bluuebunny/crossref_metadata_2025 huggingface dataset:
Siberian Trap volcanism, global warming and the Permian-Triassic mass extinction: New insights from Armenian Permian-Triassic sections
Authors: Joachimski M.M. , Alekseev A.S. , Grigoryan A. , Gatovsky Yu.A.
Published: June 2019

Permian-Triassic boundary sections from Armenia were studied for carbon isotopes of carbonates as well as oxygen isotopes of conodont apatite in order to constrain the global significance of earlier reported variations in the isotope proxies and elaborate the temporal relationship between carbon cycle changes, global warming and Siberian Trap volcanism. Carbon isotope records of the Chanakhchi and Vedi II sections show a 3–5‰ negative excursion that start in the Clarkina nodosa (C. yini) conodont Zone (latest Permian) with minimum values recorded in Hindeodus parvus to Isarcicella isarcica conodont zones (earliest Triassic). Sea surface temperatures (SST) reconstructed from oxygen isotopes of conodont apatite increase by 8–10 °C over an extrapolated time interval of ∼39 ka with the onset of global warming occurring in the C. iranica (C. meishanensis) Zone of the latest Permian. Climate warming documented in the Armenian sections is comparable to published time-equivalent shifts in SST in Iran and South China suggesting that this temperature change represents a true global signature. By correlating the Armenian and Iranian section with the radiometrically well-dated Meishan GSSP (Global Stratotype Section and Point) section (South China), the negative shift in δ13C is estimated to have occurred 12–128 ka prior to the onset of global warming. This temporal offset is unexpected given the synchrony in changes in atmospheric CO2 and global temperature as seen in Pleistocene ice core records. The negative δ13C excursion is explained by the addition of emission of isotopically light CO2 and CH4 from thermogenic heating of organic carbon-rich sediments by Siberian Trap sill intrusions. However, the observed time lag in the δ13C and δ18O shifts questions the generally assumed cause-effect relationship between emission of thermogenically produced greenhouse gases and global warming. The onset of temperature rise coincides with a significant enrichment in Hg/TOC (total organic carbon) ratios arguing for a major volcanic event at the base of the extinction interval. Whether global warming was a major factor for the Late Permian mass extinction depends on the duration of the extinction interval. Warming only starts at the base of the extinction interval, but with the extinction encompassing a time interval of 60 ± 48 ka, global climate warming in conjunction with temperature-related stressors as hypoxia and reduced nutrient availability may have been one of the major triggers of the most devastating biotic crisis in Earth history.
Barriers to implementation of stratified care in primary biliary cholangitis: a scoping exercise
Authors: Corrigan Margaret , Hirschfield Gideon , Greenfield Sheila , Parry Jayne
Published: June 2019

Patients with primary biliary cholangitis (PBC) can be stratified into low-risk and high-risk groups based on their response to treatment. Newly published guidelines from the British Society of Gastroenterology suggest low-risk patients can be managed substantially in primary care. This represents a shift from existing practice and makes assumptions about service capacity and the willingness of both patients and health care practitioners (HCPs) to make this change. The aim of this paper is to identify possible barriers to the implementation of these new care pathways through review of the PBC-specific literature and by identifying the experiences of patients and HCPs managing a different condition with comparable patients and disease characteristics. Searches of MEDLINE, CINAHL and EMBASE were undertaken. Within the existing PBC literature there is little data surrounding stakeholder perspectives on place of care. Review of the breast cancer literature highlights a number of barriers to change including primary care practitioner knowledge and work load, communication between healthcare settings, and the significance of the established doctor–patient relationship. Further research is needed to establish the extent to which these barriers may surface when changing PBC care pathways, and the actions required to overcome them.
Cesarean delivery in Nigeria: prevalence and associated factors―a population-based cross-sectional study
Authors: Adewuyi Emmanuel O , Auta Asa , Khanal Vishnu , Tapshak Samson J , Zhao Yun
Published: June 2019

Objective

To investigate the prevalence and factors associated with caesarean delivery in Nigeria.

Design

This is a secondary analysis of the nationally representative 2013 Nigeria Demographic and Health Survey (NDHS) data. We carried out frequency tabulation, χ2test, simple logistic regression and multivariable binary logistic regression analyses to achieve the study objective.

Setting

Nigeria.

Participants

A total of 31 171 most recent live deliveries for women aged 15–49 years (mother–child pair) in the 5 years preceding the 2013 NDHS was included in this study.

Outcome measure

Caesarean mode of delivery.

Results

The prevalence of caesarean section (CS) was 2.1% (95% CI 1.8 to 2.3) in Nigeria. At the region level, the South-West had the highest prevalence of 4.7%. Factors associated with increased odds of CS were urban residence (adjusted OR (AOR): 1.51, 95% CI 1.15 to 1.97), maternal age ≥35 years (AOR: 2.12, 95% CI 1.08 to 4.11), large birth size (AOR: 1.39, 95% CI 1.10 to 1.74) and multiple births (AOR: 4.96, 95% CI 2.84 to 8.62). Greater odds of CS were equally associated with maternal obesity (AOR: 3.16, 95% CI 2.30 to 4.32), Christianity (AOR: 2.06, 95% CI 1.58 to 2.68), birth order of one (AOR: 3.86, 95% CI 2.66 to 5.56), husband’s secondary/higher education level (AOR: 2.07, 95% CI 1.29 to 3.33), health insurance coverage (AOR: 2.01, 95% CI 1.37 to 2.95) and ≥4 antenatal visits (AOR: 2.84, 95% CI 1.56 to 5.17).

Conclusions

The prevalence of CS was low, indicating unmet needs in the use of caesarean delivery in Nigeria. Rural–urban, regional and socioeconomic differences were observed, suggesting inequitable access to the obstetric surgery. Intervention efforts need to prioritise women living in rural areas, the North-East and the North-West regions, as well as women of the Islamic faith.
Guidelines on the intraoperative transfusion of red blood cells: a protocol for systematic review
Authors: Baker Laura , Park Lily , Gilbert Richard , Martel Andre , Ahn Hilalion , Davies Alexandra , McIsaac Daniel I , Saidenberg Elianna , Tinmouth Alan , Fergusson Dean A , Martel Guillaume
Published: June 2019

Introduction

A significant proportion of red blood cell (RBC) transfusions are administered intraoperatively; yet there is limited evidence to guide transfusion decisions in this setting. The objective of this systematic review is to explore the availability, quality and content of clinical practice guidelines (CPGs) reporting on the indication for allogenic RBC transfusion during surgery.

Methods

Major electronic databases (MEDLINE, EMBASE and CINAHL), guideline clearinghouses and Google Scholar, will be systematically searched from inception to January 2019 for CPGs pertaining to indications for intraoperative allogenic RBC transfusion. Characteristics of eligible guidelines will be reported in a summary table. The AGREE II instrument will be used to appraise the quality of identified guidelines. Recommendations advising on indications for intraoperative RBC transfusion will be manually extracted and presented to allow for comparison of similarities and/or discrepancies in the literature.

Ethics and dissemination

The results of this systematic review will be disseminated through relevant conferences and peer-reviewed journals.

Trial registration number

CRD42018111487
General dental practitioners’ perceptions of, and attitudes towards, improving patient safety through a multidisciplinary approach to the prevention of medication-related osteonecrosis of the jaw (MRONJ): a qualitative study in the North East of England
Authors: Sturrock Andrew , Preshaw Philip M , Hayes Catherine , Wilkes Scott
Published: June 2019

Objective

To explore general dental practitioners’ (GDPs’) perceptions of, and attitudes towards, the risks of medication-related osteonecrosis of the jaw (MRONJ) and the current/potential multidisciplinary approach(es) to prevention of the condition.

Design

Interpretivist methodology using a grounded theory approach and constant comparative analysis to undertake an iterative series of semistructured interviews. Ritchie and Spencer’s framework analysis facilitated the identification and prioritisation of salient themes.

Setting

Primary care general dental practices in the North East of England.

Participants

15 GDPs.

Results

GDPs are aware of the risk of MRONJ with commonly implicated medicines; however, they report limited collaboration between professional groups in person-centred avoidance of complications, which is a key requirement of the preventive advice recommended in extant literature. Four salient and inter-related themes emerged: (1) perception of knowledge; indicating the awareness of the risk, limited knowledge of implicated medications and experience of managing the condition; (2) risk; indicating the importance of accurate medication histories, the treatment of low risk patients in primary dental care, counselling of poorly informed patients, the fear of litigation and perceived low priority of oral health in the context of general health and well-being; (3) access and isolation; referring to access to general medical records, professional isolation and somewhat limited and challenging professional collaborative relationships; (4) interprofessional working; indicating oral health education of other professional groups, collaboration and communication, and a focus on preventive care.

Conclusions

Patients continue to be at risk of developing MRONJ due to limited preventive interventions and relatively disparate contexts of multidisciplinary team healthcare. Effective collaboration, education and access to shared medical records could potentially improve patient safety and reduce the potential risk of developing MRONJ.
Psychophysiological modifications in an assault infantry manoeuvre using a chemical, biological, radiological and nuclear personal protective equipment
Authors: Merchan Alejandro , Clemente-Suárez V J
Published: June 2019

Introduction

The study of the psychophysiological response during combat actions has been poorly researched despite its importance for warfighter training and specific instruction. The aim of the present investigation was to analyse the effect of chemical, biological, radiological and nuclear personal protective equipment (PPE) on the psychophysiological response, mechanical and physical load and fine motor skills of professional soldiers in an endurance infantry manoeuvre.

Methods

16 soldiers conducted an assault manoeuvre with and without the PEE in separate days. We analysed before and after the manoeuvre the psychophysiological response, fine motor skills, shooting test accuracy and anxiety state.

Results

The use of PPE produced significantly higher (p<0.05) stress, fatigue, temperature, HR, somatic anxiety and time in middle and high HR zones and significantly lower values in speed average and maximum speed. These findings can be used to improve the training and specific instruction for professionals who require the use of PPE equipment.

Conclusion

The use of the PPE suit in an assault manoeuvre produces a decrease in the speed of movement, an increase in HR, body temperature, somatic anxiety and subjective perception of effort.
Respect your elders: effects of ageing on intracranial pressure monitor use in traumatic brain injury
Authors: Schupper Alexander J , Berndtson Allison E , Smith Alan , Godat Laura , Costantini Todd W
Published: June 2019

Background

The Brain Trauma Foundation recommends intracranial pressure (ICP) monitor placement for patients with severe traumatic brain injury (TBI). Adherence with these guidelines in elderly patients is unknown. We hypothesized that disparities in ICP monitor placement would exist based on patient age.

Methods

Using the National Trauma Data Bank (2010–2014), we identified patients admitted for blunt TBI with admission Glasgow Coma Scale (GCS) scores of 3–8. Patients were excluded if they had a non-Head Abbreviated Injury Scale (AIS) score ≥3, hospital length of stay <24 hours or were discharged from the emergency department. Demographic data, ICP monitor placement, GCS, AIS-Head, Injury Severity Score, and outcome measures were collected. Propensity score matching between ICP monitor and non-ICP monitor patients was used for logistic regression and Cox multivariate regression analyses.

Results

Of the 30 710 patients with blunt TBI with GCS scores of 3–8 included in our study, 4093 were treated with an ICP monitor. ICP monitor placement rates significantly decreased with increasing age. Multivariable analysis demonstrated that patients treated with an ICP monitor were more likely to be younger, male, have private/commercial insurance, and receive care at an institution with three or more neurosurgeons.

Conclusion

Patients ≥65 years of age with severe blunt TBI are less likely to be treated with an ICP monitor than younger patients. Age disparities in adherence to Brain Trauma Foundation guidelines may alter the outcomes for patients with severe TBI.

Level of evidence

Level IV.
A novel approach for tracing mycophagous small mammals and documenting their fungal diets
Authors: Cloutier Véronique B. , Piché Yves , Fortin J. André , Bérubé Jean. A. , Glémet Hélène , Desrochers André
Published: June 2019

We developed a method combining passive baiting (animals that are not trapped) with DNA meta-barcoding of the feces acquired, to study fungi in the diet of small mammals. Mammal and fungal species were identified using genomic DNA of 596 fecal samples collected in five regions of the eastern Canadian boreal forest. For identification of the small mammal species, the cytochrome b region was used. A total of eight species of small mammals displayed hypogeous fungi consumption, with northern flying squirrels (Glaucomys sabrinus) and red-backed voles (Myodes gapperi) as the top consumers. For identification of their fungal diets, the ribosomal internal transcribed spacer (ITS) region was used. We recovered 722 taxa of Ascomycota, 429 Basidiomycota, 81 Zygomycota, 4 Chytridiomycota, 1 Glomeromycota, and 44 unidentified fungal taxa. Of these, 28 were hypogeous sequestrate fungi (underground fructification), which presumably are dug out by small mammals for consumption. Otherwise, for the remaining fungi [epigeous (above ground fructification) or microscopic fungal species], it is unclear which ones are selected by the animal as a dietary source or result from incidental contamination. Our paper presents a promising approach for tracing mycophagy in small mammals, and our results suggest that fungal diversity is important for the diet of some small mammals.
Axial strength of steel circular hollow section (CHS) X-joints strengthened by flanged larger pipe
Authors: Gerges Peter , Gaawan Sameh , Osman Ashraf
Published: June 2019

In steel design, enhancing the structural joints’ capacity is considered a challenge that faces the designer. This challenge becomes more difficult when it comes to enhancing the capacities of circular hollow section (CHS) joints due to their closed nature that complicates the strengthening process. Recent research related to strengthening T-joints by utilizing two outer hollow ring flanges welded to additional pipe showed that this technique can significantly improve the joints’ strength. In this study, the utilization of this technique is extended for enhancing the axial strength of CHS X-joints. In this regard, a parametric study using finite element models was carried out to investigate the different design aspects that might affect the behavior of strengthened X-joints. The examined parameters included, the ring flange diameter, the stiffening pipe thickness and length for different brace diameter-to-chord diameter ratios and chord diameter to double chord thickness ratio. The results demonstrated that these strengthened X-joints gained significant axial strength that reached up to three times the axial strength of the unstrengthened joints. Guidelines for proper detailing of such strengthening scheme were provided. Finally, an equation that estimates the axial strength of strengthened joints was established based on the achieved results.
Formation of wormholes in modified gravity: Exotic matter and stability
Authors: Bhattacharya Subhra , Halder Shibaji , Chakraborty Subenoy
Published: June 2019

This work addresses the question whether exotic matter is essential for the formation of wormholes in modified gravity theories. The basic property of wormhole geometry is the flaring-out condition at the throat which essentially states the violation of null energy condition for the matter threading the wormhole in Einstein gravity. In modified gravity theories, the field equations can be written as Einstein equations with two non-interacting fluids of which one is the usual fluid under consideration and the second term, called the effective matter, comes from the extra geometric terms of the theory. So it is interesting to examine whether normal fluid with restrictions on geometry satisfies the conditions for the formation of wormholes and their stability.
Klein–Gordon oscillator in the presence of the minimal momentum
Authors: Chung Won Sang , Hassanabadi Hassan , Farahani Nasrin
Published: June 2019

In this paper, we use the higher-dimensional extended uncertainty principle to discuss the two-dimensional Klein–Gordon oscillator in the absence of the magnetic field and in the presence of the magnetic field. We find the energy levels with the extended uncertainty principle correction for two cases.
Scalar–spinor fields interaction in de Sitter ambient space formalism
Authors: Ahmadi Y. , Jalilifard F. , Takook M. V.
Published: June 2019

In de Sitter ambient space formalism, the massless minimally coupled scalar field can be constructed from a massless conformally coupled scalar field and a constant five-vector [Formula: see text]. Also, a constant five-vector [Formula: see text] appears in the interaction Lagrangian of massless minimally coupled scalar and spinor fields in this formalism. These constant five-vector fields can be fixed in the interaction case in the null curvature limit. Here, we will calculate the [Formula: see text] matrix elements of scalar–spinor field interaction in the tree level approximation. Then the constant five-vectors [Formula: see text] and [Formula: see text], will be fixed by comparing the [Formula: see text] matrix elements in the null curvature limits with the Minkowskian counterparts.
When will car owners abandon car driving? Analysis based on a survey of the parking experiences of people in Changsha, China
Authors: Pan Shuangli , Liang Zuli , Chen Qun
Published: June 2019

An appropriate parking supply in cities should not only satisfy car travel demands but also restrict the number of car trips to reduce congestion and carbon emissions on road networks. This paper analyzes when car owners will abandon car driving based on a survey of the parking experiences of people in Changsha, China. The results indicate that car owners are most likely to abandon driving when the total time expenditure (including the search time and walking time) exceeds 20 min or the walking distance between a car park and a destination exceeds 400 m. In addition, car owners’ decisions regarding different trip purposes (commuting, business, hospital trips, shopping and entertainment activities) are compared. Multinomial logistic regression models and correspondence analysis methods are applied to identify the factors influencing car owners’ decisions. The results show that public transport and the parking pricing level near work places have a substantial impact on people’s decisions: people will more readily abandon driving when the travel time of public transit decreases; age, occupation and annual household income have a significant influence on people’s parking condition preferences for business trips and trips to hospitals; and the factor that primarily influences the mode choice for shopping and entertainment trips is annual household income. The outcome of this study can provide a basis for determining the optimal parking supply level and facilitate the realization of sustainable transportation.
Theoretical investigation on the interaction between groups in LAP crystal and its linear optical properties
Authors: Wang Lei , Xiao Meixia , Tu Bingtian
Published: June 2019

LAP crystal is an excellent nonlinear optical material and it has some unexplained specificities, which makes the interaction between groups in molecule received much attention. In this paper, the first-principles calculations are performed to investigate the intergroup interactions by the electronic structure and optical properties of LAP crystal. The energy gap of LAP crystal is 5.02 eV, indicating that the electronic transition is easier than KDP crystal. The strong electronic interaction between the carboxyl, phosphate and guanidine groups is found. In addition, since the LAP molecule has the greatest dipole in [010] direction and the electronic transitions are most likely to occur between the carboxyl group, phosphate and guanidine groups located on both ends of the molecule along [010] direction, the LAP crystal shows specific optical properties in this direction. The results reveal the correlations between the optical properties and the intergroup interactions of LAP crystal.
Reanalysis Method for Second Derivatives of Static Displacement
Authors: Zuo Wenjie , Fang Jiaxin , Feng Zengming
Published: June 2019

The reanalysis method to obtain the second derivatives of static displacement is innovatively proposed in this paper. This method is based on the combined approximations method. The reanalysis formulations of the second derivative of static displacement are derived to provide a programmatic procedure of formulations construction. Besides, the normalized error and the number of algebraic operations are considered to evaluate the accuracy and efficiency, respectively. Finally, three typical numerical results verify the accuracy and robustness of the proposed method.
Method of Order Reduction for the High-Dimensional Convection-Diffusion-Reaction Equation with Robin Boundary Conditions Based on MQ RBF-FD
Authors: Li Jingwei , Gao Zhiming , Feng Xinlong , He Yinnian
Published: June 2019

A novel method of order reduction is proposed to the high-dimensional convection-diffusion-reaction equation with Robin boundary condition based on the multiquadric radial basis function-generated finite difference method (MQ RBF-FD). The main motivation is to get not only a second-order accurate solution but also a second-order accurate gradient. Key to the proposed method is introducing the intermediate variables representing the first-order derivatives to reduce the original second-order problem into an equivalent system of first-order partial differential equations. Then a discrete scheme for the latter is constructed, in which MQ RBF-FD method is applied to approximate the first-order derivatives of the original variable at the center point with decoupled method. Moreover, we can obtain an equivalent discrete scheme about the original variable and intermediate variables which can be proven all second-order convergent, that is, the convergence rate of the gradient of solution is also second-order. Finally numerical examples are presented to show the efficiency and accuracy of the proposed method.
From a Comprehensive Experimental Survey to a Cost-based Selection Strategy for Lightweight Integer Compression Algorithms
Authors: Damme Patrick , Ungethüm Annett , Hildebrandt Juliana , Habich Dirk , Lehner Wolfgang
Published: June 2019

Lightweight integer compression algorithms are frequently applied in in-memory database systems to tackle the growing gap between processor speed and main memory bandwidth. In recent years, the vectorization of basic techniques such as delta coding and null suppression has considerably enlarged the corpus of available algorithms. As a result, today there is a large number of algorithms to choose from, while different algorithms are tailored to different data characteristics. However, a comparative evaluation of these algorithms with different data and hardware characteristics has never been sufficiently conducted in the literature. To close this gap, we conducted an exhaustive experimental survey by evaluating several state-of-the-art lightweight integer compression algorithms as well as cascades of basic techniques. We systematically investigated the influence of data as well as hardware properties on the performance and the compression rates. The evaluated algorithms are based on publicly available implementations as well as our own vectorized reimplementations. We summarize our experimental findings leading to several new insights and to the conclusion that there is no single-best algorithm. Moreover, in this article, we also introduce and evaluate a novel cost model for the selection of a suitable lightweight integer compression algorithm for a given dataset.
A comparative study of mitochondrial respiration in circulating blood cells and skeletal muscle fibers in women
Authors: Rose Shannon , Carvalho Eugenia , Diaz Eva C. , Cotter Matthew , Bennuri Sirish C. , Azhar Gohar , Frye Richard E. , Adams Sean H. , Børsheim Elisabet
Published: June 2019

Skeletal muscle mitochondrial respiration is thought to be altered in obesity, insulin resistance, and type 2 diabetes; however, the invasive nature of tissue biopsies is an important limiting factor for studying mitochondrial function. Recent findings suggest that bioenergetics profiling of circulating cells may inform on mitochondrial function in other tissues in lieu of biopsies. Thus, we sought to determine whether mitochondrial respiration in circulating cells [peripheral blood mononuclear cells (PBMCs) and platelets] reflects that of skeletal muscle fibers derived from the same subjects. PBMCs, platelets, and skeletal muscle (vastus lateralis) samples were obtained from 32 young (25–35 yr) women of varying body mass indexes. With the use of extracellular flux analysis and high-resolution respirometry, mitochondrial respiration was measured in intact blood cells as well as in permeabilized cells and permeabilized muscle fibers. Respiratory parameters were not correlated between permeabilized muscle fibers and intact PBMCs or platelets. In a subset of samples ( n = 12–13) with permeabilized blood cells available, raw measures of substrate (pyruvate, malate, glutamate, and succinate)-driven respiration did not correlate between permeabilized muscle (per mg tissue) and permeabilized PBMCs (per 106 cells); however, complex I leak and oxidative phosphorylation coupling efficiency correlated between permeabilized platelets and muscle (Spearman’s ρ = 0.64, P = 0.030; Spearman’s ρ = 0.72, P = 0.010, respectively). Our data indicate that bioenergetics phenotypes in circulating cells cannot recapitulate muscle mitochondrial function. Select circulating cell bioenergetics phenotypes may possibly inform on overall metabolic health, but this postulate awaits validation in cohorts spanning a larger range of insulin resistance and type 2 diabetes status.
Linking bioenergetic function of mitochondria to tissue-specific molecular fingerprints
Authors: Kappler Lisa , Hoene Miriam , Hu Chunxiu , von Toerne Christine , Li Jia , Bleher Daniel , Hoffmann Christoph , Böhm Anja , Kollipara Laxmikanth , Zischka Hans , Königsrainer Alfred , Häring Hans-Ulrich , Peter Andreas , Xu Guowang , Sickmann Albert , Hauck Stefanie M. , Weigert Cora , Lehmann Rainer
Published: June 2019

Mitochondria are dynamic organelles with diverse functions in tissues such as liver and skeletal muscle. To unravel the mitochondrial contribution to tissue-specific physiology, we performed a systematic comparison of the mitochondrial proteome and lipidome of mice and assessed the consequences hereof for respiration. Liver and skeletal muscle mitochondrial protein composition was studied by data-independent ultra-high-performance (UHP)LC-MS/MS-proteomics, and lipid profiles were compared by UHPLC-MS/MS lipidomics. Mitochondrial function was investigated by high-resolution respirometry in samples from mice and humans. Enzymes of pyruvate oxidation as well as several subunits of complex I, III, and ATP synthase were more abundant in muscle mitochondria. Muscle mitochondria were enriched in cardiolipins associated with higher oxidative phosphorylation capacity and flexibility, in particular CL(18:2)4 and 22:6-containing cardiolipins. In contrast, protein equipment of liver mitochondria indicated a shuttling of complex I substrates toward gluconeogenesis and ketogenesis and a higher preference for electron transfer via the flavoprotein quinone oxidoreductase pathway. Concordantly, muscle and liver mitochondria showed distinct respiratory substrate preferences. Muscle respired significantly more on the complex I substrates pyruvate and glutamate, whereas in liver maximal respiration was supported by complex II substrate succinate. This was a consistent finding in mouse liver and skeletal muscle mitochondria and human samples. Muscle mitochondria are tailored to produce ATP with a high capacity for complex I-linked substrates. Liver mitochondria are more connected to biosynthetic pathways, preferring fatty acids and succinate for oxidation. The physiologic diversity of mitochondria may help to understand tissue-specific disease pathologies and to develop therapies targeting mitochondrial function.
The pregnane X receptor and its microbiota-derived ligand indole 3-propionic acid regulate endothelium-dependent vasodilation
Authors: Pulakazhi Venu Vivek Krishna , Saifeddine Mahmoud , Mihara Koichiro , Tsai Yi-Cheng , Nieves Kristoff , Alston Laurie , Mani Sridhar , McCoy Kathy D. , Hollenberg Morley D. , Hirota Simon A.
Published: June 2019

We proposed that circulating metabolites generated by the intestinal microbiota can affect vascular function. One such metabolite, indole 3-propionic acid (IPA), can activate the pregnane X receptor(PXR), a xenobiotic-activated nuclear receptor present in many tissues, including the vascular endothelium. We hypothesized that IPA could regulate vascular function by modulating PXR activity. To test this, Pxr+/+ mice were administered broad-spectrum antibiotics for 2 wk with IPA supplementation. Vascular function was evaluated by bioassay using aorta and pulmonary artery ring tissue from antibiotic-treated Pxr+/+ and Pxr−/−mice, supplemented with IPA, and using aorta tissue maintained in organ culture for 24 h in the presence of IPA. Endothelium-dependent, nitric oxide(NO)-mediated muscarinic and proteinase-activated receptor 2(PAR2)-stimulated vasodilation was assessed. Endothelial nitric oxide synthase (eNOS) abundance was evaluated in intact tissue or in aorta-derived endothelial cell cultures from Pxr+/+ and Pxr−/− mice, and vascular Pxr levels were assessed in tissues obtained from Pxr+/+ mice treated with antibiotics and supplemented with IPA. Antibiotic-treated Pxr+/+ mice exhibited enhanced agonist-induced endothelium-dependent vasodilation, which was phenocopied by tissues from either Pxr−/− or germ-free mice. IPA exposure reduced the vasodilatory responses in isolated and cultured vessels. No effects of IPA were observed for tissues obtained from Pxr−/− mice. Serum nitrate levels were increased in antibiotic-treated Pxr+/+and Pxr−/− mice. eNOS abundance was increased in aorta tissues and cultured endothelium from Pxr−/− mice. PXR stimulation reduced eNOS expression in cultured endothelial cells from Pxr+/+ but not Pxr−/− mice. The microbial metabolite IPA, via the PXR, plays a key role in regulating endothelial function. Furthermore, antibiotic treatment changes PXR-mediated vascular endothelial responsiveness by upregulating eNOS.
A New Flavanone as a Potent Antioxidant Isolated from Chromolaena odorata L. Leaves
Authors: Putri Devi Anggraini , Fatmawati Sri
Published: June 2019

Chromolaena odorata L. (Asteraceae) is one of the tropical plants which is widely used as traditional medicines for diabetes and soft tissue wounds treatment in some regions in East Indonesia. The present study was aimed at determining the bioactive compounds of C. odorata leaves. The methanol and ethyl acetate extracts of C. odorata leaves have the inhibitory activity against 2,2-diphenyl-1-picryl-hydrazyl (DPPH) and 2,2’-azinobis-(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) radicals as well as α-glucosidase rat intestine enzyme. A new flavanone was isolated from the methanol extract and elucidated as 5,3’-dihydroxy-7,6’-dimethoxyflavanone or, namely, odoratenin (1) together with two known compounds: isosakuranetin (2) and subscandenin (3). The antioxidant activity of odoratenin (1) exhibited very potent ABTS radical inhibitory activity with IC50 value of 23.74 μM which is lower than that of trolox (IC50 31.32 μM) as a positive control. The result showed that a new flavanone, odoratenin (1), should be potential as an antioxidant source.
Exploring Multicriteria Elicitation Model Based on Pairwise Comparisons: Building an Interactive Preference Adjustment Algorithm
Authors: Vasconcelos Giancarllo Ribeiro , Maria de Miranda Mota Caroline
Published: June 2019

Pairwise comparisons have been applied to several real decision making problems. As a result, this method has been recognized as an effective decision making tool by practitioners, experts, and researchers. Although methods based on pairwise comparisons are widespread, decision making problems with many alternatives and criteria may be challenging. This paper presents the results of an experiment used to verify the influence of a high number of preferences comparisons in the inconsistency of the comparisons matrix and identifies the influence of consistencies and inconsistencies in the assessment of the decision‐making process. The findings indicate that it is difficult to predict the influence of inconsistencies and that the priority vector may or may not be influenced by low levels of inconsistencies, with a consistency ratio of less than 0.1. Finally, this work presents an interactive preference adjustment algorithm with the aim of reducing the number of pairwise comparisons while capturing effective information from the decision maker to approximate the results of the problem to their preferences. The presented approach ensures the consistency of a comparisons matrix and significantly reduces the time that decision makers need to devote to the pairwise comparisons process. An example application of the interactive preference adjustment algorithm is included.
Microcrack Growth Properties of Granite under Ultrasonic High‐Frequency Excitation
Authors: Zhao Dajun , Zhang Shulei , Wang Meiyan
Published: June 2019

The failure of most rock materials is essentially a process of crack initiation and propagation. It is of great significance to study the microcrack growth characteristics of granite under ultrasonic high‐frequency excitation for understanding the failure mechanism of rock under ultrasonic vibration. In this paper, the experimental and numerical simulation methods are used to study the propagation characteristics of rock cracks under ultrasonic vibration. Scanning electron microscopy (SEM) was used to observe the growth of microcracks in granite samples after ultrasonic vibration for 0 min, 2 min, and 4 min. A discrete element software PFC2D was used to simulate and solve the cracking mechanism of rock cracks under ultrasonic vibration. Also, it is found that the action of ultrasonic vibration can effectively promote the development of microcracks in the granite samples. The main three cracks causing the failure of quartz under the ultrasonic high frequency are intragranular cracks, transgranular cracks, and grain boundary cracks. The breakage of transgranular cracks usually contributes a shell‐like fracture, that is, a regular curved surface with a concentric circular pattern appears on the fracture surface, which is a typical quartz brittle fracture mode. In addition, the feldspar grain failure is mainly caused by intragranular crack and transgranular crack. Microcracks are wavy expansion in feldspar grain. Mica failure is mainly caused by grain boundary crack, and the effect of lamellar cleavage on the failure of mica is significant. Moreover, it is also found that the mechanism of microcrack propagation is tensile failure. The failure of feldspar grains is mainly contributed to the failure of granite.
Sequential Quadratic Programming Method for Nonlinear Least Squares Estimation and Its Application
Authors: Fu Zhengqing , Liu Goulin , Guo Lanlan
Published: June 2019

In this study, we propose a direction‐controlled nonlinear least squares estimation model that combines the penalty function and sequential quadratic programming. The least squares model is transformed into a sequential quadratic programming model, allowing for the iteration direction to be controlled. An ill‐conditioned matrix is processed by our model; the least squares estimate, the ridge estimate, and the results are compared based on a combination of qualitative and quantitative analyses. For comparison, we use two equality indicators: estimated residual fluctuation of different methods and the deviation between estimated and true values. The root‐mean‐squared error and standard deviation are used for quantitative analysis. The results demonstrate that our proposed model has a smaller error than other methods. Our proposed model is thereby found to be effective and has high precision. It can obtain more precise results compared with other classical unwrapping algorithms, as shown by unwrapping using both simulated and real data from the Jining area in China.
Simvastatin Reduces Hepatic Oxidative Stress and Endoplasmic Reticulum Stress in Nonalcoholic Steatohepatitis Experimental Model
Authors: Rodrigues Graziella , Moreira Andrea Janz , Bona Silvia , Schemitt Elizângela , Marroni Cláudio Augusto , Di Naso Fábio Cangeri , Dias Alexandre Simões , Pires Thienne Rocha , Picada Jaqueline Nascimento , Marroni Norma Possa
Published: June 2019

Objective. In this study, we evaluated the efficacy of simvastatin in the treatment of nonalcoholic steatohepatitis induced by methionine and choline-deficient diet in mice and its possible effect on factors involved in the pathogenesis of the disease including oxidative stress and endoplasmic reticulum stress. Method. Male C57BL6 mice were fed either a normal diet (control) or a methionine and choline-deficient diet for four weeks and then treated orally with simvastatin (4 mg/kg once a day) for two final weeks. At the end of the experimental period, liver integrity, biochemical analysis, hepatic lipids, histology, DNA damage, biomarkers of oxidative stress, and endoplasmic reticulum stress were assessed. Results. Simvastatin treatment was able to significantly reduce hepatic damage enzymes and hepatic lipids and lower the degree of hepatocellular ballooning, without showing genotoxic effects. Simvastatin caused significant decreases in lipid peroxidation, with some changes in antioxidant enzymes superoxide dismutase and glutathione peroxidase. Simvastatin activates antioxidant enzymes via Nrf2 and inhibits endoplasmic reticulum stress in the liver. Conclusions. In summary, the results provide evidence that in mice with experimental nonalcoholic steatohepatitis induced by a methionine and choline-deficient diet, the reduction of liver damage by simvastatin is associated with attenuated oxidative and endoplasmic reticulum stress.
Orbital Emphysema as a Consequence of Forceful Nose-Blowing: Report of a Case
Authors: Ariyoshi Yukino , Naito Hiromichi , Yumoto Tetsuya , Iida Atsuyoshi , Yamamoto Hirotsugu , Fujisaki Noritomo , Aokage Toshiyuki , Tsukahara Kohei , Yamada Taihei , Mandai Yasuhiro , Osako Takaaki , Nakao Atsunori
Published: June 2019

Orbital emphysema occurs when air enters the soft tissue surrounding the orbit. Although orbital blowout fractures are often caused by face trauma, nontraumatic orbital fractures can also occur but have been rarely described. Here, a case of orbital and palpebral emphysema caused by forceful nose-blowing is presented. Examination uncovered gross swelling of the right eye and discernable subcutaneous emphysema. The patient had normal eye movement and visual acuity. Orbital computed tomography (CT) revealed orbital emphysema secondary to an orbit floor fracture into the maxillary sinus, resulting from high intranasal pressure upon blowing her nose. The patient received conservative management with antibiotics and was given instructions not to sneeze or blow her nose. She fully recovered and all her symptoms completely resolved.
Role of Regulatory B Cells in the Progression of Cervical Cancer
Authors: Chen Zhifang , Zhu Yuejie , Du Rong , Pang Nannan , Zhang Fengbo , Dong Di , Ding Jianbing , Ding Yan
Published: June 2019

This study is to investigate the role of regulatory B (Breg) cells in cervical cancer. In total, 70 cases of cervical cancer, 52 cases of cervical intraepithelial neoplasia (CIN), and 40 normal controls were enrolled. The percentage of Breg cells was detected by flow cytometry. Serum levels of IL-10 were measured by ELISA. The correlation between Breg cells and the clinical characterizations of cervical cancer was analyzed. The inhibition effect of Breg cells on CD8+ T cells was tested by blocking IL-10 in vitro. The percentage of CD19+CD5+CD1d+ Breg cells and the level of IL-10 of patients with cervical cancer or CIN were significantly higher than those in the control group (P<0.05). And the postoperative levels of Breg cells and IL-10 were significantly lower than the preoperative levels (P<0.05). Breg cells and the IL-10 level were positively correlated in cervical cancer patients (r=0.516). In addition, the Breg cell percentage was closely related to the FIGO stages, lymph node metastasis, tumor differentiation, HPV infection, and the tumor metastasis of cervical cancer (P<0.05). The Breg cell percentage was negatively correlated with CD8+ T cells of cervical cancer patients (r=‐0.669). The level of IL-10 in the culture supernatant of Bregs treated with CpG was significantly higher than that of non-Bregs (P<0.05). After coculture with Bregs, the quantity of CD8+ T cells to secrete perforin and Granzyme B was significantly decreased, and this effect was reversed after blocking IL-10 by a specific antibody. Breg cells are elevated in cervical cancer and associated with disease progression and metastasis. Moreover, they can inhibit the cytotoxicity of CD8+ T cells.
Enhancement of the Interlayer Interaction between Polystyrene and Polyvinyl Alcohol by Ozone Treatment
Authors: Su Lin , Li Jie , Li Jing , Chu Qiaomei , Li Bo , Liu Yiyang
Published: June 2019

The ozonization modification of polystyrene (PS) was conducted in acidic condition to enhance the interfacial interaction between PS and polyvinyl alcohol (PVA). Infrared spectra results revealed that the carbonyl and hydroxyl groups were successfully introduced to the PS film by ozonization. The hydrophobic PS was turned to be hydrophilic to some extent by contact angle experiment, which led to the enhancement of interfacial adhesion between PS and PVA. In addition, the adsorption of PS to PVA was also improved. Nano indenter measurement indicated the interfacial interaction between PS film and PVA film was obviously enhanced by 40% after ozonization at room temperature for 2 h in acidic condition, which will benefit for fabricating laser inertial confinement fusion container.
Chromosome 12p Amplification in Triple-Negative/BRCA1-Mutated Breast Cancer Associates with Emergence of Docetaxel Resistance and Carboplatin Sensitivity
Authors: Gómez-Miragaya Jorge , Díaz-Navarro Ander , Tonda Raul , Beltran Sergi , Palomero Luis , Palafox Marta , Dobrolecki Lacey E. , Huang Chen , Vasaikar Suhas , Zhang Bing , Wulf Gerburg M. , Collado-Sole Alejandro , Trinidad Eva M. , Muñoz Purificación , Paré Laia , Prat Aleix , Bruna Alejandra , Caldas Carlos , Arribas Joaquín , Soler-Monso María Teresa , Petit Anna , Balmaña Judith , Cruz Cristina , Serra Violeta , Pujana Miguel Angel , Lewis Michael T. , Puente Xose S. , González-Suárez Eva
Published: June 2019

Taxanes are the mainstay of treatment in triple-negative breast cancer (TNBC), with de novo and acquired resistance limiting patient's survival. To investigate the genetic basis of docetaxel resistance in TNBC, exome sequencing was performed on matched TNBC patient-derived xenografts (PDX) sensitive to docetaxel and their counterparts that developed resistance in vivo upon continuous drug exposure. Most mutations, small insertions/deletions, and copy number alterations detected in the initial TNBC human metastatic samples were maintained after serial passages in mice and emergence of resistance. We identified a chromosomal amplification of chr12p in a human BRCA1-mutated metastatic sample and the derived chemoresistant PDX, but not in the matched docetaxel-sensitive PDX tumor. Chr12p amplification was validated in a second pair of docetaxel-sensitive/resistant BRCA1-mutated PDXs and after short-term docetaxel treatment in several TNBC/BRCA1-mutated PDXs and cell lines, as well as during metastatic recurrence in a patient with BRCA1-mutated breast cancer who had progressed on docetaxel treatment. Analysis of clinical data indicates an association between chr12p amplification and patients with TNBC/basal-like breast cancer, a BRCA1 mutational signature, and poor survival after chemotherapy. Detection of chr12p amplification in a cohort of TNBC PDX models was associated with an improved response to carboplatin. Our findings reveal tumor clonal dynamics during chemotherapy treatments and suggest that a preexisting population harboring chr12p amplification is associated with the emergence of docetaxel resistance and carboplatin responsiveness in TNBC/BRCA1-mutated tumors.

Significance:

Chr12p copy number gains indicate rapid emergence of resistance to docetaxel and increased sensitivity to carboplatin, therefore sequential docetaxel/carboplatin treatment could improve survival in TNBC/BRCA1 patients.
Antibody-Based Delivery of Cytokine Payloads to Carbonic Anhydrase IX Leads to Cancer Cures in Immunocompetent Tumor-Bearing Mice
Authors: Ziffels Barbara , Stringhini Marco , Probst Philipp , Fugmann Tim , Sturm Theo , Neri Dario
Published: June 2019

Antibody–cytokine fusion proteins can have the potential to increase the density and activity of subsets of leukocytes within the tumor mass. Here, we describe the design, production, and characterization of four novel antibody–cytokine fusion proteins directed against human carbonic anhydrase IX, a highly validated marker of hypoxia that is overexpressed in clear cell renal cell carcinoma and other malignancies. As immunomodulatory payloads we used TNF, IL2, IFNα2 (corresponding to products that are in clinical use), and IL12 (as this cytokine potently activates T cells and NK cells). Therapy experiments were performed in BALB/c mice, bearing CT26 tumors transfected with human carbonic anhydrase IX, in order to assess the performance of the fusion proteins in an immunocompetent setting. The biopharmaceuticals featuring TNF, IL2, or IL12 as payloads cured all mice in their therapy groups, whereas only a subset of mice was cured by the antibody-based delivery of IFNα2. Although the antibody fusion with TNF mediated a rapid hemorrhagic necrosis of the tumor mass, a slower regression of the neoplastic lesions (which continued after the last injection) was observed with the other fusion proteins, and treated mice acquired protective anticancer immunity. A high proportion of tumor-infiltrating CD8+ T cells was specific to the retroviral antigen AH1; however, the LGPGREYRAL peptide derived from human carbonic anhydrase IX was also present on tumor cells. The results described herein provide a rationale for the clinical use of fully human antibody–cytokine fusions specific to carbonic anhydrase IX.