genetic divergence patterns have emerged independently is increasingly questioned by population genomic studies. Here, we document the extent of genetic differentiation within and among two geographic replicates of the coastal and marine ecotypes of the European anchovy (Engraulis encrasicolus) gathered from Atlantic and Mediterranean locations. Using a genome‐wide data set ofRAD‐derivedSNPs, we show that habitat type (marine vs. coastal) is the most important component of genetic differentiation among populations of anchovy. By analysing the joint allele frequency spectrum of each coastal–marine ecotype pair, we show that genomic divergence patterns between ecotypes can be explained by a postglacial secondary contact following a long period of allopatric isolation (c. 300 kyrs). We found strong support for a model including heterogeneous migration among loci, suggesting that secondary gene flow has eroded past differentiation at different rates across the genome. Markers experiencing reduced introgression exhibited strongly correlated differentiation levels among Atlantic and Mediterranean regions. These results support that partial reproductive isolation and parallel genetic differentiation among replicate pairs of anchovy ecotypes are largely due to a common divergence history prior to secondary contact. They moreover provide comprehensive insights into the origin of a surprisingly strong fine‐scale genetic structuring in a high gene flow marine fish, which should improve stock management and conservation actions.
Development and psychometric properties of ECPICID‐AVC to measure informal caregivers’ skills when caring for older stroke survivors at home
Authors: Araújo Odete , Lage Isabel , Cabrita José , Teixeira Laetitia 
Published: March 2016

IntroductionInformal caregivers provide a significant part of the total care needed by dependent older people poststroke. Although informal care is often the preferred option of those who provide and those who receive informal care, informal caregivers often report lack of preparation to take care of older dependent people. This article outlines the development and psychometric testing of informal caregivers’ skills when providing care to older people after a stroke – ECPICID‐AVC.DesignProspective psychometric instrument validation study.MethodsEleven experts participated in a focus group in order to delineate, develop and validate the instrument. Data were gathered among adult informal caregivers (n = 186) living in the community in Northern Portugal from August 2013 to January 2014.ResultsThe 32‐item scale describes several aspects of informal caregiver's skills. The scale has eight factors: skill to feed/hydrate by nasogastric feeding, skill to assist the person in personal hygiene, skill to assist the person for transferring, skill to assist the person for positioning, skill to provide technical aids, skill to assist the person to use the toilet, skill to feed/hydrate and skill to provide technical aids for dressing/undressing. Analysis demonstrated adequate internal consistency (Cronbach's alpha = 0.83) and good temporal stability 0.988 (0.984–0.991).ConclusionThe psychometric properties of the measurement tool showed acceptable results allowing its implementation in clinical practice by the nursing community staff for evaluating practical skills in informal caregivers when providing care to older stroke survivors living at home.
Flow cytometric examination of bacterial growth in a local drinking water network
Authors: Van Nevel Sam , Buysschaert Benjamin , De Gusseme Bart , Boon Nico 
Published: March 2016

AbstractBacterial growth in drinking water networks can result in health‐based implications, affect network hydrology and induce customer complaints. In this study, cultivation‐based methods were compared to flow cytometric methods for the study of growth in a local drinking water network. Comparison of flow cytometric cell concentrations indicated growth in several samples, while further data analysis with fingerprinting algorithms showed the different origin of this growth; low similarity between samples with elevated cell counts indicated that growth occurred mainly in the sampled household plumbing installations instead of centrally in the water network. Fast obtained flow cytometric data made this thorough analysis possible, while cultivation‐based methods were yielding too scarce information. Flow cytometry showed to be more rapid, complete, and accurate than cultivation‐based methods for a network growth study. It is proposed as a future useful tool for the fast detection of microbial point contaminations in drinking water networks.
The use of the land suitability rating system to assess climate change impacts on corn production in the lower Fraser Valley of British Columbia
Authors: Gasser P.-Y. , Smith C.A.S. , Brierley J.A. , Schut P.H. , Neilsen D. , Kenney E.A. 
Published: March 2016

The land suitability rating system (LSRS) is a spatial modeling tool that generates a class rating for parcels of land for specific agricultural crops based on a soil–climate–landscape potential. We applied the LSRS module for corn suitability to the agricultural portion of the lower Fraser Valley of British Columbia (BC). We used data from six UN-IPCC AR4 projections covering a range of cold to hot and wet to dry scenarios for the time periods 2010–2039, 2040–2069, and 2070–2099 to assess the impacts of climate change on corn production. To obtain satisfactory spatial results, we linked high-resolution (400 m grid) monthly temperature and precipitation values to the individual polygons of a detailed (1 : 25 000 scale) soil map available for the study area. Of the six future climate scenarios evaluated, the Goddard Institute for Space Studies (GISS_EH-A1B/3) yielded the most favourable results whereby land suitability for corn without irrigation remained relatively stable through the 21st century. Conversely, the Hadley Centre Global Environmental Model (HadGEM-A1B/1) projected a large drop in land suitabililty for corn due to increased climatic and soil moisture deficits. The wide range of climate scenario inputs generated a similarly wide range of LSRS ratings. Most scenarios generated positive impacts for land suitability up to mid-century but negative impacts by late century. Overall, increased heat and aridity will produce earlier harvest dates for corn and likely mean significant changes to the types and timing of crop management practices in the region.
Dual Targeting of Tissue Factor and CD105 for Preclinical PET Imaging of Pancreatic Cancer
Authors: Luo Haiming , England Christopher G. , Shi Sixiang , Graves Stephen A. , Hernandez Reinier , Liu Bai , Theuer Charles P. , Wong Hing C. , Nickles Robert J. , Cai Weibo 
Published: March 2016

Abstract
Purpose: Pancreatic adenocarcinoma is a highly aggressive cancer, currently treated with limited success and dismal outcomes. New diagnostic and treatment strategies offer the potential to reduce cancer mortality. Developing highly specific noninvasive imaging probes for pancreatic cancer is essential to improving diagnostic accuracy and monitoring therapeutic intervention.
Experimental Design: A bispecific heterodimer was synthesized by conjugating an anti-tissue factor (TF) Fab with an anti-CD105 Fab, via the bio-orthogonal “click” reaction between tetrazine (Tz) and trans-cyclooctene (TCO). The heterodimer was labeled with 64Cu for PET imaging of nude mice bearing BXPC-3 xenograft and orthotopic pancreatic tumors.
Results: PET imaging of BXPC-3 (TF/CD105+/+) xenograft tumors with 64Cu-labeled heterodimer displayed significantly enhanced tumor uptake (28.8 ± 3.2 %ID/g; n = 4; SD) at 30 hours postinjection, as compared with each of their monospecific Fab tracers (12.5 ± 1.4 and 7.1 ± 2.6 %ID/g; n = 3; SD). In addition, the activity–concentration ratio allowed for effective tumor visualization (tumor/muscle ratio 75.2 ± 9.4 at 30 hours postinjection.; n = 4; SD). Furthermore, 64Cu-NOTA-heterodimer enabled sensitive detection of orthotopic pancreatic tumor lesions with an uptake of 17.1 ± 4.9 %ID/g at 30 hours postinjection and tumor/muscle ratio of 72.3 ± 46.7.
Conclusions: This study demonstrates that dual targeting of TF and CD105 provided synergistic improvements in binding affinity and tumor localization of the heterodimer. Dual-targeted imaging agents of pancreatic and other cancers may assist in diagnosing pancreatic malignancies as well as reliable monitoring of therapeutic response. Clin Cancer Res; 22(15); 3821–30. ©2016 AACR.
Development and Validation of Urine-based Peptide Biomarker Panels for Detecting Bladder Cancer in a Multi-center Study
Authors: Frantzi Maria , van Kessel Kim E. , Zwarthoff Ellen C. , Marquez Mirari , Rava Marta , Malats Núria , Merseburger Axel S. , Katafigiotis Ioannis , Stravodimos Konstantinos , Mullen William , Zoidakis Jerome , Makridakis Manousos , Pejchinovski Martin , Critselis Elena , Lichtinghagen Ralph , Brand Korbinian , Dakna Mohammed , Roubelakis Maria G. , Theodorescu Dan , Vlahou Antonia , Mischak Harald , Anagnou Nicholas P. 
Published: March 2016

Abstract
Purpose: Urothelial bladder cancer presents high recurrence rates, mandating continuous monitoring via invasive cystoscopy. The development of noninvasive tests for disease diagnosis and surveillance remains an unmet clinical need. In this study, validation of two urine-based biomarker panels for detecting primary and recurrent urothelial bladder cancer was conducted.
Experimental Design: Two studies (total n = 1,357) were performed for detecting primary (n = 721) and relapsed urothelial bladder cancer (n = 636). Cystoscopy was applied for detecting urothelial bladder cancer, while patients negative for recurrence had follow-up for at least one year to exclude presence of an undetected tumor at the time of sampling. Capillary electrophoresis coupled to mass spectrometry (CE-MS) was employed for the identification of urinary peptide biomarkers. The candidate urine–based peptide biomarker panels were derived from nested cross-sectional studies in primary (n = 451) and recurrent (n = 425) urothelial bladder cancer.
Results: Two biomarker panels were developed on the basis of 116 and 106 peptide biomarkers using support vector machine algorithms. Validation of the urine-based biomarker panels in independent validation sets, resulted in AUC values of 0.87 and 0.75 for detecting primary (n = 270) and recurrent urothelial bladder cancer (n = 211), respectively. At the optimal threshold, the classifier for detecting primary urothelial bladder cancer exhibited 91% sensitivity and 68% specificity, while the classifier for recurrence demonstrated 87% sensitivity and 51% specificity. Particularly for patients undergoing surveillance, improved performance was achieved when combining the urine-based panel with cytology (AUC = 0.87).
Conclusions: The developed urine-based peptide biomarker panel for detecting primary urothelial bladder cancer exhibits good performance. Combination of the urine-based panel and cytology resulted in improved performance for detecting disease recurrence. Clin Cancer Res; 22(16); 4077–86. ©2016 AACR.
Apratoxin A Shows Novel Pancreas-Targeting Activity through the Binding of Sec 61
Authors: Huang Kuan-Chun , Chen Zhihong , Jiang Yimin , Akare Sandeep , Kolber-Simonds Donna , Condon Krista , Agoulnik Sergei , Tendyke Karen , Shen Yongchun , Wu Kuo-Ming , Mathieu Steven , Choi Hyeong-wook , Zhu Xiaojie , Shimizu Hajime , Kotake Yoshihiko , Gerwick William H. , Uenaka Toshimitsu , Woodall-Jappe Mary , Nomoto Kenichi 
Published: March 2016

Abstract
Apratoxin A is a natural product with potent antiproliferative activity against many human cancer cell lines. However, we and other investigators observed that it has a narrow therapeutic window in vivo. Previous mechanistic studies have suggested its involvement in the secretory pathway as well as the process of chaperone-mediated autophagy. Still the link between the biologic activities of apratoxin A and its in vivo toxicity has remained largely unknown. A better understanding of this relationship is critically important for any further development of apratoxin A as an anticancer drug. Here, we describe a detailed pathologic analysis that revealed a specific pancreas-targeting activity of apratoxin A, such that severe pancreatic atrophy was observed in apratoxin A–treated animals. Follow-up tissue distribution studies further uncovered a unique drug distribution profile for apratoxin A, showing high drug exposure in pancreas and salivary gland. It has been shown previously that apratoxin A inhibits the protein secretory pathway by preventing cotranslational translocation. However, the molecule targeted by apratoxin A in this pathway has not been well defined. By using a 3H-labeled apratoxin A probe and specific Sec 61α/β antibodies, we identified that the Sec 61 complex is the molecular target of apratoxin A. We conclude that apratoxin A in vivo toxicity is likely caused by pancreas atrophy due to high apratoxin A exposure. Mol Cancer Ther; 15(6); 1208–16. ©2016 AACR.
Triptolide Induces Cell Killing in Multidrug-Resistant Tumor Cells via CDK7/RPB1 Rather than XPB or p44
Authors: Yi Jun-Mei , Huan Xia-Juan , Song Shan-Shan , Zhou Hu , Wang Ying-Qing , Miao Ze-Hong 
Published: March 2016

Abstract
Multidrug resistance (MDR) is a major cause of tumor treatment failure; therefore, drugs that can avoid this outcome are urgently needed. We studied triptolide, which directly kills MDR tumor cells with a high potency and a broad spectrum of cell death. Triptolide did not inhibit P-glycoprotein (P-gp) drug efflux and reduced P-gp and MDR1 mRNA resulting from transcription inhibition. Transcription factors including c-MYC, SOX-2, OCT-4, and NANOG were not correlated with triptolide-induced cell killing, but RPB1, the largest subunit of RNA polymerase II, was critical in mediating triptolide's inhibition of MDR cells. Triptolide elicited antitumor and anti-MDR activity through a universal mechanism: by activating CDK7 by phosphorylating Thr170 in both parental and MDR cell lines and in SK-OV-3 cells. The CDK7-selective inhibitor BS-181 partially rescued cell killing induced by 72-hour treatment of triptolide, which may be due to partial rescue of RPB1 degradation. We suggest that a precise phosphorylation site on RPB1 (Ser1878) was phosphorylated by CDK7 in response to triptolide. In addition, XPB and p44, two transcription factor TFIIH subunits, did not contribute to triptolide-driven RPB1 degradation and cell killing, although XPB was reported to covalently bind to triptolide. Several clinical trials are underway to test triptolide and its analogues for treating cancer and other diseases, so our data may help expand potential clinical uses of triptolide, as well as offer a compound that overcomes tumor MDR. Future investigations into the primary molecular target(s) of triptolide responsible for RPB1 degradation may suggest novel anti-MDR target(s) for therapeutic development. Mol Cancer Ther; 15(7); 1495–503. ©2016 AACR.
Targeted Drug Delivery with an Integrin-Binding Knottin–Fc–MMAF Conjugate Produced by Cell-Free Protein Synthesis
Authors: Currier Nicolas V. , Ackerman Shelley E. , Kintzing James R. , Chen Rishard , Filsinger Interrante Maria , Steiner Alexander , Sato Aaron K. , Cochran Jennifer R. 
Published: March 2016

Abstract
Antibody–drug conjugates (ADC) have generated significant interest as targeted therapeutics for cancer treatment, demonstrating improved clinical efficacy and safety compared with systemic chemotherapy. To extend this concept to other tumor-targeting proteins, we conjugated the tubulin inhibitor monomethyl-auristatin-F (MMAF) to 2.5F–Fc, a fusion protein composed of a human Fc domain and a cystine knot (knottin) miniprotein engineered to bind with high affinity to tumor-associated integrin receptors. The broad expression of integrins (including αvβ3, αvβ5, and α5β1) on tumor cells and their vasculature makes 2.5F-Fc an attractive tumor-targeting protein for drug delivery. We show that 2.5F-Fc can be expressed by cell-free protein synthesis, during which a non-natural amino acid was introduced into the Fc domain and subsequently used for site-specific conjugation of MMAF through a noncleavable linker. The resulting knottin–Fc–drug conjugate (KFDC), termed 2.5F-Fc-MMAF, had approximately 2 drugs attached per KFDC. 2.5F–Fc–MMAF inhibited proliferation in human glioblastoma (U87MG), ovarian (A2780), and breast (MB-468) cancer cells to a greater extent than 2.5F–Fc or MMAF alone or added in combination. As a single agent, 2.5F–Fc–MMAF was effective at inducing regression and prolonged survival in U87MG tumor xenograft models when administered at 10 mg/kg two times per week. In comparison, tumors treated with 2.5F–Fc or MMAF were nonresponsive, and treatment with a nontargeted control, CTRL–Fc–MMAF, showed a modest but not significant therapeutic effect. These studies provide proof-of-concept for further development of KFDCs as alternatives to ADCs for tumor targeting and drug delivery applications. Mol Cancer Ther; 15(6); 1291–300. ©2016 AACR.
Prevalence of Voice Disturbances in the Pediatric Craniofacial Patient Population
Authors: Fritz Mark A. , Rickert Scott M. 
Published: March 2016

ObjectiveTo report on the prevalence of voice disturbances in the pediatric craniofacial population and to prove that the pediatric Voice Handicap Index (pVHI) is a useful questionnaire for this unique population.Study DesignCase series with chart review.SettingTertiary care center.SubjectsPediatric patients seen by a pediatric otolaryngologist in a craniofacial clinic.MethodsConsecutive patients (N = 366) seen by a single pediatric otolaryngologist in a craniofacial clinic from July 2011 to September 2012 were included. Any patient specifically referred for airway problems or voice difficulties completed a pVHI questionnaire. Patients each underwent an evaluation including flexible fiberoptic laryngoscopy and videostroboscopy. Voice disturbance was further characterized into dysphonia, hypernasality, or hyponasality.ResultsOf all the patients evaluated, 280 (77%) were specifically referred for airway problems or voice disturbance. Of those referred, 39 (10.7%) were found to have an organic vocal fold pathology causing dysphonia, as seen on the videostroboscopic examination; 53.7% of these lesions were attributable to potential iatrogenic causes. Hypernasality and hyponasality were seen in 116 (31.7%) and 78 (21.3%) patients, respectively. The pVHI was 3.95, 26.3, 11.34, and 10.53 for those with no voice disturbance, dysphonia, hypernasality, and hyponasality, respectively.ConclusionPediatric patients with craniofacial disorders have a higher prevalence of dysphonia than the general pediatric population. The majority of causes of dysphonia in these patients are possibly iatrogenic in origin. The pVHI serves as a useful questionnaire in this unique patient cohort to quantify the disability from not only dysphonia but also hypernasality and hyponasality.
Laryngeal Preservation in Glottic Cancer
Authors: Mandelbaum Rachel S. , Abemayor Elliot , Mendelsohn Abie H. 
Published: March 2016

ObjectiveWhen total laryngectomy is not required, organ preservation surgery or radiotherapy is considered the standard of care for primary glottic cancer. These accepted treatment options are available for early and advanced glottic cancers due to equivalent locoregional control and survival rates. However, in today’s climate of accountable care, the financial burden of treatment choices continues to increase in significance. We therefore compared hospital charges and treatment‐related morbidity between organ‐preserving surgery and radiation with or without chemotherapy—herein, (chemo)radiation—in the primary treatment of glottic cancer.Study DesignNationwide Inpatient Sample Database was analyzed to assess clinical and financial information.SettingPopulation‐based analysis.SubjectsPatients (N = 5499) with primary glottic cancer undergoing treatment with laryngeal preservation strategies.MethodsPatients were subdivided by ICD‐9 codes into 3 treatment groups: endoscopic resection, open partial laryngectomy, and (chemo)radiation. Treatment‐related outcomes, charges, and length of hospitalization were analyzed among treatment groups.ResultsWhen adjusting for sex, age, race, comorbidity, and primary payer, (chemo)radiotherapy was associated with increased direct charges (P <. 001; coefficient, $23,658.99; 95% confidence interval [95% CI]: $10,227.15‐$37,090.84) and length of hospitalization (P <. 001; hazard ratio, 0.593; 95% CI: 0.502‐0.702) when compared with endoscopic surgery. As compared with open surgery, endoscopic surgery was associated with reduced hospital charges (P =. 012; coefficient, $11,967.01; 95% CI: $2,784.17‐$21,249.85) and duration of hospitalization (P <. 001; hazard ratio, 0.749; 95% CI: 0.641‐0.876).ConclusionsThis analysis suggests that increased utilization of endoscopic surgery in patients with primary glottic cancer not requiring total laryngectomy may lead to reduced financial burden and duration of hospitalization when compared with open surgery or (chemo)radiation therapy.
Noninvasive neurostimulation methods for migraine therapy: The available evidence
Authors: Schoenen Jean , Roberta Baschi , Magis Delphine , Coppola Gianluca 
Published: March 2016

Background Migraine is one of the most disabling neurological disorders. The current pharmacological armamentarium is not satisfying for a large proportion of patients because the responder rate does not exceed 50% on average and the most effective drugs often induce intolerable side effects. During recent years, noninvasive central and peripheral neuromodulation methods have been explored for migraine treatment. Overview A review of the available evidence suggests that noninvasive neuromodulation techniques could be beneficial for migraine patients. The transcranial stimulation methods allow modulating selectively cortical activity and can thus be curtailed to the patient’s pathophysiological profile, while transcutaneous stimulation of pericranial nerves likely modulates central pain control centers. Occipital single-pulse transcranial magnetic stimulation and transcutaneous supraorbital stimulation have the strongest evidence respectively for acute and preventive treatment. Transcranial direct current stimulation and repetitive magnetic stimulation are promising in pilot studies, but large sham-controlled trials are not yet available. Conclusions The noninvasive neurostimulation methods are promising for migraine treatment and devoid of serious adverse effects allowing their combination with drug therapies. Their application in clinical practice will depend on the industry’s capacity to develop portable and user-friendly devices, and on the scientists’ capacity to prove their efficacy in randomized sham-controlled trials.