bluuebunny/crossref_metadata_2025_split huggingface dataset:
Transferrin Receptor‐Mediated Sequential Intercellular Nanoparticles Relay for Tumor Deep Penetration and Sonodynamic Therapy
Authors: Zhang Qiuhong , Wang Ning , Ma Ming , Luo Yu , Chen Hangrong 
Published: February 2019

AbstractSonodynamic therapy overcomes the tissue penetration barrier of photo‐activated therapeutics, whereas the poor tumor penetration of sonosensitizers largely lowers therapeutic effectiveness. Here, a brand‐new strategy for achieving tumor deep penetration is developed by exploiting the cellular recycling transferrin (Tf). Specifically, a new type of nanosonosensitizer self‐assembled from Tf and organic sonosensitizer protoporphyrin IX is first designed, which exhibits expected biosafety, stability, and ultrasound‐activated cytotoxic reactive oxygen species (ROS) production capability ensuring in vivo administration. More importantly, the nanosonosensitizers inherit the unique transferrin receptor (TfR)‐mediated endocytosis and exocytosis behaviors of Tf, enabling specific binding to TfR‐overexpressed tumor cells and thereafter TfR‐mediated sequential intercellular delivery of nanosonosensitizers. Consequently, tumor deep delivery of sonosensitizers is achieved in TfR‐overexpressed HeLa tumors, which is considerably beneficial for desired tumor‐suppression effect with ROS‐mediated sonodynamic therapy protocol. Such a TfR‐mediated sequential intercellular relay strategy offers an innovative concept for the deep delivery of nanomedicines in tumors.
Spatial price dynamics in the US vegetable sector
Authors: Durborow Samantha L. , Kim Seon‐Woong , Henneberry Shida R. , Brorsen B. Wade 
Published: February 2019

AbstractThis study investigates price transmission in the US fresh vegetable market, considering four important vegetables: carrots, lettuce, onions, and potatoes. An asymmetric variable‐threshold autoregressive (AvTAR) model was used to estimate price relationships between 40 pairs of terminal market vegetable prices, whereas the parity bounds model (PBM) was used to estimate the probability of 22 shipping point to terminal market pairs behaving efficiently. The estimated AvTAR models suggest market integration is higher for more perishable produce. Results for the PBM indicate that 18.2% of the markets studied had more than a 10% probability of behaving inefficiently, indicating that while the majority of markets behaved efficiently, there is room for improvement. The estimated thresholds have been suggested as an estimate of transport costs, but estimated thresholds often differ substantially from actual transport costs.
Outcomes with ibrutinib by line of therapy and post‐ibrutinib discontinuation in patients with chronic lymphocytic leukemia: Phase 3 analysis
Authors: O'Brien Susan M. , Byrd John C. , Hillmen Peter , Coutre Steven , Brown Jennifer R. , Barr Paul M. , Barrientos Jacqueline C. , Devereux Stephen , Robak Tadeusz , Reddy Nishitha M. , Kipps Thomas J. , Tedeschi Alessandra , Cymbalista Florence , Ghia Paolo , Chang Stephen , Ninomoto Joi , James Danelle F. , Burger Jan A. 
Published: February 2019

AbstractThe efficacy of ibrutinib has been demonstrated in patients with chronic lymphocytic leukemia (CLL), including as first‐line therapy. However, outcomes after ibrutinib discontinuation have previously been limited to higher‐risk populations with relapsed/refractory (R/R) disease. The objective of this study was to evaluate outcomes of ibrutinib‐treated patients based on prior lines of therapy, including after ibrutinib discontinuation. Data were analyzed from two multicenter phase 3 studies of single‐agent ibrutinib: RESONATE (PCYC‐1112) in patients with R/R CLL and RESONATE‐2 (PCYC‐1115) in patients with treatment‐naive (TN) CLL without del(17p). This integrated analysis included 271 ibrutinib‐treated non‐del(17p) patients with CLL (136 TN and 135 R/R). Median progression‐free survival (PFS) was not reached for subgroups with 0 and 1/2 prior therapies but was 40.6 months for patients with ≥3 therapies (median follow‐up: TN, 36 months; R/R, 44 months). Median overall survival (OS) was not reached in any subgroup. Overall response rate (ORR) was 92% in TN and 92% in R/R, with depth of response increasing over time. Adverse events (AEs) and ibrutinib discontinuation due to AEs were similar between patient groups. Most patients (64%) remain on treatment. OS following discontinuation was 9.3 months in R/R patients (median follow‐up 18 months, n = 51) and was not reached in TN patients (median follow‐up 10 months, n = 30). In this integrated analysis, ibrutinib was associated with favorable PFS and OS, and high ORR regardless of prior therapies in patients with CLL. The best outcomes following ibrutinib discontinuation were for patients receiving ibrutinib in earlier lines of therapy.
Rates of symptomatology are lower in recurrent sinonasal malignancy than in other recurrent cancers of the head and neck: a multi‐institutional study
Authors: Workman Alan D. , Velasquez Nathalia , Khan Nayel I. , Borchard Nicole A. , Kuan Edward C. , Palmer James N. , Wang Eric W. , Patel Zara M. , Adappa Nithin D. 
Published: February 2019

BackgroundSinonasal malignancies are a rare subset of head and neck tumors, and surveillance strategies after definitive tumor treatment are often generalized from those for overall head and neck cancer outcomes data. However, recent literature suggests that the posttreatment period in sinonasal cancer is fundamentally different and a more tailored surveillance approach may be beneficial. Although rates of symptomatology are high in head and neck cancer recurrence and patient‐driven follow‐up is common, rates of symptomatology are unknown in sinonasal cancer specifically.MethodsPatients with recurrence of sinonasal malignancy were identified at 3 academic rhinology and skull base surgery centers. Demographic, tumor, and treatment data were collected. Rates of symptomatology at presentation were tabulated and examined in the context of several other variables.ResultsFifty‐five patients had recurrence of sinonasal malignancy after definitive treatment. Fifty‐one percent of patients had no suspicious symptoms at the time of tumor recurrence, with an average time to recurrence of 33 months. Male patients and patients with stage IVA or lower disease were significantly more likely to be asymptomatic at the time of recurrence (p < 0.05).ConclusionPatients with sinonasal malignancy have a much lower rate of symptomatology during tumor recurrence than that observed in head and neck cancer overall. Furthermore, time to recurrence is substantially longer, as a majority of head and neck cancer recurrences occur in the first 12 months after treatment. These differences highlight the need for more tailored surveillance paradigms in asymptomatic patients with a history of a definitively treated sinonasal neoplasm.
β‐Selective C‐Glycosylation and its Application in the Synthesis of Scleropentaside A
Authors: Boehlich G. Jacob , Schützenmeister Nina 
Published: February 2019

AbstractC‐Glycosides are carbohydrates that bear a C−C bond to an aglycon at the anomeric center. Due to their high stability towards chemical and enzymatic hydrolysis, these compounds are widely used as carbohydrate mimics in drug development. Herein, we report a general and exclusively β‐selective method for the synthesis of a naturally abundant acyl‐C‐glycosidic structural motif first found in the scleropentaside natural product family. A Corey–Seebach umpolung reaction as the key step in the synthesis of scleropentaside A and analogues enables the β‐selective construction of the anomeric C−C bond starting from unprotected carbohydrates in only four steps. The one‐pot approach is highly atom‐efficient and avoids the use of toxic heavy metals.
Exploring environmental predictors of aquatic macrophytes in water‐dependent Natura 2000 sites of high conservation value: Results from a long‐term study of macrophytes in Greek lakes
Authors: Stefanidis Konstantinos , Sarika Maria , Papastegiadou Eva 
Published: February 2019

Abstract

Aquatic macrophytes play a key role in lake dynamics, but human activities and eutrophication have resulted in macrophyte loss in many lakes throughout Europe. In this study, the relationships between aquatic macrophytes and gradients of environmental factors were explored using an extensive set of data collected from 13 lakes of the Greek mainland that are part of the European network Natura 2000.
The main objectives were to assess the importance of key abiotic predictors and estimate possible environmental thresholds of macrophyte richness, diversity, and abundance using boosted regression trees (BRTs), as well as to explore further the distribution of dominant macrophyte taxa along environmental gradients.
The results reveal conductivity as a significant predictor of macrophyte total cover and diversity. In addition, orthophosphate and nitrate nitrogen appear to play an important role for several macrophyte species and assemblages, reflecting a major effect of eutrophication on the distribution of taxa. The majority of macrophyte assemblages were found in waters characterized by high nutrient content, although their distribution extends along a wide range of phosphorus and nitrogen concentration. In contrast, charophyte species show the optimum of their distribution in clear, oligotrophic waters.
This integrated study can be used for ranking environmental factors that influence macrophyte distribution in the lakes of Greece and for identifying taxa or macrophyte assemblages that can be used as effective indicators of changes in the abiotic environment. In addition, the results can contribute to the conservation of freshwater habitats in the protected areas studied. In particular, measures that aim to improve water quality are expected also to restore oligotrophic habitats that are characterized by benthic charophyte vegetation. Overall, the links between macrophyte assemblages and abiotic factors are critically important in improving freshwater biodiversity management and environmental policies in east Mediterranean lakes.
Keratoconus at a Molecular Level: A Review
Authors: Volatier Thomas L. A. , Figueiredo Francisco C. , Connon Che J. 
Published: February 2019

ABSTRACTKeratoconus is the most common ectatic disease of the cornea. The disease is usually detected between ages 15 and 25. Incidence is estimated at one out of every 2000 individuals, with some specific ethnic groups being more at risk. Keratoconus manifests itself as a progressive stromal thinning and deformation of the corneal tissue into a conical shape. The etiology of keratoconus is uncertain, although several studies have associated the disease to environmental factors, behavioral conditions and certain genetic disorders. In an effort to better understand how the corneal stroma becomes compromised, multiple experiments have been conducted over the last few years looking at the cells themselves and the factors they produce. The secretion pathways and levels of inflammatory molecules, growth factors, digestive enzymes, and apoptotic factors are all relevant to keratoconus. This review describes the current knowledge of keratoconic pathological signaling pathways within the cornea that may help future developments in disease prevention, treatment and modeling. Anat Rec, 2019. © 2019 Wiley Periodicals, Inc.
An X‐ray microtomography‐based method for detailed analysis of the three‐dimensional morphology of fungal pellets
Authors: Schmideder Stefan , Barthel Lars , Friedrich Tiaan , Thalhammer Michaela , Kovačević Tijana , Niessen Ludwig , Meyer Vera , Briesen Heiko 
Published: February 2019

AbstractFilamentous fungi are widely used in the production of biotechnological compounds. Since their morphology is strongly linked to productivity, it is a key parameter in industrial biotechnology. However, identifying the morphological properties of filamentous fungi is challenging. Owing to a lack of appropriate methods, the detailed three‐dimensional morphology of filamentous pellets remains unexplored. In the present study, we used state‐of‐the‐art X‐ray microtomography (µCT) to develop a new method for detailed characterization of fungal pellets. µCT measurements were performed using freeze‐dried pellets obtained from submerged cultivations. Three‐dimensional images were generated and analyzed to locate and quantify hyphal material, tips, and branches. As a result, morphological properties including hyphal length, tip number, branch number, hyphal growth unit, porosity, and hyphal average diameter were ascertained. To validate the potential of the new method, two fungal pellets were studied—one from Aspergillus niger and the other from
Penicillium chrysogenum. We show here that µCT analysis is a promising tool to study the three‐dimensional structure of pellet‐forming filamentous microorganisms in utmost detail. The knowledge gained can be used to understand and thus optimize pellet structures by means of appropriate process or genetic control in biotechnological applications.
The clinical implication of CD45RA+ naïve T cells and CD45RO+ memory T cells in advanced pancreatic cancer: a proxy for tumor biology and outcome prediction
Authors: Hang Junjie , Huang Junjie , Zhou Siyuan , Wu Lixia , Zhu Yingwei , Zhu Lina , Zhou Hanyu , Xu Kequn , Jiang Hua , Yang Xuguang 
Published: February 2019

AbstractNaïve and memory T cells play a pivotal role in solid tumor pathogenesis but their role in pancreatic cancer progression remains elusive. Thus, we aimed to investigate their clinical potential in advanced pancreatic cancer (APC). Flow cytometry was performed to evaluate the level of baseline peripheral naïve and memory T cells from 137 APC patients before receiving first‐line chemotherapy. Interrelationships between naïve, memory T cells and clinicopathological variables were evaluated using Pearson’s correlation. The prognostic impact of naïve and memory T cells were assessed by Kaplan‐Meier analysis and Cox regression. The correlation between naïve/memory T cells and tumor progression was investigated by Student’s t test. CD4+ naïve/memory ratio showed close correlations with hemoglobin, red blood cell (RBC), absolute neutrophil count (ANC) and platelet while CD8+ naïve/memory ratio was correlated with hemoglobin, RBC and CEA. Higher baseline lever of CD4+CD45RO+/CD4+ was correlated with better overall survival (OS) (P = 0.036). Patients with CD4+ naïve/memory ratio ≥0.36 had a poorer OS than those with CD4+ naïve/memory ratio <0.36 (P = 0.021). In addition, CD4+ naïve/memory ratio showed independent prognostic impact (HR 1.427, 95% CI 1.033‐1.973, P = 0.031). Furthermore, poorer clinical response was correlated with higher level of CD8+ naïve/memory ratio after the third cycle of chemotherapy (P = 0.01). Besides, patients with a lower level of CD8+ naïve/memory ratio had longer progression‐free survival (PFS) (P = 0.028). We propose CD4+ naïve/memory ratio as a novel prognostic biomarker for APC. In addition, CD8+ naïve/memory ratio can be a candidate marker for predicting PFS and the change of its level may reflect the progression of APC.
A Concise, Modular Antibody–Oligonucleotide Conjugation Strategy Based on Disuccinimidyl Ester Activation Chemistry
Authors: Li Gang , Moellering Raymond E. 
Published: February 2019

AbstractThe synthesis of antibody–oligonucleotide conjugates has enabled the development of highly sensitive bioassays for specific epitopes in the laboratory and clinic. Most synthetic schemes to generate these hybrid molecules require expensive reagents, significant quantities of input antibody, and multistep purification routes; thus limiting widespread application. Herein a facile and robust conjugation strategy is reported that involves “plug‐and‐play” antibody conjugation with succinimidyl‐functionalized oligonucleotides, which are high yielding and compatible for use directly after buffer exchange. The succinimidyl‐linked oligonucleotides are synthesized with 5′‐amine‐modified oligonucleotides and disuccinimidyl suberate (DSS), both of which are inexpensive and commercially available. Direct incubation of the resulting stable succinimidyl– oligonucleotide conjugates with commercial antibodies yields conjugates ready for use after benchtop buffer exchange. It is demonstrated that the resulting oligonucleotide–antibody and oligonucleotide–streptavidin conjugates retain potent and specific binding in activity‐dependent proximity ligation imaging, and proximity ligation‐mediated qPCR detection of endogenous proteins in native cellular contexts down to picogram levels of whole proteome. This DSS conjugation strategy should be widely applicable in the synthesis of protein–oligonucleotide conjugates.
A Layered Lithium‐Rich Li(Li0.2Ni0.15Mn0.55Co0.1)O2 Cathode Material: Surface Phase Modification and Enhanced Electrochemical Properties for Lithium‐Ion Batteries
Authors: Zhang Li , He Wei , Peng Dong‐Liang , Xie Qingshui , Xie Rong‐Jun 
Published: February 2019

AbstractLayered lithium‐rich oxides are recognized as promising cathode materials for lithium‐ion batteries (LIBs), owing to their high‐energy density, high voltage, high specific capacity, and low cost. However, it remains a critical challenge to realize the high capacity of layered lithium‐rich oxides. Herein, we synthesize the Li‐rich Li(Li0.2Ni0.15Mn0.55Co0.1)O2 cathode material by using the sol‐gel method and induced a spinel phase on its surface through carbonization‐reduction engineering. The surface‐modified sample exhibited both improved capacity and rate capabilities. The initial discharge capacity of the treated sample reached 279.6 mAh g−1 at 0.1 C, which was 11 % higher when compared to the as‐prepared sample (252.6 mAh g−1). In addition, a discharge capacity of 239.4 and 235.9 mAh g−1 after 100 cycles at 0.5 C and 1 C (1 C=250 mAh g−1) could be still obtained for the modified sample, respectively. The enhanced properties were attributed to the increased ionic conductivity through the formation of 3D diffusion paths and reduced structural transformation, owing to the spinel structure decoration on the surface.
SiOx/C‐Decorated CoO Nanosheets as a Long‐life Anode for Lithium‐Ion Batteries
Authors: Wang Pu , Hou Shuang , Pang Fang , Liu Miao , Li Yanxin , Liu Tiezhong , Luo Yizhen , Fan YaMeng , Zhao Lingzhi 
Published: February 2019

AbstractUnique hierarchical mosaic‐structure SiOx/C@CoO nanosheets were successfully synthesized from SiOx/C nanospheres embedded in CoO nanosheets through a high‐energy ball milling and hydrothermal self‐assembly process. The SiOx/C@CoO material exhibited good cyclic performance with a reversible discharge capacity of 1079 mAh g−1 over 250 cycles at a current density of 1000 mA g−1. It also displayed an excellent rate capability (with an average specific reversible discharge capacity of 777.8 mAh g−1 at 2000 mA g−1 and 480 mAh g−1 at 5000 mA g−1). The stable skeleton structure of SiOx/C‐embedded CoO nanosheets and the synergistic effect between the two materials should be responsible for the improvement of the lithium storage. This work proposes a feasible approach to promote CoO application in lithium‐ion batteries.
Hyperprogressive disease in early‐phase immunotherapy trials: Clinical predictors and association with immune‐related toxicities
Authors: Kanjanapan Yada , Day Daphne , Wang Lisa , Al‐Sawaihey Hamad , Abbas Engy , Namini Amirali , Siu Lillian L. , Hansen Aaron , Razak Albiruni Abdul , Spreafico Anna , Leighl Natasha , Joshua Anthony M. , Butler Marcus O. , Hogg David , Chappell Mary Anne , Soultani Ludmilla , Chow Kayla , Boujos Samantha , Bedard Philippe L. 
Published: February 2019

BackgroundA subset of patients treated with immune checkpoint inhibitors experience an accelerated tumor growth rate (TGR) in comparison with pretreatment kinetics; this is known as hyperprogression. This study assessed the relation between hyperprogressive disease (HPD) and treatment‐related toxicity and clinical factors.MethodsThis study reviewed patients with solid tumors who were enrolled in early‐phase immunotherapy trials at Princess Margaret Cancer Centre between August 2012 and September 2016 and had computed tomography scans in the pre‐immunotherapy (reference) and on‐immunotherapy (experimental) periods. HPD was defined as progression according to Response Evaluation Criteria in Solid Tumors 1.1 at the first on‐treatment scan and a ≥2‐fold increase in TGR between the reference and experimental periods. Treatment‐related toxicities requiring systemic therapy, drug delays, or discontinuation were considered clinically significant adverse events (CSAEs).ResultsOf 352 patients, 182 were eligible for analysis. The median age was 60 years, and 54% were male. The Eastern Cooperative Oncology Group performance status was 0 (32%) or 1 (68%). The Royal Marsden Hospital (RMH) prognostic score was 0/1 in 59%. Single‐agent immunotherapy was given to 80% of the patients. Most patients (89%) received anti‐programmed death (ligand) 1 antibodies alone or in combination with other therapies. HPD occurred in 12 of 182 patients (7%). A higher proportion of females was seen among HPD patients (P = .01), but no association with age, performance status, tumor type, RMH prognostic score, combination immunotherapy, or CSAEs was found. The 1‐year overall survival rate was 28% for HPD patients and 53% for non‐HPD patients (hazard ratio, 1.7; 95% confidence interval, 0.9‐3.3; P = .11).ConclusionsHPD was observed in 7% of patients with solid tumors treated with immunotherapy. HPD was not associated with CSAEs, age, tumor type, or the type of immunotherapy but was more common in females.
Altered mitochondrial trafficking as a novel mechanism of cancer metastasis
Authors: Furnish Madison , Caino M. Cecilia 
Published: February 2019

AbstractBackgroundMammalian cells must constantly reprogram the distribution of mitochondria in order to meet the local demands for energy, calcium, redox balance, and other mitochondrial functions. Mitochondrial localization inside the cell is a result of a combination of movement along the microtubule tracks plus anchoring to actin filaments.Recent findingsRecent advances show that subcellular distribution of mitochondria can regulate tumor cell growth, proliferation/motility plasticity, metastatic competence, and therapy responses in tumors. In this review, we discuss our current understanding of the mechanisms by which mitochondrial subcellular distribution is regulated in tumor cells.ConclusionsMitochondrial trafficking is dysregulated in tumors. Accumulation of mitochondria at the leading edge of the cell supports energy expensive processes of focal adhesion dynamics, cell membrane dynamics, migration, and invasion.
On the parallelization of Hirschberg's algorithm for multi‐core and many‐core systems
Authors: João Mario , Sena Alexandre C. , Rebello Vinod E. F. 
Published: February 2019

SummaryFinding the longest common subsequence between two strings in acceptable time frames is crucial to solving various problems in different fields of study. To ensure the optimal solution is found, algorithms based on dynamic programming are employed almost exclusively. While the most commonly adopted algorithm, proposed by Needleman and Wunsch, has quadratic time and space complexity, the linear space complexity of Hirschberg's algorithm favors the comparisons of longer sequences. However, it too has a quadratic time complexity and therefore the effective exploitation of parallelism has become essential. This paper focuses on improving the execution efficiency of Hirschberg's algorithm on multi‐core and many‐core systems. To achieve this goal, first, enhancements to the sequential version are proposed to take advantage of SIMD instructions available on modern processors. Second, the impact on the performance of different parallelization strategies is investigated and evaluated. Results show that combining these two aspects can greatly improve the performance of Hirschberg's algorithm on these architectures. In relation to the original version, speedups of over 46 were achieved on a dual 18‐core server for sequences of 1.6 million characters. Furthermore, experiments with a 68‐core Intel Xeon Phi (many‐core) system obtained speedups of up to 105 for the same sequence size.