bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evaluation of a Methodology for Estimating HbA1c Value by a New Glucose Meter
Authors: Sieber Jochen , Flacke Frank , Dumais Bonnie , Peters Casey C. , Mallery Erin B. , Taylor Liz 
Published: May 2015

Background: Accuracy/robustness of HbA1c estimation (eA1c) with an algorithm built into the MyStar Extra blood glucose (BG) meter has been demonstrated by in silico testing. We evaluated the performance and use of eA1c in a clinical setting. Methods: Subjects took the BG meter home for 4 months to obtain eA1c in this open-label, single-center study. Laboratory HbA1c values were obtained approximately every 2 weeks and the corresponding eA1c documented. Subjects completed a questionnaire at study end (NCT01885546). Results: There were 133 enrolled subjects (mean [SD] age 60.0 [15.0] years, 69 males, 104 with diabetes, HbA1c 7.0% [1.4]). A total of 1008 pairs of eA1c and laboratory HbA1c values were available. In subjects with diabetes, 97.5% of the eA1c results fell within ±20% of the laboratory HbA1c, 95.0% within ±18%, and 90.7% within ±15%. When results were limited to the reportable HbA1c range of ≥6 to ≤10%, 99.3% of eA1c values fell within ±20% of the laboratory HbA1c, 98.5% within ±18%, and 96.2% within ±15% Most subjects agreed/strongly agreed that the eA1c section in the user guide and flash cards was easy to follow (72%), they would use the system to track their eA1c (70%), they found the eA1c tool helpful (79%), and the tool may motivate them to manage their diabetes better (83%). Conclusions: Accuracy of the eA1c feature in this clinical setting was similar to the performance in silico. The majority of subjects found this tool helpful and agreed it may motivate to manage their diabetes better.
How I treat Waldenström macroglobulinemia
Authors: Treon Steven P. 
Published: May 2015

AbstractWaldenström macroglobulinemia (WM) is a B-cell neoplasm manifested by the accumulation of clonal immunoglobulin (Ig)M-secreting lymphoplasmacytic cells. MYD88 and CXCR4 warts, hypogammaglobulinemia, infections, myelokathexis syndrome-like somatic mutations are present in >90% and 30% to 35% of WM patients, respectively, and impact disease presentation, treatment outcome, and overall survival. Familial predisposition is common in WM. Asymptomatic patients should be observed. Patients with disease-related hemoglobin <10 g/L, platelets <100 × 109/L, bulky adenopathy and/or organomegaly, symptomatic hyperviscosity, peripheral neuropathy, amyloidosis, cryoglobulinemia, cold-agglutinin disease, or transformed disease should be considered for therapy. Plasmapheresis should be used for patients with symptomatic hyperviscosity and before rituximab for those with high serum IgM levels to preempt a symptomatic IgM flare. Treatment choice should take into account specific goals of therapy, necessity for rapid disease control, risk of treatment-related neuropathy, immunosuppression and secondary malignancies, and planning for future autologous stem cell transplantation. Frontline treatments include rituximab alone or rituximab combined with alkylators (bendamustine and cyclophosphamide), proteasome inhibitors (bortezomib and carfilzomib), nucleoside analogs (fludarabine and cladribine), and ibrutinib. In the salvage setting, an alternative frontline regimen, ibrutinib, everolimus, or stem cell transplantation can be considered. Investigational therapies under development for WM include agents that target MYD88, CXCR4, BCL2, and CD27/CD70 signaling, novel proteasome inhibitors, and chimeric antigen receptor-modified T-cell therapy.
Lenalidomide augments actin remodeling and lowers NK-cell activation thresholds
Authors: Lagrue Kathryn , Carisey Alex , Morgan David J. , Chopra Rajesh , Davis Daniel M. 
Published: May 2015

Key Points
Lenalidomide augments nanoscale rearrangements in cortical actin at the human NK-cell immune synapse. Lenalidomide lowers the threshold for NK-cell activation, allowing activation by low levels of ligands on tumor cells.
CC-122, a pleiotropic pathway modifier, mimics an interferon response and has antitumor activity in DLBCL
Authors: Hagner Patrick R. , Man Hon-Wah , Fontanillo Celia , Wang Maria , Couto Suzana , Breider Mike , Bjorklund Chad , Havens Courtney G. , Lu Gang , Rychak Emily , Raymon Heather , Narla Rama Krishna , Barnes Leo , Khambatta Gody , Chiu Hsiling , Kosek Jolanta , Kang Jian , Amantangelo Michael D. , Waldman Michelle , Lopez-Girona Antonia , Cai Ti , Pourdehnad Michael , Trotter Matthew , Daniel Thomas O. , Schafer Peter H. , Klippel Anke , Thakurta Anjan , Chopra Rajesh , Gandhi Anita K. 
Published: May 2015

Key Points
CC-122 is a novel agent for DLBCL with antitumor and immunomodulatory activity. CC-122 binds CRBN and degrades Aiolos and Ikaros resulting in a mimicry of IFN signaling and apoptosis in DLBCL.
Sequence-based ultra-dense genetic and physical maps reveal structural variations of allopolyploid cotton genomes
Authors: Wang Sen , Chen Jiedan , Zhang Wenpan , Hu Yan , Chang Lijing , Fang Lei , Wang Qiong , Lv Fenni , Wu Huaitong , Si Zhanfeng , Chen Shuqi , Cai Caiping , Zhu Xiefei , Zhou Baoliang , Guo Wangzhen , Zhang Tianzhen 
Published: May 2015

Abstract
Background
SNPs are the most abundant polymorphism type, and have been explored in many crop genomic studies, including rice and maize. SNP discovery in allotetraploid cotton genomes has lagged behind that of other crops due to their complexity and polyploidy. In this study, genome-wide SNPs are detected systematically using next-generation sequencing and efficient SNP genotyping methods, and used to construct a linkage map and characterize the structural variations in polyploid cotton genomes.

Results
We construct an ultra-dense inter-specific genetic map comprising 4,999,048 SNP loci distributed unevenly in 26 allotetraploid cotton linkage groups and covering 4,042 cM. The map is used to order tetraploid cotton genome scaffolds for accurate assembly of G. hirsutum acc. TM-1. Recombination rates and hotspots are identified across the cotton genome by comparing the assembled draft sequence and the genetic map. Using this map, genome rearrangements and centromeric regions are identified in tetraploid cotton by combining information from the publicly-available G. raimondii genome with fluorescent in situ hybridization analysis.

Conclusions
We report the genotype-by-sequencing method used to identify millions of SNPs between G. hirsutum and G. barbadense. We construct and use an ultra-dense SNP map to correct sequence mis-assemblies, merge scaffolds into pseudomolecules corresponding to chromosomes, detect genome rearrangements, and identify centromeric regions in allotetraploid cottons. We find that the centromeric retro-element sequence of tetraploid cotton derived from the D subgenome progenitor might have invaded the A subgenome centromeres after allotetrapolyploid formation. This study serves as a valuable genomic resource for genetic research and breeding of cotton.
Markers for the identification of tendon-derived stem cells in vitro and tendon stem cells in situ – update and future development
Authors: Lui Pauline Po Yee 
Published: May 2015

AbstractThe efficacy of tendon-derived stem cells (TDSCs) for the promotion of tendon and tendon-bone junction repair has been reported in animal studies. Modulation of the tendon stem cell niche in vivo has also been reported to influence tendon structure. There is a need to have specific and reliable markers that can define TDSCs in vitro and tendon stem cells in situ for several reasons: to understand the basic biology of TDSCs and their subpopulations in vitro; to understand the identity, niches and functions of tendon/progenitor stem cells in vivo; to meet the governmental regulatory requirements for quality of TDSCs when translating the exciting preclinical findings into clinical trial/practice; and to develop new treatment strategies for mobilizing endogenous stem/progenitor cells in tendon. TDSCs were reported to express the common mesenchymal stem cell (MSC) markers and some embryonic stem cell (ESC) markers, and there were attempts to use these markers to label tendon stem cells in situ. Are these stem cell markers useful for the identification of TDSCs in vitro and tracking of tendon stem cells in situ? This review aims to discuss the values of the panel of MSC, ESC and tendon-related markers for the identification of TDSCs in vitro. Important factors influencing marker expression by TDSCs are discussed. The usefulness and limitations of the panel of MSC, ESC and tendon-related markers for tracking stem cells in tendon, especially tendon stem cells, in situ are then reviewed. Future research directions are proposed.
Synthesis, characterization, and preclinical validation of a PET radiopharmaceutical for interrogating Aβ (β-amyloid) plaques in Alzheimer’s disease
Authors: Sundaram Guruswami SM , Dhavale Dhruva , Prior Julie L , Sivapackiam Jothilingam , Laforest Richard , Kotzbauer Paul , Sharma Vijay 
Published: May 2015

Abstract

Background
PET radiopharmaceuticals capable of imaging β-amyloid (Aβ) plaque burden in the brain could offer highly valuable diagnostic tools for clinical studies of Alzheimer’s disease. To further supplement existing armamentarium of FDA-approved agents as well as those under development, and to correlate multiphoton-imaging data reported earlier, herein, we describe preclinical validation of a PET tracer.

Methods
A novel PET radiopharmaceutical (18F-7B) was synthesized and characterized. To assess its affinity for Aβ, binding assays with Aβ1-42 fibrils, Alzheimer’s disease (AD) homogenates, and autoradiography studies and their IHC correlations were performed. For assessing its overall pharmacokinetic profiles in general and its ability to cross the blood-brain barrier (BBB) in particular, biodistribution studies in normal mice were performed. Finally, for evaluating potential for 18F-7B to serve as a targeted Aβ probe, the microPET/CT imaging was performed in age-matched amyloid precursor protein/presenilin-1 (APP/PS1) mice and wild-type (WT) counterparts.

Results
The radiotracer 18F-7B shows saturable binding to autopsy-confirmed AD homogenates (K
d = 17.7 nM) and Aβ1-42 fibrils (K
d = 61 nM). Preliminary autoradiography studies show binding of 18F-7B to cortical Aβ plaques in autopsy-confirmed AD tissue sections, inhibition of that binding by unlabeled counterpart 7A-indicating specificity, and a good correlation of tracer binding with Aβ immunostaining. The agent indicates high initial penetration into brains (7.23 ± 0.47%ID/g; 5 min) of normal mice, thus indicating a 5-min/120-min brain uptake clearance ratio of 4.7, a benchmark value (>4) consistent with the ability of agents to traverse the BBB to enable PET brain imaging. Additionally, 18F-7B demonstrates the presence of parental species in human serum. Preliminary microPET/CT imaging demonstrates significantly higher retention of 18F-7B in brains of transgenic mice compared with their WT counterparts, consistent with expected binding of the radiotracer to Aβ plaques, present in APP/PS1 mice, compared with their age-matched WT counterparts lacking those Aβ aggregates.

Conclusions
These data offer a platform scaffold conducive to further optimization for developing new PET tracers to study Aβ pathophysiology in vitro and in vivo.
Optimal site for facial nerve transection and neurorrhaphy: A randomized prospective animal study
Authors: Mendez Adrian I. , Seikaly Hadi , Biron Vincent , Zhu Lin-fu , Côté David W. J. 
Published: May 2015

Background Since the first facial allograft transplantation was performed, several institutions have performed the procedure with the main objectives being restoration of the aesthetic appearance and expressive function of the face. The optimal location to transect the facial nerve during flap harvest in transplantation to preserve facial movement function is currently unknown. There are currently two primary methods to perform facial nerve neurorrhaphy between the donor and recipient-one protocol involves transection and repair of the facial nerve at the main trunk while the another protocol advocates for the neurorrhaphy to be performed distally at the main branches. The purpose of this study is to establish the optimal location for transection and repair of the facial nerve to optimize functional recovery of facial movement. Methods A prospective randomized controlled trial using a rat model was performed. Two groups of 12 rats underwent facial nerve transection and subsequent repair either at the main trunk of the nerve (group 1) or 2 cm distally, at the main bifurcation (group 2). Primary outcome of nerve functional recovery was measured using a previously validated laser curtain model, which measured amplitude of whisking at 2, 4, and 6 post-operatively. The deflection of the laser curtain sent a digital signal that was interpreted by central computer software. Results At week 2 post-nerve surgery, the average amplitude observed for group 1 and 2 was 4.4 and 10.8 degrees, respectively. At week 4, group 1 showed improvement with an average amplitude of 9.7 degrees, while group 2 displayed an average of 10.2 degrees. The week 6 results showed the greatest improvement from baseline for group 1. Group 1 and 2 had average amplitudes of 17.2 and 6.9 degrees, respectively. There was no statistically significant difference between the two groups at 2, 4, and 6 weeks after facial nerve surgery ( p > 0.05). Conclusions We found no statistical difference between these two locations of nerve repair using identical methods. Therefore, the authors recommend a single versus multiple nerve repair technique. This finding has potential implications for future facial allograft transplantations and at minimum necessitates further study with long-term follow-up data.
Sexual dimorphism in echolocation pulse parameters of the CF-FM bat, Hipposideros pratti
Authors: Fu Zi-Ying , Dai Xing-Yue , Xu Na , Shi Qing , Li Gao-Jing , Li Bin , Li Juan , Li Jie , Tang Jia , Jen Philip Hung-Sun , Chen Qi-Cai 
Published: May 2015

Abstract

Background
Previous studies of sexual dimorphism in the echolocation pulses of the constant frequency-frequency modulating (CF-FM) bat have been mainly concentrated on the difference in the frequency of the CF component of the predominant second harmonic while neglected other pulse parameters. However, recent studies have shown that other pulse parameters of the predominant second harmonic are also biologically significant to the bat hunting. To complement and advance these studies, we have examined sexual dimorphism of multiple parameters (e.g., duration, frequency, bandwidth of the FM component, and repetition rate of emitted pulses) of the echolocation pulses of the CF-FM bat, Hipposideros pratti.

Results
Our studies of the predominant second harmonic show that on average the male bat has higher frequency of the CF component, wider FM bandwidth, and higher pulse repetition rate while the female bat has longer duration of the CF and FM components.

Conclusions
These observations suggest that bats may potentially use this sexual dimorphism in echolocation pulse parameters for social communication and species and sex identification.
Interactions between rat alveolar epithelial cells and bone marrow-derived mesenchymal stem cells: an in vitro co-culture model
Authors: Ito Hiroyuki , Uchida Tokujiro , Makita Koshi 
Published: May 2015

Abstract

Background
Bone marrow-derived mesenchymal stem cells (BMSCs) reduced the severity of acute lung injury after transplantation in multiple experimental studies, and several paracrine soluble factors secreted by the cells likely contribute to their therapeutic effect. The direct interactions between BMSCs and alveolar epithelial cells (AECs) may be an important part of their beneficial effects. Therefore, we assessed the interactions between BMSCs and AECs using a co-culture model of these two cell types from rats.

Methods
BMSCs and AECs were co-cultured using a Transwell system under the following conditions: (1) separated co-culture—AECs seeded on the insert and BMSCs in the base of the well; and (2) mixed co-culture—AECs on top of the monolayer of BMSCs on the culture insert and no cells in the base of the well. After 21 days of culture, the cells on the membrane of the culture insert were fixed and stained with antibodies against the receptor for advanced glycation end-products (RAGE), surfactant protein D (SP-D), and zona occludens protein-1, and then analyzed by confocal microscopy.

Results
In the separated co-culture condition, the phenotype of the AECs was maintained for 21 days, and cluster formation of SP-D-positive cells was induced in the AEC monolayer. We also found cluster formations of phospholipid-positive cells covered with RAGE-positive epithelial cells. In the mixed co-culture condition, the BMSCs induced alveolar-like structures covered with an epithelial cell layer. To determine the effect of keratinocyte growth factor (KGF) on this three-dimensional structure formation, we treated the mixed co-cultures with siRNA for KGF. While KGF siRNA treatment induced a significant reduction in surfactant protein transcript expression, formation of the alveolar-like structure was unaffected. We also assessed whether Gap26, a functional inhibitor of connexin-43, could mitigate the effect of the BMSCs on the AECs. However, even at 300 μM, Gap26 did not inhibit formation of the alveolar-like structure.

Conclusions
BMSCs release soluble factors that help maintain and sustain the AEC phenotype for 21 days, and direct interaction between these two cell types can induce a cyst-like, three-dimensional structure covered with AECs.
Matrix compliance and the regulation of cytokinesis
Authors: Sambandamoorthy Savitha , Mathew-Steiner Shomita , Varney Scott , Zuidema Jonathan M. , Gilbert Ryan J. , Van De Water Livingston , LaFlamme Susan E. 
Published: May 2015

ABSTRACTIntegrin-mediated cell adhesion to the ECM regulates many physiological processes in part by controlling cell proliferation. It is well established that many normal cells require integrin-mediated adhesion to enter S phase of the cell cycle. Recent evidence indicates that integrins also regulate cytokinesis. Mechanical properties of the ECM can dictate entry into S phase; however, it is not known whether they also can affect the successful completion of cell division. To address this issue, we modulated substrate compliance using fibronectin-coated acrylamide-based hydrogels. Soft and hard substrates were generated with approximate elastic moduli of 1600 and 34,000 Pascals (Pa) respectively. Our results indicate that dermal fibroblasts successfully complete cytokinesis on hard substrates, whereas on soft substrates, a significant number fail and become binucleated. Cytokinesis failure occurs at a step following the formation of the intercellular bridge connecting presumptive daughter cells, suggesting a defect in abscission. Like dermal fibroblasts, mesenchymal stem cells require cell-matrix adhesion for successful cytokinesis. However, in contrast to dermal fibroblasts, they are able to complete cytokinesis on both hard and soft substrates. These results indicate that matrix stiffness regulates the successful completion of cytokinesis, and does so in a cell-type specific manner. To our knowledge, our study is the first to demonstrate that matrix stiffness can affect cytokinesis. Understanding the cell-type specific contribution of matrix compliance to the regulation of cytokinesis will provide new insights important for development, as well as tissue homeostasis and regeneration.
Dysregulated LIF-STAT3 pathway is responsible for impaired embryo implantation in a Streptozotocin-induced diabetic mouse model
Authors: Wang Tong-Song , Gao Fei , Qi Qian-Rong , Qin Fu-Niu , Zuo Ru-Juan , Li Zi-Long , Liu Ji-Long , Yang Zeng-Ming 
Published: May 2015

ABSTRACT
The prevalence of diabetes is increasing worldwide with the trend of patients being young and creating a significant burden on health systems, including reproductive problems, but the effects of diabetes on embryo implantation are still poorly understood. Our study was to examine effects of diabetes on mouse embryo implantation, providing experimental basis for treating diabetes and its complications. Streptozotocin (STZ) was applied to induce type 1 diabetes from day 2 of pregnancy or pseudopregnancy in mice. Embryo transfer was used to analyze effects of uterine environment on embryo implantation. Our results revealed that the implantation rate is significantly reduced in diabetic mice compared to controls, and the change of uterine environment is the main reason leading to the decreased implantation rate. Compared to control, the levels of LIF and p-STAT3 are significantly decreased in diabetic mice on day 4 of pregnancy, and serum estrogen level is significantly higher. Estrogen stimulates LIF expression under physiological level, but the excessive estrogen inhibits LIF expression. LIF, progesterone or insulin supplement can rescue embryo implantation in diabetic mice. Our data indicated that the dysregulated LIF-STAT3 pathway caused by the high level of estrogen results in the impaired implantation in diabetic mice, which can be rescued by LIF, progesterone or insulin supplement.
Inexhaustible hair-cell regeneration in young and aged zebrafish
Authors: Pinto-Teixeira Filipe , Viader-Llargués Oriol , Torres-Mejía Elen , Turan Melissa , González-Gualda Estela , Pola-Morell Laura , López-Schier Hernán 
Published: May 2015

ABSTRACTAnimals have evolved two general strategies to counter injury and maintain physiological function. The most prevalent is protection by isolating vital organs into body cavities. However, protection is not optimal for sensory systems because their external components need to be exposed to the environment to fulfill their receptive function. Thus, a common strategy to maintain sensory abilities against persistent environmental insult involves repair and regeneration. However, whether age or frequent injuries affect the regenerative capacity of sensory organs remains unknown. We have found that neuromasts of the zebrafish lateral line regenerate mechanosensory hair cells after recurrent severe injuries and in adulthood. Moreover, neuromasts can reverse transient imbalances of Notch signaling that result in defective organ proportions during repair. Our results reveal inextinguishable hair-cell regeneration in the lateral line, and suggest that the neuromast epithelium is formed by plastic territories that are maintained by continuous intercellular communication.
Structures, properties, and functions of the stings of honey bees and paper wasps: a comparative study
Authors: Zhao Zi-Long , Zhao Hong-Ping , Ma Guo-Jun , Wu Cheng-Wei , Yang Kai , Feng Xi-Qiao 
Published: May 2015

ABSTRACT
Through natural selection, many animal organs with similar functions have evolved different macroscopic morphologies and microscopic structures. Here, we comparatively investigate the structures, properties and functions of honey bee stings and paper wasp stings. Their elegant structures were systematically observed. To examine their behaviors of penetrating into different materials, we performed penetration–extraction tests and slow motion analyses of their insertion process. In comparison, the barbed stings of honey bees are relatively difficult to be withdrawn from fibrous tissues (e.g. skin), while the removal of paper wasp stings is easier due to their different structures and insertion skills. The similarities and differences of the two kinds of stings are summarized on the basis of the experiments and observations.