bluuebunny/crossref_metadata_2025_split huggingface dataset:
Hypoxia‐related carbonic anhydrase IX expression is associated with unfavourable response to first‐line therapy in classical Hodgkin's lymphoma
Authors: Méhes Gábor , Matolay Orsolya , Beke Livia , Czenke Marianna , Jóna Ádám , Miltényi Zsofia , Illés Árpád , Bedekovics Judit 
Published: January 2019

AimsThe present study evaluates the impact of hypoxia‐related carbonic anhydrase IX and XII isoenzyme expression as a basic adaptive mechanism to neutralise intracellular acidosis in classical Hodgkin's lymphoma (cHL).Methods and resultsEighty‐one primary biopsies and 15 relapsed tissue samples diagnosed with cHL were analysed for necrosis, CAIX and CAXII expression and cell proliferation to compare hypoxia‐related histological and functional data with survival characteristics. Variable, but highly selective cell membrane CAIX expression could be demonstrated in Hodgkin–Reed–Sternberg (HRS) cells in 39 of 81 samples (48.1%), while virtually no staining presented in their microenvironment. In contrast, CAXII expression in HRS cells could be demonstrated in only 18 of 77 samples (23.4%), with significant stromal positivity (50 of 77, 64.9%). The CAIX+ positive phenotype was strongly associated with lymphocyte depletion (four of four, 100%) and nodular sclerosis (29 of 51, 56.9%) subtypes. CAIX/Ki‐67 dual immunohistochemistry demonstrated suppressed cell proliferation in CAIX+ positive compared to CAIX− negative HRS cells (P < 0.001). Seventy‐two months’ progression‐free survival (PFS) was significantly lower for the CAIX positive group (0.192) compared with the CAIX negative group (0.771) (P < 0.001), while the overall survival (OS) did not differ (P = 0.097).ConclusionHypoxic stress‐related adaptation – highlighted by CAIX expression – results in cellular quiescence in HRS cells, potentially contributing to the short‐term failure of the standard chemotherapy in cHL.
Neoadjuvant chemoradiation for patients with advanced oesophageal cancer – which response grading system best impacts prognostic discrimination?
Authors: Puetz Katharina , Bollschweiler Elfriede , Semrau Robert , Mönig Stefan P , Hölscher Arnulf H , Drebber Uta 
Published: January 2019

AimsNeoadjuvant chemoradiation reduces tumour volume and improves the R0 resection rate, followed by extended survival for patients with advanced oesophageal cancer. The degree of tumour regression has high prognostic relevance. To date, there is still no generally accepted tumour regression grading system. The aim of this study was to compare the prognostic discrimination power of different histological regression grading systems: (i) the fibrosis/tumour ratio within the primary tumour (Mandard classification), (ii) the percentage of residual vital tumour cells (VTC) compared to the original primary tumour (Cologne Regression) and (iii) the ypT category, in patients with cT3 carcinoma of the oesophagus after neoadjuvant chemoradiation.Methods and resultsThis study included 216 patients with oesophageal cancer clinically staged as cT3NxM0 and treated from 2009 to 2012 with standardised chemoradiation followed by oesophagectomy [median age 62 years, 176 (81%) male and 138 (64%) adenocarcinoma patients]. The subgroup frequencies of the three classification systems were ypT category: ypT0 = 18%, ypT1 = 14%, ypT2 = 23%, ypT3 = 44%, ypT4 = 1%; Mandard classification: TRG1 = 18%, TRG2 = 26%, TRG3 = 24%, TRG4 = 30%, TRG5 = 2%; and Cologne Regression Scale: no tumour = 18%, 1–10% VTC = 27%, 10–50% VTC = 26% and >50% VTC = 29%. The Mandard and Cologne Regression classifications showed better prognostic differentiation for the subgroups than the ypT category. The four‐tiered Cologne Regression system had a good prognostic relevance. Comparing results of the re‐evaluated Cologne Regression classification with the classification by routine pathological report showed very good inter‐rater agreement, with kappa value 0.891.ConclusionCompared to the original primary tumour, the tumour regression grading system using the percentage of residual vital tumour has prognostic relevance.
Predator density influences nest attendance of Yellow‐headed BlackbirdsXanthocephalus xanthocephalus
Authors: Behrens Colby , Ruff Zachary J. , Harms Tyler M. , Dinsmore Stephen J. 
Published: January 2019

Nest attendance behaviour in birds is a function of the careful balance between the risk of nest predation and the needs of the parents and nestlings. This attendance must be carefully regulated, as increased parental activity at the nest increases nest predation risk. We tested the long‐standing hypothesis that nest predation risk influences parental behaviour by evaluating the influence of local Marsh WrenCistothorus palustrisdensity on the off‐bout frequency of Yellow‐headed BlackbirdsXanthocephalus xanthocephalus. Marsh Wren density was negatively correlated with Yellow‐headed Blackbird off‐bout frequency during the morning (05:00–10:00 h) and evening (16:00–21:00 h), suggesting that Yellow‐headed Blackbirds alter their nest attendance behaviour in response to a perceived increased risk of nest predation. We suggest that Yellow‐headed Blackbirds are sensitive to nest predation risk and alter their behaviour accordingly to increase overall fitness, although future research is needed to evaluate the influence of Marsh Wren nest predation on the reproductive success of Yellow‐headed Blackbirds.
Mechanisms of anionic surfactant penetration into human skin: Investigating monomer, micelle and submicellar aggregate penetration theories
Authors: Morris Stephanie A. V. , Thompson Ryan T. , Glenn Robert W. , Ananthapadmanabhan K. P. , Kasting Gerald B. 
Published: January 2019

AbstractObjectiveOnce penetrated into the stratum corneum, anionic surfactants bind to and denature stratum corneum proteins as well as intercalate into and extract intercellular lipids. With repeated exposures, this leads to skin dryness and irritation, compromising barrier function and skin health. The mechanisms of anionic surfactant penetration into the skin, however, are still widely debated. The objective of this study was to evaluate current theories of surfactant penetration into human skin.MethodsA test set comprising 15 anionic surfactant systems and one non‐ionic surfactant, all having either dodecyl or lauryl alkyl chains, was tested for surfactant penetration into split‐thickness human cadaver skin in vitro using radiolabelled sodium dodecyl sulphate (14C‐SDS). Select physical properties of these formulations thought to be associated with skin penetration including critical micelle concentration, micelle diameter, filtrate concentration and zeta potential were also measured.Results14C‐SDS penetration into human cadaver skin from surfactant systems in vitro was found to correlate well with CMC (R2 = 0.34, P < 0.05), filtrate concentration (R2 = 0.36, P < 0.05) and zeta potential (R2 = 0.76, P < 0.001), but poorly with micelle diameter (R2 = 0.12). Furthermore, the latter measure correlated inversely with penetration compared to what would be expected based on the micelle penetration theory.ConclusionNeither monomer nor micelle penetration theories are sufficient to explain anionic surfactant penetration into human skin. Submicellar (or premicellar) aggregate penetration theory is difficult to defend at relevant surfactant concentrations. We propose a new hypothesis for this mechanism in which short‐term penetration is based on monomer concentration and longer term penetration is based on surfactant‐induced damage to the skin barrier.
Evaluating the evolution and function of the dynamic Venom Y protein in ectoparasitoid wasps
Authors: Martinson E. O. , Siebert A. L. , He M. , Kelkar Y. D. , Doucette L. A. , Werren J. H. 
Published: January 2019

AbstractVenom of the parasitoid wasp Nasonia vitripennis changes the metabolism and gene expression in its fly host Sarcophaga bullata to induce developmental arrest, suppression of the immune response and various other venom effects. Yet, the venom of ectoparasitoid wasps has not been fully characterized. A major component of N. vitripennis venom is an uncharacterized, high‐expressing protein referred to as Venom Y. Here we describe the evolutionary history and possible functions of this venom protein. We found that Venom Y is a relatively young gene that has duplicated to form two distinct paralogue groups. A copy of Venom Y has been recruited as a venom protein in at least five wasp species. Functional analysis found that Venom Y affects detoxification and immunity genes in envenomated fly hosts. Many of these genes are fat‐body specific, suggesting that Venom Y may have a targeted effect on fat body tissue. We also show that Venom Y may mitigate negative effects of other venom proteins. Finally, protein sequencing indicates that Venom Y is post‐translationally modified. This study contributes to elucidating parasitoid venom by using RNA interference knockdown to investigate venom protein function in the context of the whole venom cocktail.
Tunable photoluminescence of apatite phosphor Ca5.95−xSrxLa4(SiO4)2(PO4)4O2:0.05Eu2+ and its application in light‐emitting diodes
Authors: Yu Haojun , Xia Yufei , Liu Yan‐gai , Wang Baochen , Huang Zhaohui , Fang Minghao 
Published: January 2019

AbstractA series of new apatite phosphors Ca5.95−xSrxLa4(SiO4)2(PO4)4O2:0.05Eu2+ (x = 0‐5.95) were prepared with the solid‐state method. The variations of the occupation rate and cell parameters were investigated in detail, demonstrating that the phosphors are pure phases and that the different occupation rates of La3+, Ca2+, and Sr2+ ions are due to the different electrostatic bond strengths. The reflectance and photoluminescence excitation spectra prove that the phosphors can be efficiently excited with near‐ultraviolet (n‐UV) light. The broad redshift (50 nm) in the photoluminescence spectra is attributed to the increase in the crystal field splitting when the Ca2+ ion is replaced by the larger Sr2+ ion. At 150°C, the obtained phosphors maintain an emission intensity of ~67%‐77% of that at room temperature (25°C), which indicates relatively the high performance of apatite phosphors in the temperature‐dependence experiment. Because of the substitution of the small Ca2+ ion by the large Sr2+ ion, the emission color changes from green to yellow. Finally, a series of self‐made light emitting diodes lamps were fabricated by coating the Ca5.95−xSrxLa4(SiO4)2(PO4)4O2:0.05Eu2+ phosphors with commercial blue and red phosphors on an n‐UV chip (λex = 370 nm). The self‐made white‐emitting lamps display a continuous changing correlated color temperature (4053‐9353 K) or commission international de L'eclairgae (from [0.29, 0.28] to [0.38, 0.37]), implying that the series apatite phosphors have great potential to meet the different requirements of applications.
Strategies to improve the efficiency of mesenchymal stem cell transplantation for reversal of liver fibrosis
Authors: Hu Chenxia , Zhao Lingfei , Duan Jinfeng , Li Lanjuan 
Published: January 2019

AbstractEnd‐stage liver fibrosis frequently progresses to portal vein thrombosis, formation of oesophageal varices, hepatic encephalopathy, ascites, hepatocellular carcinoma and liver failure. Mesenchymal stem cells (MSCs), when transplanted in vivo, migrate into fibrogenic livers and then differentiate into hepatocyte‐like cells or fuse with hepatocytes to protect liver function. Moreover, they can produce various growth factors and cytokines with anti‐inflammatory effects to reverse the fibrotic state of the liver. In addition, only a small number of MSCs migrate to the injured tissue after cell transplantation; consequently, multiple studies have investigated effective strategies to improve the survival rate and activity of MSCs for the treatment of liver fibrosis. In this review, we intend to arrange and analyse the current evidence related to MSC transplantation in liver fibrosis, to summarize the detailed mechanisms of MSC transplantation for the reversal of liver fibrosis and to discuss new strategies for this treatment. Finally, and most importantly, we will identify the current problems with MSC‐based therapies to repair liver fibrosis that must be addressed in order to develop safer and more effective routes for MSC transplantation. In this way, it will soon be possible to significantly improve the therapeutic effects of MSC transplantation for liver regeneration, as well as enhance the quality of life and prolong the survival time of patients with liver fibrosis.
Masticatory behavior for different solid foods in preschool children according to their oral state
Authors: Linas Natacha , Peyron Marie‐Agnès , Hennequin Martine , Eschevins Caroline , Nicolas Emmanuel , Delfosse Caroline , Collado Valérie 
Published: January 2019

AbstractGradual introduction of solid foods in early childhood takes part in the maturation of mastication. The impact of any oral state alteration on food oral processing development is poorly documented for this age group. This study investigated the masticatory behavior in 3 to 6 year‐old children with or without early childhood caries (ECC) for three solid foods of different textures. Twenty‐one children with healthy oral state and 23 children with severe ECC were observed during complete mastication of calibrated samples of raw carrot, cheese and breakfast cereals. Food refusals and kinematic parameters (Ti: chewing time, Nc: number of cycles and Fq: chewing frequency) were used to assess children masticatory behavior. Oral Health‐related Quality of Life and orofacial dysfunctions were evaluated using, respectively the early childhood oral health impact scale (ECOHIS) and the Nordic orofacial dysfunction test screening (NOT‐S). Children suffering from ECC exhibited significantly higher ECOHIS and NOT‐S scores, in particular for the mastication domain. Accordingly, lower chewing frequencies values were recorded in children with ECC (i.e., carrot Fq: 1.21 ± 0.20 vs 1.35 ± 0.22, p ≤ 0.01), as well as more frequent refusals for carrots. Kinematic parameters were shown to be repeatable in all children for successive samples of the same food, and tended to vary depending on the proposed food. Some masticatory behavior regulation according to food properties could already be present in preschool children. Children with ECC developed alternative behavioral strategies to overcome feeding difficulties. Further studies should investigate food bolus properties according to oral health, as well as nutritional issues.Practical applicationsDuring childhood, the way solid foods are processed in the oral cavity to be safely swallowed and then digested in available nutrients, is poorly documented. In this study, preschool children have been shown to repeatedly adapt their masticatory behavior to a given food. The collection of various food boli as recorded at the moment of swallowing could then be considered in further food bolus properties research investigations. Moreover, this study suggested that children with altered dentition modified their masticatory kinematic parameters and developed alternative strategies, including food or texture selection, to overcome their feeding difficulties. The development of a mastication evaluation protocol could help medical professionals to detect children masticatory deficiencies and then propose diet adaptations. Considering the importance of food diversity in mastication development and maturation, food industries may consider to develop a range of texture adapted foods for young children, especially designed to gradually rehabilitate the masticatory function.
Retrospective evaluation of clinical outcome after chemotherapy for lymphoma in 15 equids (1991‐2017)
Authors: Luethy Daniela , Frimberger Angela E. , Bedenice Daniela , Byrne Barbara S. , Groover Erin S. , Gardner Rachel B. , Lewis Trisha , MacDonald Valerie S. , Proctor‐Brown Lauren , Tomlinson Joy E. , Rassnick Kenneth M. , Johnson Amy L. 
Published: January 2019

BackgroundPrognosis associated with lymphoma in horses is poorly characterized, and treatment is often palliative. Long‐term outcome after chemotherapy for horses with lymphoma is not well documented.ObjectiveTo report long‐term outcome of horses with lymphoma treated with chemotherapy.AnimalsFifteen equids.MethodsRetrospective case series. Medical record search and call for cases on the ACVIM listserv for horses treated with chemotherapy for lymphoma.ResultsFifteen cases with adequate data were identified. Complete remission was achieved in 5 horses (33.3%), partial response was achieved in 9 equids (60%), and stable disease was achieved in 1 horse. Overall response rate was 93.3% (14/15). Overall median survival time was 8 months (range, 1‐46 months). Nine horses experienced a total of 14 adverse effects attributable to chemotherapy. Adverse effects were graded according to the Veterinary Cooperative Oncology Group common terminology criteria for adverse events grading system (grade 1 alopecia, n = 2; grade 1 neutropenia, n = 2; grade 1 lymphopenia, n = 3; grade 1 lethargy, n = 1; grade 2 neurotoxicity, n = 1; grade 2 colic, n = 1; grade 1 hypersensitivity, n = 1; grade 2 hypersensitivity, n = 2; grade 5 hypersensitivity, n = 1). Higher grade adverse effects most commonly were associated with doxorubicin administration (n = 4), including 1 horse that died 18 hours post‐administration.Conclusions and Clinical ImportanceChemotherapy can be used successfully for treatment of horses with lymphoma. Adverse effects, most commonly mild, occurred in approximately two‐thirds of treated horses.
Quantification of adherens junction disruption and contiguous paracellular protein leak in human lung endothelial cells under septic conditions
Authors: Wang Lefeng , Chung Justin , Gill Sean E. , Mehta Sanjay 
Published: January 2019

AbstractObjectiveSepsis is associated with dysfunction of MVEC resulting in organ edema and inflammation. VE‐cadherin, a component of MVEC adherens junctions, may be disrupted in sepsis. However, the direct connection between individual MVEC VE‐cadherin disruption and increased paracellular permeability is uncertain.MethodsHuman pulmonary MVEC were cultured on a biotin matrix and treated with cytomix, as a model of sepsis, vs PBS. MVEC permeability was assessed by trans‐MVEC monolayer leak of Oregon green 488‐conjugated avidin, which bound subcellular biotin to localize sites of paracellular leak. Leak was correlated with individual cell‐specific MVEC surface VE‐cadherin continuity by fluorescence microscopy.ResultsCytomix treatment reduced total MVEC VE‐cadherin density, disrupted surface VE‐cadherin continuity, was associated with intercellular gap formation, and enhanced paracellular avidin leak. Cytomix‐induced MVEC paracellular avidin leak was strongly correlated temporally and was highly contiguous with focal MVEC surface VE‐cadherin disruption. Total cellular VE‐cadherin density was less strongly correlated with MVEC paracellular avidin leak and individual cell‐specific focal surface VE‐cadherin discontinuity.ConclusionsThese data support a mechanistic link between septic human lung MVEC VE‐cadherin disruption and contiguous paracellular protein leak, and will permit more detailed assessment of individual cell‐specific mechanisms of septic MVEC barrier dysfunction.
Synthetic developmental regulator MciZ targets FtsZ across Bacillus species and inhibits bacterial division
Authors: Araújo‐Bazán Lidia , Huecas Sonia , Valle Javier , Andreu David , Andreu José M. 
Published: January 2019

SummaryCell division in most bacteria is directed by FtsZ, a conserved tubulin‐like GTPase that assembles forming the cytokinetic Z‐ring and constitutes a target for the discovery of new antibiotics. The developmental regulator MciZ, a 40‐amino acid peptide endogenously produced during Bacillus subtilis sporulation, halts cytokinesis in the mother cell by inhibiting FtsZ. The crystal structure of a FtsZ:MciZ complex revealed that bound MciZ extends the C‐terminal β‐sheet of FtsZ blocking its assembly interface. Here we demonstrate that exogenously added MciZ specifically inhibits B. subtilis cell division, sporulation and germination, and provide insight into MciZ molecular recognition by FtsZ from different bacteria. MciZ and FtsZ form a complex with sub‐micromolar affinity, analyzed by analytical ultracentrifugation, laser biolayer interferometry and isothermal titration calorimetry. Synthetic MciZ analogs, carrying single amino acid substitutions impairing MciZ β‐strand formation or hydrogen bonding to FtsZ, show a gradual reduction in affinity that resembles their impaired activity in bacteria. Gene sequences encoding MciZ spread across genus Bacillus and synthetic MciZ slows down cell division in Bacillus species, including pathogenic Bacillus cereus and Bacillus anthracis. Moreover, B. subtilis MciZ is recognized by the homologous FtsZ from Staphylococcus aureus and inhibits division when it is expressed into S. aureus cells.
YpdA, a putative bacillithiol disulfide reductase, contributes to cellular redox homeostasis and virulence in Staphylococcus aureus
Authors: Mikheyeva Irina V. , Thomas Jason M. , Kolar Stacey L. , Corvaglia Anna‐Rita , Gaϊa Nadia , Leo Stefano , Francois Patrice , Liu George Y. , Rawat Mamta , Cheung Ambrose L. 
Published: January 2019

SummaryThe intracellular redox environment of Staphylococcus aureus is mainly buffered by bacillithiol (BSH), a low molecular weight thiol. The identity of enzymes responsible for the recycling of oxidized bacillithiol disulfide (BSSB) to the reduced form (BSH) remains elusive. We examined YpdA, a putative bacillithiol reductase, for its role in maintaining intracellular redox homeostasis. The ypdA mutant showed increased levels of BSSB and a lower bacillithiol redox ratio vs. the isogenic parent, indicating a higher level of oxidative stress within the bacterial cytosol. We showed that YpdA consumed NAD(P)H; and YpdA protein levels were augmented in response to stress. Wild type strains overexpressing YpdA showed increased tolerance to oxidants and electrophilic agents. Importantly, YpdA overexpression in the parental strain caused an increase in BSH levels accompanied by a decrease in BSSB concentration in the presence of stress, resulting in an increase in bacillithiol redox ratio vs. the vector control. Additionally, the ypdA mutant exhibited decreased survival in human neutrophils (PMNs) as compared with the parent, while YpdA overexpression protected the resulting strain from oxidative stress in vitro and from killing by human neutrophils ex vivo. Taken together, these data present a new role for YpdA in S. aureus physiology and virulence through the bacillithiol system.