bluuebunny/crossref_metadata_2025 huggingface dataset:
Gold‐forming potential of the granitic plutons in the Xiaoqinling gold province, southern margin of the North China Craton: Perspectives from zircon U–Pb isotopes and geochemistry
Authors: Wen Zi‐Hao , Li Lin , Li Sheng‐Rong , Santosh M. , Alam Masroor , Yuan Mao‐Wen , Li Shi‐Sheng , Zhi Ze‐Ya , Liu Jia‐Wei
Published: August 2019

The large‐scale concentration of Au associated with Mesozoic granitoid intrusions in the North China Craton (NCC) has inspired many investigations to explore the genetic relationship between the magmatism and gold metallogeny. The Xiaoqinling gold province is located in the southern margin of the North China Craton. The Wenyu and Huashan monzonitic granites formed at Early Cretaceous represent two of the important intrusions in this region, and a large number of gold deposits occur around the Wenyu pluton. Here we present results from an integrated study using in situ zircon U–Pb ages, trace elements, and Hf isotope to infer the composition and environmental changes during different evolution stages of the fertile Wenyu pluton and compare with the infertile Huashan pluton. The Huashan pluton was emplaced at 144.0 ± 0.6 Ma, whereas the fertile Wenyu pluton experienced multistage magmatic activity from 141.4 ± 0.6 to 129.6 ± 0.5 Ma. Temperatures computed from Ti‐in‐zircon thermometry indicate that the late‐stage Wenyu magma crystalized at 644°C, the Huashan magma, and early‐stage Wenyu magma crystalized at around 750°C. And the oxygen fugacity (Ce4+/Ce3+ > 200 and Eu/Eu* > 0.7) and the water content of the late‐stage Wenyu magma stay at higher levels. The U/Yb–Hf and U/Yb–Y relationship with εHf(t) (−15.63 to −17.89) of the late‐stage Wenyu magma suggest that the ancient lower crust with subsequent inputted basaltic components make up the source of the fertile and infertile plutons. Combined with previous geochronological data and geodynamics studies, we propose that the late‐stage intrusion of the Wenyu pluton experienced intensive magma mixing. And the formation of Wenyu pluton created conducive heat energy, oxygen fugacity, and water conditions for the formation of high‐grade gold deposits.
Nitric oxide upregulates microglia phagocytosis and increases transient receptor potential vanilloid type 2 channel expression on the plasma membrane
Authors: Maksoud Matthew J. E. , Tellios Vasiliki , An Dong , Xiang Yun‐Yan , Lu Wei‐Yang
Published: August 2019

Microglia phagocytosis is critical for central nervous system development, and dysregulation of phagocytosis may contribute to a variety of neurological disorders. During initial stages of phagocytosis, microglia display increased nitric oxide (NO) production via inducible nitric oxide synthase (iNOS) activity and amplified calcium entry through transient receptor potential vanilloid type 2 (TRPV2) channels. The present study investigated the regulatory role of iNOS/NO signaling in microglial phagocytosis and TRPV2 channel activation using phagocytosis assay, calcium imaging, patch clamp electrophysiology, immunocytochemistry, and immunoblot assays. Results showed that primary microglia from iNOS‐knockout (iNOS−/−) mice exhibited substantial deficits in phagocytic capacity and TRPV2 channel activity relative to wild‐type (WT) controls. Specifically, iNOS−/− microglia displayed a lower level of TRPV2 protein localized on the plasma membrane (PM) without any significant change in the mRNA levels of Fc‐gamma receptors and TRPV2. In addition, iNOS−/− microglia, unlike their WT controls, failed to elicit a calcium influx in response to application of the TRPV2‐agonist 2‐aminoethoxydiphenyl borate (2APB). Importantly, the phagocytic capacity and the PM expression and activity of TRPV2 in iNOS−/− microglia were largely corrected by pretreatment with NO‐donors. Accordingly, the 2APB‐evoked calcium influx and the PM expression of TRPV2 in WT microglia were significantly decreased by selective inhibition of iNOS, protein kinase‐G (PKG), or phosphoinositide‐3‐kinase (PI3K), respectively. Together, results from this study indicated that iNOS/NO signaling upregulates microglial phagocytosis and increases TRPV2 trafficking to the PM via PKG/PI3K dependent pathway(s).
Neuron‐generated thrombin induces a protective astrocyte response via protease activated receptors
Authors: Rajput Padmesh S. , Lamb Jessica , Kothari Shweta , Pereira Benedict , Soetkamp Daniel , Wang Yizhou , Tang Jie , Van Eyk Jennifer E. , Mullins Eric S. , Lyden Patrick D.
Published: August 2019

Astrocytes protect neurons during cerebral injury through several postulated mechanisms. Recent therapeutic attention has focused on enhancing or augmenting the neuroprotective actions of astrocytes but in some instances astrocytes can assume a neurotoxic phenotype. The signaling mechanisms that drive astrocytes toward a protective versus toxic phenotype are not fully known but cell–cell signaling via proteases acting on cell‐specific receptors underlies critical mechanistic steps in neurodevelopment and disease. The protease activated receptor (PAR), resides in multiple brain cell types, and most PARs are found on astrocytes. We asked whether neuron‐generated thrombin constituted an important astrocyte activation signal because our previous studies have shown that neurons contain prothrombin gene and transcribed protein. We used neuron and astrocyte mono‐cell cultures exposed to oxygen‐glucose deprivation and a model of middle cerebral artery occlusion. We found that ischemic neurons secrete thrombin into culture media, which leads to astrocyte activation; such astrocyte activation can be reproduced with low doses of thrombin. Media from prothrombin‐deficient neurons failed to activate astrocytes and adding thrombin to such media restored activation. Astrocytes lacking PAR1 did not respond to neuron‐generated thrombin. Induced astrocyte activation was antagonized dose‐dependently with thrombin inhibitors or PAR1 antagonists. Ischemia‐induced astrocyte activation in vivo was inhibited after neuronal prothrombin knockout, resulting in larger strokes. Restoring prothrombin to neurons with a lentiviral gene vector restored astrocyte activation and reduced stroke damage. We conclude that neuron‐generated thrombin, released during ischemia, acts via PAR1 and may cause astrocyte activation and paracrine neuroprotection.
Joint contributions of cortical morphometry and white matter microstructure in healthy brain aging: A partial least squares correlation analysis
Authors: Hoagey David A. , Rieck Jenny R. , Rodrigue Karen M. , Kennedy Kristen M.
Published: August 2019

Cortical atrophy and degraded axonal health have been shown to coincide during normal aging; however, few studies have examined these measures together. To lend insight into both the regional specificity and the relative timecourse of structural degradation of these tissue compartments across the adult lifespan, we analyzed gray matter (GM) morphometry (cortical thickness, surface area, volume) and estimates of white matter (WM) microstructure (fractional anisotropy, mean diffusivity) using traditional univariate and more robust multivariate techniques to examine age associations in 186 healthy adults aged 20–94 years old. Univariate analysis of each tissue type revealed that negative age associations were largest in frontal GM and WM tissue and weaker in temporal, cingulate, and occipital regions, representative of not only an anterior‐to‐posterior gradient, but also a medial‐to‐lateral gradient. Multivariate partial least squares correlation (PLSC) found the greatest covariance between GM and WM was driven by the relationship between WM metrics in the anterior corpus callosum and projections of the genu, anterior cingulum, and fornix; and with GM thickness in parietal and frontal regions. Surface area was far less susceptible to age effects and displayed less covariance with WM metrics, while regional volume covariance patterns largely mirrored those of cortical thickness. Results support a retrogenesis‐like model of aging, revealing a coupled relationship between frontal and parietal GM and the underlying WM, which evidence the most protracted development and the most vulnerability during healthy aging.
Problematic alcohol consumption in homeless Australians: A narrative review of the causes, barriers to receiving help and possible solutions
Authors: Scholes Gemma
Published: August 2019

Issue addressed

Problematic alcohol consumption (PAC) affects one‐third of homeless Australians, and it is expected that the rates will increase as the population ages. However, current policy does not recognise the importance of this problem. The aim of this narrative review was to examine the social determinants and other risk factors contributing to PAC in homeless Australians, the barriers to receiving help and possible solutions for the Australian context.

Methods

PubMed and PsycINFO databases and Australian government websites were examined for the keywords “alcohol” and “homeless,” and pertinent articles were selected for inclusion and for citation tracking of further relevant articles.

Results

The causes of PAC in homeless Australians are multifactorial, and multidirectional, and include risk factors such as low socio‐economic status, mental illness and having experienced trauma. There is significant stigma associated with both homelessness and PAC, which further isolates this group. Current policies to address PAC in the homeless are inadequate; however, there are a range of possible programs to reduce PAC in this group, and international harm reduction strategies have also shown success in improving outcomes for this group.

Conclusion

There are numerous social risk factors that influence the development of PAC in the homeless. The introduction of harm reduction strategies, programs to enhance motivation and personal skills, as well as better mental health treatment, would all fill important gaps in services for homeless Australians with PAC.

So what?

Health professionals can be advised that there are many social determinants that influence PAC in homeless Australians. There are important structural barriers to providing this marginalised group with the services they require; however, there is scope for the introduction of new programs, including harm reduction strategies, to meet the fundamental needs of this group.
Numerical investigation of nonuniform transverse magnetic field effects on the flow and heat transfer of magnetic nanofluid in a sintered porous channel
Authors: Kamali Mir Amin , Aminfar Habib , Mohammadpourfard Mousa , Jahanshaloo Leila
Published: August 2019

In this paper, fluid flow and convective heat transfer of a ferrofluid (water and 4 vol% Fe3O4) in sintered Aluminum porous channel, which is subjected to a nonuniform transverse magnetic field have been studied. The numerical simulations supposed an ordinary cubic and staggered arrangement organized by uniformly sized particles with a small contact area for the porous media and constant heat flux at the surface of the microchannel. A wire, in which the electric current passes creates a nonuniform magnetic field, which is perpendicular to the flow direction. To do this simulation, the control volume technique and the two‐phase mixture model have been employed. The results show that the obtained local heat transfer coefficient on the channel surface increased with increasing mass flow rate and decreased slightly along the axial direction. Moreover, exerting the above‐mentioned magnetic field increases the Nusselt number that enhances the heat transfer rate while it has no effect on the pressure drop along the channel.
Extreme returns and intensity of trading
Authors: Lin Wei , González‐Rivera Gloria
Published: August 2019

Asymmetric information models of market microstructure claim that variables such as trading intensity are proxies for latent information on the value of financial assets. We consider the interval‐valued time series (ITS) of low/high returns and explore the relationship between these extreme returns and the intensity of trading. We assume that the returns (or prices) are generated by a latent process with some unknown conditional density. At each period of time, from this density, we have some random draws (trades) and the lowest and highest returns are the realized extreme observations of the latent process over the sample of draws. In this context, we propose a semiparametric model of extreme returns that exploits the results provided by extreme value theory. If properly centered and standardized extremes have well‐defined limiting distributions, the conditional mean of extreme returns is a nonlinear function of the conditional moments of the latent process and of the conditional intensity of the process that governs the number of draws. We implement a two‐step estimation procedure. First, we estimate parametrically the regressors that will enter into the nonlinear function, and in a second step we estimate nonparametrically the conditional mean of extreme returns as a function of the generated regressors. Unlike current models for ITS, the proposed semiparametric model is robust to misspecification of the conditional density of the latent process. We fit several nonlinear and linear models to the 5‐minute and 1‐minute low/high returns to seven major banks and technology stocks, and find that the nonlinear specification is superior to the current linear models and that the conditional volatility of the latent process and the conditional intensity of the trading process are major drivers of the dynamics of extreme returns.
Focus on exosomes—From pathogenic mechanisms to the potential clinical application value in lymphoma
Authors: Liu Jiarui , Wang Xin
Published: August 2019

Exosomes are highly specialized and functional bilayer membranous particles. They have been considered as vehicles for transporting and delivering a large number of proteins, lipids, and nucleic acids (gene, noncoding RNA, DNA) from parental to recipient cells. In hematological malignancies, exosomes are involved in the tumorigenesis, including producing growth factors, hindering antitumor immunoreaction, promote inflammation, angiogenesis, and hypercoagulation. With the deepening of understanding, exosomes have ignited great interests and ever‐increasing efforts into the therapeutic application among scientists, such as biomarkers, therapeutic target, drug delivery system, and vaccines. Here, we discuss the most recent studies on the functions and the emerging therapeutic applications of exosomes in lymphoma.
miR‐605‐5p promotes invasion and proliferation by targeting TNFAIP3 in non–small‐cell lung cancer
Authors: Liao Youxia , Cao Lirong , Wang Fang , Pang Rong
Published: August 2019

Lung cancer is an significant cause of death worldwide, and non–small‐cell lung cancer (NSCLC) is the most common type of lung cancer. MicroRNAs (miRNAs) have been identified to play key roles in NSCLC development. Recently, it has been reported that miR‐605‐5p is a cancer‐related miRNA in several types of tumors. In this study, we study the role of miR‐605‐5p in NSCLC cells. We find that miR‐605‐5p is upregulated in NSCLC cells. Overexpression of miR‐605‐5p significantly promotes lung cancer invasion and migration in H460 and H1299 cells. Besides this, miR‐605‐5p also promotes lung cancer cell carcinoma proliferation and metastasis in vivo. However, downregulation of miR‐605‐5p inhibits cell invasion and migration by inhibiting lung cancer cell carcinoma proliferation and metastasis. In addition, the luciferase report assay identifies 3′‐untranslated region tumor necrosis factor α‐induced protein 3 (TNFAIP3) as a target of miR‐605‐5p. Silencing of TNFAIP3 promotes invasion and proliferation in lung cancer. In addition, the knockdown of TNFAIP3 restores the significant decrease in invasion and proliferation in miR‐605‐5p‐inhibitor–transfected lung cancer cells. In conclusion, miR‐605‐5p promotes invasion and proliferation by targeting TNFAIP3 in NSCLC, and may provide possible biomarkers for NSCLC therapy.
Knockdown of LINC01116 inhibits cell migration and invasion in head and neck squamous cell carcinoma through epithelial‐mesenchymal transition pathway
Authors: Wu Jing , Chen Zhizhao , Zhang Li , Cao Jun , Li Xiaoyu , Gong Zhaojian , Bo Hao , Zhang Shanshan , He Dong
Published: August 2019

Long noncoding RNAs (lncRNAs) are linked to tumor development and progression. The aim of this study was to determine the prognostic significance and biological role of LINC01116 in head and neck squamous cell carcinoma (HNSCC). We identified 21 aberrantly expressed lncRNAs specific to HNSCC that were common in two microarray datasets. LINC01116 was highly overexpressed in HNSCC tissues and was correlated to shorter overall survival and relapse‐free survival duration, as analyzed by the online Gene Expression Profiling Interactive Analysis platform. LINC01116 was also overexpressed in oral squamous cell carcinoma and nasopharyngeal carcinoma tissues, and LINC01116 silencing significantly inhibited the migration and invasion capacities of both cell lines by blocking the epithelial‐mesenchymal transition process. In addition, 125 coexpressing genes were identified by circlncRNAnet, and were mainly located on human autosomes and enriched in transforming growth factor‐β signaling pathway. These findings indicate that LINC01116 might be a potential therapeutic target for HNSCC.
Effect of miR‐499a‐5p on damage of cardiomyocyte induced by hypoxia‐reoxygenation via downregulating CD38 protein
Authors: Zhao Lei , Wang BaoHua , Zhang WeiJia , Sun LiXia
Published: August 2019

The aim is to investigate the mechanism of miR‐499a‐5p on the damage of cardiomyocyte induced by hypoxia/reoxygenation. The activity of lactate dehydrogenase (LDH), apoptosis rate and the expression of miR‐499a‐5p and cluster of differentiation 38 (CD38) in hypoxia‐reoxygenation model cells were detected by LDH Cytotoxicity Assay Kit, flow cytometry, real‐time polymerase chain reaction, and Western blot analysis, respectively. Apoptosis, the activity of LDH was detected after overexpression of miR‐499a‐5p or silencing of CD38 in H9c2 cells. The target relationship between miR‐499a‐5p and CD38 was verified by Targetscan online prediction and dual‐luciferase assay. Apoptosis, the activity of LDH was detected after overexpression of miR‐499a‐5p and CD38. Apoptosis, the activity of LDH and the expression of CD38 were increased (P < .05) while expression of miR‐499a‐5p was decreased (P < .05) in hypoxia/reoxygenation model cells. Apoptosis and the activity of LDH in H9c2 cells after overexpression of miR‐499a‐5p or silence of CD38 were decreased (P < .05). The results of Targetscan online prediction and dual‐luciferase assay indicated that CD38 was a potential target gene of miR‐499a‐5p. Overexpression of CD38 could reverse the inhibition of miR‐499a‐5p on LDH activity and apoptosis in H9c2 cells. miR‐499a‐5p could relief the injury of cardiomyocytes induced by hypoxia/reoxygenation via targeting CD38.
Pain catastrophizing and pain acceptance are associated with pain severity and interference among methadone‐maintained patients
Authors: Mun Chung Jung , Beitel Mark , Oberleitner Lindsay , Oberleitner David E. , Madden Lynn M. , Bollampally Pooja , Barry Declan T.
Published: August 2019

Objective

The present study examined whether pain catastrophizing and pain acceptance, two important targets of psychosocial interventions for chronic pain, are uniquely associated with pain severity and pain interference among patients on methadone maintenance treatment (MMT).

Method

A total of 133 MMT patients who reported experiencing some pain during the previous week completed a battery of self‐report measures. Multiple regression was used to test whether pain catastrophizing and pain acceptance are related to pain severity and pain interference above and beyond covariates including demographics, emotional distress, and current methadone dose.

Results

Both pain acceptance and catastrophizing were significantly associated with pain severity and pain interference while controlling for covariates.

Conclusions

Consistent with previous literature on patients with chronic pain but without opioid use disorder, our findings suggest that both pain catastrophizing and pain acceptance are potentially important intervention targets among MMT patients with co‐occurring opioid use disorder and chronic pain.
Integrative depiction of the male reproductive system of the commercial purple crab Homalaspis plana (Platyxanthidae): Structure and function
Authors: Pardo Luis M. , Zara Fernando J. , Riveros Marcela P. , Paschke Kurt , Pretterebner Katrin , Mantelatto Fernando L.
Published: August 2019

The information available on structures and function of reproductive systems are female‐biased in many animal groups and crabs are not an exception. However, knowledge about the male reproductive system can help us to understand evolutionary and ecological processes such as the mating system and mating behavior. This study focuses on an integrative description of the principal regions of the male reproductive system of the purple crab, Homalaspis plana, a commercially exploited crab from the southeastern Pacific. For this description a combination of morphological observation, gravimetric records, histological and histochemical techniques and biochemical analysis were used. Also, a gross description of the seminal receptacle of the female was performed. The male reproductive system of H. plana was highly extended and complex, with a great capacity to produce and store spermatophores and secrete, at least, two kinds of seminal fluids. Sperm production, sperm packaging in spermatophores, storage of spermatophores and seminal liquid secretion were functions localized in specific regions. The vasosomatic index was the highest recorded to date in crabs, symptomatic of a high investment in reproduction. All these traits allow identification of H. plana as an internal sperm plug producer, which matches well with the highly extensible seminal receptacle of females. The great quantity of seminal material transferred to females during mating indicates that males may be able to mate only one time in the reproductive season and thus this species could be vulnerable to sperm depletion in males and sperm limitation in females if the fishery substantively reduced the abundance of males in the populations.
Fabrication of capsaicin emulsions: improving the stability of the system and relieving the irritation to the gastrointestinal tract of rats
Authors: Han Jingjing , Zhang Shuhan , Liu Xuebo , Xiao Chunxia
Published: August 2019

BACKGROUND

Capsaicin, as a major pungent ingredient of peppers, has many health benefits. However, the strong irritation effect of capsaicin inhibits its application in the food industry. Emulsions can be an effective approach to alleviate the irritation.

RESULTS

In this study, we used tocopheryl polyethylene glycol 1000 succinate (TPGS) as an emulsifier to prepare capsaicin emulsions through high‐pressure homogenization. Capsaicin emulsions with a particle size of about 100 nm, −36.4 mV zeta potential, and 91.9% encapsulation efficiency were prepared successfully and showed better environmental stability and higher antioxidant activity. Emulsions reduced the cumulative release of capsaicin and had no toxic effect on buffalo rat liver (BRL‐3A) cells. Moreover, the gastrointestinal injury model of rats showed that emulsions reduced the strong irritation of capsaicin.

CONCLUSION

This work provides a theoretical basis for the application of irritant ingredients in food industry. © 2019 Society of Chemical Industry
The extent of extrathyroidal extension is a key determinant of prognosis in T4a papillary thyroid cancer
Authors: Abraham Earl , Roshan David , Tran Bryan , Wykes James , Campbell Peter , Ebrahimi Ardalan
Published: August 2019

Background and Objectives

In papillary thyroid cancer (PTC), the adverse prognostic impact of extrathyroidal extension (macro‐ETE) invading the subcutaneous soft tissues, larynx, trachea, esophagus, or recurrent laryngeal nerve (T4a disease) is well established. We investigated whether the extent of macro‐ETE, defined as “limited” with single structure involvement (lim‐ETE) and “extensive” with multiple structures involved (ext‐ETE), influences prognosis in T4a PTC.

Methods

A retrospective analysis of 610 patients with PTC identified 39 with T4a disease, including 26 with lim‐ETE and 13 with ext‐ETE. Univariate Cox regression was used to assess the relationship between the extent of macro‐ETE and recurrence‐free survival (RFS).

Results

Ext‐ETE was associated with a five times increased risk of recurrence compared to lim‐ETE (HR 5.0, P < .030), with or without adjustment for radioactive iodine administration and after adjustment for margin status (HR 4.7; P = .041). A low‐risk subset of T4a disease comprising of patients aged less than 55 years with lim‐ETE and clear margins accounted for one‐third of the cohort and demonstrated an excellent 5‐year RFS of 92%.

Conclusions

The extent of macro‐ETE appears to be an important determinant of prognosis in T4a PTC. A low‐risk subset of T4a disease exists with an excellent prognosis.
The Transverse Infrapatellar View: A New Ultrasound Technique to Measure Distal Femoral Cartilage Thickness
Authors: Lee Se Won , Patel Jasal , Van Dien Craig , Ayutyanont Napatkamon , Naguib Abir , Emam Mohammed , Kim Sooyeon
Published: August 2019

Objectives

To examine the reliability and face validity of ultrasound (US) measurements of distal femoral cartilage thickness (CT) using the infrapatellar view (IPV) with knee extension compared to the traditional suprapatellar view (SPV) with knee hyperflexion in young asymptomatic participants and patients with painful knee osteoarthritis (KOA).

Methods

The IPV was obtained in an extended knee position by placing the US transducer on the patellar tendon at a 60° angle tilted toward the distal femoral condyle in 19 young adults (control group) and 70 patients with KOA. The CT was measured at the medial femoral condyle, the intercondylar notch, and the lateral femoral condyle.

Results

The inter‐rater intraclass correlation coefficient was higher for IPV‐based CT measurement (range, 0.856–0.858) compared to SPV‐based CT measurement (range, 0.315–0.523) among the patients with symptomatic KOA. The IPV‐based CT differed significantly between the control group and the KOA group at the intercondylar notch (P < .001) and lateral femoral condyle (P = .006). The SPV‐based CT differed significantly between the control group and the KOA group only at the lateral femoral condyle region (P = .014).

Conclusions

An infrapatellar US evaluation of the distal femoral CT can be a reliable alternative method to a suprapatellar US evaluation for patients with KOA.
Appetite for destruction: Counterintuitive effects of attractive faces on people's food choices
Authors: Otterbring Tobias
Published: August 2019

Faces in general and attractive faces, in particular, are frequently used in marketing, advertising, and packaging design. However, few studies have examined the effects of attractive faces on people's choice behavior. The present research examines whether attractive (vs. unattractive) faces increase individuals’ inclination to choose either healthy or unhealthy foods. In contrast to the beliefs held by most marketing professors, but consistent with visceral state theories, exposure to attractive (vs. unattractive) opposite‐sex faces increased choice likelihood of unhealthy foods. This effect was moderated by self‐view‐relevant attributes and exerted a particularly powerful influence on individuals who were single (vs. in a relationship) and individuals rating themselves as unattractive (vs. attractive). Furthermore, the effect was mediated by arousal, was stronger for men than for women, but did not generalize after exposure to attractive (vs. unattractive) same‐sex faces. As pictorial exposure is sufficient for the effect to occur, these findings have important implications for marketing, advertising, and public health.
High Molecular Weight Polyester Obtained by Polymerization of Dimethylketene Using Metallocene Initiators: A Step toward Ziegler–Natta Supporting Application in Non‐Olefin Systems
Authors: Jiang Bo , Desilles Nicolas , Burel Fabrice
Published: August 2019

In this report, highly active metallocene initiators are used for the polymerization of a ketene monomer, dimethylketene, which typically contains two adjacent double bonds (R2CCO). By using the methylzirconocene methyltriarylborate complex (Cp2ZrMe+MeB(C6F5)3−) as the activation system, associated with the possible cleavage of CC and CO bonds in ketene monomers, a structure‐specific and high‐molecular‐weight polyester ( > 300 000 g mol−1) can be afforded. The resulting polyester structure, comprehensively characterized by NMR, indicates a significant reactive selectivity of the “bent‐sandwich” cationic site Cp2ZrMe+. It reveals that the positively charged zirconium (Zr+) prefers to coordinate with a negatively charged oxygen (O−) when it is already bonded to the carbon, while a negatively charged carbon (C−) will be assigned in priority if the oxygen–zirconium bond exists. This report allows for broadening the application field of metallocene initiators in non‐olefin reactions and deepening our insight into the mechanism of the living insertion/Ziegler–Natta polymerization.
Uniparental isodisomy caused autosomal recessive diseases: NGS‐based analysis allows the concurrent detection of homogenous variants and copy‐neutral loss of heterozygosity
Authors: Xiao Bing , Wang Lili , Liu Huili , Fan Yanjie , Xu Yan , Sun Yu , Qiu Wenjuan
Published: August 2019

Background

Uniparental disomy (UPD) leading to autosomal recessive (AR) diseases is rare. We found an unusual homozygous state in two nonconsanguineous families, and only one parent in each family was a heterozygote.

Methods

Two patients with homozygosity for pathogenic variants were revealed by whole‐exome sequencing (WES), further Sanger sequencing found that only one of the parents was a heterozygote. Initial genotype and copy number variations analysis from WES data of probands involving whole chromosomes 1 and 9 containing these two pathogenic variants were performed, genome‐wide single‐nucleotide polymorphism (SNP) array analysis was used to confirm these results.

Results

Whole‐exome sequencing identified a homozygous c.3423_3424delTG mutation in AGL in patient 1 and a homozygous c.241‐1G>C mutation in SURF1 in patient 2. Further parental testing found that only the two patients’ healthy fathers were heterozygous. WES‐based copy number and genotype analysis found a copy‐neutral loss of heterozygosity (LOH) of whole chromosome 1 in patient 1 and of whole chromosomes 9 and 10 in patient 2. Further genome‐wide SNP array and family haplotype analyses confirmed whole paternal uniparental isodisomy (UPiD) 1 in patient 1 and paternal UPiD 9 and maternal UPiD 10 in patient 2. Therefore, UPiD caused AR monogenic glycogen storage disease type‐III (GSDIII) in patient 1 and Leigh syndrome in patient 2 through non‐Mendelian inheritance of two mutant copies of a gene from each patient's father.

Conclusion

Our report highlights that a single NGS‐based analysis could allow us to find homozygous sequence variants and copy‐neutral LOH in such cases. Our report also describes the first case of GSDIII caused by UPiD 1 and Leigh syndrome caused by UPiD 9.
The aging bladder phenotype is not the direct consequence of bladder aging
Authors: Hardy Cara C. , Keilich Spencer R. , Harrison Andrew G. , Knight Brittany E. , Baker Dylan S. , Smith Phillip P.
Published: August 2019

Aims

The prevalence of urinary dysfunction increases with age, yet therapies are often suboptimal. Incomplete understanding of the linkages between system, organ, and tissue domains across lifespan remains a knowledge gap. If tissue‐level changes drive the aging bladder phenotype, parallel changes should be observed across these domains. In contrast, a lack of inter‐domain correlation across age groups would support the hypothesis that urinary performance is a measure of the physiologic reserve, dependent on centrally‐mediated adaptive mechanisms in the aging system.

Methods

Male and female mice across four age groups underwent sequential voiding spot assays, pressure/flow cystometry, bladder strip tension studies, histology, and quantitative PCR analyses. The primary objective of this study was to test the impact of age on the cortical, autonomic, tissue functional and structural, and molecular domains, and identify inter‐domain correlations among variables showing significant changes with age within these domains.

Results

Behavior revealed diminished peripheral voiding and spot size in aged females. Cystometry demonstrated increased postvoid residual and loss of volume sensitivity, but the preservation of voiding contraction power, with almost half of oldest‐old mice failing under cystometric stress. Strip studies revealed no significant differences in adrenergic, cholinergic, or EFS sensitivity. Histology showed increased detrusor and lamina propria thickness, without a change in collagen/muscle ratio. Adrb2 gene expression decreased with age. No consistent inter‐domain correlations were found across age groups.

Conclusions

Our findings are consistent with a model in which centrally‐mediated adaptive failures to aging stressors are more influential over the aging bladder phenotype than local tissue changes.
Suggestions for creating the International Scientific Foundation of Saliva Diagnosis (ISFSD): New research strategies, development, and technologies
Authors: Mediouni Mohamed , Kaczor‐Urbanowicz Karolina Elżbieta , Madiouni Riadh
Published: August 2019

Saliva is an emerging biofluid for personalized/precision medicine application. As it has recently become a major tool for biological research and biomarker discovery, it is of vital importance to develop and optimize the diagnostics standards to decipher the omics constituents in saliva in order to achieve better oral and systemic health. Although current variations in saliva sampling, study designs, and developmental methods of salivary biomarkers prevent direct comparisons of the data obtained from different studies, the lack of standardization and unification of the processing procedures undermines saliva's diagnostic potential. Thus, it motivated us to propose the idea of creating an International Scientific Foundation of Salivary Diagnosis (ISFSD) that could encourage collaborative efforts to establish international guidelines and standardized protocols for saliva collection and laboratorial processing as well as clinical diagnostics. The ISFSD can accelerate the validation of biomarkers in larger groups of patients, their regulatory approval, and implementation of saliva diagnostics into a real clinical practice. It will also result in identification of practical and achievable priorities, and will present policy initiatives critical to the implementation of oral health improvement programs. The establishment of ISFSD will be of great interest and influence in the fields of oral health, dentistry, and medicine.
Did advice on the prescription of sodium valproate reduce prescriptions to women? An observational study in three European countries between 2007 and 2016
Authors: Charlton Rachel , Damase‐Michel Christine , Hurault‐Delarue Caroline , Gini Rosa , Loane Maria , Pierini Anna , Puccini Aurora , Neville Amanda , Snowball Julia , Morris Joan K. ,   on behalf of the EUROmediSAFE consortium
Published: August 2019

Objectives

In November 2014, the CMDh (a regulatory body representing EU Member States) advised doctors not to prescribe sodium valproate for epilepsy or bipolar disorder in preg nant women, in women who can become pregnant, or in girls unless other treatments are ineffective or not tolerated. This study aimed to determine if this warning led to changes in prescription patterns.

Design and setting

Cohort of 5.4 million women aged between 10 and 50 years identified in electronic health care data from United Kingdom, France, and Italy (2007–2016).

Main outcome measures

Anti‐epileptic drug (AED) prescriptions.

Results

The prevalence of women receiving AED prescriptions in 2016 varied from 12.2 per 1000 to 29 per 1000 in the four regions. The incidence of prescribing any AED (excluding clonazepam, gabapentin, and pregabalin) fell each year on average by 7.5% (95% CI, 7.0%‐8.0%; Emilia Romagna), 9.6% (8.3%‐11.0%; France), 7.1% (6.7%‐7.6%; Tuscany), and 0.4% (0.2%‐1.0%; United Kingdom). The relative odds of prescribing sodium valproate rather than any other AED decreased more after 2014 compared with before the end of 2014 in France (OR = 0.77; 95% CI, 0.60‐0.98), Tuscany (0.81; 0.76‐0.86), Emilia Romagna (0.83; 0.76‐0.90), and the United Kingdom (0.92; 0.80‐1.06; not statistically significant).

Conclusions

There is evidence that the CMDh warning did lead to changes in prescription patterns of sodium valproate in women of childbearing age. There were considerable differences in prescribing practice amongst regions of Europe.
Effect of blend ratio and compatibilisation on the electrical and dielectric properties of nylon copolymer (6, 66)/EPDM rubber blends
Authors: Komalan Cibi , Poothanari Mohammed Arif , J. Maria Hanna , Thomas Sabu
Published: August 2019

In this work, morphological, electrical, and dielectric performance of nylon copolymer (PA6, 66)/ethylene propylene diene rubber (EPDM) blends were systematically studied with reference to blend ratio and compatibilisation. As the concentration of PA6, 66 and the percentage of compatibiliser in the blend increases the resistivity values decreases. The existence of two phases, PA6, 66 and EPDM with different conductivity and interfacial polarization are responsible for the increase in the dielectric properties of the blends. Compatibilisation of the blends improved the dielectric constant of the blend system. Addition of 2.5% of compatibiliser gave the highest value of dielectric constant. At a high concentration of EPM‐g‐MA, the polarity of the compatibilised blends was found to be increased, which resulted in the substantial increase in the value of loss and dissipation factor. The dielectric values of the blends were correlated with blend phase morphology. Finally the experimental data was compared with various theoretical predications. POLYM. ENG. SCI., 59:2195–2201, 2019. © 2019 Society of Plastics Engineers
Implementation of a Multimodal Pain Management Order Set Reduces Perioperative Opioid Use after Liver Transplantation
Authors: Tong Kimhouy , Nolan William , O'Sullivan David M. , Sheiner Patricia , Kutzler Heather L.
Published: August 2019

Study Objective

Nonopioid strategies to optimize pain management in patients after liver transplantation remain underexplored. The purpose of this study was to evaluate whether the use of a multimodal pain management (MPM) order set would reduce postoperative opioid use in adult patients after liver transplantation.

Design

Retrospective pre– and post–order set implementation study.

Setting

Large academic tertiary care hospital.

Patients

Thirty‐one adults who underwent liver transplantation were included; of these, 18 received provider‐managed pain regimens (pre‐MPM group: August 20, 2016–January 17, 2018), and 13 received the MPM order set (post‐MPM group: January 18–July 31, 2018) after implementation of the order set on January 18, 2018.

Measurements and Main Results

The MPM order set included standardized receipt of acetaminophen 650 mg every 6 hours, gabapentin 300 mg every 8 hours (adjusted for renal function), and opioids for breakthrough pain. Patients managed with the MPM order set received, on average, 30.6 fewer opioid morphine milligram equivalents per day after final extubation than patients who did not receive MPM (median 16, interquartile range [IQR] 4.5–45.6 vs median 46.6, IQR 30.1–75.2; Mann‐Whitney U test, p=0.031). Although patients in the post‐MPM group had significantly worse renal function at baseline, no other statistically significant differences in baseline characteristics, pain scores, or prescribed outpatient opioids were noted between groups. Patients in the pre‐MPM group had a shorter intensive care unit and overall length of stay; however, patients in the post‐MPM group may have had more complex postoperative courses contributing to these differences.

Conclusion

Implementation of the MPM order set significantly reduced postoperative opioid use in liver transplant recipients. Our results provide a compelling rationale to further investigate the use of a non–opioid‐centered strategy to optimize pain management in patients recovering from liver transplantation, a population vulnerable to the risks of opioid use such as opioid use disorder, increased susceptibility to adverse effects, and poor allograft and survival outcomes.
Novel azomethine Pd (II)‐ and VO (II)‐based metallo‐pharmaceuticals as anticancer, antimicrobial, and antioxidant agents: Design, structural inspection, DFT investigation, and DNA interaction
Authors: Abu‐Dief Ahmed M. , Abdel‐Rahman Laila H. , Shehata Mohamed R. , Abdel‐Mawgoud Azza A. Hassan
Published: August 2019

The new NO bidentate imine ligand, namely, (2‐[(3‐nitro‐benzylidene)‐amino]‐benzoic acid) (NBA) imine ligand (L), and its Pd (II) and VO (II) complexes have been synthesized and characterized by utilizing different physiochemical methods including elemental analyses, Fourier transform infrared (FT‐IR), nuclear magnetic resonance (NMR), molar conductance, and magnetic susceptibility measurements. The stability constant of these complexes has also been determined. In studies of these complexes, they were found to have [M(L)] composition where the ligand acts as a bidentate and coordinates with the various metal ions through azomethine and one oxygen atom. Moreover, the suggested geometrical structure of Pd (II) and VO (II) complexes is square planar and a distorted square pyramid, respectively. Density functional theory (DFT) calculations for the different metal complexes were studied and show a good agreement with the experiment data. The minimum inhibitory concentration method has been applied to evaluate the in vitro antimicrobial activity. Furthermore, the interaction of calf thymus DNA with the metal‐imine chelates has been assessed, and Pd (II) complex showed the strongest interaction with DNA for a binding constant value of (9.72 × 104 kcal mol−1). The cytotoxic activity of the new metal chelates has been evaluated against three human cancer cell lines (hepatic carcinoma HepG2 cells, breast carcinoma cells MCF‐7, and colon carcinoma cells HCT‐116). It has found that NBAPd complex exhibited a significant decrease in the time and dose of the cell viability than did the reference drug vinblastine. The antioxidant activity of the tested compounds was determined and compared with that of vitamin C as a standard drug. It has been found that the metal complexes exhibit higher activity than the free ligand. The finding from this investigation revealed that the new compounds are considered to be prospective antibiotic and anticancer agents.
Flight Heritage of Ammonium Dinitramide (ADN) Based High Performance Green Propulsion (HPGP) Systems
Authors: Persson Mathias , Anflo Kjell , Friedhoff Pete
Published: August 2019

The flight heritage for ECAPS’ propulsion technology based of Ammonium DiNitramide (ADN), started 2010 with a successful 5 years on orbit demonstration mission of the PRISMA satellite. Since 2016, launches of satellites from 3 different continents continues to add to the flight heritage. Thirteen SkySat earth observation satellites with ADN‐based propulsion have added more than 28 years of accumulated flight heritage for LMP‐103S and ECAPS’ 1 N HPGP thrusters.
Metagenomic analysis reveals a rich bacterial content in high‐risk prostate tumors from African men
Authors: Feng Ye , Jaratlerdsiri Weerachai , Patrick Sean M. , Lyons Ruth J. , Haynes Anne‐Maree , Collins Colin C. , Stricker Phillip D. , Bornman M.S. Riana , Hayes Vanessa M.
Published: August 2019

Background

Inflammation is a hallmark of prostate cancer (PCa), yet no pathogenic agent has been identified. Men from Africa are at increased risk for both aggressive prostate disease and infection. We hypothesize that pathogenic microbes may be contributing, at least in part, to high‐risk PCa presentation within Africa and in turn the observed ethnic disparity.

Methods

Here we reveal through metagenomic analysis of host‐derived whole‐genome sequencing data, the microbial content within prostate tumor tissue from 22 men. What is unique about this study is that patients were separated by ethnicity, African vs European, and environments, Africa vs Australia.

Results

We identified 23 common bacterial genera between the African, Australian, and Chinese prostate tumor samples, while nonbacterial microbes were notably absent. While the most abundant genera across all samples included: Escherichia, Propionibacterium, and Pseudomonas, the core prostate tumor microbiota was enriched for Proteobacteria. We observed a significant increase in the richness of the bacterial communities within the African vs Australian samples (t = 4.6‐5.5; P = .0004‐.001), largely driven by eight predominant genera. Considering core human gut microbiota, African prostate tissue samples appear enriched for Escherichia and Acidovorax, with an abundance of Eubacterium associated with host tumor hypermutation.

Conclusions

Our study provides suggestive evidence for the presence of a core, bacteria‐rich, prostate microbiome. While unable to exclude for fecal contamination, the observed increased bacterial content and richness within the African vs non‐African samples, together with elevated tumor mutational burden, suggests the possibility that bacterially‐driven oncogenic transformation within the prostate microenvironment may be contributing to aggressive disease presentation in Africa.
Multi‐annual contemporary flood event overbank sedimentation within the vegetated lower Orinoco floodplain, Venezuela
Authors: Rodríguez Militza , Steiger Johannes , Rosales Judith , Laraque Alain , López José Luis , Castellanos Bartolo , Guerrero Omar Antonio
Published: August 2019

Multi‐annual contemporary flood event overbank sedimentation rates were quantified on the World's third largest river in terms of discharge, the tropical lower Orinoco. We discuss the role of variables at the basin and reach scales that contributed to the complexity of spatio‐temporal overbank sediment deposition patterns. Monitored in situ plots were characterized by distance to the main channel, hydroperiod, different geomorphological units, and vegetation cover. Flood event sedimentation rates showed a high spatial variability ranging from the absence of sediment deposition up to 225.46 kg m‐2 yr‐1. Banks and levees received relatively high amounts of sediment (39.6 kg m‐2 yr‐1), whereas observed mean sedimentation rates on the more distant floodplain and backswamps tended to be lower (17.7 kg m‐2 yr‐1). Significant differences in sedimentation rates were observed in two major vegetation types: dense herbaceous and shrubby vegetation (42.2 kg m‐2 yr‐1) and floodplain forest (12.7 kg m‐2 yr‐1). However, overbank sedimentation patterns also reflected imbricated hydrosedimentary and biogeomorphological vegetation feedbacks that co‐construct fluvial landforms. The incidence of an El Niño–Southern Oscillation–La Niña episode during the study period on sediment availability and floodplain sedimentation suggests that within whitewater rivers, where suspended sediment concentrations are naturally high, hydrological connectivity seems to be more important for floodplain sedimentation than variations in suspended sediment concentrations. These results may provide a good basis for future biogeomorphological investigation projects using complementary methodologies, in order to better anticipate global change and fluctuations in the occurrence, strength or duration of El Niño–La Niña episodes in the tropical zone and their consequences for flood discharge and sediment dynamics during channel–floodplain exchanges.