bluuebunny/crossref_metadata_2025 huggingface dataset:
Diagnostic potential of hypermethylation of the cysteine dioxygenase 1 gene (CDO1) promoter DNA in pancreatic cancer
Authors: Nishizawa Nobuyuki , Harada Hiroki , Kumamoto Yusuke , Kaizu Takashi , Katoh Hiroshi , Tajima Hiroshi , Ushiku Hideki , Yokoi Keigo , Igarashi Kazuharu , Fujiyama Yoshiki , Okuwaki Kosuke , Iwai Tomohisa , Watanabe Masahiko , Yamashita Keishi
Published: July 2019

DNA markers for pancreatic ductal adenocarcinoma (PDAC) are urgently needed for detection of minimally invasive disease. The epigenetic relevance of the cysteine dioxygenase 1 gene (CDO1) has been never investigated in PDAC. Three studies, including cellular experiments, tissue validation, and pilot testing for pancreatic cytology, were carried out. Promoter DNA methylation value (MV) of CDO1 was quantified by quantitative methylation‐specific PCR. CDO1 expression was consistent with its promoter DNA methylation in 7 PDAC cell lines. In 160 retrospectively collected primary PDAC tumor tissues, MV was significantly higher compared to the corresponding noncancerous pancreas (area under the receiver operating characteristic curve [AUC] = 0.97, P < .0001), and CDO1 hypermethylation was highly specific to PDAC tumor tissues. CDO1 hypermethylation group (MV over 19) was significantly associated with diverse prognostic factors in PDAC. Surprisingly, it was significantly higher in prospectively collected PDAC cytology samples (n = 37), including both pancreatic juice (n = 12) and endoscopic ultrasound‐fine needle aspiration (EUS‐FNA) cytology (n = 25) compared to pancreatic benign diseases (AUC = 0.96, P < .0001). Detection of PDAC was confirmed by DNA testing in 35 of 37 patients (95% sensitivity); thus, it was more sensitive than cytology (33%) or EUS‐FNA cytology (88%). Promoter DNA methylation of CDO1 is extremely specific for PDAC tumors, and accumulates with PDAC tumor progression. It could be a definitive diagnostic marker of PDAC in pancreatic juice or EUS‐FNA cytology.
Cancer‐associated fibroblast‐derived interleukin‐1β activates protumor C‐C motif chemokine ligand 22 signaling in head and neck cancer
Authors: Huang Yu‐Hsuan , Chang Che‐Ying , Kuo Yi‐Zih , Fang Wei‐Yu , Kao Hung‐Ying , Tsai Sen‐Tien , Wu Li‐Wha
Published: July 2019

Oral cancer, a subtype of head and neck cancer, is characterized by increased infiltrating regulatory T cells (Treg); however, the pathological significance of the increase in Tregs in disease prognosis and progression and their underlying mechanism remain unestablished. C‐C motif chemokine ligand 22 (CCL22) has been implicated in the recruitment of Tregs. We used RT‐qPCR to determine CCL22 mRNA expression in clinical specimens and cultured cells. Loss‐of‐function and gain‐of‐function studies were carried out to analyze the effects of CCL22 modulations on cell proliferation, migration, invasion, and tumorigenesis and the mechanism involved in the deregulation of CCL22. In oral cancer specimens, CCL22 mRNA was upregulated. The increase was not only associated with reduced disease‐free survival but also strongly correlated with an increase in FOXP3 mRNA, a master regulator of Treg development and functions. Silencing CCL22 expression reduced cell proliferation, migration, and invasion, whereas ectopic overexpression showed opposite effects. Manipulation of CCL22 expression in cancer cells altered tumorigenesis in both immune‐compromised and ‐competent mice, supporting both autonomous and non‐autonomous actions of CCL22. Release of interleukin 1β (IL‐1β) from cancer‐associated fibroblasts (CAF) induces CCL22 mRNA expression in oral cancer cells by activating transcription factor nuclear factor kappa B (NF‐κB). Our data support a model in which CAF‐derived IL‐1β, CCL22, and its receptor CCR4 foster a protumor environment by promoting cell transformation and Treg infiltration. Intervention of the IL‐1β‐CCL22‐CCR4 signaling axis may offer a novel therapeutic strategy for oral cancer treatment.
Long noncoding RNA TP53TG1 promotes pancreatic ductal adenocarcinoma development by acting as a molecular sponge of microRNA‐96
Authors: Zhang Yufeng , Yang Haiyan , Du Yong , Liu Pingping , Zhang Jing , Li Yue , Shen Haitao , Xing Lingxiao , Xue Xiaoying , Chen Jie , Zhang Xianghong
Published: July 2019

Long noncoding RNAs (lncRNAs) are emerging as key regulators in cancer initiation and progression. TP53TG1 is a recently identified lncRNA and several studies have shown that TP53TG1 may play the role of tumor suppressor gene or oncogene in different tumors. Nevertheless, the involvement of TP53TG1 in carcinogenesis of pancreatic ductal adenocarcinoma (PDAC) has not been characterized. In our studies, we identified that TP53TG1 was highly expressed in PDAC and was a novel regulator of PDAC development. Knockdown of TP53TG1 inhibited proliferation, induced apoptosis, and decreased migration and invasion in PDAC cells, whereas enhanced expression of TP53TG1 had the opposite effects. Mechanistically, TP53TG1 could directly bind to microRNA (miR)‐96 and effectively function as a sponge for miR‐96, thus antagonizing the functions of miR‐96 and leading to derepression of its endogenous target KRAS, which is a core oncogene in the initiation and maintenance of PDAC. Taken together, these observations imply that TP53TG1 contributes to the growth and progression of PDAC by acting as a competing endogenous RNA (ceRNA) to competitively bind to miR‐96 and regulate KRAS expression, which highlights the importance of the complicated miRNA‐lncRNA network in modulating the progression of PDAC.
Postural, Visual, and Manual Coordination in the Development of Prehension
Authors: Rachwani Jaya , Herzberg Orit , Golenia Laura , Adolph Karen E.
Published: July 2019

We investigated the real‐time cascade of postural, visual, and manual actions for object prehension in 38 6‐ to 12‐month‐old infants (all independent sitters) and eight adults. Participants’ task was to retrieve a target as they spun past it at different speeds on a motorized chair. A head‐mounted eye tracker recorded visual actions and video captured postural and manual actions. Prehension played out in a coordinated sequence of postural–visual–manual behaviors starting with turning the head and trunk to bring the toy into view, which in turn instigated the start of the reach. Visually fixating the toy to locate its position guided the hand for toy contact and retrieval. Prehension performance decreased at faster speeds, but quick planning and implementation of actions predicted better performance.
Developmental Trends in Sexual Attraction Among Puerto Rican Early Adolescents in Two Contexts
Authors: Elkington Katherine S. , Wainberg Milton L. , Ramos‐Olazagasti Maria , Chen Chen , Ortin Ana , Canino Glorisa J. , Bird Hector R. , Duarte Cristiane S.
Published: July 2019

Sexual attraction (SA), the earliest stage of sexual orientation, is scarcely studied. This prospective study examined, over 3 years, prevalence, changes in SA, and the role of context, among 946 Puerto Rican youth, aged 11–13 years at initial assessment in the South Bronx (SBx), New York City, and Puerto Rico (PR). Overall, 98.1% of boys and 95.3% of girls reported opposite‐sex only SA at some point, whereas 13.8% of girls and 12.0% of boys reported any‐same SA. Opposite‐sex only SA increased over time, whereas other SAs decreased except for any same‐sex SA among SBx girls. Girls in the SBx and younger youth in PR reported more any same‐sex SA. Context and culture may play a role in the developmental trajectories of adolescents’ SA.
Evidence‐based approaches to the application of precautionary allergen labelling: Report from two iFAAM workshops
Authors: DunnGalvin Audrey , Roberts Graham , Schnadt Sabine , Astley Siân , Austin Moira , Blom W. Marty , Baumert Joseph , Chan Chun‐Han , Crevel René W.R. , Grimshaw Kate E.C. , Kruizinga Astrid G. , Regent Lynne , Taylor Stephen , Walker Michael , Mills E. N. Clare
Published: July 2019

Food allergy is a major public health concern with avoidance of the trigger food(s) being central to management by the patient. Food information legislation mandates the declaration of allergenic ingredients; however, the labelling of the unintentional presence of allergens is less defined. Precautionary allergen labelling (PAL) was introduced by the food industry to help manage and communicate the risk of reaction from the unintended presence of allergens in foods. In its current form, PAL is counterproductive for consumers with food allergies as there is no standardized approach to applying PAL. Foods with a PAL often do not contain the identified food allergen while some products without a PAL contain quantities of common food allergens that are capable of inducing an allergic reaction. Integrated Approaches to Food Allergen and Allergy Risk Management (iFAAM) was an EU‐funded project that aimed to improve the management of food allergens by the food industry for the benefit of people with food allergies. Within iFAAM, a clinically validated tiered risk assessment approach for food allergens was developed. Two cross‐stakeholder iFAAM workshops were held on 13‐14 December 2016 and 19‐20 April 2018. One of the objectives of these workshops was to develop a proposal to make PAL effective for consumers. This paper describes the outcomes from these workshops. This provides the basis for the development of more informative and transparent labelling that will ultimately improve management and well‐being in consumers with food allergy.
Interleukin‐1 and histamine are essential for inducing nickel allergy in mice
Authors: Bando Kanan , Kuroishi Toshinobu , Sugawara Shunji , Endo Yasuo
Published: July 2019

Background

We previously reported that (a) lipopolysaccharide (LPS) is a potent adjuvant for inducing Nickel (Ni) allergy in mice at both the sensitization and elicitation steps, (b) LPS induces Interleukin‐1 (IL‐1) and histidine decarboxylase (HDC, the histamine‐forming enzyme), and IL‐1 induces HDC, (c) Ni allergy is induced in mast cell–deficient, but not IL‐1–deficient (IL‐1‐KO) or HDC‐KO mice.

Objective

To examine the roles of IL‐1 and HDC (or histamine) and their interrelationship during the establishment of Ni allergy.

Methods

Ni (NiCl2) 1 mmol/L containing IL‐1β and/or histamine was injected intraperitoneally (sensitization step). Ten days later, test substance(s) were intradermally injected into ear pinnas (elicitation step), and ear swelling was measured.

Results

In wild‐type mice, Ni + LPS or Ni + IL‐1β injection at sensitization step followed by Ni alone at elicitation step induced Ni allergy. In IL‐1‐KO, injection of Ni + IL‐1β (but not Ni + histamine) was required at both sensitization and elicitation steps to induce Ni allergy. In HDC‐KO, Ni + IL‐1β + histamine at sensitization step followed by Ni + histamine at elicitation step induced Ni allergy. In histamine H1 receptor–deficient mice, IL‐1β induced HDC, but was ineffective as an adjuvant for inducing Ni allergy. In wild‐type mice, injection into ear pinnas of Ni 10 mmol/L alone or Ni 1 mmol/L + LPS induced IL‐1β, HDC and a prolonged swelling of ear pinnas. In non‐sensitized mice, injection of IL‐1β by itself into ear pinnas in IL‐1‐KO mice induced prolonged ear swelling. Ni augmented IL‐1 production (both IL‐1α and IL‐1β) and HDC induction in wild‐type mice sensitized to Ni.

Conclusions

In mice: (a) for inducing Ni allergy, IL‐1 is essential at both the sensitization and elicitation steps, and HDC induction is involved in the effect of IL‐1, (b) stimulation of H1 receptor is also essential for inducing Ni allergy at both sensitization and elicitation steps, and (c) the ‘sensitization to Ni’ state may be a state where tissues are primed for augmented production of IL‐1α and/or IL‐1β in response to Ni. (within 300 words, now 300).
Iodine deficiency among pregnant women living in Northern Ireland
Authors: McMullan Paul , Hamill Lesley , Doolan Katy , Hunter Alyson , McCance David , Patterson Chris , Smyth Peter , Woodside Jayne V. , Mullan Karen
Published: July 2019

Objective

Mild iodine deficiency has re‐emerged among school girls in the UK. We wished to study a contemporaneous pregnant population because a relationship between maternal iodine deficiency and offspring cognitive scores has recently been reported. The WHO has set a median population urinary iodine concentration (UIC) of ≥100 and ≥150 µg/L to define adequacy outside of and during pregnancy, respectively. Iodine creatinine ratio (ICR) is also used to correct for dilution effects (sufficiency ≥150 µg/g creatinine in pregnancy).

Design and methods

A total of 241 women were followed across trimesters (T) into the postpartum period (PPP) along with 80 offspring with spot urine sampling and food frequency questionnaires.

Results

Median UIC was 73 µg/L in the 1st T (ICR 102 µg/g creatinine) despite 55% taking iodine‐containing supplements. Median UICs were 94, 117 and 90 µg/L in the 2nd T, 3rd T and PPP, respectively. Corresponding ICRs were 120, 126 and 60 µg/g creatinine. ICR was associated with volume of milk consumed throughout pregnancy. Median UIC among the offspring was 148 µg/L, with no difference between the breast‐ and formula‐fed babies.

Conclusions

Pregnant women living in Northern Ireland may be at risk of iodine deficiency across pregnancy and into the PPP while the offspring are iodine sufficient. This is the first study of its kind in the UK with data for pregnant women and their offspring. The UK does not provide an iodine fortification programme nor offer routine iodine dietary advice in pregnancy and this requires consideration by public health agencies.
Visual outcome and surgical results in children with Marfan syndrome
Authors: Rezar‐Dreindl Sandra , Stifter Eva , Neumayer Thomas , Papp Andrea , Gschliesser Andreas , Schmidt‐Erfurth Ursula
Published: July 2019

Importance

To determine visual and surgical results in children with Marfan syndrome.

Background

Marfan syndrome involves ocular complications which can lead to visual disturbance and amblyopia. Data about the visual and surgical results in children with Marfan syndrome is vital for the clinical management of these patients.

Design

Retrospective data analysis.

Participants

Eighty‐two eyes of 41 patients with a genetically proved diagnosis of Marfan syndrome.

Methods

Medical records of patients with Marfan syndrome were reviewed between 2007 and 2017. Ocular complications, visual acuity (VA) of patients with/without lensectomy and surgical method were evaluated.

Main Outcome Measures

VA outcomes of patients with Marfan syndrome with/without surgical repair of ectopia lentis.

Results

In 27 (66%) of the 41 patients a bilateral subluxation of the lens was visible and 14 (52%) patients received lensectomy. The mean age at initial presentation was 12.3 ± 9 years and mean follow‐up was 3 years (range 1‐7). VA varied from 1.2 to −0.1 logMAR at first examination. At initial presentation, mean VA was 0.1 ± 0.7 logMAR in patients with a normal lens status (n = 14) and 0.3 ± 0.5 logMAR in patients with subluxation of the lens (n = 27) (P < .01). VA improved from 0.2 ± 0.5 logMAR to 0.1 ± 0.5 logMAR (P = .06) in children with subluxation of the lens who did not need a lensectomy (n = 12) and from 0.5 ± 0.5 logMAR to 0.2 ± 0.5 logMAR (P = .02) in patients who were referred to lensectomy with/without secondary lens implantation.

Conclusions and Relevance

In Marfan syndrome subluxation of the lens was found in the majority of children. Improvement of VA resulted in children with subluxation of the lens and following lensectomy.
Preoperative plasma fibrinogen as a predictive factor for post‐tonsillectomy haemorrhage
Authors: Grasl Stefan , Janik Stefan , Vyskocil Erich , Kadletz Lorenz , Grasl Matthaeus C. , Erovic Boban M.
Published: July 2019

Objectives

To assess whether preoperative plasma fibrinogen is able to predict severe post‐tonsillectomy haemorrhage.

Study design

Retrospective chart review.

Methods

We included 456 patients who underwent tonsillectomy between 2008 and 2013. Preoperative plasma fibrinogen levels (PFL) were assessed in patients who developed severe bleeding requiring surgical revision under general anesthesia compared to those with uneventful postoperative courses.

Results

414 (90.8%) had no severe post‐tonsillectomy haemorrhage. In contrast, 42 (9.2%) patients needed surgical hemostasis. PFL were significantly higher (P = .023) in patients with a severe bleeding. Univariate Cox‐regression analysis revealed that elevated preoperative fibrinogen represents a significant worse (P = .003; HR 2.66; 95% CI 1.38‐5.10) prognostic factor for postoperative bleeding. Even at multivariable analysis, increased PFLs were a significantly worse prognostic factor for post‐tonsillectomy haemorrhage (P = .016; HR 15.4; 95% CI 0.01‐0.6). High preoperative PFL was associated with significantly higher risk for post‐tonsillectomy haemorrhage within the first 31 days after surgery (65% vs 90%; P = .002). Moreover, accurate negative predictive value (NPV) of 95.1% pointed out that PFL could be used as a reliable preoperative screening marker.

Conclusions

Elevated PFL represents an independent worse prognostic factor for severe bleeding after tonsillectomy and could be helpful to identify patients at higher risk for PTH.
Yellow mutant of the Neotropical green lacewing Chrysoperla externa: trait inheritance and predator performance
Authors: Bestete Luziani Rezende , Torres Jorge Braz , Henry Charles S.
Published: July 2019

The Neotropical green lacewing Chrysoperla externa (Hagen) (Neuroptera: Chrysopidae) is a key predator of various small soft‐bodied pest species. Chrysopidae species are known as ‘green lacewings’ due to their overall green body coloration. However, yellow mutant individuals were observed emerging from our lacewing rearing colony. Thus, the mode of inheritance of the yellow trait was studied and the hypothesis of an autosomal recessive allele for yellow color was tested using hybridization and backcrossing techniques. Furthermore, the possible implications of this color variation on specific life‐history characteristics of C. externa and the predation rates of each morph were evaluated. In both yellow and green morphs, basic life‐history characteristics were monitored, including time to hatching and viability of eggs, duration, and viability of larval and pupal stages, emergence rate and survivorship of adults, and fecundity and longevity of females. The yellow and green morphs were indistinguishable with respect to all life‐history traits evaluated and the predation rate of their larvae. Crossing experiments revealed the yellow color to be caused by a homozygous recessive allele, without sex‐linked expression. We conclude that the allele for yellow color is occurring at high frequency in the laboratory colony, supporting the existence of a genetic polymorphism for body ground color.
Productivity losses in patients with newly diagnosed multiple myeloma following stem cell transplantation and the impact of maintenance therapy
Authors: Jackson Graham , Galinsky Jayne , Alderson David E. C. , D'Souza Vijay K. , Buchanan Vanessa , Dhanasiri Sujith , Walker Simon
Published: July 2019

Objective

This study examined productivity losses in European patients with newly diagnosed multiple myeloma (NDMM) undergoing autologous stem cell transplantation (ASCT), to better understand and model the impact of NDMM and lenalidomide maintenance therapy on productivity from a patient and societal perspective.

Methods

A cross‐sectional online patient survey was conducted across the UK, Germany, France, Spain and Italy. A partitioned survival model was used to estimate productivity loss and the impact of maintenance therapy, using human capital (HC) and friction cost approaches.

Results

Of the 115 eligible survey respondents, 76.5% were economically active at the time of diagnosis and highlighted return to work as an important factor affecting their quality of life; only 39.1% of respondents were economically active post‐ASCT. HC analyses estimated average total productivity losses per ASCT patient at EUR 290,601 over a 20‐year period. Modelling the impact of maintenance therapy alone for these patients reduced average productivity losses by just over 10%.

Conclusion

Patients with NDMM aspire to engage in productive lives post‐ASCT, but most are unable to do so. Access to treatments extending remission and supporting engagement in a productive life can have a positive impact both for patients and wider society.
Altered monoamine levels in the dorsal striatum of the rat are associated with alterations in behavioural selection and motivation following peripheral nerve injury and acute stress
Authors: Gemikonakli Gizem , Keay Kevin A. , Kendig Michael D. , Kang James W. M. , Corbit Laura H. , Mor David
Published: July 2019

Chronic neuropathic pain and psychological stress interact to compromise goal‐directed control over behaviour following mild psychological stress. The dorsomedial (DMS) and dorsolateral (DLS) striatum in the rat are crucial for the expression of goal‐directed and habitual behaviours, respectively. This study investigated whether changes in monoamine levels in the DMS and DLS following nerve injury and psychological stress reflect these behavioural differences. Neuropathic pain was induced by a chronic constriction injury (CCI) of the sciatic nerve in Sprague–Dawley rats. Acute stress was induced using a 15‐min restraint. Behavioural flexibility was assessed using the outcome devaluation paradigm. Noradrenaline, serotonin, dopamine and associated metabolites were measured bilaterally from the DLS and DMS. In uninjured rats, restraint increased dopaminergic markers in the left and serotonergic markers in the right of both the DMS and DLS, indicating a possible left hemisphere‐mediated dominance. CCI led to a slightly different lateralised effect, with a larger effect in the DMS than in the DLS. Individual differences in behavioural flexibility following CCI negatively correlated with dopaminergic markers in the right DLS, but positively correlated with these markers in the left DMS. A combination of CCI and restraint reduced behavioural flexibility, which was associated with the loss of the left/DMS dominance. These data suggest that behavioural flexibility following psychological stress or pain is associated with a left hemisphere dominance within the dorsal striatum. The loss of behavioural flexibility following the combined stressors is then associated with a transition from left to right, and DMS to DLS dominance.
Mitotic activity, modulation of DNA processing, and purinergic signalling in the adult rat auditory brainstem following sensory deafferentation
Authors: Illing Robert‐Benjamin , Buschky Helena , Tadic Annamaria
Published: July 2019

A complex scenario of cellular network reorganization is caused by unilateral sensory deafferentation (USD) in the adult rat central auditory system. We asked whether this plasticity response involves mitosis. Immunohistochemistry was applied to brainstem sections for the detection and localization of mitotic markers Ki67 and PCNA, the growth‐associated protein Gap43 and purine receptor P2X4. Fluorescent double staining was done for Ki67:PCNA and for both of them with HuC/HuD (neurons), S100 (astrocytes), Iba1 (microglia) and P2X4. Inquiring 1–7 days after USD, we found Ki67 expression to be changed in cellular profiles of cochlear nucleus (CN) with a significant increase in number by 1–3 days, followed by reset to control level within 1 week. USD‐induced mitosis exclusively occurred in microglia and was absent elsewhere in the auditory brainstem. PCNA staining of small cellular profiles increased similarly but remained elevated. PCNA staining intensity also changed in CN, superior olive and inferior colliculus in neuronal nuclei, suggesting shifts in DNA processing. No apoptotic cell death was detected in any region of the adult auditory brainstem after USD. A comparison of anterograde and retrograde effects of nerve damage revealed proliferating microglia expressing P2X4 receptors in CN upon USD, but not in the facial nucleus after facial nerve transection. In conclusion, the deafferentation model studied here permits insight into the capacity of the adult mammalian brain to invoke mitosis among glia cells, adjustment of gene processing in neurons and purinergic signalling between them, jointly accounting for a multilayered neuro‐ and glioplastic response.
Randomized controlled trial of the effectiveness of three different oral moisturizers in palliative care patients
Authors: Kvalheim Siri F. , Marthinussen Mihaela C. , Haugen Dagny F. , Berg Einar , Strand Gunhild V. , Lie Stein‐Atle
Published: July 2019

Most patients in palliative care have problems with dry mouth caused by medication or as a direct result of their condition. Dry mouth may cause problems that affect the primary disease negatively and contribute to poorer quality of life in palliative patients. This randomized controlled trial compared the efficacy of three different oral moisturizers: 17% watery solution of glycerol; oxygenated glycerol triester (marketed as Aequasyal in Europe and as Aquoral in the USA); and a newly developed product, Salient. Of the three products, glycerol provided the best relief from xerostomia directly after application, but had no effect after 2 h. By contrast, the effects of Aequasyal and Salient were largely maintained over the same period. The findings for oral discomfort and pain and speech problems showed a similar pattern. Despite its poor effect after 2 h, patients preferred glycerol over Salient and Aequasyal, probably because of the unpleasant taste of Aequasyal and the consistency and mode of application of Salient. Within the limitations of this study, none of the three products tested was found to be clinically completely adequate. However, the glycerol solution was preferred by this group of patients, and its short‐lived effect can be compensated for by frequent applications.
Stereoelectroencephalography electrode placement: Detection of blood vessel conflicts
Authors: Li Kuo , Vakharia Vejay N. , Sparks Rachel , Rodionov Roman , Vos Sjoerd B. , McEvoy Andrew W. , Miserocchi Anna , Wang Maode , Ourselin Sebastien , Duncan John S.
Published: July 2019

Objective

Various forms of vascular imaging are performed to identify vessels that should be avoided during stereoelectroencephalography (SEEG) planning. Digital subtraction angiography (DSA) is the gold standard for intracranial vascular imaging. DSA is an invasive investigation, and a balance is necessary to identify all clinically relevant vessels and not to visualize irrelevant vessels that may unnecessarily restrict electrode placement. We sought to estimate the size of vessels that are clinically significant for SEEG planning.

Methods

Thirty‐three consecutive patients who underwent 354 SEEG electrode implantations planned with computer‐assisted planning and DSA segmentation between 2016 and 2018 were identified from a prospectively maintained database. Intracranial positions of electrodes were segmented from postimplantation computed tomography scans. Each electrode was manually reviewed using “probe‐eye view” with the raw preoperative DSA images for vascular conflicts. The diameter of vessels and the location of conflicts were noted. Vessel conflicts identified on raw DSA images were cross‐referenced against other modalities to determine whether the conflict could have been detected.

Results

One hundred sixty‐six vessel conflicts were identified between electrodes and DSA‐identified vessels, with 0‐3 conflicts per electrode and a median of four conflicts per patient. The median diameter of conflicting vessels was 1.3 mm (interquartile range [IQR] = 1.0‐1.5 mm). The median depth of conflict was 31.0 mm (IQR = 14.3‐45.0 mm) from the cortical surface. The addition of sulcal models to DSA, magnetic resonance venography (MRV), and T1 + gadolinium images, as an exclusion zone during computer‐assisted planning, would have prevented the majority of vessel conflicts. We were unable to determine whether vessels were displaced or transected by the electrodes.

Significance

Vascular segmentation from DSA images was significantly more sensitive than T1 + gadolinium or MRV images. Electrode conflicts with vessels 1‐1.5 mm in size did not result in a radiologically detectable or clinically significant hemorrhage and could potentially be excluded from consideration during SEEG planning.
Fraxin inhibits lipopolysaccharide‐induced inflammatory cytokines and protects against endotoxic shock in mice
Authors: Li Weifeng , Li Wenqi , Yu JinJin , Liu Fang , Zang Lulu , Xiao Xin , Zhao Jinmeng , Yao Qing , Niu Xiaofeng
Published: July 2019

Fraxin, the effective component isolated from Cortex Fraxini, has been reported to have anti‐inflammation effects. The aim of this study was to explore the effect of fraxin on lipopolysaccharide (LPS)‐induced endotoxic shock in mice. We used Kunming male mice to establish the model, and we found that fraxin could improve the survival rate of the LPS‐induced mice. Histopathological study showed that fraxin could mitigate the injuries in LPS‐induced lung and liver tissues. The levels of tumour necrosis factor‐α and interleukin‐6 both in serum and lung, liver tissues, and the productions of nitric oxide (NO), aspartate transaminase and alanine transaminase in serum were decreased by fraxin. Western blot assay demonstrated that the pretreatment with fraxin could downregulate LPS‐induced protein expressions of nuclear factor‐kappa B (NF‐κB) and NLRP3 inflammatory corpuscle signalling pathways. Overall, fraxin had protective effects on LPS‐induced endotoxic shock mice and the possible mechanisms might activate through NF‐κB and NLRP3 inflammatory corpuscle signalling pathways.
Environmental controls on bacteriohopanepolyol profiles of benthic microbial mats from Lake Fryxell, Antarctica
Authors: Matys Emily D. , Mackey Tyler , Grettenberger Christen , Mueller Elliott , Jungblut Anne , Sumner Dawn Y. , Hawes Ian , Summons Roger E.
Published: July 2019

Bacteriohopanepolyols (BHPs) are pentacyclic triterpenoid lipids that contribute to the structural integrity and physiology of some bacteria. Because some BHPs originate from specific classes of bacteria, BHPs have potential as taxonomically and environmentally diagnostic biomarkers. For example, a stereoisomer of bacteriohopanetetrol (informally BHT II) has been associated with anaerobic ammonium oxidation (anammox) bacteria and suboxic to anoxic marine environments where anammox is active. As a result, the detection of BHT II in the sedimentary record and fluctuations in the relative abundance of BHT II may inform reconstructions of nitrogen cycling and ocean redox changes through the geological record. However, there are uncertainties concerning the sources of BHT II and whether or not BHT II is produced in abundance in non‐marine environments, both of which are pertinent to interpretations of BHT II signatures in sediments. To address these questions, we investigate the BHP composition of benthic microbial mats from Lake Fryxell, Antarctica. Lake Fryxell is a perennially ice‐covered lake with a sharp oxycline in a density‐stabilized water column. We describe the diversity and abundance of BHPs in benthic microbial mats across a transect from oxic to anoxic conditions. Generally, BHP abundances and diversity vary with the morphologies of microbial mats, which were previously shown to reflect local environmental conditions, such as irradiance and oxygen and sulfide concentrations. BHT II was identified in mats that exist within oxic to anoxic portions of the lake. However, anammox bacteria have yet to be identified in Lake Fryxell. We examine our results in the context of BHPs as biomarkers in modern and ancient environments.
Methane yield and species diversity dynamics of perennial wild plant mixtures established alone, under cover crop maize (Zea mays L.), and after spring barley (Hordeum vulgare L.)
Authors: von Cossel Moritz , Steberl Kathrin , Hartung Jens , Pereira Lorena A. , Kiesel Andreas , Lewandowski Iris
Published: July 2019

The cultivation of perennial wild plant mixtures (WPMs) in biogas cropping systems dominated by maize (Zea mays L.) restores numerous ecosystem functions and improves both spatial and temporal agrobiodiversity. In addition, the colorful appearance of WPM can help enhance landscape beauty. However, their methane yield per hectare (MYH) varies greatly and amounts to only about 50% that of maize. This study aimed at decreasing MYH variability and increasing accumulated MYH of WPM by optimizing the establishment method. A field trial was established in southwest Germany in 2014, and is still running. It tested the effects of three WPM establishment procedures (E1: alone [without maize, in May], E2: undersown in cover crop maize [in May], E3: WPM sown after whole‐crop harvest of spring barley [Hordeum vulgare L.] in June) on both MYH and species diversity of two WPMs [S1, S2]). Mono‐cropped maize and cup plant (Silphium perfoliatum L.) were used as reference crops. Of the WPM treatments tested, S2E2 achieved the highest (19,296 , 60.5% of maize) and S1E1 the lowest accumulated MYH (8,156 , 25.6% of maize) in the years 2014–2018. Cup plant yielded slightly higher than S2E2 (19,968 , 62.6% of maize). In 2014, the WPM sown under maize did not significantly affect the cover crop performance. From 2015 onward, E1 and E2 had comparable average annual MYH and average annual number of WPM species. With a similar accumulated MYH but significantly higher number of species (3.5–10.2), WPM S2E2 outperformed cup plant. Overall, the long‐term MYH performance of WPM cultivation for biogas production can be significantly improved by undersowing with maize as cover crop. This improved establishment method could help facilitate the implementation of WPM cultivation for biogas production and thus reduce the trade‐off between bioenergy and biodiversity.
The national blueprint for future factor VIII inhibitor clinical trials: NHLBI State of the Science (SOS) Workshop on factor VIII inhibitors
Authors: Ragni Margaret V. , George Lindsey A. ,   on behalf of the Members of Working Group 1, the NHLBI State of the Science Workshop on factor VIII inhibitors: Generating a national blueprint for future research
Published: July 2019

Introduction

Inhibitor formation is a major complication of haemophilia for which clinical trials are planned. Despite emerging novel haemostatic agents, challenges of rare disease trials are limited subjects and lack of an organized research organization with strategic resources and partnerships.

Aim

The charge to Working Group 1 was to establish scientific priorities and innovative implementation strategies to conduct inhibitor prevention and eradication trials. To determine feasibility of trial design and strategic resources and partnerships to be leveraged, two clinical trial concepts were considered.

Results

For the Inhibitor Prevention Trial, we considered adaptive design with early stopping rules, dynamic randomization and Master Protocol models to reduce sample size; and registries to provide concurrent controls and natural history data. For the Inhibitor Eradication Trial using gene therapy, an adaptive design was considered in a small number of subjects, and, if safe and meeting regulatory requirements, enrolment would be expanded. A Haemophilia Clinical Trials Group (HCTG) infrastructure was envisioned, with uniform procedures and standardized outcomes, data collection and assays, within which trial concepts would be developed, vetted and prioritized by a Steering Committee, and submitted to NIH and other research sponsors for review and funding. Mechanistic studies would be embedded within the trials, early stage investigators trained and mentored, and the research infrastructure established within the haemophilia centre (HTC) network and supported by partnerships with foundations, community, federal partners and industry.

Conclusion

The success of inhibitor trials will depend on innovative trial design and an organized HCTG research infrastructure, leveraged through community partnerships.
Translating the Cochrane EMBASE RCT filter from the Ovid interface to Embase.com: a case study
Authors: Glanville Julie , Foxlee Ruth , Wisniewski Susi , Noel‐Storr Anna , Edwards Mary , Dooley Gordon
Published: July 2019

Background

Information specialists frequently translate search filters from one interface to another. Publications advise that translation can be complex and should be undertaken carefully.

Objectives

To investigate the issues arising when translating the Cochrane Embase RCT search filter from one interface (Ovid) to another (Embase.com).

Methods

We drafted a translation of the Cochrane Ovid RCT filter to run in Embase.com. We compared the line‐by‐line results of the Ovid filter with the results of the translation. We revised the filter. We identified differences between database versions including records with different publication years and subject headings. Some records were in Embase in one interface but not in the other. We encountered expected interface differences relating to proximity operators. We also encountered unexpected interface issues around truncation and the use of the original title or original abstract field.

Discussion

Filter conversion is challenging and time consuming revealing unexpected differences in interfaces and databases. Careful planning can pre‐empt some issues, but others may only emerge during testing. We identified interface anomalies that have led database publishers to review aspects of the way their interfaces work.

Conclusions

Translators should be vigilant for known and unknown differences in both interfaces and database versions.
Impact of family income in early life on the financial independence of young adults: Evidence from a matched panel data
Authors: Cui Xu , Xiao Jing Jian , Yi Jingtao , Porto Nilton , Cai Yi
Published: July 2019

This study investigates whether the family income level in early life influences the financial independence of young adults. Using a large nationally representative U.S. sample (constructed based on the data from the 1999 to 2015 Panel Study of Income Dynamics, its 2009 to 2015 Transition to Adulthood Supplement and its 1997 to 2007 Child Development Supplement), we find that the relationship between one's family income level during adolescence and the financial independence of young adults follows an inverted U‐shape. We find that the college graduation status plays an important role in determining the financial independence of young adults. Once young adults graduate from the college, their financial independence is no longer influenced by their family income level during adolescence. The results show similar patterns after controlling for cognitive and noncognitive abilities and financial behaviours of young adults when they were children or teenagers. The findings of this study have significant implications for policymakers and educators.
Mangiferin nanoparticles fortified dairy beverage as a low glycemic food product: its quality attributes and antioxidant properties
Authors: Samadarsi Rohini , Mishra Divyani , Dutta Debjani
Published: July 2019

Mangiferin‐encapsulated β‐lactoglobulin–chitosan (mangiferin/βLG‐CS) nanoparticles were fortified in milk to obtain a low glycemic index (GI) food product with high antioxidant capacity. The present study evaluated the bioaccessibility and bioavailability of mangiferin in milk fortified with nanoparticles. Fortification reduced the GI of milk by 34.5%. A mathematical model was developed to evaluate the lactose digestion, in terms of reducing sugar formed in milk by determining the digestion rate (k), and a significant reduction in k was observed. The bioaccessibility of mangiferin was enhanced by fortification. Fortified milk showed good antioxidant, lipid peroxidation inhibition and protein oxidation inhibition properties. Mangiferin nanoparticles fortified dairy beverage as an ideal food product with high antioxidant capacity and can inhibit lipid peroxidation and protein oxidation. It may be used as a low GI food product.
Elevated CO2 affects plant nitrogen and water‐soluble carbohydrates but not in vitro metabolisable energy
Authors: Panozzo Joe Francis , Walker Cassandra Kiely , Maharjan Pankaj , Partington Debra L. , Korte Chris J.
Published: July 2019

The effects of elevated concentrations of atmospheric CO2 (e[CO2]) on the nutritive value of wheat vegetative matter and grain as a feedstock for ruminants were investigated in a study undertaken at the Australian grains free‐air CO2 enrichment (AGFACE) facility. The study included two commercial wheat cultivars (Janz and Yitpi) and two genetic selections from a Seri/Babex population (SB003 and SB062) which had previously been characterised for low and high water‐soluble carbohydrate accumulation efficiency. The trial was grown under ambient (~390 µmol/mol) and elevated (~550 µmol/mol) CO2 conditions, and plants harvested at tillering, anthesis and physiological maturity. Composition analyses to determine the nutritive value for ruminant feed were undertaken on stems, leaves and grain. Plant and grain nitrogen were reduced in the e[CO2] treatments, and as expected, the water‐soluble carbohydrates increased. All genotypes responded to e[CO2] with the effects of altered composition evident within 60 days of sowing. Determinants of ruminant feed quality such as neutral and acid detergent fibre and estimated in vitro metabolisable energy were not significantly affected. The reduced plant and grain N will impact on the nutritive value and supplementation may be required. The impact of e[CO2] on chemical composition of wheat plants may be greater if the predicted climate change is associated with concomitant abiotic stress such as high ambient temperature or low soil moisture.
Effects of crystal structure and cation size on molten silicate reactivity with environmental barrier coating materials
Authors: Stokes Jamesa L. , Harder Bryan J. , Wiesner Valerie L. , Wolfe Douglas E.
Published: July 2019

Rare earth (RE) disilicates are utilized in environmental barrier coatings to protect Si‐based engine components from destructive reactions with water vapor and other combustion species. These coating materials, however, degrade when exposed to molten silicate deposits in the engine. Four RE‐disilicates (RE2Si2O7, RE = Er, Dy, Gd, Nd) are analyzed herein in thermochemical interactions with glassy calcium‐magnesium‐aluminosilicate (CMAS) compositions at 1400°C. Crystalline reaction products included RE2Si2O7, SiO2, and a Ca2+yRE8+x(SiO4)6O2+3x/2+y apatite‐type silicate. RE2Si2O7 formation was favored in interactions with CMAS having low CaO:SiO2 ratios. Increased reactivity was observed for higher CaO:SiO2 ratios in CMAS combined with larger RE3+ cation size, resulting in apatite formation of varying stoichiometry and changes in lattice parameters. The crystallization of SiO2 was dependent on both thermodynamic equilibrium at low CaO:SiO2 ratios and sequestration of silicate modifiers at higher CaO:SiO2 ratios, although residual amorphous content after CMAS exposure in both cases was still substantial.
Correlative models for perovskites with rock salt B‐site ordering
Authors: Smith Evan , Adams Claire , Ubic Rick
Published: July 2019

Empirically derived predictive models describing synthesis‐structure relationships have the potential to significantly improve and guide future research in a more cost‐effective and timely manner; however, few of these models exist for cation ordering in perovskites. In this study, four compositions within the AZn0.5Ti0.5O3 system (A = Nd, Sm, Nd0.5La0.5, Nd0.5Gd0.5) were synthesized using a conventional solid‐state mixed‐oxide method. X‐ray diffraction data show evidence of long‐range 1:1 rock salt cation ordering on the B site for all compositions. Additional data for other rock salt B‐site ordered compositions were mined from literature. Correlative models for the B‐site shrinkage (ΔrB) have been derived for each B‐site ordered system, and a general model has been developed for rock salt B‐site ordering from these specific models. This general model allows for the prediction of the room‐temperature volume shrinkage resulting from rock salt B‐site ordering using only published ionic radii data.
Element‐specific displacements in defect‐enriched TiO2: Indication of a flash sintering mechanism
Authors: Jongmanns Malte , Wolf Dietrich E.
Published: July 2019

Flash sintering experiments of ceramics indicate the formation of a state far from equilibrium. It is hypothesized that this state is enriched by Frenkel defects. The possibility is investigated that such lattice defects are being generated by a proliferation of lattice vibrations that lie close to the Brillouin zone edge. We show by means of Molecular Dynamics simulations of rutile TiO2 that this mechanism generates Frenkel defects in concentrations far beyond equilibrium. These defects deform the whole lattice in a way that the mean‐square displacements of the vibration amplitudes of the Ti and O atoms are specifically enhanced. This finding compares well to atomic displacement data of flash sintered rutile TiO2 reported recently.
Propionate alleviates high-fat diet-induced lipid dysmetabolism by modulating gut microbiota in mice
Authors: Song B. , Zhong Y.Z. , Zheng C.B. , Li F.N. , Duan Y.H. , Deng J.P.
Published: July 2019

Aims

The aims were to examine whether oral sodium propionate supplementation regulate lipid metabolism through modulating gut microbiota.

Methods and Results

ICR male mice (26·98 ± 0·30 g) were randomly assigned to three groups (n = 10) and fed control diet (Con), high-fat diet (HFD) and HFD plus propionate (Pro) respectively. In this study, we found that HFD increased the weight of final body, inguinal white adipose tissues (iWAT), epididymal white adipose tissue (eWAT) and perirenal white adipose tissue (pWAT), as well as the adipocyte mean area of iWAT and eWAT in mice (P < 0·05), whereas sodium propionate treatment reduced the weight of iWAT and pWAT as well as adipocyte mean area of iWAT in mice fed a HFD (P < 0·05). Moreover, in the iWAT, the mRNA expression of lipogenesis genes, including peroxisome proliferator activated receptor γ, acetyl-CoA carboxylase and carnitine palmitoyl transferase-1β, was upregulated by HFD challenge (P < 0·05), and the elevation of these genes was nearly reversed to the level of control diet-fed mice by sodium propionate treatment. Meanwhile, sodium propionate treatment increased the hormone-sensitive lipase mRNA expression in the iWAT of HFD-fed mice (P < 0·05). High-throughput pyrosequencing of the 16S rRNA demonstrated that sodium propionate treatment significantly recovered the gut microbiota dysbiosis in HFD-fed mice, including the richness and diversity of microbiota and the ratio of Firmicutes to Bacteroidetes. Furthermore, the HFD-induced reductions in colonic levels of butyrate and valerate were reversed by sodium propionate treatment, which also normalized the serum LPS level seen in HFD-fed mice to the levels of the control diet-fed mice.

Conclusions

Collectively, these results indicated that sodium propionate treatment could improve lipid metabolism in HFD-fed mice, and the potential mechanisms might be via regulating gut microbiota.

Significance and Impact of the Study

We demonstrated for the first time that oral sodium propionate significantly improved HFD-induced dysbiosis of gut microbiota, indicating that the mitigative effect of propionate for HFD-induced lipid dysmetabolism might be mediated by gut microbiota in mice.