bluuebunny/crossref_metadata_2025_split huggingface dataset:
The derivation of effects threshold concentrations of lead for European freshwater ecosystems
Authors: Van Sprang Patrick A. , Nys Charlotte , Blust Ronny J.P. , Chowdhury Jasim , Gustafsson Jon P. , Janssen Colin J. , De Schamphelaere Karel A.C. 
Published: November 2015

Abstract

The main objective of the present study was to derive ecologically relevant effect threshold concentrations of (dissolved) Pb for selected European Union (EU) freshwater rivers, using the 2008 EU Voluntary Risk Assessment Report as a starting point and more advanced methodologies than those used in the Voluntary Risk Assessment Report. This included 1) implementing more robust quality criteria for selecting chronic toxicity data; 2) the conversion of total to dissolved Pb concentrations using a combination of an empirical equation relating inorganic Pb solubility and geochemical speciation modeling to account for effects of dissolved organic matter; 3) the use of bioavailability models for chronic toxicity for species belonging to 3 different trophic levels; and 4) the use of robust methods for large data set handling (such as species sensitivity distribution [SSD] analysis). The authors used published bioavailability models for an algal species (Pseudokirchneriella subcapitata) and a daphnid (Ceriodaphnia dubia) and developed a new model for the fathead minnow (Pimephales promelas). The research has shown that these models are also useful for, and reasonably accurate in, predicting chronic toxicity to other species, including a snail, a rotifer, midge larvae, and an aquatic plant (read-across). A comprehensive chronic toxicity data set for Pb was compiled, comprising 159 individual high-quality toxicity data for 25 different species. By applying the total dissolved conversion and the bioavailability models, normalized toxicity values were obtained, which were then entered into a SSD analysis. Based on the parametric best-fitting SSDs, the authors calculated that ecological threshold concentrations of Pb protecting 95% of freshwater species for 7 selected European freshwater scenarios were between 6.3 μg dissolved Pb/L and 31.1 μg dissolved Pb/L. Environ Toxicol Chem 2016;35:1310–1320. © 2015 SETAC
Ustekinumab for patients with primary biliary cholangitis who have an inadequate response to ursodeoxycholic acid: A proof‐of‐concept study
Authors: Hirschfield Gideon M. , Gershwin M. Eric , Strauss Richard , Mayo Marlyn J. , Levy Cynthia , Zou Bin , Johanns Jewel , Nnane Ivo P. , Dasgupta Bidisha , Li Katherine , Selmi Carlo , Marschall Hanns‐Ulrich , Jones David , Lindor Keith ,   ; for the PURIFI Study Group
Published: November 2015

The interleukin (IL)‐12 signaling cascade has been associated with primary biliary cholangitis (PBC). This multicenter, open‐label, proof‐of‐concept study evaluated the anti‐IL12/23 monoclonal antibody, ustekinumab (90 mg subcutaneous at weeks 0 and 4, then every 8 weeks through week 20), in adults with PBC and an inadequate response to ursodeoxycholic acid therapy (i.e., alkaline phosphatase [ALP] >1.67× upper limit of normal [ULN] after ≥6 months). ALP response was defined as a >40% decrease from baseline and ALP remission as ALP normalization (if baseline ALP 1.67×‐2.8× ULN) or <1.67× ULN (if baseline ALP >2.8× ULN). Changes in Enhanced Liver Fibrosis (ELF) scores and serum bile acids were also assessed. At baseline, patients had median disease duration of 3.2 years, median ELF score of 9.8, and highly elevated total bile acid concentration (median, 43.3 μmol/L); 13 of 20 (65%) patients had baseline ALP >3× ULN. Although steady‐state serum ustekinumab concentrations were reached by week 12, no patient achieved ALP response or remission. Median percent ALP reduction from baseline to week 28 was 12.1%. ELF score decreased slightly from baseline to week 28 (median reduction: 0.173), and total serum bile acid concentrations decreased from baseline to week 28 (median reduction: 8.8 μmol/L). No serious infections or discontinuations resulting from adverse events were reported through week 28. One patient had a serious upper gastrointestinal hemorrhage considered unrelated to test agent by the investigator. Conclusion: Open‐label ustekinumab therapy, though associated with a modest decrease in ALP after 28 weeks of therapy, did not otherwise appreciably change ALP and overt proof‐of‐concept was not established as per prespecified primary endpoint of proposed efficacy. No new ustekinumab safety signals were observed. (Hepatology 2016;64:189‐199)
Quantitative, 3D Visualization of the Initiation and Progression of Vertebral Fractures Under Compression and Anterior Flexion
Authors: Jackman Timothy M , Hussein Amira I , Curtiss Cameron , Fein Paul M , Camp Anderson , De Barros Lidia , Morgan Elise F 
Published: November 2015

ABSTRACT

The biomechanical mechanisms leading to vertebral fractures are not well understood. Clinical and laboratory evidence suggests that the vertebral endplate plays a key role in failure of the vertebra as a whole, but how this role differs for different types of vertebral loading is not known. Mechanical testing of human thoracic spine segments, in conjunction with time-lapsed micro–computed tomography, enabled quantitative assessment of deformations occurring throughout the entire vertebral body under axial compression combined with anterior flexion (“combined loading”) and under axial compression only (“compression loading”). The resulting deformation maps indicated that endplate deflection was a principal feature of vertebral failure for both loading modes. Specifically, the onset of endplate deflection was temporally coincident with a pronounced drop in the vertebra's ability to support loads. The location of endplate deflection, and also vertebral strength, were associated with the porosity of the endplate and the microstructure of the underlying trabecular bone. However, the location of endplate deflection and the involvement of the cortex differed between the two types of loading. Under the combined loading, deflection initiated, and remained the largest, at the anterior central endplate or the anterior ring apophysis, depending in part on health of the adjacent intervertebral disc. This deflection was accompanied by outward bulging of the anterior cortex. In contrast, the location of endplate deflection was more varied in compression loading. For both loading types, the earliest progression to a mild fracture according to a quantitative morphometric criterion occurred only after much of the failure process had occurred. The outcomes of this work indicate that for two physiological loading modes, the vertebral endplate and underlying trabecular bone are critically involved in vertebral fracture. These outcomes provide a strong biomechanical rationale for clinical methods, such as algorithm-based qualitative (ABQ) assessment, that diagnose vertebral fracture on the basis of endplate depression. © 2015 American Society for Bone and Mineral Research.
Molecular Mechanisms Associated With Particulate and Soluble Heteroglycan Mediated Immune Response
Authors: Devi K. Sanjana P. , Krishna Dhanesh , Das Joyjyoti , Agarwal Tarun , Kumari Kalpana , Maji Somnath , Ghosh Sudip K. , Maiti Tapas K. 
Published: November 2015

ABSTRACTImmune responses are outcomes of complex molecular machinery which occur inside the cells. Unravelling the cellular mechanisms induced by immune stimulating molecules such as glycans and determining their structure‐function relationship are therefore important factors to be assessed. With this viewpoint, the present study identifies the functional receptor binding unit of a well characterized heteroglycan and also delineates the cellular and molecular processes that are induced upon heteroglycan binding to specific cell surface receptors in immune cells. The heteroglycan was acid hydrolysed and it was revealed that 10–30 kDa fractions served as the functional receptor binding unit of the molecule. Increasing the size of 10–30 kDa heteroglycan showed prominent immune activity. The whole soluble heteroglycan was also conjugated with hyperbranched dendrimers so as to generate a particulate form of the molecule. Dectin‐1 and TLR2 were identified as the major receptors in macrophages that bind to particulate as well as soluble form of the heteroglycan and subsequently caused downstream signaling molecules such as NF‐κβ and MAPK to get activated. High levels of 1L‐1β and IL‐10 mRNA were observed in particulate heteroglycan treated macrophages, signifying that increasing the size and availability of the heteroglycan to its specific receptors is pertinent to its biological functioning. Upregulated expression of PKC and iNOS were also noted in particulate heteroglycan treated RAW 264.7 cells than the soluble forms. Taken together, our results indicate that biological functions of immunomodulatory heteroglycan are dependent on their size and molecular weight. J. Cell. Biochem. 117: 1580–1593, 2016. © 2015 Wiley Periodicals, Inc.
Increased Rat Placental Fatty Acid, but Decreased Amino Acid and Glucose Transporters Potentially Modify Intrauterine Programming
Authors: Nüsken Eva , Gellhaus Alexandra , Kühnel Elisabeth , Swoboda Isabelle , Wohlfarth Maria , Vohlen Christina , Schneider Holm , Dötsch Jörg , Nüsken Kai‐Dietrich 
Published: November 2015

ABSTRACTRegulation of placental nutrient transport significantly affects fetal development and may modify intrauterine growth restriction (IUGR) and fetal programming. We hypothesized that placental nutrient transporters are differentially affected both by utero‐placental insufficiency and prenatal surgical stress. Pregnant rats underwent bilateral uterine artery and vein ligation (LIG), sham operation (SOP) or no operation (controls, C) on gestational day E19. Placentas were obtained by caesarean section 4 h (LIG, n=20 placentas; SOP, n=24; C, n=12), 24 h (LIG, n=28; SOP, n=20; C, n=12) and 72 h (LIG, n=20; SOP, n=20; C, n=24) after surgery. Gene and protein expression of placental nutrient transporters for fatty acids (h‐FABP, CD36), amino acids (SNAT1, SNAT2) and glucose (GLUT‐1, Connexin 26) were examined by qRT‐PCR, western blot and immunohistochemistry. Interestingly, the mean protein expression of h‐FABP was doubled in placentas of LIG and SOP animals 4, 24 (SOP significant) and 72 h (SOP significant) after surgery. CD36 protein was significantly increased in LIG after 72 h. SNAT1 and SNAT2 protein and gene expressions were significantly reduced in LIG and SOP after 24 h. Further significantly reduced proteins were GLUT‐1 in LIG (4 h, 72 h) and SOP (24 h), and Connexin 26 in LIG (72 h). In conclusion, placental nutrient transporters are differentially affected both by reduced blood flow and stress, probably modifying the already disturbed intrauterine milieu and contributing to IUGR and fetal programming. Increased fatty acid transport capacity may affect energy metabolism and could be a compensatory reaction with positive effects on brain development. J. Cell. Biochem. 117: 1594–1603, 2016. © 2015 Wiley Periodicals, Inc.
Red Raspberry Phenols Inhibit Angiogenesis: A Morphological and Subcellular Analysis Upon Human Endothelial Cells
Authors: Sousa M. , Machado V. , Costa R. , Figueira M.E. , Sepodes B. , Barata P. , Ribeiro L. , Soares R. 
Published: November 2015

ABSTRACTPolyphenols are a class of natural compounds whose potential as antioxidant, anti‐inflammatory, and anti‐angiogenesis has been reported in many pathological conditions. Red raspberry extract, rich in polyphenols, has been reported to exert anti‐inflammatory effects and prevent cell proliferation in distinct animal models. However, the signaling pathways involved remain unknown. Herein, we used human microvascular endothelial cells (HMVECs) to determine the influence of red raspberry phenolic compound extract concentrations, ranging from 10 to 250 µg gallic acid equivalents (GAE)/mL, on endothelium viability (MTS assay), proliferation (BrdU incorporation), migration (injury assay), and capillary‐like structures formation (Matrigel assay). Protein expression in cell lysates was determined by Western blot analysis. We showed that red raspberry extracts reduced cell viability (GI50 = 87,64 ± 6,59 μg GAE/mL) and proliferation in a dose‐dependent manner. A significant abrogation of cells ability to migrate to injured areas, even at low concentrations, was observed by injury assay. Cell assembly into capillary‐like structures on Matrigel also decreased in a dose dependent‐manner for higher extract concentrations, as well as the number of branching points per unit of area. Protein expression analysis showed a dose‐dependent decrease in Phospho‐VEGFR2 expression, implying abrogation of VEGF signaling activity. We also showed for the first time that red raspberry phenolic compounds induce the rearrangement of filamentous actin cytoskeleton, with an isotropy increase found for higher testing concentrations. Taken together, our findings corroborate the anti‐angiogenic potential of red raspberry phenolic compounds and provide new insights into their mode of action upon endothelium. J. Cell. Biochem. 117: 1604–1612, 2016. © 2015 Wiley Periodicals, Inc.
Danionella dracula, an escape from the cypriniform Bauplan via developmental truncation?
Authors: Britz Ralf , Conway Kevin W. 
Published: November 2015

ABSTRACTWe provide a detailed account of the osteology of the miniature Asian freshwater cyprinid fish Danionella dracula. The skeleton of D. dracula shows a high degree of developmental truncation when compared to most other cyprinids, including its close relative the zebrafish Danio rerio. Sixty‐one bones, parts thereof or cartilages present in most other cyprinids are missing in D. dracula. This impressive organism‐wide case of progenesis renders it one of the most developmentally truncated bony fishes or even vertebrates. Danionella dracula lacks six of the eight unique synapomorphies that define the order Cypriniformes and has, thus, departed from the cypriniform Bauplan more dramatically than any other member of this group. This escape from one of the most successful Baupläne among bony fishes may have been facilitated by the organism‐wide progenesis encountered in D. dracula. By returning in its skeletal structure to the early developmental condition of other cypriniforms, D. dracula may have managed to overcome the evolutionary constraints associated with this Bauplan and opened up new evolutionary avenues that enabled it to evolve a number of striking morphological novelties, including its tooth‐like odontoid processes and a complex drumming apparatus. J. Morphol. 277:147–166, 2016. © 2015 Wiley Periodicals, Inc.
Pigment cell mechanism of postembryonic stripe pattern formation in the Japanese four‐lined snake
Authors: Murakami Arata , Hasegawa Masami , Kuriyama Takeo 
Published: November 2015

ABSTRACTPostembryonic changes in the dermal and epidermal pigment cell architecture of the striped and nonstriped morph of the Japanese four‐lined snake Elaphe quadrivirgata were examined to reveal stripe pattern formation after hatching. The striped and nonstriped morphs were distinguishable at the hatching, suggesting that the basis of stripe pattern was formed during embryonic development. In the striped morph, the color of stripes changed from red‐brown in juveniles to vivid dark‐brown in adults, and density of dermal melanophore increased much more in the stripe than background dorsal scales with growth. This increase in density of dermal melanophore was accompanied not only by the increased epidermal melanophore density but also by the change in vertical structures of dermal melanophore. By contrast, the density of epidermal and dermal melanophore evenly increased over the dorsal scales in the nonstriped morph. Thus, the increased vividness of the stripe pattern after hatching is achieved through localized increase of melanophore density particularly in the stripe region but not over the whole dorsal scales. J. Morphol. 277:196–203, 2016. © 2015 Wiley Periodicals, Inc.
Subjective and objective voice outcomes after transoral laser microsurgery for early glottic cancer
Authors: Fink Daniel S. , Sibley Haley , Kunduk Melda , Schexnaildre Mell , Kakade Anagha , Sutton Collin , McWhorter Andrew J. 
Published: November 2015

Objectives/HypothesisTransoral laser microsurgery (TLM) continues to gain popularity as a treatment modality for early glottic cancer. Oncologic outcomes have been well‐defined, but there are little data to date describing functional outcomes accounting for stage of resection.Study DesignRetrospective review.MethodsWe retrospectively reviewed patient‐rated voice handicap and observer‐rated vocal quality of patients who underwent TLM for early glottic carcinoma. Patients were grouped by European Laryngological Society (ELS) resection type, and the data were combined for ELS type I–III and compared with advanced resections (ELS IV–VI). The Voice Handicap Index (VHI) was used for patient‐rated voice outcomes, and voice recordings were graded by two senior speech‐language pathologists. Voice recordings and VHI scores were taken preoperatively and at least 1 month postoperatively.ResultsNo major complications were encountered. Six of 49 patients underwent repeat resection for suspicious findings with pathology, demonstrating moderate dysplasia in two cases, carcinoma in situ in two cases, and inflamed mucosa only in two cases. There was no significant difference in preoperative VHI scores or objective voice grades among patients who underwent limited (ELS I–III) and those who required more advanced (ELS IV–VI) resection. There was a significant improvement in VHI scores in patients after ELS type I to III resection, from 38.77 to 22.86 (P = .006). There was no significant difference between mean preoperative and postoperative perceptual evaluation scores in patients who underwent ELS type I, II, or III resections (62.25 and 64.32 respectively, P = .621).ConclusionsPatients who undergo limited ELS resections can be assured of having a similar to improved voice after healing. Patients who undergo extended resections have poorer vocal outcomes.Level of Evidence4 Laryngoscope, 126:405–407, 2016
Volumetric analysis of tumor control following subtotal and near‐total resection of vestibular schwannoma
Authors: Jacob Jeffrey T. , Carlson Matthew L. , Driscoll Colin L. , Link Michael J. 
Published: November 2015

Objectives/HypothesisThe primary goals of microsurgery for vestibular schwannoma (VS) include preservation of neural function and complete tumor removal. In a subset of patients, adherent tumor remnant may be intentionally left behind in order to minimize risk of new neurologic deficits. It is not well established if residual tumor volume predicts likelihood of tumor remnant growth.MethodsPatients with sporadic VS who underwent near‐total (NTR) or subtotal (STR) VS resection between 2000 and 2014 were reviewed. Postoperative tumor remnants were volumetrically contoured using T1‐weighted gadolinium‐enhanced magnetic resonance imaging obtained within 3 months of surgery.ResultsA total of 103 patients met study criteria, and the median duration of radiographic follow‐up was 41 months (mean 56.1 months, range 12–150 months). Fifty patients underwent NTR and 53 received STR. Overall 14 (13.6%) tumors recurred at a median of 41.0 months. Patients who underwent STR were over 13 times more likely to recur compared with those treated with NTR (hazard ratio 13.31; 95% confidence interval 1.71–103.91; P = 0.014). The median time to recurrence following NTR was 124 months compared to 32 months after STR (P < 0.001).ConclusionsLong‐term follow‐up in patients undergoing incomplete resection is essential. Near‐total resection has a significantly lower rate of recurrence compared to STR. Maximal surgical resection should be the goal in VS microsurgery. The decision to pursue less than complete resection should be based on intraoperative impression, when it is felt that continued dissection of adherent disease would compromise neurologic outcome.Level of Evidence4. Laryngoscope, 126:1877–1882, 2016
Computed tomography scan does not correlate with patient experience of nasal obstruction
Authors: Ardeshirpour Farhad , McCarn Kate E. , McKinney Alexander M. , Odland Rick M. , Yueh Bevan , Hilger Peter A. 
Published: November 2015

Objectives/HypothesisThird‐party payors have begun to demand imaging studies to document septal deviation prior to authorizing septoplasties. This study aims to determine whether septal deviation findings on computed tomography (CT) correlate with symptoms of nasal obstruction as determined by the Nasal Obstruction Symptom Evaluation (NOSE) scale.Study DesignProspective and retrospective chart review.MethodsPatients 18 years or older undergoing CT scans, which included the nasal septum, were asked to complete a NOSE scale survey and report the laterality of any possible obstruction. Coronal CT images of subjects were graded by two blinded otolaryngologists and two blinded neuroradiologists using a grading system devised by the authors.ResultsSeventy‐three subjects met inclusion/exclusion criteria. Interobserver reliability about the degree of septal deviation on CT scans was moderately good to substantial (κ values, 0.43 to 0.72). There was poor correlation between NOSE scores and degree of deviation on CT scans (Kendall's τ, 0.031 to 0.045; P values all >.05). There was poor concordance between the side of symptoms that patients reported and the side that observers thought was most deviated on CT.ConclusionsThere is little correlation between septal deviation findings on CT scans and symptoms of nasal obstruction. The results do not support a role for CT scans as either a clinically meaningful or necessary test to investigate uncomplicated nasal obstruction.Level of Evidence4 Laryngoscope, 126:820–825, 2016
Construction and validation of the chronic acquired polyneuropathy patient‐reported index (CAP‐PRI): A disease‐specific, health‐related quality‐of‐life instrument
Authors: Gwathmey Kelly G. , Conaway Mark R. , Sadjadi Reza , Joshi Amruta , Barnett Carolina , Bril Vera , Ng Eduardo , David William , Gable Karissa , Guptill Jeffrey T. , Hobson‐Webb Lisa D. , Dineen Jennifer , Hehir Michael , Brannagan Thomas H. , Byun Esther , Adler Margaret , Burns Ted M. 
Published: November 2015

ABSTRACTIntroduction: Generic health‐related quality‐of‐life (HRQOL) patient‐reported outcome measures have been used in patients with chronic immune‐mediated polyneuropathies. We have created a disease‐specific HRQOL instrument. Methods: The chronic acquired polyneuropathy patient‐reported index (CAP‐PRI) was developed and validated in multiple steps. Items were initially generated through patient and specialist input. The performance of the preliminary 20 items was analyzed via a prospective, 5‐center study involving chronic immune‐mediated polyneuropathy patients. Results: Data analysis suggested modification to a 15‐item scale with 3 response categories rather than 5. The final CAP‐PRI was validated in another prospective, 5‐center study. The CAP‐PRI appeared to be a unidimensional outcome measure that fit the Rasch model in our multicenter cohort. It correlated appropriately with outcome measures commonly used in this patient population. Conclusions: The CAP‐PRI is a simple disease‐specific HRQOL measure that appears to be useful for clinical care and possibly also for clinical trials. Muscle Nerve 54: 9–17, 2016