bluuebunny/crossref_metadata_2025 huggingface dataset:
Oral intake of lingonberry and amla fruit extract improves skin conditions in healthy female subjects: A randomized, double‐blind, placebo‐controlled clinical trial
Authors: Uchiyama Taro , Tsunenaga Makoto , Miyanaga Miho , Ueda Osamu , Ogo Masashi
Published: July 2019

In this study, we examined the effect of ingestion of lingonberry and amla fruit extract (LAE) on several human skin conditions. To conduct a randomized, double‐blinded, placebo‐controlled study, we randomly divided 99 healthy female subjects into three groups; the first group received a drink containing 25 mg of lingonberry extract and 30 mg of amla fruit extract; the second group received a drink containing double the volume of extracts received by the first group; and the third group received a placebo drink. Each participant drank 50 mL of their assigned drink once daily for 12 weeks. The primary endpoint was skin elasticity, and the secondary endpoints included skin thickness, stratum corneum water content, and degree of wrinkles around the eyes. After 12 weeks of LAE drink intake, skin elasticity showed significant, dose‐dependent improvements (P < 0.01). Skin thickness, stratum corneum water content, and the degree of wrinkles also significantly improved (P < 0.001) in a dose‐dependent manner. The improvements in skin elasticity and thickness, as well as in the stratum corneum water content and the degree of wrinkles, observed upon oral intake of LAE indicate that LAE may be considered a candidate anti‐aging agent for preventing skin weakening.
Cutaneous metastases of lung cancer
Authors: Fukuda Yosuke , Mikuni Hatsuko , Homma Tetsuya , Sagara Hironori
Published: July 2019

Cutaneous metastases of lung cancer are rare. It was often painless and less likely to be noticed. Similar to SVC syndrome, cutaneous metastases may cause upper limb edema. We need to keep in mind that cutaneous metastases may account for the radiotherapy‐resistant upper limb edema.
A zero‐current switching switched‐capacitor DC‐DC converter with reduction in cost, complexity, and size
Authors: Abbasi Maysam , Abbasi Ehsan , Tousi Behrouz , Gharehpetian Gevork B.
Published: July 2019

This paper presents a new step‐up switched‐capacitor (SC) DC‐DC converter which has many advantages such as reduction in investment cost, control complexity, number of components, voltage stress on components, and size over traditional topologies. In the proposed structure, power switches are reduced in number which in turn leads to the merits mentioned earlier and makes the converter more suitable for industrial applications. Furthermore, a previously introduced zero‐current switching (ZCS) method is used here which provides soft switching for the devices. There is also a reduction in the number of required inductors to achieve ZCS due to the decreased number of switches in the proposed converter. The proposed converter is validated by comprehensive simulation results in MATLAB Simulink environment and also precise experimental results which show the acceptable performance of the proposed topology.
Anticancer activity of newly synthesized 1,1‐disubstituted cyclohexane‐1‐carboxamides: in vitro caspases mediated apoptosis activators in human cancer cell lines and their molecular modeling
Authors: Abd‐Allah Walaa Hamada , Salman Asmaa , Sabry Saad Samah
Published: July 2019

Novel 1,1‐disubstituted cyclohexane‐1‐carboxamides 6a‐h, 7a‐e, and 8a‐b were designed and synthesized as apoptotic inducers. Cytotoxicity test revealed that some compounds have strong to moderate effect, while others displayed weak action against different cancer cell lines including, MCF‐7, HepG2, A549, and HTC‐116. A549 carcinoma cell line exhibited higher sensitivity toward all synthesized candidates especially compounds 6a and 8a which offered the lowest IC50 values 3.03 and 5.21 μM, respectively, relative to the positive control doxorubicin with IC50 value of 3.01 μM. Compared to doxorubicin treatment, compounds 6a and 8a induced caspases‐3, ‐8, and ‐9 activities and G2/M growth arrest in A549 carcinoma cell line. The expression levels of p53 (tumor suppressor protein that in humans is encoded by the TP53 gene), Bax (apoptosis regulator protein in humans that is encoded by bax gene), and the Bax/Bcl‐2 ratio were all higher than those in doxorubicin‐treated cells (Bcl‐2, B‐cell lymphoma 2, encoded in humans by the Bcl‐2 gene). Additionally, compounds 6a and 8a appeared to exhibit higher selectivity against MCF‐10 human breast normal cell line. The synthesized congeners could be considered as potent apoptotic inducers interfering with extrinsic and intrinsic apoptotic pathways. Moreover, compound 6a was able to form complex with zinc ions as indicated by UV spectrophotometry which revealed its ability for being caspase activator. Molecular docking studies expected the interactions and binding modes of the synthesized inhibitors in the caspase‐3 active site.
Plant‐driven changes in soil microbial communities influence seed germination through negative feedbacks
Authors: Miller Lee C. , Perron Gabriel G. , Collins Cathy D.
Published: July 2019

Plant–soil feedbacks (PSFs) drive plant community diversity via interactions between plants and soil microbes. However, we know little about how frequently PSFs affect plants at the seed stage, and the compositional shifts in fungi that accompany PSFs on germination.

We conducted a pairwise PSF experiment to test whether seed germination was differentially impacted by conspecific versus heterospecific soils for seven grassland species. We used metagenomics to characterize shifts in fungal community composition in soils conditioned by each plant species. To investigate whether changes in the abundance of certain fungal taxa were associated with multiple PSFs, we assigned taxonomy to soil fungi and identified putative pathogens that were significantly more abundant in soils conditioned by plant species that experienced negative or positive PSFs.

We observed negative, positive, and neutral PSFs on seed germination. Although conspecific and heterospecific soils for pairs with significant PSFs contained host‐specialized soil fungal communities, soils with specialized microbial communities did not always lead to PSFs. The identity of host‐specialized pathogens, that is, taxa uniquely present or significantly more abundant in soils conditioned by plant species experiencing negative PSFs, overlapped among plant species, while putative pathogens within a single host plant species differed depending on the identity of the heterospecific plant partner. Finally, the magnitude of feedback on germination was not related to the degree of fungal community differentiation between species pairs involved in negative PSFs.

Synthesis. Our findings reveal the potential importance of PSFs at the seed stage. Although plant species developed specialized fungal communities in rhizosphere soil, pathogens were not strictly host‐specific and varied not just between plant species, but according to the identity of plant partner. These results illustrate the complexity of microbe‐mediated interactions between plants at different life stages that next‐generation sequencing can begin to unravel.
Developments of SiC devices and SiC inverters aimed at electric power applications
Authors: Sugawara Yoshitaka
Published: July 2019

The developments of SiC power devices has been proceeded remarkably since 1990. SiC power devices have been payed attentions as one of the candidate power devices for next HVDC transmissions and its R&Ds have been started in the KANSAI electric power company since 1995. In this paper, a series of R&Ds for the SiC devices and SiC inverters performed in the company are presented from the historical viewpoints.
Rearrangement Reactions in Aza‐Vinylogous Povarov Products: Metal‐Free Synthesis of C3‐Functionalized Quinolines and Studies on their Synthetic Application
Authors: Clerigué José , Bianchini Giulia , Ribelles Pascual , Tejero Tomás , Merino Pedro , Ramos M. Teresa , Menéndez J. Carlos
Published: July 2019

Several types of C4‐functionalized 4‐alkyl‐2‐aryl‐1,2,3,4‐tetrahydroquinolines underwent rearrangement of their functional groups to C3, with concomitant aromatization, by simple reflux in 1,2‐dichlorobenzene. The functional groups that were shown to undergo the C4 to C3 migration were –CH=CH‐Z (where Z = CO2Et, CN, NO2, COCH3, CH2OH) and –CH=C(Y)–Z (where Y = CN and Z = CO2Et or Y = Z = CN). On the other hand, the dimethylhydrazono group failed to migrate under thermal conditions but was shown to undergo a smooth dehydrogenation/C4 to C3 rearrangement/ dehydrogenation sequence at room temperature in the presence of DDQ, with a broad scope that includes 4‐alkyl‐2‐aryl‐ and 2‐acyl‐1,2,3,4‐tetrahydroquinolines. We also report a computational and experimental study of the mechanism of both reactions, which supports an unusual intramolecular aza‐ene pathway. The ready availability by this method of 2,3‐difunctionalized quinolines allowed the simple preparation of fused heterocyclic systems derived from the pyrrolo[3,4‐b]quinoline framework, using both reductive and non‐reductive domino processes.
The more you have, the more you want? Higher social class predicts a greater desire for wealth and status
Authors: Wang Zhechen , Jetten Jolanda , Steffens Niklas K.
Published: July 2019

Traditional theories have focused on the intentions of lower‐class individuals to climb on the social ladder, yet they have paid relatively little attention to the motivations of upper‐class individuals to ascend even higher. Addressing this issue, Studies 1 and 2 provided cross‐national evidence that higher social class is associated with a greater desire for wealth and status. Moreover, by manipulating perceived social class, Studies 3 and 5 experimentally confirmed that compared to people in the lower‐class group, those in the upper‐class group express a stronger desire for wealth and status. Furthermore, in line with self‐categorization theory predictions, Studies 3–5 showed that upper‐class individuals tend to see and use wealth and status as important attributes in defining and categorizing self, and this tendency explains the effect of social class on desire for wealth and status. Together, our findings demonstrate a “having more—wanting more” relationship, and its consequences are further discussed.
Study on Preferential Solvation of Water by Electrochemical Method
Authors: Yan Chunxia , Huang Ximing , Chen Jingchao , Guo Haixia , Shao Huibo
Published: July 2019

The preferential solvation of water plays an important role in ferrocene research which is a subject of current interest. Voltammetric investigations were carried out for Au electrode in acetonitrile/water, showing preferential solvation of water. In our work, the preferential solvation of water in acetonitrile/water was studied by electrochemical methods including cyclic volitammetry, electrochemical impedance spectra and double‐step chronoamperometry. Ferrocenemethanol (FcCH2OH) molecules as a solute spontaneously adsorb on the electrode surface in anhydrous acetonitrile, resulting from acetonitrile molecules tend to form an acetonitrile solvent layer on the surface of the electrode and acetonitrile solvent layer has a lower energy barrier than the aqueous solvent layer, which has been obtained by modeling solvation. The solvent strongly influences electrochemical behavior of solute. Once there is an amount of water in acetonitrile solvent, FcCH2OH that adsorbed on the electrode surface desorb. This is because water preferentially solvate with FcCH2OH in term of intermolecular forces between solvent and solute. Moreover, hydrogen bond between water molecules and FcCH2OH molecules is stronger than dipole‐dipole interaction between acetonitrile molecules and FcCH2OH molecules in solvation effect. Through electrochemical behavior of FcCH2OH changing, preferential solvation of water is analyzed by electrochemical methods.
Voltammetric and Impedimetric Detection of Interaction Between Dacarbazine and Nucleic Acids
Authors: Eksin Ece , Polat Derya , Erdem Arzum
Published: July 2019

Dacarbazine (DTIC) is a chemotherapy drug that is used for the treatment of Hodgkin's lymphoma, malignant melanoma, childhood solid tumors and soft tissue sarcoma. The surface confined interaction between DTIC and nucleic acids was investigated for the first time in this study by using both differential pulse voltammetry (DPV) and electrochemical impedance spectroscopy (EIS) in combination with disposable pencil graphite electrodes. The oxidation signals of DTIC and guanine were measured before and after interaction process using DPV technique. The interaction of DTIC with nucleic acids; poly[A], poly[G], or double stranded of poly[A]‐poly[T] and poly[G]‐poly[C] was also examined using DPV. Furthermore, EIS technique was utilized for detection of the interaction between DTIC and nucleic acids; ssDNA/dsDNA, poly[A], poly[G], or double stranded poly[A]‐poly[T] and poly[G]‐poly[C].
Comparison of the General Threshold Model of Survival and Dose–Response Models in Simulating the Acute Toxicity of Metals to Danio rerio
Authors: He An , Liu Xinyong , Qu Liang , Gao Yongfei , Feng Jianfeng , Zhu Lin
Published: July 2019

We exposed zebrafish (Danio rerio) to different concentrations of lead and cadmium, and monitored them for survival at 24, 48, 72, and 96 h. Metal toxicity was predicted and compared using the dose–response and general threshold survival models in terms of required data sets, fit performance, and applicability. Environ Toxicol Chem 2019;38:2169–2177. © 2019 SETAC.
Occurrence of Toxigenic Microalgal Species and Phycotoxin Accumulation in Mesozooplankton in Northern Patagonian Gulfs, Argentina
Authors: D'Agostino Valeria C. , Krock Bernd , Degrati Mariana , Sastre Viviana , Santinelli Norma , Krohn Torben , Hoffmeyer Mónica S.
Published: July 2019

In the Northern Patagonian gulfs of Argentina (Golfo Nuevo and Golfo San José), blooms of toxigenic microalgae and the detection of their associated phycotoxins are recurrent phenomena. The present study evaluated the transfer of phycotoxins from toxigenic microalgae to mesozooplankton in Golfo Nuevo and Golfo San José throughout an annual cycle (December 2014–2015 and January 2015–2016, respectively). In addition, solid-phase adsorption toxin tracking (SPATT) samplers were deployed for the first time in these gulfs, to estimate the occurrence of phycotoxins in the seawater between the phytoplankton samplings. Domoic acid was present throughout the annual cycle in SPATT samplers, whereas no paralytic shellfish poisoning toxins were detected. Ten toxigenic species were identified: Alexandrium catenella, Dinophysis acuminata, Dinophysis acuta, Dinophysis tripos, Dinophysis caudata, Prorocentrum lima, Pseudo-nitzschia australis, Pseudo-nitzschia calliantha, Pseudo-nitzschia fraudulenta, and Pseudo-nitzschia pungens. Lipophilic and hydrophilic toxins were detected in phytoplankton and mesozooplankton from both gulfs. Pseudo-nitzschia spp. were the toxigenic species most frequent in these gulfs. Consequently, domoic acid was the phycotoxin most abundantly detected and transferred to upper trophic levels. Spirolides were detected in phytoplankton and mesozooplankton for the first time in the study area. Likewise, dinophysistoxins were found in mesozooplankton from both gulfs, and this is the first report of the presence of these phycotoxins in zooplankton from the Argentine Sea. The dominance of calanoid copepods indicates that they were the primary vector of phycotoxins in the pelagic trophic web. Environ Toxicol Chem 2019;38:2209–2223. © 2019 SETAC.
Redefining Cirrhotic Cardiomyopathy for the Modern Era
Authors: Izzy Manhal , VanWagner Lisa B. , Lin Grace , Altieri Mario , Findlay James Y. , Oh Jae K. , Watt Kymberly D. , Lee Samuel S. ,   on behalf of The Cirrhotic Cardiomyopathy Consortium
Published: July 2019

Cirrhotic cardiomyopathy (CCM) is cardiac dysfunction in patients with end‐stage liver disease in the absence of prior heart disease. First defined in 2005 during the World Congress of Gastroenterology, CCM criteria consisted of echocardiographic parameters to identify subclinical cardiac dysfunction in the absence of overt structural abnormalities. Significant advancements in cardiovascular imaging over the past 14 years, including the integration of myocardial deformation imaging into routine clinical practice to identify subclinical cardiovascular dysfunction, have rendered the 2005 CCM criteria obsolete. Therefore, new criteria based on contemporary cardiovascular imaging parameters are needed. In this guidance document, assembled by a group of multidisciplinary experts in the field, new core criteria based on contemporary cardiovascular imaging parameters are proposed for the assessment of CCM. This document provides a critical assessment of the diagnosis of CCM and ongoing assessment aimed at improving clinical outcomes, particularly surrounding liver transplantation. Key points and practice‐based recommendations for the diagnosis of CCM are provided to offer guidance for clinicians and identify gaps in knowledge for future investigations.
Mitochondrial General Control of Amino Acid Synthesis 5 Like 1 Regulates Glutaminolysis, Mammalian Target of Rapamycin Complex 1 Activity, and Murine Liver Regeneration
Authors: Wang Lingdi , Zhu Lu , Wu Kaiyuan , Chen Yong , Lee Duck‐Yeon , Gucek Marjan , Sack Michael N.
Published: July 2019

Background and Aims

The regenerative capacity of the liver plays a protective role against hepatotoxins and impaired regeneration exacerbates liver dysfunction in nonalcoholic fatty liver disease (NAFLD). Mitochondrial bioenergetic and ‐synthetic functions are important contributory factors in hepatic regeneration, and the control of mitochondrial protein acetylation is implicated in the mitochondrial susceptibility to liver stressors. Here, we evaluated the role of general control of amino acid synthesis 5 like 1 (GCN5L1), a mediator of mitochondrial metabolism and acetylation, in modulating murine liver regeneration (LR) in response to acute CCl4‐induced hepatotoxicity.

Approach and Results

Initial metabolomic screening found that liver GCN5L1 knockout (LKO) mice have augmented glutaminolysis. Absence of GCN5L1 modified enzyme activity of liver‐enriched glutaminase enzyme (glutaminase 2; GLS2), and GCN5L1 levels modulated GLS2 oligomerization and acetylation. This metabolic remodeling resulted in the elevation of α‐ketoglutarate levels, which are known to activate mammalian target of rapamycin complex 1 (mTORC1). This signaling pathway was induced with increased phosphorylation of S6 kinase in LKO hepatocytes, and inhibition of glutaminolysis reversed aberrant mTORC1 signaling. At the same time, glutaminolysis, activity of GLS2, and activation of mTORC1 signaling were reversed by the genetic reintroduction of the mitochondrial isoform of GCN5L1 into LKO primary hepatocytes. Finally, LKO mice had a more robust regenerative capacity in response to CCl4 hepatoxicity, and this response was blunted by both the mTORC1 inhibitor, rapamycin, and by pharmacological blunting of glutaminolysis.

Conclusions

These data point to a central role of glutaminolysis in modulating the regenerative capacity in the liver. Furthermore, inhibition of mitochondrial GCN5L1 to augment LR may be a useful strategy in disease states linked to hepatotoxicity.
National Experience on Down‐Staging of Hepatocellular Carcinoma Before Liver Transplant: Influence of Tumor Burden, Alpha‐Fetoprotein, and Wait Time
Authors: Mehta Neil , Dodge Jennifer L. , Grab Joshua D. , Yao Francis Y.
Published: July 2019

Background and Aims

United Network for Organ Sharing (UNOS) recently implemented a national policy granting priority listing for liver transplantation (LT) in patients who achieved down‐staging of hepatocellular carcinoma (HCC) to Milan criteria. We aimed to evaluate the national experience on down‐staging by comparing two down‐staging groups with (1) tumor burden meeting UNOS down‐staging (UNOS‐DS) inclusion criteria and (2) “all‐comers” (AC‐DS) with initial tumor burden beyond UNOS‐DS criteria versus patients always within Milan.

Approach and Results

This is a retrospective analysis of the UNOS database of 3,819 patients who underwent LT from 2012 to 2015, classified as always within Milan (n = 3,276), UNOS‐DS (n = 422), and AC‐DS (n = 121). Median time to LT was 12.8 months in long wait regions, 6.5 months in mid wait regions (MWR), and 2.6 months in short wait regions (SWR). On explant, vascular invasion was found in 23.7% of AC‐DS versus 16.9% of UNOS‐DS and 14.4% of Milan (P = 0.002). Kaplan‐Meier 3‐year post‐LT survival was 83.2% for Milan, 79.1% for UNOS‐DS (P = 0.17 vs. Milan), and 71.4% for AC‐DS (P = 0.04 vs. Milan). Within down‐staging groups, risk of post‐LT death in multivariable analysis was increased in SWR or MWR (hazard ratio [HR], 3.1; P = 0.005) and with alpha‐fetoprotein (AFP) ≥ 100 ng/mL at LT (HR, 2.4; P = 0.009). The 3‐year HCC recurrence probability was 6.9% for Milan, 12.8% for UNOS‐DS, and 16.7% for AC‐DS (P < 0.001). In down‐staging groups, AFP ≥ 100 (HR, 2.6; P = 0.02) was the only independent predictor of HCC recurrence.

Conclusions

Our results validated UNOS‐DS criteria based on comparable 3‐year survival between UNOS‐DS and Milan groups. Additional refinements based on AFP and wait time may further improve post‐LT outcomes in down‐staging groups, especially given that reported 3‐year recurrence was higher than in those always within Milan criteria.
Modulation of the Tryptophan Hydroxylase 1/Monoamine Oxidase‐A/5‐Hydroxytryptamine/5‐Hydroxytryptamine Receptor 2A/2B/2C Axis Regulates Biliary Proliferation and Liver Fibrosis During Cholestasis
Authors: Kyritsi Konstantina , Chen Lixian , O’Brien April , Francis Heather , Hein Travis W. , Venter Julie , Wu Nan , Ceci Ludovica , Zhou Tianhao , Zawieja David , Gashev Anatoliy A. , Meng Fanyin , Invernizzi Pietro , Fabris Luca , Wu Chaodong , Skill Nicholas J. , Saxena Romil , Liangpunsakul Suthat , Alpini Gianfranco , Glaser Shannon S.
Published: July 2019

Background and Aims

Serotonin (5HT) is a neuroendocrine hormone synthetized in the central nervous system (CNS) as well as enterochromaffin cells of the gastrointestinal tract. Tryptophan hydroxylase (TPH1) and monoamine oxidase (MAO‐A) are the key enzymes for the synthesis and catabolism of 5HT, respectively. Previous studies demonstrated that 5‐hydroxytryptamine receptor (5HTR)1A/1B receptor agonists inhibit biliary hyperplasia in bile‐duct ligated (BDL) rats, whereas 5HTR2B receptor antagonists attenuate liver fibrosis (LF) in mice. Our aim was to evaluate the role of 5HTR2A/2B/2C agonists/antagonists in cholestatic models.

Approach and Results

While in vivo studies were performed in BDL rats and the multidrug resistance gene 2 knockout (Mdr2–/–
) mouse model of PSC, in vitro studies were performed in cell lines of cholangiocytes and hepatic stellate cells (HSCs). 5HTR2A/2B/2C and MAO‐A/TPH1 are expressed in cholangiocytes and HSCs from BDL rats and Mdr2–/–

‐ mice. Ductular reaction, LF, as well as the mRNA expression of proinflammatory genes increased in normal, BDL rats, and Mdr2–/–

‐ mice following treatment 5HTR2A/2B/2C agonists, but decreased when BDL rats and Mdr2–/–
mice were treated with 5HTR2A/2B/2C antagonists compared to BDL rats and Mdr2–/–
mice, respectively. 5HT levels increase in Mdr2–/–
mice and in PSC human patients compared to their controls and decrease in serum of Mdr2–/–
mice treated with 5HTR2A/2B/2C antagonists compared to untreated Mdr2–/–
mice. In vitro, cell lines of murine cholangiocytes and human HSCs express 5HTR2A/2B/2C and MAO‐A/TPH1; treatment of these cell lines with 5HTR2A/2B/2C antagonists or TPH1 inhibitor decreased 5HT levels as well as expression of fibrosis and inflammation genes compared to controls.

Conclusions

Modulation of the TPH1/MAO‐A/5HT/5HTR2A/2B/2C axis may represent a therapeutic approach for management of cholangiopathies, including PSC.
Transcriptional profiling of breast cancer‐associated lymphatic vessels reveals VCAM‐1 as regulator of lymphatic invasion and permeability
Authors: Dieterich Lothar C. , Kapaklikaya Kübra , Cetintas Timur , Proulx Steven T. , Commerford Catharina D. , Ikenberg Kristian , Bachmann Samia B. , Scholl Jeannette , Detmar Michael
Published: July 2019

Tumor‐associated lymphangiogenesis and lymphatic invasion of tumor cells correlate with poor outcome in many tumor types, including breast cancer. Various explanations for this correlation have been suggested in the past, including the promotion of lymphatic metastasis and an immune‐inhibitory function of lymphatic endothelial cells (LECs). However, the molecular features of tumor‐associated lymphatic vessels and their implications for tumor progression have been poorly characterized. Here, we report the first transcriptional analysis of tumor‐associated LECs directly isolated from the primary tumor in an orthotopic mouse model of triple negative breast cancer (4T1). Gene expression analysis showed a strong upregulation of inflammation‐associated genes, including endothelial adhesion molecules such as VCAM‐1, in comparison to LECs derived from control tissue. In vitro experiments demonstrated that VCAM‐1 is not involved in the adhesion of tumor cells to LECs but unexpectedly promoted lymphatic permeability by weakening of lymphatic junctions, most likely through a mechanism triggered by interactions with integrin α4 which was also induced in tumor‐associated LECs. In line with this, in vivo blockade of VCAM‐1 reduced lymphatic invasion of 4T1 cells. Taken together, our findings suggest that disruption of lymphatic junctions and increased permeability via tumor‐induced lymphatic VCAM‐1 expression may represent a new target to block lymphatic invasion and metastasis.
Cachexia and Sarcopenia in Companion Animals: An Under‐Utilized Natural Animal Model of Human Disease
Authors: Freeman Lisa M.
Published: July 2019

While laboratory small animal models of cachexia and sarcopenia are well‐suited and critical for studying mechanisms and early pre‐clinical phases for potential treatments, they are not similar enough to the human conditions to always be good predictors for results in human clinical trials. As a result, translational failures can occur when large‐scale human clinical trials are conducted on drugs, even when they appear promising in pre‐clinical studies in rodent models. What is needed is a way to more efficiently and successfully translate information gained from basic science and rodent research into human clinical trials that produce effective approved drugs. Naturally‐occurring cachexia and sarcopenia in companion animals is a more representative model of human disease that can serve as a stepping stone between basic science and human clinical trials. Many of the common diseases of humans also affect companion animals, particularly pet dogs and cats. Pet dogs and cats commonly develop heart failure, cancer, and kidney disease, as well as acute trauma or illness. The population of elderly companion animals also is increasing as pets' lifespans have become longer. As a result, both cachexia and sarcopenia are very common in companion animals. Studying these conditions in dogs and cats – either in colonies or in animal clinical trials ‐ can help to identify successful treatments that can benefit both humans and companion animals.
MYCN gene polymorphisms and Wilms tumor susceptibility in Chinese children
Authors: Huang Xiaokai , Zhao Jie , Zhu Jinhong , Chen Shanshan , Fu Wen , Tian Xiaoqian , Lou Susu , Ruan Jichen , He Jing , Zhou Haixia
Published: July 2019

Background

Wilms tumor, derived from embryonic cells, accounts for a large proportion of pediatric renal tumors. MYCN encoded by MYCN proto‐oncogene, a member of the MYC family, is a BHLH transcription factor. It plays a critical role in tumorigenesis and predicts poor clinical outcomes in various types of cancer. However, the role of MYCN remained unclarified in Wilms tumor. In this study, we investigated the association between MYCN gene polymorphisms and Wilms tumor susceptibility.

Methods

Four MYCN gene polymorphisms (rs57961569 G > A, rs9653226 T > C, rs13034994 A > G, and rs60226897 G > A) were genotyped in 183 cases and 603 controls. Adjusted odds ratios (AORs) and 95% confidence intervals (CIs) were calculated to evaluate the association between MYCN gene polymorphisms and Wilms tumor susceptibility.

Results

Overall, no significant association was found for any of the four MYCN gene polymorphisms. Interestingly, in the stratification analysis, the rs57961569 was found to be associated with decreased Wilms tumor susceptibility in the children older than 18 months (AOR = 0.65, 95% CI = 0.42‐1.00, P = .050). Moreover, older children carrying 2‐4 risk genotypes were at increased risk of Wilms tumor (OR = 1.55, 95% CI = 1.001‐2.40, P = .0497). Haplotype GCAA was shown to significantly increased Wilms tumor risk (AOR = 2.40, 95% CI = 1.12‐5.14, P = .024).

Conclusion

Our study demonstrated that these MYCN gene polymorphisms might be low penetrant variants in Wilms tumor.
FASt single‐breathhold 2D multislice myocardial T1 mapping (FAST1) at 1.5T for full left ventricular coverage in three breathholds
Authors: Huang Li , Neji Radhouene , Nazir Muhummad Sohaib , Whitaker John , Duong Phuoc , Reid Fiona , Bosio Filippo , Chiribiri Amedeo , Razavi Reza , Roujol Sébastien
Published: July 2019

Background

Conventional myocardial T1 mapping techniques such as modified Look–Locker inversion recovery (MOLLI) generate one T1 map per breathhold. T1 mapping with full left ventricular coverage may be desirable when spatial T1 variations are expected. This would require multiple breathholds, increasing patient discomfort and prolonging scan time.

Purpose

To develop and characterize a novel FASt single‐breathhold 2D multislice myocardial T1 mapping (FAST1) technique for full left ventricular coverage.

Study Type

Prospective.

Population/Phantom

Numerical simulation, agarose/NiCl2 phantom, 9 healthy volunteers, and 17 patients.

Field Strength/Sequence

1.5T/FAST1.

Assessment

Two FAST1 approaches, FAST1‐BS and FAST1‐IR, were characterized and compared with standard 5‐(3)‐3 MOLLI in terms of accuracy, precision/spatial variability, and repeatability.

Statistical Tests

Kruskal‐Wallis, Wilcoxon signed rank tests, intraclass correlation coefficient analysis, analysis of variance, Student's t‐tests, Pearson correlation analysis, and Bland–Altman analysis.

Results

In simulation/phantom, FAST1‐BS, FAST1‐IR, and MOLLI had an accuracy (expressed as T1 error) of 0.2%/4%, 6%/9%, and 4%/7%, respectively, while FAST1‐BS and FAST1‐IR had a precision penalty of 1.7/1.5 and 1.5/1.4 in comparison with MOLLI, respectively. In healthy volunteers, FAST1‐BS/FAST1‐IR/MOLLI led to different native myocardial T1 times (1016 ± 27 msec/952 ±22 msec/987 ± 23 msec, P < 0.0001) and spatial variability (66 ± 10 msec/57 ± 8 msec/46 ± 7 msec, P < 0.001). There were no statistically significant differences between all techniques for T1 repeatability (P = 0.18). In vivo native and postcontrast myocardial T1 times in both healthy volunteers and patients using FAST1‐BS/FAST1‐IR were highly correlated with MOLLI (Pearson correlation coefficient ≥0.93).

Data Conclusion

FAST1 enables myocardial T1 mapping with full left ventricular coverage in three separated breathholds. In comparison with MOLLI, FAST1 yield a 5‐fold increase of spatial coverage, limited penalty of T1 precision/spatial variability, no significant difference of T1 repeatability, and highly correlated T1 times. FAST1‐IR provides improved T1 precision/spatial variability but reduced accuracy when compared with FAST1‐BS.

Level of Evidence: 1

Technical Efficacy: Stage 3

J. Magn. Reson. Imaging 2020;51:492–504.
Bioclimatic conditions of the Portuguese wine denominations of origin under changing climates
Authors: Santos Mónica , Fonseca André , Fraga Helder , Jones Gregory V. , Santos João A.
Published: July 2019

Wine production and quality are highly sensitive to local weather variability and climatic conditions. To assess these characteristics, this research examines high‐resolution bioclimatic zoning over 50 protected denominations of origin (DOs)/sub‐regions in mainland Portugal through the analysis of two selected bioclimatic indices (dryness and Huglin indices). The analysis is based on a new very high‐resolution dataset over mainland Portugal and for a baseline period (1981–2015). Climate change projections are also assessed for two scenarios (RCP4.5 and RCP8.5) and using a 5‐member climate model ensemble over the future periods of 2041–2070 and 2071–2100. A principal component analysis was applied to the time mean spatial patterns of the two selected bioclimatic indices, for the baseline period (1981–2015) and only over the planted vineyard cover areas in each region, isolating a new optimized combined index which was used for subsequent analysis. The results for the present conditions highlight the spatial variability of Portuguese DO/sub‐regions. This study also shows that for the future periods, and regardless of the scenario, the wine sector in Portugal will likely see important bioclimatic changes across most DOs. Increases in the growing‐season mean temperatures in all the Portuguese winemaking DO/sub‐regions, accompanied by increasing severe dryness, are projected in future climates, mainly in south‐eastern Portugal and along the upper Douro Valley (Douro Superior) in north‐eastern Portugal. These DO/sub‐regions are projected to become much drier than currently so that irrigation or the introduction of new varieties are likely adaptation measures to maintain the viability and sustainability of regional viticulture in future decades.
Pretreatment Posttraumatic Stress Disorder Symptom Network Metrics Predict the Strength of the Association Between Node Change and Network Change During Treatment
Authors: Papini Santiago , Rubin Mikael , Telch Michael J. , Smits Jasper A. J. , Hien Denise A.
Published: July 2019

Network analysis has been increasingly applied in an effort to understand complex interactions among symptoms in posttraumatic stress disorder (PTSD). Although methods that initially focused on identifying central symptoms in cross‐sectional networks have been extended to longitudinal data that can reveal the relative roles of acute symptoms in the emergence of the PTSD syndrome, the association between network metrics and symptom change during treatment have yet to be explored in PTSD. To address this gap, we estimated pretreatment PTSD symptom networks in a sample of patients from a multisite clinical trial for women with full or subthreshold PTSD and substance use. We tested the hypothesis that node metrics calculated in the pretreatment network would be predictive of the strength of the association between a symptom's change and the change in the severity of all other symptoms through the course of treatment. A symptom node's strength and predictability in the pretreatment network were each strongly correlated with the association between that symptom's change and overall change across the symptom network, r(15) = .79, p < .001 and r(15) = .75, p < .001, respectively, whereas a symptom's mean severity at pretreatment was not, r(15) = .27, p = .292. These findings suggest that a node's centrality prior to treatment engagement is a predictor of its association with overall symptom change throughout the treatment process.
Local stable manifolds for nonlinear planar fractional differential equations with order 1<α<2
Authors: Liao Binghui , Zeng Caibin
Published: July 2019

This paper reports the local stable manifolds near hyperbolic equilibria for nonlinear planar fractional differential equations of order 1<α<2. By using several useful estimates of Mittag‐Leffler function and fractional calculus technique, we construct two suitable Lyapunov‐Perron operators and set up their fixed points as the desired stable manifolds. We further present a specific example to compute explicitly the corresponding stable manifold as the application.
Assessment of the systematic errors caused by diffusion gradient inhomogeneity in DTI‐computer simulations
Authors: Borkowski Karol , Krzyżak Artur T.
Published: July 2019

Diffusion tensor imaging (DTI) is a powerful MRI modality that allows the investigation of the microstructure of tissues both in vivo and noninvasively. Its reliability is strictly dependent on the performance of diffusion‐sensitizing gradients, of which spatial nonuniformity is a known issue in the case of virtually all clinical MRI scanners.

The influence of diffusion gradient inhomogeneity on the accuracy of the diffusion tensor imaging was investigated by means of computer simulations supported by an MRI experiment performed at the isocenter and 15 cm away. The DTI measurements of two diffusion phantoms were simulated assuming a nonuniform diffusion‐sensitizing gradient and various levels of noise. Thereafter, the tensors were calculated by two methods: (i) assuming a spatially constant b‐matrix (standard DTI) and (ii) applying the b‐matrix spatial distribution in the DTI (BSD‐DTI) technique, a method of indicating the b‐matrix for each voxel separately using an anisotropic phantom as a standard of diffusion. The average eigenvalues and fractional anisotropy across the homogeneous region of interest were calculated and compared with the expected values.

Diffusion gradient inhomogeneity leads to overestimation of the largest eigenvalue, underestimation of the smallest one and thus overestimation of fractional anisotropy. The effect is similar to that caused by noise; however, it could not be corrected by increasing SNR.

The MRI measurements, performed using a 3 T clinical scanner, revealed that the split of the eigenvalues measured 15 cm away from the isocenter is significant (up to 25%). The BSD‐DTI calibration allowed the reduction of the measured fractional anisotropy of the isotropic medium from 0.174 to 0.031, suggesting that gradient inhomogeneity was the main cause of this error. For the phantom measured at the isocenter, however, the split was almost not observed; the average eigenvalues were shifted from the expected value by ~ 5%.
Micronutrient Deficiencies in Children With Inflammatory Bowel Diseases
Authors: Ehrlich Shay , Mark Anat Guz , Rinawi Firas , Shamir Raanan , Assa Amit
Published: July 2019

Background

Children with inflammatory bowel diseases (IBDs) are at risk of developing nutrition deficiencies, particularly because of reduced intake, restrictive diets, malabsorption, and excessive nutrient loss. In this study, we aimed to assess the status of trace elements, minerals, and vitamins in a large cohort of children with IBDs.

Methods

Medical records of children diagnosed with IBDs during 2000–2016 were reviewed retrospectively. Retrieved data included demographics, disease characteristics, disease activity indices, anthropometric measures, and specific trace elements, minerals, and vitamins at diagnosis and during follow‐up.

Results

Out of 359 children with IBD (158 [44%] females, median age at diagnosis 14.1 years, interquartile range [IQR] 12.0–16.0), 240 (67%) were diagnosed with Crohn's disease (CD) and 119 (33%) with ulcerative colitis (UC). Median follow‐up time was 7 years (IQR 5–10). The prevalence of deficiencies in patients with CD at diagnosis and last follow‐up, respectively, were iron (88% and 39.5%), zinc (53% and 11.5%), vitamin D (39% and 36%), and folic acid (10% and 13%). In patients with UC, frequencies were: iron (77% and 40%), vitamin D (49% and 33%), zinc (31% and 10%), and folic acid (3.8% and 9.7%). Magnesium and vitamin B12 deficiencies were rare. For both diseases, iron deficiency was associated with hypoalbuminemia. Deficiencies in iron and zinc were more common in patients with CD than those with UC.

Conclusions

Deficiencies in iron, zinc, and vitamin D are common at pediatric IBD diagnosis with limited improvement during follow‐up, whereas deficiencies in magnesium and vitamin B12 are rare.
Associations of dry skin, skin care habits, well‐being, sleep quality and itch in nursing home residents: Results of a multicentre, observational, cross‐sectional study
Authors: Hahnel Elisabeth , Blume‐Peytavi Ulrike , Kottner Jan
Published: July 2019

Aim

Dry skin is one of the most frequent cutaneous problems in aged long‐term care residents. Although it is clinically relevant, the impact on quality of life is unclear. The objective was to measure well‐being, sleep quality and itch in nursing home residents being 65 years and older and to explore possible associations with demographics, dry skin and skincare habits.

Design

Multicentre, observational, cross‐sectional.

Methods

Sleep quality was assessed with the Richards‐Campbell Sleep Quality Questionnaire, well‐being with the WHO‐Five Well‐being Index and itch with the 5‐D Itch scale. Skin dryness was measured using the Overall Dry Skin score.

Results

A total of 51 residents were included. The item scores of the sleep quality and itch questionnaires were strongly associated with each other. Demographics, dry skin and skincare habits were not associated with the questionnaires. It is unclear whether basic skincare activities can improve the quality of life in this population.
Scale dependency in drivers of outdoor recreation in England
Authors: Graham Laura J. , Eigenbrod Felix
Published: July 2019

Managing landscapes for multiple, sometimes conflicting, objectives requires an understanding of the trade‐offs and synergies between ecosystem services (ES). These trade‐offs and synergies are often the result of drivers acting at different scales. Therefore, in order to understand trade‐offs and synergies it is important that we understand the scale dependency in drivers of ES.

Here, we examine scale dependencies in the drivers of outdoor recreation in England to better understand trade‐offs between different aspects of this ES. We focus on outdoor recreation because it is culturally and economically important; it is the result of a range of social and biophysical attributes which vary at different scales; and proxies that are independent of these drivers exist.

First, we tested the hypothesis that a social media‐based proxy (photographs from Flickr) represents ‘destination’ recreation (e.g. day trips and overnight visits). We did so by comparing to a survey‐based proxy, which is known to represent ‘day‐to‐day’ recreation (e.g. dog walking, visiting local parks). Second, we examined the scale dependencies in the social and biophysical drivers of both types of outdoor recreation.

Flickr data were best explained by variables capturing supply of recreation; whereas, the survey data were best explained by variables capturing demand for recreation. This confirms our hypothesis that Flickr data measure ‘destination’ recreation given that the survey data measure ‘day‐to‐day’ recreation. In both cases, the importance of demand variables increased with increasing spatial resolution.

Understanding what a proxy measures provides us with information about how to use it. We conclude that Flickr data may be useful to plan at broad scales, but that to plan for equitable day‐to‐day recreation, specially designed survey data may be more appropriate. Estimating the scale dependencies in drivers of outdoor recreation gets us a step closer to a mechanistic understanding of the social‐ecological system.

A free Plain Language Summary can be found within the Supporting Information of this article.
Current transport efficiency analysis of multijunction solar cells by luminescence imaging
Authors: Xu Hao , Delamarre Amaury , Yu Jeco Bernice Mae F. , Johnson Hugh , Watanabe Kentaroh , Okada Yoshitaka , Guillemoles Jean‐François , Nakano Yoshiaki , Sugiyama Masakazu
Published: July 2019

Multijunction solar cells are currently leading in efficiency among all types of solar cells. However, the efficiency of those cells under concentrated illumination is limited by the trade‐off between shadowing by the contact grid and series resistances. In this paper, we provide a method using luminescence to image the current transport efficiency for a precise and rapid measurement of the resistance effect. Light beam induced current (LBIC) measurement is used for the first time to calculate current transport efficiency in comparison with that of the luminescence method. Profiles of transport efficiency in both means are in good agreement. Furthermore, a quasi‐3‐D simulation using SPICE is used to explain the transport efficiency image. We find that the carrier transport efficiency distribution is primarily influenced by the perimeter recombination of the middle cell.
Effect of estimation under nonnormality on the phase II performance of linear profile monitoring approaches
Authors: Aytaçoğlu Burcu , Türker Bayrak Özlem
Published: July 2019

The number of studies about control charts proposed to monitor profiles, where the quality of a process/product is expressed as function of response and explanatory variable(s), has been increasing in recent years. However, most authors assume that the in‐control parameter values are known in phase II analysis and the error terms are normally distributed. These assumptions are rarely satisfied in practice. In this study, the performance of EWMA‐R, EWMA‐3, and EWMA‐3(d2) methods for monitoring simple linear profiles is examined via simulation where the in‐control parameters are estimated and innovations have a Student's t distribution or gamma distribution. Instead of the average run length (ARL) and the standard deviation of run length, we used average and standard deviation of the ARL as performance measures in order to capture the sampling variation among different practitioners. It is seen that the estimation effect becomes more severe when the number of phase I profiles used in estimation decreases, as expected, and as the distribution deviates from normality to a greater extent. Besides, although the average ARL values get closer to the desired values as the amount of phase I data increases, their standard deviations remain far away from the acceptable level indicating a high practitioner‐to‐practitioner variability.
A Pt(II)‐based Hexagonal Ionic Supramolecular Coordination Complex and its DNA Interactions.
Authors: Singh Khushwant , Kumari Sonam , Jana Achintya , Das Prolay , Das Neeladri
Published: July 2019

A pyrimidine based organic donor clip with pendant pyridyl rings has been designed for its use in construction of a supramolecular coordination complex (SCC). This molecule is a new addition to the library of “nitrogen donor ligands” that have been used as building blocks to yield SCCs of various shapes and sizes. Its self‐assembly with a suitable complementary metal based acceptor tecton yielded a unique [1 + 1] hexagonal macrocycle that was characterized using a suite of analytical tools. The platina metallacycle has a hexagonal cavity and is nano‐dimensional in size. The self‐assembled ensembles were found to interact significantly with DNA and they also demonstrate positive nuclease activity with DNA relative to its donor/acceptor building blocks.