bluuebunny/crossref_metadata_2025 huggingface dataset:
Identification of drug transporters contributing to oxaliplatin‐induced peripheral neuropathy
Authors: Fujita Shunsuke , Hirota Takeshi , Sakiyama Ryo , Baba Misaki , Ieiri Ichiro
Published: October 2018

Oxaliplatin is widely used as a key drug in the treatment of colorectal cancer. However, its administration is associated with the dose‐limiting adverse effect, peripheral neuropathy. Platinum accumulation in the dorsal root ganglion (DRG) is the major mechanism responsible for oxaliplatin‐induced neuropathy. Some drug transporters have been identified as platinum complex transporters in kidney or tumor cells, but not yet in DRG. In the present study, we investigated oxaliplatin transporters and their contribution to peripheral neuropathy. We identified 12 platinum transporters expressed in DRG with real‐time PCR, and their transiently overexpressing cells were established. After exposure to oxaliplatin, the accumulation of platinum in these overexpressing cells was evaluated using a coupled plasma mass spectrometer. Octn1/2‐ and Mate1‐expressing cells showed the intracellular accumulation of oxaliplatin. In an animal study, peripheral neuropathy developed after the administration of oxaliplatin (4 mg/kg, intravenously, twice a week) to siRNA‐injected rats (0.5 nmol, intrathecally, once a week) was demonstrated with the von Frey test. The knockdown of Octn1 in DRG ameliorated peripheral neuropathy, and decreased platinum accumulation in DRG, whereas the knockdown of Octn2 did not. Mate1 siRNA‐injected rats developed more severe neuropathy than control rats. These results indicate that Octn1 and Mate1 are involved in platinum accumulation at DRG and oxaliplatin‐induced peripheral neuropathy.

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Post‐metamorphic ontogeny of Zoroaster fulgens Thomson, 1873 (Asteroidea, Forcipulatacea)
Authors: Fau Marine , Villier Loïc
Published: October 2018

The complete ontogenetic development of an asteroid skeleton has never been described formally for any species. Here, we describe in detail the post‐metamorphic ontogeny of Zoroaster fulgens Thomson, 1873. The major novelty of our work is the description of patterns of plate addition, the ontogeny of the internal ossicles, as well as the variability of ossicles according to their position along series. Seven specimens collected in the Rockall Basin (North Atlantic) were dissected with bleach and their anatomy was documented using a scanning electron microscope. The external anatomy was additionally observed on more than 30 specimens. We found that the overall structure of the skeleton does not change much between juveniles and adults, but the shape of individual ossicle changes during growth. Allometric scaling was particularly visible on the orals, ambulacrals and adambulacrals. The shape of an ossicle is more dependent of its position along the arm series than of its individual size. Many morphological features differentiate progressively during ontogeny, while others are expressed consistently among specimens. The study of this ontogenetic series allows discussing the homology between the structures present on the ossicles of Z. fulgens in particular and other forcipulatacean sea stars in general (i.e. muscles insertions and articulation areas). The new data obtained in this study provide a comprehensive framework of the anatomy and ontogeny of Z. fulgens that will help resolve taxonomic and phylogenetic controversies in the future.
Alteration of serum and tissue tumor necrosis factor alpha levels: A possible mechanism of action of oral pulse steroids in the treatment of alopecia areata
Authors: Abdel Halim Dalia , Abu Zeid Ola M. , Rashed Laila , Saleh Marwah Adly
Published: October 2018

Background

Alopecia areata (AA) is a multifactorial disease in which tumor necrosis factor alpha (TNF‐α) plays an important role.

Objective

To study the effect of oral pulse steroids on both serum and tissue levels of TNF‐α in AA patients.

Methods

Skin biopsies and serum samples were collected from 20 patients with patchy AA before and after treatment (oral prednisolone for two consecutive days every week for 3 months) for determination of the levels of TNF‐α levels using ELISA technique.

Results

Both serum and tissue levels of TNF‐α in AA patients were significantly higher than in controls before (P < 0.001) as well as after treatment (P = 0.0169 and P = 0.3051), respectively. The duration of disease negatively correlated with tissue TNF‐α before treatment (P < 0.0001). Serum and tissue levels of TNF‐α dropped significantly after treatment (P < 0.0001). The percentage of reduction of both tissue and serum TNF‐α levels correlated positively with the percentage of clinical improvement (r = 0.682, P = 0.0009; r = 0.567, P = 0.009, respectively).

Conclusion

TNF‐α plays an important role in the evolution of AA lesions, and alteration in both serum and tissue levels of TNF‐α could be considered one of the important mechanisms of action of systemic oral pulse steroids in the treatment of AA.
Financial Markets Where Traders Neglect the Informational Content of Prices
Authors: EYSTER ERIK , RABIN MATTHEW , VAYANOS DIMITRI
Published: October 2018

We model a financial market where some traders of a risky asset do not fully appreciate what prices convey about others' private information. Markets comprising solely such “cursed” traders generate more trade than those comprising solely rationals. Because rationals arbitrage away distortions caused by cursed traders, mixed markets can generate even more trade. Per‐trader volume in cursed markets increases with market size; volume may instead disappear when traders infer others' information from prices, even when they dismiss it as noisier than their own. Making private information public raises rational and “dismissive” volume, but reduces cursed volume given moderate noninformational trading motives.
MRI‐Guided High‐Intensity Focused Ultrasound as an Emerging Therapy for Stroke: A Review
Authors: Zafar Atif , Quadri Syed A. , Farooqui Mudassir , Ortega‐Gutiérrez Santiago , Hariri Omid R. , Zulfiqar Maryam , Ikram Asad , Khan Muhammad Adnan , Suriya Sajid S. , Nunez‐Gonzalez Joel R. , Posse Stefan , Mortazavi Martin M. , Yonas Howard
Published: October 2018

Stroke, either ischemic or hemorrhagic, accounts for significantly high morbidity and mortality rates around the globe effecting millions of lives annually. For the past few decades, ultrasound has been extensively investigated to promote clot lysis for the treatment of stroke, myocardial infarction, and acute peripheral arterial occlusions, with or without the use of tPA or contrast agents. In the age of modern minimal invasive techniques, magnetic resonance imaging‐guided high‐intensity focused ultrasound is a new emerging modality that seems to promise therapeutic utilities for both ischemic and hemorrhagic stroke. High‐intensity focused ultrasound causes thermal heating as the tissue absorbs the mechanical energy transmitted by the ultrasonic waves leading to tissue denaturation and coagulation. Several in‐vitro and in‐vivo studies have demonstrated the viability of this technology for sonothrombolysis in both types of stroke and have warranted clinical trials. Apart from safety and efficacy, initiation of trials would further enable answers regarding its practical application in a clinical setup. Though this technology has been under study for treatment of various brain diseases for some decades now, relatively very few neurologists and even neurosurgeons seem to be acquainted with it. The aim of this review is to provide basic understanding of this powerful technology and discuss its clinical application and potential role as an emerging viable therapeutic option for the future management of stroke.
The Conometric Concept: A Two‐Year Follow‐Up of Fixed Partial CEREC Restorations Supported By Cone‐In‐Cone Abutments
Authors: Degidi Marco , Nardi Diego , Sighinolfi Gianluca , Degidi Davide , Piattelli Adriano
Published: October 2018

Purpose

To evaluate the performance of definitive, implant‐supported, lithium disilicate fixed dental prostheses (LS2 FDPs) manufactured with a computer‐assisted design/computer‐assisted manufacturing (CAD/CAM) system. All patients received two‐unit restorations placed in posterior regions, supported by osseointegrated implants with cone‐in‐cone connection abutments.

Materials and Methods

Two implants (Ankylos) were placed into healed sites or fresh extraction sockets in the maxillary/mandibular posterior regions of partially edentulous patients. Definitive digital impressions were made 3 months after surgery. Twenty‐four patients received fixed  monolithic LS2 restorations manufactured with the CEREC system. All restorations were connected to the implants using cone‐in‐cone connection abutments. Peri‐implant pocket depths were recorded for 2 years at each follow‐up visit. Esthetic, functional, and biologic United States Public Health Services (USPHS) parameters modified by the FDI World Dental Federation study design were assessed yearly until the last follow‐up appointment. The opposing dentitions were identified by type of restoration and supporting structures at the time of placement of the definitive restorations and at the 2‐year follow‐up visits.

Results

One patient (4.16%) moved to an unknown location during the study. A total of 23 FDPs (95.8%) supported by 46 implants reached the 2‐year follow‐up. None of the prostheses failed, or became loose or detached. No significant difference involving probing levels between the experimental times were found.

Conclusions

The results of this research indicated that the abutment‐prostheses connection using a cone‐in‐cone approach was successful within the 2‐year period of this study. None of the studied monolithic LS2 glass‐ceramic prostheses milled using the CEREC CAD/CAM system fractured or became detached.
A Pilot Study to Determine the Effect of Three Months of Oral Appliance Therapy using a Mandibular Advancement Device on HbA1c in Subjects with Type 2 Diabetes Mellitus and Obstructive Sleep Apnea
Authors: Baslas Varun , Chand Pooran , Jurel Sunit Kumar , Tripathi Shuchi , Arya Deeksha , Tripathi Suryakant , Singh Balendra Pratap , Dubey Abhishek
Published: October 2018

Purpose

Continuous positive air pressure (CPAP) is recommended for obstructive sleep apnea (OSA) with type 2 diabetes mellitus (T2DM) but cost and compliance are major barriers. A mandibular advancement device (MAD) may be an economical, feasible alternative to CPAP. Various studies have been published to recommend MAD as an alternative to CPAP for OSA, but not regarding its efficacy for patients having OSA as well as T2DM. This study aims to objectively and subjectively evaluate oral appliance therapy using a MAD in patients having OSA as well as T2DM.

Materials and Methods

Patients who visited the hospital clinic having OSA as well as T2DM were recruited. After giving informed consent, participants were divided into three equally sized groups of three grades of OSA (mild, moderate, severe) on the basis of a polysomnography report and were given intervention of MAD at 50% of maximum mandibular protrusion and 20% of maximum interincisal opening. Objective outcomes were HbA1c level and apnea hypopnea index score (AHI). Subjective outcomes were Epworth Sleepiness Scale (ESS) and the Berlin Questionnaire. All outcomes were assessed before and after 3 months of intervention.

Results

A statistically significant difference was seen in all outcomes after intervention with MAD (p < 0.01) in all groups except HbA1c level in participants having severe OSA.

Conclusion

MAD may be recommended in patients having OSA as well as T2DM. This study provides evidence to inform health care workers about possible use of MAD in OSA with T2DM.
Transgender adolescents and legal reform: How improved access to healthcare was achieved through medical, legal and community collaboration
Authors: Telfer Michelle , Kelly Fiona , Feldman Debi , Stone Georgie , Robertson Rebekah , Poulakis Zeffie
Published: October 2018

Transgender children and adolescents face hardships in all domains of their lives, with many experiencing family rejection, social exclusion, discrimination, bullying and assaults. The mental health implications of these experiences include high rates of depression, anxiety, self‐harm and attempted suicide. Gender‐affirming social support and medical treatment has been shown to ameliorate the poor mental health outcomes of transgender youth, with those who are supported in their social and medical transition reporting rates of depression and self‐worth equivalent to general population levels. Advocacy efforts that improve access to support and medical treatment are therefore likely to produce significant positive health and well‐being outcomes for this vulnerable population. The transgender community in Australia identified the legal restrictions placed on children and adolescents accessing medical treatment as a significant barrier to positive psychological well‐being. Australian law, unique internationally, required the parents of transgender adolescents to apply for court authorisation prior to the commencement of their child's gender‐affirming medical treatment. Concerned by the harm created by this process, a coalition of experts, including transgender children, adolescents and their parents, as well as academic and clinical experts in the fields of law and medicine, was created to advocate for reform. Over a period of approximately 4 years, a collaborative process was undertaken, which ultimately led to law reform and improved access to medical treatment for the transgender community.
Child with multiple problems: Clinical complexity and uncertainty
Authors: McDowell Michael
Published: October 2018

When practising neurodevelopmental–behavioural paediatrics, responsibility rests with the individual clinician to interpret research evidence in their daily work. This is not necessarily an easy task. Children do not usually present with single, easily definable problems. Complexity and uncertainty are present from the outset due to heterogeneity inherent in the diagnoses available, patterns of comorbid problems and the unique challenges of each child's social context. This article examines the resulting clinical challenge and offers potential responses. Rather than striving to eliminate uncertainty with strategies such as extensive assessment, the goal is to work effectively and efficiently within the limits of what can be readily known. Suggested strategies address complexity by considering the components of what is going on (biological, developmental, transactional) as hypotheses shared within each child's system of care. These hypotheses can then be tested and revised systematically as further information arises along the journey of treatment and longitudinal care.
Anxiety‐related disorders: An overview
Authors: Riordan Denise M , Singhal Deepa
Published: October 2018

Anxiety‐related disorders are common in the child and adolescent population. They cause significant distress, which can affect social, emotional, family and academic functioning. They frequently present in general paediatric and primary care settings. Comprehensive assessment should include the child as well as parent and family functioning because anxiety‐related disorders in other family members are common and, if untreated, can affect outcomes for the child. There are good evidence‐based psychological interventions available, which should be the first line of treatment offered; accessing appropriate therapies for an adequate duration of treatment can, however, be challenging. Medication, particularly selective serotonin reuptake inhibitors, may have a role to play but should be used in the context of psychologically based therapies. Prevention of anxiety‐related disorders in childhood is a major public health issue. Prevention programmes are available and should commence in the antenatal period through infancy, early childhood and adolescence, promoting positive attachments and resilience.
The Roles of Knowledge Providers, Knowledge Recipients, and Knowledge Usage in Bridging Structural Holes
Authors: Ozer Muammer , Zhang Guangxi
Published: October 2018

Studies have suggested that firms can benefit from bridging two or more otherwise disconnected firms in their ego networks (i.e., structural holes) as a potentially useful source of external knowledge for innovation. However, past research also noted that the relationship between bridging structural holes and firm innovation varies significantly. Building on the earlier research that has examined the industrial, structural, and institutional dimensions of this relationship, the purpose of this research is to study how the different characteristics of the external knowledge provided by bridging structural holes in a focal firm’s ego network might moderate the relationship between bridging structural holes and firm innovation. Using longitudinal data from the U.S. computer industry, this study showed that focal firms that bridged otherwise disconnected firms in their ego networks enjoyed higher levels of innovation. In addition, it showed that this relationship was particularly stronger when the focal firms and the disconnected firms that they bridged operated in similar rather than different markets but when the focal firms and the disconnected firms worked on different rather than similar technological domains. The results also revealed that the relationship was stronger when the focal firms’ knowledge specialization was low rather than high and when the focal firms emphasized incremental rather than breakthrough innovation. These findings show companies how they can benefit from bridging otherwise disconnected firms in their ego networks and help them make more informed decisions pertaining to such bridging activities.
Interleukin‐10 gene polymorphisms and chronic periodontitis susceptibility: Evidence based on 33 studies
Authors: Zhang Zheng , Zheng Youli , Li Xinyue
Published: October 2018

The purpose of the meta‐analysis was to investigate the potential association of interleukin‐10 (IL‐10) polymorphisms with susceptibility to chronic periodontitis (CP). A total of 33 studies involving 3487 cases and 4356 controls were identified through a search of multiple electronic databases (last search was updated on 19 July 2018). Three single nucleotide polymorphisms (SNPs) were included in the meta‐analysis: ‐1082A>G(rs1800896), ‐819C>T(rs1800871), and ‐592C>A(rs1800872). Odds ratios (ORs) and their 95% confidence intervals (CIs) using allele, dominant, and recessive genetic models were computed to assess the strength of the association. The ‐1082A>G(rs1800896) polymorphism was found to be associated with decreased CP risk in both Caucasians and Latinos under the dominant model. The ‐819C>T(rs1800871) and ‐592C>A(rs1800872) polymorphisms were both associated with increased CP risk in Latinos under the allele and dominant models. In Asians, no associations were observed for any of the polymorphisms under all comparison models. The present meta‐analysis suggests that the ‐1082A>G(rs1800896) polymorphism might be a protective factor for CP in both Caucasians and Latinos, but the ‐819C>T(rs1800871) and ‐592C>A(rs1800872) polymorphisms might contribute to CP pathogenesis in Latinos.
A novel IkB kinase inhibitor attenuates ligature‐induced periodontal disease in mice
Authors: Kure Keitetsu , Sato Hiroki , Suzuki Jun‐ichi , Itai Akiko , Aoyama Norio , Izumi Yuichi
Published: October 2018

Backgrounds and Objectives

IMD‐0354 is a novel I kappa‐B kinase (IKK) inhibitor, which regulates inflammation. The purpose of this study was to examine the effect of the reagent on bone loss for ligature‐induced periodontitis.

Material and Methods

We ligated around the upper right second molars of 8‐week‐old C57BL/6J mice in the split‐mouth model. The test mice were injected intraperitoneally with IMD‐0354 before the placement of the ligature. The control mice were injected intraperitoneally with 0.5% carboxymethylcellulose (CMC) as vehicle before the placement of the ligature. To determine the optimum concentration of the reagent on ligature‐induced periodontitis in the mice, we examined the effect of three types of concentration, which were 1, 5, and 10 mg/kg of IMD‐0354, as a preliminary experiment. After we determined 10 mg/kg as the optimum concentration for the IMD group by micro‐CT analysis, both the IMD and CMC groups (n = 15 each in total, including all the analyses) were subdivided into two small groups, respectively, for further analyses: I group (unligated side of IMD group), IL group (ligated side of IMD group), C group (unligated side of CMC group) and CL group (ligated side of CMC group). The mice in the IMD and CMC groups were treated with each reagent daily and sacrificed 8 days after the ligation. For assessment of bone resorption, we performed micro‐CT and histological analyses. We also carried out real‐time PCR to investigate proinflammatory and bone metabolic markers.

Results

There were significant differences for linear bone loss and volumetric parameter in the test (IMD) group compared to the control (CMC) group 8 days after ligation. In terms of the mRNA expression level of gingival tissue, the level of RANKL was significantly suppressed in the IMD group compared to the CMC group. IMD‐0354 also tended to suppress the levels of interleukin‐1 beta, tumor necrosis factor‐alpha, and osteoprotegerin. For histological analysis, the relative numbers of TRAP‐positive multinucleated cells decreased significantly in the IMD group compared to the CMC group.

Conclusion

IMD‐0354 regulated bone resorption by ligature‐induced periodontitis, and it is suggested that the inhibition of IKK via down‐regulation of NF kappa‐B may provide periodontal patients with an effective approach to prevent or suppress the disease.
The periodontal stem/progenitor cell inflammatory‐regenerative cross talk: A new perspective
Authors: Fawzy El‐Sayed Karim M. , Elahmady Maryam , Adawi Zeina , Aboushadi Nour , Elnaggar Ali , Eid Maryam , Hamdy Nayera , Sanaa Dalia , Dörfer Christof E.
Published: October 2018

Adult multipotent stem/progenitor cells, with remarkable regenerative potential, have been isolated from various components of the human periodontium. These multipotent stem/progenitor cells include the periodontal ligament stem/progenitor cells (PDLSCs), stem cells from the apical papilla (SCAP), the gingival mesenchymal stem/progenitor cells (G‐MSCs), and the alveolar bone proper stem/progenitor cells (AB‐MSCs). Whereas inflammation is regarded as the reason for tissue damage, it also remains a fundamental step of any early healing process. In performing their periodontal tissue regenerative/reparative activity, periodontal stem/progenitor cells interact with their surrounding inflammatory micro‐environmental, through their expressed receptors, which could influence their fate and the outcome of any periodontal stem/progenitor cell‐mediated reparative/regenerative activity. The present review discusses the current understanding about the interaction of periodontal stem/progenitor cells with their surrounding inflammatory micro‐environment, elaborates on the inflammatory factors influencing their stemness, proliferation, migration/homing, differentiation, and immunomodulatory attributes, the possible underlying intracellular mechanisms, as well as their proposed relationship to the canonical and noncanonical Wnt pathways.
Spontaneous primary hypothyroidism in 7 adult cats
Authors: Peterson Mark E. , Carothers Marcia A. , Gamble David A. , Rishniw Mark
Published: October 2018

Background

Naturally occurring hypothyroidism in adult cats is rare, with only 4 cases reported.

Objectives

To describe the historical, clinical, laboratory, and scintigraphic features of adult cats with spontaneous hypothyroidism.

Animals

Seven adult cats referred for suspected hypothyroidism.

Methods

Prospective case series. We collected data on cats’ signalment, clinical signs, results of physical examination, routine laboratory and thyroid hormone testing, and thyroid imaging (thyroid scintigraphy or ultrasound). We subsequently treated cats with levothyroxine and evaluated their response to treatment.

Results

Cats ranged from 3.5 to 11 years, with no apparent breed predilection; 6/7 cats were male. Only 2/7 cats were initially tested because of signs of hypothyroidism (hair‐coat changes, lethargy, obesity); others were tested for routine thyroid monitoring or palpable thyroid nodules. Four were azotemic (serum creatinine, 2.2‐3.4 mg/dL). Six of the cats had low serum thyroxine (T4) and free T4(fT4) concentrations, whereas all 7 cats had high thyroid‐stimulating hormone (TSH) concentrations. In 6/7 cats, thyroid scintigraphy revealed bilateral goiter with intense radionuclide uptake; imaging showed no visible thyroid tissue in the other. After levothyroxine treatment, serum concentrations of T4and fT4increased and TSH fell; high serum creatinine normalized in azotemic cats; and repeat imaging showed reduction in goiter size.

Conclusions and Clinical Importance

Primary hypothyroidism develops in adult cats, with a higher prevalence than previously thought. Most cats appear to develop a goitrous form of hypothyroidism associated with thyroid hyperplasia, whereas thyroid atrophy appears to be less common. With levothyroxine replacement, clinical and laboratory abnormalities improve or resolve.
Equine asthma: Integrative biologic relevance of a recently proposed nomenclature
Authors: Bond Stephanie , Léguillette Renaud , Richard Eric A. , Couetil Laurent , Lavoie Jean‐Pierre , Martin James G. , Pirie R. Scott
Published: October 2018

The term “equine asthma” has been proposed as a unifying descriptor of inflammatory airway disease (IAD), recurrent airway obstruction (RAO), and summer pasture‐associated obstructive airway disease. Whilst the term will increase comprehensibility for both the lay and scientific communities, its biologic relevance must be compared and contrasted to asthma in human medicine, recognizing the limited availability of peer‐reviewed equine‐derived data, which are largely restricted to clinical signs, measures of airway obstruction and inflammation and response to therapy. Such limitations constrain meaningful comparisons with human asthma phenotypes. Suggested minimum inclusion criteria supporting the term asthma, as well as similarities and differences between IAD, RAO, and multiple human asthma phenotypes are discussed. Furthermore, differences between phenotype and severity are described, and typical features for equine asthma subcategories are proposed. Based on shared features, we conclude that mild/moderate (IAD) and severe (RAO) equine asthma are biologically appropriate models for both allergic and non‐allergic human asthma, with RAO (severe equine asthma) also being an appropriate model for late‐onset asthma. With the development of new biologic treatments in humans and the application of more targeted therapeutic approaches in the horse, it would appear appropriate to further investigate the allergic (Th‐2) and non‐allergic (non‐Th‐2) phenotypes of equine asthma. Further research is required to more fully determine the potential clinical utility of phenotype classification.
Modeling and Kinematic Path Selection of Retractable Kirigami Roof Structures
Authors: Cai Jianguo , Zhang Qian , Feng Jian , Xu Yixiang
Published: October 2018

This article proposes a numerical method for the kinematic path modeling of retractable roof structures based on the concept of kirigami. The kinematics of origami structures have been studied by many researchers. However, the singular point in the kinematic path which will crucially affect the overall performance of the structure has not been investigated. In this article, the method to detect the singular point in the kinematic path is first introduced. Then, a prediction‐correction algorithm is developed to simulate the motion along a uniquely determined path. A second‐order program is used to select kinematic paths deviating from a singular point. After that, the proposed method is applied in the kinematic modeling of a kirigami structure to show its accuracy.
Taiwan renal care system: A learning health‐care system
Authors: Wu Mei‐Yi , Wu Mai‐Szu
Published: October 2018

Taiwan renal care system is an evolving learning health‐care system. There are four facets of this system. From the early history of dialysis and Taiwan Renal Registry Data System, it facilitates the generation of data to knowledge. National multidisciplinary pre‐end‐stage renal disease care project and outcome enhances knowledge to practice. Early chronic kidney disease (CKD) programs and 2015 Taiwan CKD clinical guidelines implicate the practice to customer, and then explore the causes of CKD help to resume customer to data. A learning health‐care system allows better and safer care at lower cost, enhancement of public health and patient empowerment. The successful development of a learning health‐care system was to collect, accumulate and analyze data, interpret results, deliver tailored message and take action to change practice. Through the established database and data analysis, an integrated care system would be able to improve clinical outcomes and achieve the most cost‐effectiveness care. Acute kidney injury, CKD with unknown origin, palliative care and kidney transplant are our new focuses to struggle.
Towards take‐all control: a C‐21β oxidase required for acylation of triterpene defence compounds in oat
Authors: Leveau Aymeric , Reed James , Qiao Xue , Stephenson Michael J. , Mugford Sam T. , Melton Rachel E. , Rant Jenni C. , Vickerstaff Robert , Langdon Tim , Osbourn Anne
Published: October 2018

Oats produce avenacins, antifungal triterpenes that are synthesized in the roots and provide protection against take‐all and other soilborne diseases. Avenacins are acylated at the carbon‐21 position of the triterpene scaffold, a modification critical for antifungal activity. We have previously characterized several steps in the avenacin pathway, including those required for acylation. However, transfer of the acyl group to the scaffold requires the C‐21β position to be oxidized first, by an as yet uncharacterized enzyme.

We mined oat transcriptome data to identify candidate cytochrome P450 enzymes that may catalyse C‐21β oxidation. Candidates were screened for activity by transient expression in Nicotiana benthamiana.

We identified a cytochrome P450 enzyme AsCYP72A475 as a triterpene C‐21β hydroxylase, and showed that expression of this enzyme together with early pathway steps yields C‐21β oxidized avenacin intermediates. We further demonstrate that AsCYP72A475 is synonymous with Sad6, a previously uncharacterized locus required for avenacin biosynthesis. sad6 mutants are compromised in avenacin acylation and have enhanced disease susceptibility.

The discovery of AsCYP72A475 represents an important advance in the understanding of triterpene biosynthesis and paves the way for engineering the avenacin pathway into wheat and other cereals for control of take‐all and other diseases.
Terrestrial LiDAR: a three‐dimensional revolution in how we look at trees
Authors: Disney Mathias
Published: October 2018

Terrestrial laser scanning (TLS) is providing new, very detailed three‐dimensional (3D) measurements of forest canopy structure. The information that TLS measurements can provide in describing detailed, accurate 3D canopy architecture offers fascinating new insights into the variety of tree form, environmental drivers and constraints, and the relationship between form and function, particularly for tall, hard‐to‐measure trees. TLS measurements are helping to test fundamental ecological theories and enabling new and better exploitation of other measurements and models that depend on 3D structural information. This Tansley insight introduces the background and capabilities of TLS in forest ecology, discusses some of the barriers to progress, and identifies some of the directions for new work.
Detection of MAPK/ERK pathway proteins and KRAS mutations in adenomatoid odontogenic tumors
Authors: Bologna‐Molina Ronell , Ogawa Ikuko , Mosqueda‐Taylor Adalberto , Takata Takashi , Sánchez‐Romero Celeste , Villarroel‐Dorrego Mariana , Takeda Yasunori , Mikami Toshinari
Published: October 2018

Objective

This study aimed to assess the frequency of KRAS mutation and its association with the presence of the MAPK/ERK signaling pathway proteins in adenomatoid odontogenic tumors.

Study Design

Paraffin‐embedded tissue samples from nine cases of adenomatoid odontogenic tumor were used.

Genomic DNA was extracted from each sample; in one case, genetic mutations in 50 cancer‐associated genes were examined by next‐generation sequencing. Hotspot mutations in the RAS family were analyzed by Luminex assay using the remaining eight cases. Subsequently, immunohistochemistry for KRAS, CRAF, BRAF, EGFR, ERK, MEK, and BRAFV600E was performed.

Results

A KRAS G12D missense mutation was detected in the DNA sequence of the tumor cells, but it was not detected in the stromal tissue. KRAS G12V and KRAS G12R mutations were detected in two and four cases, respectively. For immunohistochemistry, all the cases were EGFR, KRAS, BRAF, CRAF positive, one case was ERK negative,and one case was MEK and ERK negative, all the other remaining cases were MEK and ERK positive.

Conclusion

KRAS mutation at codon 12 and the presence of MAPK/ERK pathway proteins were detected suggesting their association with tumorigenesis of adenomatoid odontogenic tumors.
Coastal phytoplankton community dynamics and coexistence driven by intragroup density‐dependence, light and hydrodynamics
Authors: Barraquand F. , Picoche C. , Maurer D. , Carassou L. , Auby I.
Published: October 2018

Phytoplanktonic communities maintain a high diversity in a seemingly homogeneous environment, competing for the same set of resources. Many theories have been proposed to explain this coexistence despite likely competition, such as contrasted responses to temporal environmental variation. However, theory has developed at a faster pace than empirical evaluation using field data, which requires inferring drivers of community dynamics from observational time series. Here, we combine autoregressive models with a data set spanning more than 20 years of phytoplankton counts every two weeks, together with nutrients and physical variables. By comparing models dominated by nutrients or physical variables (hydrodynamics and climate), we first explore which abiotic factors contribute more to phytoplankton growth and decline. We find that physical drivers – such as irradiance, wind, and salinity – explain some of the variability in abundances unexplained by biotic interactions. In contrast, responses to nutrients explain less of the phytoplankton variability. Concerning biotic drivers of community dynamics, multivariate autoregressive models reveal that competition between different groups (genera) has a much weaker effect on population growth rates than competition within a group. In fact, the few biotic interactions between genera that are detected are frequently positive. Hence, our system is unlikely to be best represented as a set of competitors whose differing responses to fluctuating environments allow coexistence, as in ‘paradox of the plankton’ models with a storage effect or a relative nonlinearity of competition. Coexistence is more likely to result from high intragroup density‐dependence. Competition between phytoplanktonic groups and nutrient limitation are often invoked as drivers of phytoplankton dynamics; our findings suggest instead that more attention should be given to the physical structure of the environment and natural enemies such as grazers and pathogens, that could explain the high intraspecific density dependence found here.
Dilutional coagulopathy in pediatric scoliosis surgery: A single center report
Authors: Baker Courtney E. , Marvi Tanya , Austin Thomas M. , Payne Shelby , Mignemi Megan E. , Gailani David , Wheeler Allison P. , Nguyen Thanh T. , Lovejoy Steven A. , Martus Jeffrey E. , Mencio Gregory A. , Schoenecker Jonathan G.
Published: October 2018

Background

Children undergoing posterior spinal fusion experience high blood loss often necessitating transfusion. An appropriately activated coagulation system provides hemostasis during surgery, but pathologic dysregulation can cause progressive bleeding and increased transfusions. Despite receiving antifibrinolytics for clot stabilization, many patients still require transfusions.

Aims

We sought to examine the association of dilutional coagulopathy with blood loss and blood transfusion in posterior spinal fusion for pediatric scoliosis patients.

Methods

A retrospective, single institution study of children undergoing posterior spinal fusion >6 levels with a standardized, prospective anesthetic protocol utilizing antifibrinolytics. Blood loss was evaluated using a hematocrit‐based calculation. To evaluate transfusions, a normalized Blood Product Transfusion calculation was developed. Factors associated with blood loss and blood transfusions were determined by univariate analysis and multivariate regression modeling with multicollinearity and mediation analysis.

Results

Patients received 73.7 mL/kg (standard deviation ±30.8) of fluid poor in coagulation factors. Estimated blood loss was 42.6 mL/kg (standard deviation ±18.0). There was a significant association between estimated blood loss and total fluids delivered (Spearman's rho = 0.51, 95% confidence interval 0.33‐0.65, P < 0.001). Factors significantly associated with normalized Blood Product Transfusion in this cohort included age, weight, scoliosis type, levels fused, total osteotomies, pelvic fixation, total fluid, maximum prothrombin time, and minimum fibrinogen. Regression modeling showed the best combination of variables for modeling normalized Blood Product Transfusion included patient weight, number of levels fused, total fluid administered, and maximum prothrombin time.

Conclusion

Blood product transfusion remains a frustrating problem in pediatric scoliosis. Identifying and controlling dilutional coagulopathy in these patients may reduce blood loss and the need for blood transfusion.
Ascariasis as a model to study the helminth/allergy relationships
Authors: Caraballo Luis , Acevedo Nathalie , Zakzuk Josefina
Published: October 2018

Ascariasis is the most frequent soil transmitted helminthiasis and, as well as other helminth infections, is expected to influence the clinical presentation of allergic diseases such as asthma. Indeed, several clinical and experimental works have shown an important impact either increasing or suppressing symptoms, and the same effects have been detected on the underlying immune responses. In this review we analyze the work on this field performed in Colombia, a Latin American tropical country, including aspects such as the molecular genetics of the IgE response to Ascaris; the allergenic activity of Ascaris IgE‐binding molecular components and the immunological and clinical influences of ascariasis on asthma. The analysis allows us to conclude that the impact of ascariasis on the inception and evolution of allergic diseases such as asthma deserves more investigation, but advances have been made during the last years. The concurrent parasite‐induced immunostimulatory and immunosuppressive effects during this helminthiasis do modify the natural history of asthma and some aspects of the practice of allergology in the tropics. Theoretically it can also influence the epidemiological trends of allergic diseases either by its absence or presence in different regions and countries.
Regulation by biotic stress of tannins biosynthesis in Quercus ilex: Crosstalk between defoliation and Phytophthora cinnamomi infection
Authors: Gallardo Alejandro , Morcuende David , Solla Alejandro , Moreno Gerardo , Pulido Fernando , Quesada Alberto
Published: October 2018

Sustainability of the Mediterranean forest is threatened by oak decline, a disease of holm oak and other Quercus species that is initiated by infection with the oomycete Phytophthora cinnamomi. Focusing on the role of tannins in the chemical defense of plants, this work investigated whether tannins content in Quercus ilex is regulated by biotic stress. Screening of published genomes allowed the identification of Quercus sequences encoding enzymes for early steps of the biosynthesis of phenolic compounds, like hydrolysable tannins and condensed tannins (CT) among others, plus genes involved in the late steps of CT biosynthesis. Four days after treatment of Q. ilex seedlings by mechanical defoliation, P. cinnamomi infection and both stressors simultaneously, mRNA concentrations for tannins biosynthesis enzymes were measured in leaves. Among the transcript amount for shikimate dehydrogenase (SDH, EC 1.1.1.25), anthocyanidin reductase (EC 1.3.1.77), anthocyanidin synthase (EC 1.14.11.19) and leucoanthocyanidine reductase (EC 1.17.1.3), defoliation induced gene expression for SDH2 isoenzyme. About 4 days after infection of roots by P. cinnamomi, this up‐regulation was canceled and SDH enzyme activity decreased. Furthermore, during this late stage of biotrophic interaction the pathogen switched off the correlation engaged by defoliation between the expression of SDH1 and SDH2 encoding genes and chemical defenses corresponding to total tannins, which were down‐regulated. Thus, tannins biosynthesis in seedlings of Q. ilex is induced after mechanical defoliation whereas infection by the pathogen interferes with this regulation, potentially increasing the susceptibility of plants to herbivory and aggravating the impact of biotic stress.
Obesity and loneliness. Findings from a longitudinal population‐based study in the second half of life in Germany
Authors: Hajek André , König Hans‐Helmut
Published: October 2018

Aim

Little is known about whether changes to obesity are associated with changes in loneliness scores. Therefore, using a longitudinal approach, we aimed to determine whether the onset of obesity (explanatory variable) is associated with changes in loneliness (outcome measure) among older adults.

Methods

For the present study, data from wave 2 (2002) to wave 5 (2014) of the German Ageing Survey were analyzed. This is a representative sample of community‐dwelling individuals in Germany (≥40 years). A validated six‐item scale by Gierveld and van Tilburg was used to quantify loneliness. Obesity was defined as body mass index ≥30 kg/m2. Fixed effects regressions were used.

Results

Fixed effects regressions showed that loneliness increased with the onset of obesity among men but not among women. The sex × obesity interaction term was significant (P = 0.02).

Conclusions

Findings stress the importance of the onset of obesity for loneliness among older men. Weight management strategies might also be a promising strategy to reduce loneliness scores.
Sequential fishways reconnect a coastal river reflecting restored migratory pathways for an entire fish community
Authors: Rourke Meaghan L. , Robinson Wayne , Baumgartner Lee J. , Doyle Jonathon , Growns Ivor , Thiem Jason D.
Published: October 2018

River regulation infrastructure has been implicated in worldwide aquatic biodiversity loss. In‐stream barriers such as weirs prevent fish migration and the impact can be particularly severe for diadromous species. Fishways are frequently installed on in‐stream barriers to reconnect migratory pathways and rehabilitate diadromous fish populations. Sequential fishways may be necessary in rivers where multiple barriers prevent migration. We monitored a coastal fish community's response to fish passage restoration at 10 predominantly low‐level weirs in the freshwater reaches of the Nepean River in southeastern Australia. Few studies have simultaneously assessed fish community passage at successive fishways within a river system. Prior to the installation of the fishways, there was a gradient of reduced species diversity in an upstream direction including the absence of many diadromous species, despite the regular inundation frequency of most weirs. Following the installation of the fishways, species diversity was still greater in the downstream monitoring sites; however, there was evidence of a positive change in fish community structure in middle and upstream sites. Most notably, three diadromous species rapidly expanded their distribution upstream and one amphidromous species expanded its downstream distribution. This study demonstrates appropriately designed successive fishways can successfully reconnect river systems for an entire fish community, encompassing species with a broad range of swimming abilities and diverse life histories.
Mapping Socioeconomic Exposure for Flood Risk Assessment in Italy
Authors: Amadio Mattia , Mysiak Jaroslav , Marzi Sepehr
Published: October 2018

Detailed spatial representation of socioeconomic exposure and the related vulnerability to natural hazards has the potential to improve the quality and reliability of risk assessment outputs. We apply a spatially weighted dasymetric approach based on multiple ancillary data to downscale important socioeconomic variables and produce a grid data set for Italy that contains multilayered information about physical exposure, population, gross domestic product, and social vulnerability. We test the performances of our dasymetric approach compared to other spatial interpolation methods. Next, we combine the grid data set with flood hazard estimates to exemplify an application for the purpose of risk assessment.
Non-parametric Predictive Inference for the Validation of Credit Rating Systems
Authors: Coolen-Maturi T. , Coolen F. P. A.
Published: October 2018

Credit rating or credit scoring systems are important tools for estimating the obligor’s creditworthiness and for providing an indication of the obligor’s future status. The discriminatory power of a credit rating or credit scoring system refers to its ex ante ability to distinguish between two or more classes of borrowers. One of the most popular tools for the validation of the power of credit rating or credit scoring models to distinguish between two (or more) classes of borrowers is the receiver operating characteristic (ROC) curve (hypersurface) and its widely used overall summary, the area (hypervolume) under the curve (hypersurface). As the end goal of building such models is to predict and quantify uncertainty about future loans, prediction methods are especially valuable in this context. For this, non-parametric predictive inference is a promising candidate for such inference as it is a frequentist statistical method that is explicitly aimed at using few modelling assumptions, enabled through the use of lower and upper probabilities to quantify uncertainty. The aim of the paper is to introduce non-parametric predictive inference for ROC analysis within a banking context, for which novel results on ROC hypersurfaces for more than three groups are presented. Examples are provided to illustrate the method.
Optimal Design of Experiments for Non-Linear Response Surface Models
Authors: Huang Yuanzhi , Gilmour Steven G. , Mylona Kalliopi , Goos Peter
Published: October 2018

Many chemical and biological experiments involve multiple treatment factors and often it is convenient to fit a non-linear model in these factors. This non-linear model can be mechanistic, empirical or a hybrid of the two. Motivated by experiments in chemical engineering, we focus on D-optimal designs for multifactor non-linear response surfaces in general. To find and study optimal designs, we first implement conventional point and co-ordinate exchange algorithms. Next, we develop a novel multiphase optimization method to construct D-optimal designs with improved properties. The benefits of this method are demonstrated by application to two experiments involving non-linear regression models. The designs obtained are shown to be considerably more informative than designs obtained by using traditional design optimality algorithms.