bluuebunny/crossref_metadata_2025 huggingface dataset:
Effects of single‐agent bortezomib as post‐transplant consolidation therapy on multiple myeloma‐related bone disease: a randomized phase II study
Authors: Sezer Orhan , Beksac Meral , Hajek Roman , Sucak Gülsan , Cagirgan Seckin , Linkesch Werner , Meltem Akay Olga , Gülbas Zafer , Nahi Hareth , Plesner Torben , Snowden John A. , Timurağaoğlu Ayşen , Dechow Tobias , Lang Alois , Tuğlular Tülin , Drach Johannes , Armbrecht Gabriele , Potamianou Anna , Couturier Catherine , Olie Robert A. , Feys Caroline , Allietta Nathalie , Terpos Evangelos
Published: April 2017

This phase II study explored the effects of bortezomib consolidation versus observation on myeloma‐related bone disease in patients who had a partial response or better after frontline high‐dose therapy and autologous stem cell transplantation. Patients were randomized to receive four 35‐day cycles of bortezomib 1·6 mg/m2 intravenously on days 1, 8, 15 and 22, or an equivalent observation period, and followed up for disease status/survival. The modified intent‐to‐treat population included 104 patients (51 bortezomib, 53 observation). There were no meaningful differences in the primary endpoint of change from baseline to end of treatment in bone mineral density (BMD). End‐of‐treatment rates (bortezomib versus observation) of complete response/stringent complete response were 22% vs. 11% (P = 0·19), very good partial response or better of 80% vs. 68% (P = 0·17), and progressive disease of 8% vs. 23% (P = 0·06); median progression‐free survival was 44·9 months vs. 21·8 months (P = 0·22). Adverse events observed ≥15% more frequently with bortezomib versus observation were diarrhoea (37% vs. 0), peripheral sensory neuropathy (20% vs. 4%), nausea (18% vs. 0) and vomiting (16% vs. 0). Compared with observation, bortezomib appeared to have little impact on bone metabolism/health, but was associated with trends for improved myeloma response and survival.
Shrubs shed light on 20th century Greenland Ice Sheet melting
Authors: Buras Allan , Lehejček Jiří , Michalová Zuzana , Morrissey Robert C. , Svoboda Miroslav , Wilmking Martin
Published: April 2017

The Greenland Ice Sheet (GrIS) is a key element of the global climate system and thus knowledge about its melting in the past is desirable. However, GrIS‐melt records only date back until 1979 and climate data based reconstructions covering the 20th century differ with respect to absolute values. To extend our knowledge about the Greenland Ice Sheet we examined the potential of shrub ring‐widths and wood‐anatomy as proxies for GrIS‐melt. We found significant correlations between shrub cell‐wall thickness and regional melt derived from passive microwave satellite brightness for 7% of the total GrIS area. A respective transfer function calibrated over the period 1979 to 2007 successfully passed model calibration‐verification tests and explained 42% of GrIS‐melt variability. Consequently, the first GrIS‐melt reconstruction based on shrub wood‐anatomy covering the period 1909 to 2012 is presented and compared against two temperature‐based reconstructions. For the period prior to 1930 the new reconstruction contrasts with existing literature but generally confirms that most recent record melt rates are amongst the highest since the early 20th century. We discuss the sensitivity of shrubs to several influencing factors besides summer temperature as possible reason for the observed differences and highlight the potential of using shrubs as multi‐parameter proxies within a network to increase our knowledge about 20th century Greenland Ice Sheet dynamics.
Timing and magnitude of early to middle Holocene warming in East Greenland inferred from chironomids
Authors: Axford Yarrow , Levy Laura B. , Kelly Meredith A. , Francis Donna R. , Hall Brenda L. , Langdon Peter G. , Lowell Thomas V.
Published: April 2017

Much of Greenland experienced summers warmer than present in parts of the early to middle Holocene, during a precession‐driven positive anomaly in summer insolation. However, the magnitude of that warmth remains poorly known, and its timing and spatial pattern are uncertain. Here we describe the first quantitative Holocene palaeotemperature reconstruction from central East Greenland based upon insect (chironomid) assemblages preserved in lake sediments. We postulate that landscapes like our study site, characterized by minimal soil and vegetation development through the Holocene and thus little influenced by some important secondary gradients, are especially well suited to the use of chironomids to reconstruct Holocene temperatures. The inferred timing of warmth at our study site near Scoresby Sund agrees well with other nearby evidence, including glacial geological reconstructions and temperatures inferred from precipitation isotopes at Renland ice cap, supporting the use of chironomids to reconstruct temperatures at this site. We infer highest temperatures from c. 10 to 5.5 ka, followed by gradual cooling after 5.5 ka and progressively colder and less productive conditions after 3.5 ka. Models based upon two independent training sets yield similar inferred temperature trends, and suggest an average summer temperature anomaly from c. 10 to 5.5 ka of 3 to 4 °C relative to the preindustrial last millennium. The estimated overall rate of Neoglacial cooling averaged over the period from 5.5 to 0.5 ka was 0.6 to 0.8 °C per thousand years, more than twice the rate previously estimated for the Arctic as a whole. Given strong apparent spatial variability in Holocene climate around the Arctic, and the utility of palaeoclimate data for improving climate and ice‐sheet models, it should be a priority to further quantify past temperature changes around the margins of the Greenland Ice Sheet, where few quantitative reconstructions exist and future warming will affect global sea level.
Prenatal Risk and Infant Regulation: Indirect Pathways via Fetal Growth and Maternal Prenatal Stress and Anger
Authors: Schuetze Pamela , Eiden Rina D. , Colder Craig R. , Huestis Marilyn A. , Leonard Kenneth E.
Published: April 2017

Pathways from maternal tobacco, marijuana, stress, and anger in pregnancy to infant reactivity and regulation (RR) at 9 months of infant age were examined in a low‐income, diverse sample beginning in the first trimester of pregnancy, with fetal growth and postnatal stress/anger as potential mediators, and infant sex as a moderator. Participants were 247 dyads (173 substance‐exposed infants). There were no direct effects of prenatal risk on RR and no moderation by sex. However, there were significant indirect effects on RR via poor fetal growth and higher postnatal anger. The study adds to the sparse literature on joint effects of tobacco and marijuana, and highlights the role of fetal growth and maternal anger as important pathways from prenatal risk to infant RR.
Applying network theory to prioritize multispecies habitat networks that are robust to climate and land‐use change
Authors: Albert Cécile H. , Rayfield Bronwyn , Dumitru Maria , Gonzalez Andrew
Published: April 2017

Designing connected landscapes is among the most widespread strategies for achieving biodiversity conservation targets. The challenge lies in simultaneously satisfying the connectivity needs of multiple species at multiple spatial scales under uncertain climate and land‐use change. To evaluate the contribution of remnant habitat fragments to the connectivity of regional habitat networks, we developed a method to integrate uncertainty in climate and land‐use change projections with the latest developments in network‐connectivity research and spatial, multipurpose conservation prioritization. We used land‐use change simulations to explore robustness of species’ habitat networks to alternative development scenarios. We applied our method to 14 vertebrate focal species of periurban Montreal, Canada. Accounting for connectivity in spatial prioritization strongly modified conservation priorities and the modified priorities were robust to uncertain climate change. Setting conservation priorities based on habitat quality and connectivity maintained a large proportion of the region's connectivity, despite anticipated habitat loss due to climate and land‐use change. The application of connectivity criteria alongside habitat‐quality criteria for protected‐area design was efficient with respect to the amount of area that needs protection and did not necessarily amplify trade‐offs among conservation criteria. Our approach and results are being applied in and around Montreal and are well suited to the design of ecological networks and green infrastructure for the conservation of biodiversity and ecosystem services in other regions, in particular regions around large cities, where connectivity is critically low.
Post‐transplant lymphoproliferative disease in lung transplantation: A nested case‐control study
Authors: Leyssens Annelies , Dierickx Daan , Verbeken Eric K. , Tousseyn Thomas , Verleden Stijn E. , Vanaudenaerde Bart M. , Dupont Lieven J. , Yserbyt Jonas , Verleden Geert M. , Van Raemdonck Dirk E. , Vos Robin
Published: April 2017

Post‐transplant lymphoproliferative disorder (PTLD) may compromise long‐term outcome of lung transplant (LTx) recipients. A case‐control study was performed, comparing LTx recipients with PTLD (n=31) to matched recipients without PTLD (Controls, n=62). Risk factors for PTLD and post‐transplant outcomes were assessed. PTLD prevalence was 3.9%, time to PTLD 323 (166‐1132) days; and 54.8% had early‐onset PTLD versus 45.2% late‐onset PTLD. At LTx, more Epstein‐Barr virus (EBV)‐seronegative patients were present in PTLD (42%) compared to Controls (5%) (P<.0001); most of whom had undergone EBV seroconversion upon PTLD diagnosis. EBV viral load was higher in PTLD versus Controls (P<.0001). Overall, lower hemoglobin and higher C‐reactive protein levels were present in PTLD versus Controls (P<.0001). EBV status at LTx (P=.0073) and EBV viral load at PTLD (P=.0002) were the most important risk determinates for later PTLD. Patients with PTLD demonstrated shorter time to onset of chronic lung allograft dysfunction (CLAD) (P=.0006) and poorer 5‐year survival post‐LTx (66.6% versus 91.5%), resulting in worse CLAD‐free survival (HR 2.127, 95%CI 1.006‐4.500; P=.0483) and overall survival (HR 3.297 95%CI 1.473‐7.382; P=.0037) compared to Controls. Late‐onset PTLD had worse survival compared to early‐onset PTLD (P=.021). Primary EBV infection is a risk for PTLD; which is associated with worse long‐term outcome post‐LTx.
Development of infant sustained attention and its relation to EEG oscillations: an EEG and cortical source analysis study
Authors: Xie Wanze , Mallin Brittany M. , Richards John E.
Published: April 2017

The current study examined the relation between infant sustained attention and infant EEG oscillations. Fifty‐nine infants were tested at 6 (N = 15), 8 (N = 17), 10 (N = 14), and 12 (N = 13) months. Three attention phases, stimulus orienting, sustained attention, and attention termination, were defined based on infants' heart rate changes. Frequency analysis using simultaneously recorded EEG focused on infant theta (2–6 Hz), alpha (6–9 Hz), and beta (9–14 Hz) rhythms. Cortical source analysis of EEG oscillations was conducted with realistic infant MRI models. Theta synchronization was found over fontal pole, temporal, and parietal electrodes during infant sustained attention for 10 and 12 months. Alpha desynchronization was found over frontal, central and parietal electrodes during sustained attention. This alpha effect started to emerge at 10 months and became well established by 12 months. No difference was found for the beta rhythm between different attention phases. The theta synchronization effect was localized to the orbital frontal, temporal pole, and ventral temporal areas. The alpha desynchronization effect was localized to the brain regions composing the default mode network including the posterior cingulate cortex and precuneus, medial prefrontal cortex, and inferior parietal gyrus. The alpha desynchronization effect was also localized to the pre‐ and post‐central gyri. The present study demonstrates a connection between infant sustained attention and EEG oscillatory activities.
Clinical clues for autoimmunity and neuroinflammation in patients with autistic regression
Authors: Scott Ori , Shi Diya , Andriashek Diana , Clark Brenda , Goez Helly R
Published: April 2017

Aim

Autistic regression is a unique variant within the autism spectrum disorders (ASDs), with recent reports raising the possibility of immune aetiology. This study explores clinical clues for an association between autistic regression and autoimmunity.

Method

Single‐centre charts of children diagnosed with ASD in 2014 were reviewed. We compared the rates of: (1) familial autoimmunity in first‐degree and second‐degree relatives; (2) febrile illness preceding initial parental concern, as a potential precipitant of immune activation; and (3) possible non‐immune precipitants such as pregnancy and postnatal complications.

Results

The charts of 206 children with ASD and 33 diagnosed with autistic regression variant were reviewed. The incidence of febrile illness in the 6 months prior to initial parental concern was significantly higher in the children with autistic regression compared with those with ASD (30% vs 0%; p<0.001). The overall prevalence of familial autoimmunity was also higher in children with autistic regression compared with those with ASD (33% vs 12%; p<0.001). Type 1 diabetes and autoimmune thyroiditis were both more common in families with children with autistic regression. Other non‐immune risk factors did not differ between the two groups.

Interpretation

Our findings suggest that predisposition to autoimmunity, and immune/inflammatory activation, may be associated with autistic regression.
Plant‐mediated species networks: the modulating role of herbivore density
Authors: PINEDA ANA , SOLER ROXINA , PASTOR VICTORIA , LI YEHUA , DICKE MARCEL
Published: April 2017

1. When herbivores of distinct feeding guilds, such as phloem feeders and leaf chewers, interact, the outcome of these interactions often shows facilitation. However, whether this facilitation turns into competition at stronger herbivory pressure remains unknown.

2. Using an integrative approach that links ecological processes (behavioural choices of insects) with physiological plant mechanisms (nutrient and phytohormone levels) for the wild crucifer Brassica nigra (L.) Koch., this study evaluates preferences of leaf chewers for plants previously infested with several densities of the specialist aphid Brevicoryne brassicae L. (Hemiptera, Aphididae). As leaf chewers, four species of caterpillars (Lepidoptera) were selected that differ in their degree of specialisation in crucifers.

3. These results show that, whereas at low and medium aphid densities caterpillars displayed a preference for aphid‐infested plants or no preference, at high aphid infestation density, all four species of caterpillar preferred uninfested plants, with a significant difference for Pieris rapae and Mamestra brassicae.

4. In contrast to our expectation, the consistent preference for uninfested plants at a high aphid density could not be associated with a decrease in plant nutrition. However, while jasmonate concentrations [i.e. 12‐oxo‐phytodienoic acid and jasmonic acid (JA)] at medium aphid‐density infestation decreased compared with low levels of infestation, at high infestation level, the jasmonates JA as well as JA conjugated with the amino acid isoleucine were present at higher levels compared with low‐infestation treatments.

5. This work provides evidence that positive interactions observed in herbivore communities can be transient, leading to negative interactions mediated by changes in plant defences rather than in plant nutrition.
No detectable role for predators mediating effects of aquatic habitat size and permanence on populations and communities of container‐dwelling mosquitoes
Authors: WESTBY KATIE M. , JULIANO STEVEN A.
Published: April 2017

1. General theory from aquatic ecology predicts that smaller aquatic habitats have shorter hydroperiods favouring species that are better resource competitors and complete development quickly. Larger habitats are predicted to have longer hydroperiods enabling longer‐lived predators to persist. Habitats with long hydroperiods and predators are predicted to favour slower‐developing, predator‐resistant species, rather than competitive species.

2. In a field experiment, habitat size and hydroperiod were manipulated independently in water‐filled containers, to test these hypotheses about processes structuring aquatic communities. Human‐made containers were used that are dominated by mosquitoes that vary in desiccation resistance, competitive ability, and predation resistance.

3. Habitat size and drying had significant effects on abundances of larvae of the common species in these communities. There was sorting of species by habitat size and by drying, with species that are better competitors relatively more abundant in smaller, more ephemeral habitats, and predator‐resistant, slower‐developing species relatively more abundant in larger or permanently flooded habitats. There were no detectable effects of habitat size or drying on the dominant predator.

4. Habitat size and its interaction with drying affected inputs of eggs to containers. Habitat size also affected relative abundances of the two dominant species in the egg population.

5. Although habitat size and hydroperiod significantly affected composition of these communities, these impacts did not appear to be mediated through effects on predator abundance. Species‐specific differences in habitat size and drying regime preferences, and habitat‐dependent larval performance appear to be the main forces shaping these communities.
Lewis revisited: tropical polities competing on the world market, 1830–1938
Authors: Federico Giovanni , Tena‐Junguito Antonio
Published: April 2017

Since the seminal work by W. A. Lewis, exports of primary products have been deemed the main or sole source of growth in tropical countries before the Great Depression. However, this conventional wisdom relies on very limited evidence. This article analyses the growth of exports with a constant market share analysis for 84 tropical polities. Exports grew a lot, but less than total trade, while relative prices of tropical products remained roughly constant. We thus tentatively infer that the decline in the tropical shares of world trade reflects an insufficient demand for tropical products. Asia dealt well with these headwinds throughout the whole period, while African polities blossomed after the First World War. The loser was (South) America, and most notably the Caribbean former slave colonies, especially before 1870.
Secretory breast carcinoma with a papillary‐predominant pattern: an unusual morphological variant
Authors: Shui Ruohong , Cheng Yufan , Bai Qianming , Yang Wentao
Published: April 2017

Aims

Secretory breast carcinoma is a rare, low‐grade, translocation‐associated invasive carcinoma with unique morphology and excellent prognosis. Three patterns (microcystic, tubular, solid) have often been described in secretory carcinoma. Herein, we reported one case of secretory breast carcinoma with an uncommon papillary‐predominant growth pattern.

Methods and results

The patient was a 53‐year‐old female with a mass located in outer upper quadrant of her right breast. The patient had one positive axillary lymph node. Morphologically, tumour cells were arranged in a papillary growth pattern with sclerosis in most areas; glandular and microcystic patterns were observed only in focal areas at the periphery. The presence of intracellular and extracellular secretory material was observed. Tumour cells were mild‐to‐moderately atypical with granular eosinophilic to foamy cytoplasm. Tumour cells were triple‐negative [negative for oestrogen receptor (ER), progestogen receptor (PR) and human epidermal growth factor receptor 2 (HER2)] with a basal‐like phenotype, and strongly positive for S‐100 protein. P63 and calponin staining showed the absence of myoepithelial cells around tumour cells. Fluorescence in‐situ hybridization (FISH) analysis showed ETS variant 6 (ETV6) gene rearrangement.

Conclusions

Our study indicated that besides typical growth patterns (microcystic, solid and tubular), secretory carcinoma could also present with a papillary‐predominant architecture. These cases should be differentiated from other breast tumours with a papillary pattern. It may have clinical significance to recognize this uncommon morphology variant of secretory carcinoma in routine practice.
New test method for the evaluation of the preservation efficacy of soaps at very alkaline pH made by saponification
Authors: Témoin‐Fardini S. , Servant J. , Sellam S.
Published: April 2017

Objective

The aim of this study was to develop a test method to evaluate the preservation efficacy for a specific product, a very high‐alkaline liquid soap (pH around 10) made by a saponification process. Several manufacturers have experienced contamination issues with these high‐pH soaps despite passing a classic preservative efficacy challenge test or even a multi‐inoculation challenge test.

Methods

Bacteria were isolated from contaminated soaps and were identified using 16S rRNA gene sequencing. High‐alkaline‐pH unpreserved soaps were tested using the Thor Personal Care internal multichallenge test method (TM206) with classical microorganisms and then with the bacterial strains isolated from various contaminated soaps (TM768). Preservatives were added to these soaps and assessed for their efficacy using the newly developed test.

Results

Four different species of bacteria (Nesterenkonia lacusekhoensis, Dermacoccus sp., Halomonas sp. and Roseomonas sp.) were identified by sequencing among the contaminants of the various soaps tested. Among these, only one bacterial species, Nesterenkonia lacusekhoensis, appeared to be responsible for the specific contamination of these high‐alkaline soaps. Thus, one specific wild‐type strain of Nesterenkonia lacusekhoensis, named as strain 768, was used in a new multi‐inoculation test (TM768). Unlike the single inoculation challenge test, the multi‐inoculation test using the Nesterenkonia strain 768 was able to predict the sensitivity of a product towards this bacterium. Among the 27 different preservatives tested, 10 were able to protect the formula against contamination with this bacterium.

Conclusion

This study enabled the development of a test method to evaluate the efficacy of preservation using a specific bacterium, Nesterenkonia lacusekhoensis, responsible for the contamination of very alkaline soaps made by saponification and identify an appropriate preservative system.
Dimethyl fumarate ameliorates myoclonus stemming from protein misfolding in oligodendrocytes
Authors: Southwood Cherie M. , Garshott Danielle M. , Richardson Chelsea R. , Seraji‐Bozorgzad Navid , Fribley Andrew M. , Gow Alexander
Published: April 2017

Multiple sclerosis (MS) is considered a primary autoimmune disease; however, this view is increasingly being challenged in basic and clinical science arenas because of the growing body of clinical trials’ data showing that exclusion of immune cells from the CNS only modestly slows disease progression to disability. Accordingly, there is significant need for expanding the scope of potential disease mechanisms to understand the etiology of MS. Concomitantly, the use of a broader range of pre‐clinical animal models for characterizing existing efficacious clinical treatments may elucidate additional or unexpected mechanisms of action for these drugs that augment insight into MS etiology. Herein, we explore the in vivo mechanism of action of dimethyl fumarate, which has been shown to suppress oxidative stress and immune cell responses in psoriasis and MS. Rather than studying this compound in the context of an experimental autoimmune‐induced attack on the CNS, we have used a genetic model of hypomyelination, male rumpshaker (rsh) mice, which exhibit oligodendrocyte metabolic stress and startle‐induced subcortical myoclonus during development and into adulthood. We find that myoclonus is reduced 30‐50% in treated mutants but we do not detect substantial changes in metabolic or oxidative stress response pathways, cytokine modulation, or myelin thickness (assessed by anova). All procedures involving vertebrate animals in this study were reviewed and approved by the IACUC committee at Wayne State University.

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Differences in fatigue severity in a sample of adult cancer patients
Authors: Gonzalez Velda J , Tofthagen Cindy S , Chen Xusheng , Pedro Elsa , Saligan Leorey N
Published: April 2017

Aims and objectives

To describe differences in fatigue severity in a sample of adult Puerto Rican patients during and postcancer treatments.

Background

Hispanics, including Puerto Ricans, are an understudied population who are under‐represented in clinical trials, especially in symptom research. Although symptom management is a clinical priority in oncology care, treatment‐related differences in Puerto Rican cancer patients’ report of fatigue severity have not been well described.

Design/Methods

A cross‐sectional survey was conducted from data of self‐report of 138 Puerto Rican patients during and postcancer treatments at two ambulatory facilities located in San Juan, Puerto Rico. Fatigue severity was assessed using the Fatigue subscale from the Functional Assessment of Cancer Therapy‐Fatigue quality of life questionnaire Spanish version. Differences in fatigue severity across type of treatment (radiation therapy, chemotherapy, combined radiation chemotherapy and post‐treatment) were evaluated using nonparametric (Kruskal–Wallis and Mann–Whitney test) statistical tests.

Results

The majority of the participants had prostate (33%) and breast (32%) cancers and were receiving radiation therapy (43%) or chemotherapy (28%). The Kruskal–Wallis test showed that there was a statistically significant difference in fatigue scores between the different four treatment conditions, χ2(3) = 39.1, p = .001 with patients on combined radiation chemotherapy or chemotherapy alone experiencing more severe fatigue.

Conclusions

Findings from the current study suggest that type of treatment is a key component of the symptom burden of fatigue among the Puerto Rican oncology population. Specially, patients receiving combined therapy or chemotherapy alone were at increased risk for experiencing severe fatigue, compared to radiation therapy and post‐treatment patients.

Relevance to clinical practice

With the worldwide increase in migration of Puerto Rican families, nurses need to recognise that type of treatment is a key component of the symptom burden of fatigue among the Puerto Rican population. The results of this study will improve understanding of treatment‐related fatigue to identify therapeutic targets and improve quality of life of patients.
Reproducibility, repeatability, and level of difficulty of two methods for tumor budding evaluation in oral squamous cell carcinoma
Authors: Leão Priscila Laiza Rubim , Marangon Junior Helvécio , Melo Victória Vasconcellos Moreira , Caixeta Ângela Braga , Souza Paulo Eduardo Alencar , de Aguiar Maria Cássia Ferreira , Horta Martinho Campolina Rebello
Published: April 2017

Background

This study aimed to analyze the reproducibility, repeatability, and level of difficulty of two methods for tumor budding evaluation in oral squamous cell carcinoma (OSCC): staining by hematoxylin and eosin (HE) and immunostaining for multicytokeratin.

Methods

The evaluation of tumor budding was performed by three examiners in 103 samples of OSCC, using the two methods. A Likert‐type scale was used to measure the difficulty in the assessment. The interexaminer agreement (reproducibility) was estimated using Fleiss's kappa and the intra‐examiner agreement (repeatability) was estimated using Cohen's kappa. The agreement between the two methods was evaluated using Cohen's Kappa. The Friedman test was used to compare the three examiners’ perceived levels of difficulty of assessment. The Wilcoxon test was used to compare the level of difficulty of the evaluation between the two methods.

Results

Reproducibility by the immunostaining method for multicytokeratin was substantial, being higher than the only fair agreement by the HE. Repeatability by the HE ranged from moderate to substantial among examiners, regardless of the examiner's experience. Repeatability by the immunostaining method for multicytokeratin did not vary among examiners, showing almost perfect agreement. The agreement between the two methods ranged from fair to moderate among examiners, being lower in the less experienced examiner. All the examiners presented greater difficulty in the evaluation by the HE.

Conclusion

In view of the unsatisfactory agreement between the two methods of tumor budding evaluation in OSCC, it is recommended that this evaluation should be performed by the immunostaining method for multicytokeratin, considering its higher reproducibility, greater replicability, and lower difficulty compared to the HE.
The Hollow Maxillary Complete Denture: A Simple, Precise, Single‐Flask Technique Using a Caramel Spacer
Authors: Bhushan Prem , Aras Meena A. , Chitre Vidya , Mysore Ashwin R. , Mascarenhas Kennedy , Kumar Swati
Published: April 2017

The success of removable prostheses ultimately depends on a number of factors such as retention, stability, support, esthetics, and masticatory function. Increased intraoral inter‐arch distance leads to an increase in the weight of the prosthesis. This may compromise the retention and resistance, which are key for a successful removable prosthesis. Various methods, techniques, and materials have been reported to minimize the weight of a prosthesis. This article describes a simple, unique, precise single‐flask technique for the fabrication of a lightweight maxillary prosthesis using caramel as a 3D spacer, which was “indexed” to obtain a uniform thickness of acrylic around the hollow cavity.
Effects of Silica Coating by Physical Vapor Deposition and Repeated Firing on the Low‐Temperature Degradation and Flexural Strength of a Zirconia Ceramic
Authors: Cakir‐Omur Tutku , Gozneli Rifat , Ozkan Yasemin
Published: April 2017

Purpose

To examine the application of physical vapor deposition (PVD) silica coating as an approach to retard low temperature degradation (LTD) for dental applications. Accelerated aging characteristics of heat‐ and surface‐treated zirconia material were also investigated by exposing specimens to hydrothermal treatment.

Materials and Methods

The specimens (90 disc‐shaped specimens [15 mm ×1.2 mm]) were divided into 9 groups (n = 10) according to the test protocol: Ctrl, control (no surface treatment); Ag, autoclave aging; GrAg, grinding + aging; SiAg, silica coating + aging; GrSiAg, grinding + silica coating + aging; 3FAg, 3‐time firing + aging; Gr3FAg, grinding + 3‐time firing + aging; 5FAg, 5‐time firing + aging; Gr5FAg, grinding + 5‐time firing + aging. Accelerated aging was performed in a steam autoclave (134°C, 2 bars) for 12 hours. Following each treatment protocol, X‐ray diffraction (XRD) analysis was used to estimate the relative amount of monoclinic phase and corresponding transformed zone depth (TZD). Additionally, a biaxial flexure test was used to calculate the flexural strength. Statistical analysis was conducted with one‐way ANOVA and Fisher's LSD test (p< 0.05).

Results

The tetragonal‐to‐monoclinic transformation was retarded by PVD silica coating only on ground surfaces. Ground and heat‐treated specimens exhibited the lowest monoclinic content after aging. The biaxial flexural strength value of the GrAg group was significantly higher than the values in all of the other groups except the SiAg group. The flexural strength value of the GrSiAg group was significantly higher than that of the 3FAg group. There was no statistically significant difference between the other groups (p> 0.05).

Conclusions

Grinding decreased the susceptibility of zirconia to LTD and increased the flexural strength. PVD silica coating and repeated firing decreased the monoclinic content only in ground specimens during aging.
Associations between arterial structure and function and serum levels of liver enzymes in obese adolescents
Authors: Man Elim , Cheung Pik‐to , Cheung Yiu‐fai
Published: April 2017

Aim

To determine the structural and functional alterations of systemic arteries in obese adolescents and their relationships with adiposity, metabolic and lipid profile, and serum liver enzyme levels.

Methods

Carotid intima‐media thickness (IMT), carotid stiffness index, and brachial‐ankle pulse wave velocity (baPWV) were measured in 56 obese adolescents and 58 lean controls. Obese adolescents had additional liver ultrasound and determination of fasting blood indices of glucose metabolism and lipid profile, and serum levels of liver enzymes.

Results

Carotid IMT (P < 0.0001), carotid stiffness index (P < 0.0001) and baPWV (P = 0.001) were significantly greater in obese than control subjects. Thirty‐seven (66%) obese subjects had fatty liver changes and their aspartate aminotransferase, alanine aminotransferase (ALT), alkaline phosphatase, and gamma‐glutamyl transferase levels were significantly higher than those without (all P < 0.05). Univariate analyses showed positive correlations between serum ALT (r = 0.29, P = 0.03) and alkaline phosphatase (r = 0.28, P = 0.04) levels and carotid IMT, aspartate aminotransferase level and carotid stiffness (r = 0.41, P = 0.002), and gamma‐glutamyl transferase level and baPWV (r = 0.34, P = 0.02) in obese subjects. Multivariate linear regression revealed serum ALT level (β = 0.02, P = 0.006) as an independent correlate of carotid stiffness.

Conclusion

Obese adolescents have increased carotid IMT and stiffness, which are associated positively with serum liver enzyme levels.
Concurrent suppression of NF-κB, p38 MAPK and reactive oxygen species formation underlies the effect of a novel compound isolated from Curcuma comosa Roxb. in LPS-activated microglia
Authors: Jiamvoraphong Nittaya , Jantaratnotai Nattinee , Sanvarinda Pantip , Tuchinda Patoomratana , Piyachaturawat Pawinee , Thampithak Anusorn , Sanvarinda Pimtip
Published: April 2017

Objective

We investigated the molecular mechanisms underlying the effect of (3S)-1-(3,4-dihydroxyphenyl)-7-phenyl-(6E)-6-hepten-3-ol, also known as compound 092, isolated from Curcuma comosa Roxb on the production of pro-inflammatory mediators and oxidative stress in lipopolysaccharide (LPS)-activated highly aggressive proliferating immortalized (HAPI) microglial cell lines.

Method

Nitric oxide (NO) production was determined using the Griess reaction, and reverse transcription polymerase chain reaction was used to measure the expression of inducible nitric oxide synthase (iNOS) mRNA. Western blotting was used to determine the levels of pro-inflammatory mediators and their related upstream proteins.

Key finding

Compound 092 suppressed NO production and iNOS expression in LPS-stimulated HAPI cells. These effects originated from the ability of compound 092 to attenuate the activation of nuclear factor (NF)-κB as determined by the reduction in p-NF-κB and p-IκB kinase (IKK) protein levels. Compound 092 also significantly lowered LPS-activated intracellular reactive oxygen species production and p38 mitogen-activated protein kinase (MAPK) activation.

Conclusion

Compound 092 suppresses microglial activation through attenuation of p38 MAPK and NF-κB activation. Compound 092 thus holds the potential to treat neurodegenerative disorders associated with neuroinflammation and oxidative stress.
Therapy of Canine Hyperlipidemia with Bezafibrate
Authors: De Marco V. , Noronha K.S.M. , Casado T.C. , Nakandakare E.R. , Florio J.C. , Santos E.Z. , Gilor C.
Published: April 2017

Background

Bezafibrate (BZF) is effective in the treatment of hypertriglyceridemia in human patients, but there are no data on its use in dogs.

Objective

To assess the safety of BZF in hyperlipidemic dogs and its efficacy in decreasing serum triglyceride (TG) and cholesterol (CHO) concentrations.

Animals

Forty‐six dogs, 26 females and 20 males, mean (±SD) age of 9 (±3) years, with TG ≥150 mg/dL (33 dogs also were hypercholesterolemic [>300 mg/dL]).

Methods

Prospective, uncontrolled clinical trial. Dogs were treated with bezafibrate once daily, using 200 mg tablets at a dosage of 4–10 mg/kg (depending on body weight). Serum TG and CHO concentrations and alanine aminotransferase (ALT) and creatine kinase (CK) activity before and after 30 days of treatment were compared.

Results

Sixteen dogs (34.8%) had primary hyperlipidemia, and 30 dogs (65.2%) had secondary hyperlipidemia (including spontaneous hyperadrenocorticism [41.3%, n = 19/46], chronic treatment with glucocorticoids [10.8%, n = 5/46], and hypothyroidism [15.2%, n = 7/46]). After 30 days, serum TG concentration normalized (<150 mg/dL) in 42 dogs (91.3%) and CHO concentration normalized (<270 mg/dL) in 22 of 33 dogs (66.7%). There was no difference in baseline TG concentration between the primary and secondary hyperlipidemia subgroups, but the decrease in TG concentration after treatment was greater in the primary hyperlipidemia subgroup. No adverse effects were observed, but ALT activity decreased significantly after 30 days of treatment.

Conclusions and Clinical Importance

Over 30 days, BZF was safe and effective in treatment of primary and secondary hyperlipidemia in dogs.
Forelimb and hind limb loading patterns during below branch quadrupedal locomotion in the two‐toed sloth
Authors: Granatosky M. C. , Schmitt D.
Published: April 2017

The living sloths are the most suspensory of all extant mammals, and therefore represent ideal models for investigating the effects that suspensory behaviours have on bone and joint morphology. While the anatomy and kinematics of sloths are well known, no research has reported kinetic patterns of sloth locomotion. This study examines peak force patterns generated by the two‐toed slothCholoepus didactylusduring below branch quadrupedal walking to infer how kinetic patterns of sloths compare to data reported on non‐human primates. Values for vertical, fore‐aft, and mediolateral peak forces were collected for the forelimb and hind limb, and analyses between the magnitude and timing of these peaks were compared between forelimbs and hind limbs. Patterns and timing of fore‐aft peak forces were similar between sloths and non‐human primates, and were characterized by first a propulsive force as the limb first made contact with the support followed by braking force prior to lift‐off. Similarly, both sloths and primates demonstrate a medially directed force bias onto the substrate during below branch quadrupedal locomotion, although the magnitude observed in sloths exceeds values reported in primates. Peak vertical forces applied by the forelimbs and hind limbs of sloths were not statistically different in magnitude from each other. Data from this study indicate the forelimbs and hind limbs of sloths are functioning similarly to each other during below branch quadrupedal locomotion, and that forelimb‐biased weight support, the pattern typical of primates, is not a mechanical requirement of suspensory locomotion across all mammals. These findings provide important information about the mechanical necessities of below branch movement, and data from this study should be used when considering mechanical convergence among suspensory taxa and the interpretation of suspensory limb adaptations in the fossil record.
Eliciting information from human sources: Training handlers in the Scharff technique
Authors: Oleszkiewicz Simon , Granhag Pär Anders , Kleinman Steven M.
Published: April 2017

Purpose

In previous laboratory‐based work, the Scharff technique has proved successful for gathering intelligence from human sources. However, little is known about whether the technique can be taught to practitioners, and whether Scharff‐trained practitioners will interview more effectively than colleagues using their conventional approaches and tactics.

Method

We examined professional handlers from the Norwegian Police (n = 64), all experienced in interacting with informants. Half received training in the Scharff technique, and their performance was compared against handlers receiving no Scharff training and free to use the approaches they saw fit. All handlers received the same case file describing a source holding information about a future terrorist attack and were given the same interview objectives. Police trainees (n = 64) took on the role of semicooperative sources and were given incomplete information about the attack.

Results

The trained handlers adhered to the Scharff training as they (1) aimed to establish the illusion of ‘knowing‐it‐all’, (2) posed claims to collect information, and (3) asked few (if any) explicit questions. In contrast, the untrained handlers tried to evoke the sources’ motivation to reveal information and asked a high number of explicit questions. Scharff‐trained handlers were perceived as less eager to gather information, but collected comparatively more new information.

Conclusions

The Scharff‐trained interviewers utilized more specific elicitation tactics (e.g., posing claims) and fewer general interview strategies (e.g., evoking motivation), and they collected comparatively more new information. This captures the essence of the Scharff technique: It is subtle, yet effective.
Silver potentiates aminoglycoside toxicity by enhancing their uptake
Authors: Herisse Marion , Duverger Yohann , Martin‐Verstraete Isabelle , Barras Frédéric , Ezraty Benjamin
Published: April 2017

The predicted shortage in new antibiotics has prompted research for chemicals that could act as adjuvant and enhance efficacy of available antibiotics. In this study, we tested the effects of combining metals with aminoglycosides on Escherichia coli survival. The best synergizing combination resulted from mixing aminoglycosides with silver. Using genetic and aminoglycoside uptake assays, we showed that silver potentiates aminoglycoside action in by‐passing the PMF‐dependent step, but depended upon protein translation. We showed that oxidative stress or Fe–S cluster destabilization were not mandatory factors for silver potentiating action. Last, we showed that silver allows aminoglycosides to kill an E. coli gentamicin resistant mutant as well as the highly recalcitrant anaerobic pathogen Clostridium difficile. Overall this study delineates the molecular basis of silver's potentiating action on aminoglycoside toxicity and shows that use of metals might offer solutions for battling against increased bacterial resistance to antibiotics.
Transpeptidase activity of penicillin‐binding protein SpoVD in peptidoglycan synthesis conditionally depends on the disulfide reductase StoA
Authors: Bukowska‐Faniband Ewa , Hederstedt Lars
Published: April 2017

Endospore cortex peptidoglycan synthesis is not required for bacterial growth but essential for endospore heat resistance. It therefore constitutes an amenable system for research on peptidoglycan biogenesis. The Bacillus subtilis sporulation‐specific class B penicillin‐binding protein (PBP) SpoVD and many homologous PBPs contain two conserved cysteine residues of unknown function in the transpeptidase domain – one as residue x in the SxN catalytic site motif and the other in a flexible loop near the catalytic site. A disulfide bond between these residues blocks the function of SpoVD in cortex synthesis. With a combination of experiments with purified proteins and B. subtilis mutant cells, it was shown that in active SpoVD the two cysteine residues most probably interact by hydrogen bonding and that this is important for peptidoglycan synthesis in vivo. It was furthermore demonstrated that the sporulation‐specific thiol‐disulfide oxidoreductase StoA reduces SpoVD and that requirement of StoA for cortex synthesis can be suppressed by two completely different types of structural alterations in SpoVD. It is concluded that StoA plays a critical role mainly during maturation of SpoVD in the forespore outer membrane. The findings advance our understanding of essential PBPs and redox control of extra‐cytoplasmic protein disulfides in bacterial cells.
Self‐compatibility is over‐represented on islands
Authors: Grossenbacher Dena L. , Brandvain Yaniv , Auld Josh R. , Burd Martin , Cheptou Pierre‐Olivier , Conner Jeffrey K. , Grant Alannie G. , Hovick Stephen M. , Pannell John R. , Pauw Anton , Petanidou Theodora , Randle April M. , Rubio de Casas Rafael , Vamosi Jana , Winn Alice , Igic Boris , Busch Jeremiah W. , Kalisz Susan , Goldberg Emma E.
Published: April 2017

Because establishing a new population often depends critically on finding mates, individuals capable of uniparental reproduction may have a colonization advantage. Accordingly, there should be an over‐representation of colonizing species in which individuals can reproduce without a mate, particularly in isolated locales such as oceanic islands. Despite the intuitive appeal of this colonization filter hypothesis (known as Baker's law), more than six decades of analyses have yielded mixed findings.

We assembled a dataset of island and mainland plant breeding systems, focusing on the presence or absence of self‐incompatibility. Because this trait enforces outcrossing and is unlikely to re‐evolve on short timescales if it is lost, breeding system is especially likely to reflect the colonization filter.

We found significantly more self‐compatible species on islands than mainlands across a sample of > 1500 species from three widely distributed flowering plant families (Asteraceae, Brassicaceae and Solanaceae). Overall, 66% of island species were self‐compatible, compared with 41% of mainland species.

Our results demonstrate that the presence or absence of self‐incompatibility has strong explanatory power for plant geographical patterns. Island floras around the world thus reflect the role of a key reproductive trait in filtering potential colonizing species in these three plant families.
Growing evidence for facultative biotrophy in saprotrophic fungi: data from microcosm tests with 201 species of wood‐decay basidiomycetes
Authors: Smith Gabriel R. , Finlay Roger D. , Stenlid Jan , Vasaitis Rimvydas , Menkis Audrius
Published: April 2017

Ectomycorrhizal (ECM) symbioses have evolved a minimum of 78 times independently from saprotrophic lineages, indicating the potential for functional overlap between ECM and saprotrophic fungi. ECM fungi have the capacity to decompose organic matter, and although there is increasing evidence that some saprotrophic fungi exhibit the capacity to enter into facultative biotrophic relationships with plant roots without causing disease symptoms, this subject is still not well studied.

In order to determine the extent of biotrophic capacity in saprotrophic wood‐decay fungi and which systems may be useful models, we investigated the colonization of conifer seedling roots in vitro using an array of 201 basidiomycete wood‐decay fungi. Microtome sectioning, differential staining and fluorescence microscopy were used to visualize patterns of root colonization in microcosm systems containing Picea abies or Pinus sylvestris seedlings and each saprotrophic fungus.

Thirty‐four (16.9%) of the tested fungal species colonized the roots of at least one tree species. Two fungal species showed formation of a mantle and one showed Hartig net‐like structures. These features suggest the possibility of an active functional symbiosis between fungus and plant.

The data indicate that the capacity for facultative biotrophic relationships in free‐living saprotrophic basidiomycetes may be greater than previously supposed.