bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of structural carbohydrates and lignin content on the anaerobic digestion of paper and paper board materials by anaerobic granular sludge
Authors: Gonzalez‐Estrella Jorge , Asato Caitlin M. , Jerke Amber C. , Stone James J. , Gilcrease Patrick C.
Published: November 2016

Anaerobic digestion (AD) of lignocellulosic materials is commonly limited by the hydrolysis step. Unlike unprocessed lignocellulosic materials, paper and paper board (PPB) are processed for their fabrication. Such modifications may affect their methane yields and methane production rates. Previous studies have investigated the correlation between lignin and biomethane yields of unprocessed lignocellulosic materials; nevertheless, there is limited knowledge regarding the relationship between the AD kinetic parameters and composition of PPB. This study evaluated correlations of methane yields and Monod and Gompertz kinetic parameters with structural carbohydrates, lignin, and ash concentration of five types of PPBs. All components were used as single and combined independent variables in linear regressions to predict methane yield, maximum specific methanogenic activity (SMAmax), saturation constant (Ks), and lag phase (λ). Additionally, microbial community profiles were obtained for each PPB assay. Results showed methane yields ranging from 69.2 ± 8.61 to 97.2 ± 2.29% of PPB substrates provided. The highest correlation coefficients were obtained for SMAmax as function of hemicellulose/(lignin + ash) (R2 = 0.86) and for λ as a function of lignin + cellulose (R2 = 0.85). All other parameters exhibited weaker correlations (R2 ≤ 0.77). Relative abundance analyses revealed no major changes in the community profile for each of the substrates evaluated. The overall findings of this study are: (i) combinations of structural carbohydrates, lignin, and ash used as ratios of degradable to either non‐degradable or slowly degradable fractions predict AD kinetic parameters of PPB materials better than single independent variables; and (ii) other components added during their fabrication may also influence both methane yield and kinetic parameters. Biotechnol. Bioeng. 2017;114: 951–960. © 2016 Wiley Periodicals, Inc.
Toward high solids loading process for lignocellulosic biofuel production at a low cost
Authors: Jin Mingjie , Sarks Cory , Bals Bryan D. , Posawatz Nick , Gunawan Christa , Dale Bruce E. , Balan Venkatesh
Published: November 2016

High solids loadings (>18 wt%) in enzymatic hydrolysis and fermentation are desired for lignocellulosic biofuel production at a high titer and low cost. However, sugar conversion and ethanol yield decrease with increasing solids loading. The factor(s) limiting sugar conversion at high solids loading is not clearly understood. In the present study, we investigated the effect of solids loading on simultaneous saccharification and co‐fermentation (SSCF) of AFEX™ (ammonia fiber expansion) pretreated corn stover for ethanol production using a xylose fermenting strain Saccharomyces cerevisiae 424A(LNH‐ST). Decreased sugar conversion and ethanol yield with increasing solids loading were also observed. End‐product (ethanol) was proven to be the major cause of this issue and increased degradation products with increasing solids loading was also a cause. For the first time, we show that with in situ removal of end‐product by performing SSCF aerobically, sugar conversion stopped decreasing with increasing solids loading and monomeric sugar conversion reached as high as 93% at a high solids loading of 24.9 wt%. Techno‐economic analysis was employed to explore the economic possibilities of cellulosic ethanol production at high solids loadings. The results suggest that low‐cost in situ removal of ethanol during SSCF would significantly improve the economics of high solids loading processes. Biotechnol. Bioeng. 2017;114: 980–989. © 2016 Wiley Periodicals, Inc.
MRI depiction and 3D visualization of three anterior cruciate ligament bundles
Authors: Otsubo H. , Akatsuka Y. , Takashima H. , Suzuki T. , Suzuki D. , Kamiya T. , Ikeda Y. , Matsumura T. , Yamashita T. , Shino K.
Published: November 2016

The anterior cruciate ligament (ACL) is divided into three fiber bundles (AM‐M: anteromedial‐medial, AM‐L: anteromedial‐lateral, PL: posterolateral). We attempted to depict the three bundles of the human ACL on MRI images and to obtain 3‐dimensional visualization of them. Twenty‐four knees of healthy volunteers (14 males, 10 females) were scanned by 3T‐MRI using the fat suppression 3D coherent oscillatory state acquisition for the manipulation of imaging contrast (FS 3D‐COSMIC). The scanned images were reconstructed after the isotropic voxel data, which allows the images to be reconstructed in any plane, was acquired. We conducted statistical examination on the identification rate of the three ACL bundles by 2D planes. Segmentation and 3D visualization of the fiber bundles using volume rendering were performed. The triple‐bundle ACL was best depicted in the oblique axial plane. While the AM‐M and AM‐L bundles were clearly depicted in all cases, the PL bundle was not clearly visualized in two knees (8%). Therefore, the three ACL bundles were depicted in 22 knees (92%). The results of 3D visualization of the fiber arrangement agreed well with macroscopic findings of previous anatomical studies. 3T‐MRI and the isotropic voxel data from FS 3D‐COSMIC made it possible to demonstrate the identifiable depiction of three ACL bundles in nearly all cases. 3D visualization of the bundles could be a useful tool to understand the ACL fiber arrangement. Clin. Anat. 30:276–283, 2017. 2016 The Authors. Clinical Anatomy published by Wiley Periodicals, Inc. on behalf of American Association of Clinical Anatomists.
Muscle RAS oncogene homolog (MRAS) recurrent mutation in Borrmann type IV gastric cancer
Authors: Yasumoto Makiko , Sakamoto Etsuko , Ogasawara Sachiko , Isobe Taro , Kizaki Junya , Sumi Akiko , Kusano Hironori , Akiba Jun , Torimura Takuji , Akagi Yoshito , Itadani Hiraku , Kobayashi Tsutomu , Hasako Shinichi , Kumazaki Masafumi , Mizuarai Shinji , Oie Shinji , Yano Hirohisa
Published: November 2016

The prognosis of patients with Borrmann type IV gastric cancer (Type IV) is extremely poor. Thus, there is an urgent need to elucidate the molecular mechanisms underlying the oncogenesis of Type IV and to identify new therapeutic targets. Although previous studies using whole‐exome and whole‐genome sequencing have elucidated genomic alterations in gastric cancer, none has focused on comprehensive genetic analysis of Type IV. To discover cancer‐relevant genes in Type IV, we performed whole‐exome sequencing and genome‐wide copy number analysis on 13 patients with Type IV. Exome sequencing identified 178 somatic mutations in protein‐coding sequences or at splice sites. Among the mutations, we found a mutation in muscle RAS oncogene homolog (MRAS), which is predicted to cause molecular dysfunction. MRAS belongs to the Ras subgroup of small G proteins, which includes the prototypic RAS oncogenes. We analyzed an additional 46 Type IV samples to investigate the frequency of MRAS mutation. There were eight nonsynonymous mutations (mutation frequency, 17%), showing that MRAS is recurrently mutated in Type IV. Copy number analysis identified six focal amplifications and one homozygous deletion, including insulin‐like growth factor 1 receptor (IGF1R) amplification. The samples with IGF1R amplification had remarkably higher IGF1R mRNA and protein expression levels compared with the other samples. This is the first report of MRAS recurrent mutation in human tumor samples. Our results suggest that MRAS mutation and IGF1R amplification could drive tumorigenesis of Type IV and could be new therapeutic targets.
Marijuana use and inpatient outcomes among hospitalized patients: analysis of the nationwide inpatient sample database
Authors: Vin‐Raviv Neomi , Akinyemiju Tomi , Meng Qingrui , Sakhuja Swati , Hayward Reid
Published: November 2016

The purpose of this paper is to examine the relationship between marijuana use and health outcomes among hospitalized patients, including those hospitalized with a diagnosis of cancer. A total of 387,608 current marijuana users were identified based on ICD‐9 codes for marijuana use among hospitalized patients in the Nationwide Inpatient Sample database between 2007 and 2011. Logistic regression analysis was performed to determine the association between marijuana use and heart failure, cardiac disease, stroke, and in‐hospital mortality. All models were adjusted for age, gender, race, residential income, insurance, residential region, pain, and number of comorbidities. Among hospitalized patients, marijuana use was associated with a 60% increased odds of stroke (OR: 1.60, 95% CI: 1.44–1.77) compared with non‐users, but significantly reduced odds of heart failure (OR: 0.78, 95% CI: 0.75–0.82), cardiac disease (OR: 0.86, 95% CI: 0.82–0.91), or in‐hospital mortality (OR: 0.41, 95% CI: 0.38–0.44). Among cancer patients, odds of in‐hospital mortality was significantly reduced among marijuana users compared with non‐users (OR: 0.44, 95% CI: 0.35–0.55). Hospitalized marijuana users were more likely to experience a stroke compared with non‐users, but less likely to experience in‐hospital mortality. Prospective studies will be needed to better characterize the health effects of marijuana use, especially among older, sicker, and/or hospitalized patients. In the meantime, conversations regarding marijuana use/misuse may be warranted in the clinical setting in order for patients and healthcare providers to adequately weigh the anticipated benefits of marijuana use with potentially significant health risks.
GPX3 methylation in bone marrow predicts adverse prognosis and leukemia transformation in myelodysplastic syndrome
Authors: Zhou Jing‐Dong , Lin Jiang , Zhang Ting‐Juan , Ma Ji‐Chun , Yang Lei , Wen Xiang‐Mei , Guo Hong , Yang Jing , Deng Zhao‐Qun , Qian Jun
Published: November 2016

Epigenetic inactivation of GPX3 has been identified in various cancers including leukemia. Moreover, aberrant DNA methylation was also found as a dominant mechanism of disease progression in myelodysplastic syndrome (MDS). This study intended to explore GPX3 promoter methylation and its clinical relevance in 110 patients with MDS. GPX3 methylation was examined by real‐time quantitative methylation‐specific PCR (RQ‐MSP) and bisulfite sequencing PCR (BSP). GPX3 methylation was identified in 15% (17/110) MDS patients, and significantly higher than controls, and lower than acute myeloid leukemia (AML) patients (P = 0.024 and 0.041). GPX3 methylated patients had older age and higher frequency of DNMT3A mutation (P = 0.015 and 0.066). Cases with GPX3 methylation showed significantly shorter overall survival (OS) time than those with GPX3 unmethylation analyzed with Kaplan–Meier analysis (P = 0.012). Moreover, Cox regression analysis revealed that GPX3 methylation might act as an independent prognostic indicator in MDS (HR = 1.847, P = 0.072). GPX3 methylation density was significantly increased during the progression from MDS to secondary acute myeloid leukemia (sAML) in three follow‐up paired patients. Our study concludes that GPX3 methylation in bone marrow is associated with adverse prognosis and leukemia transformation in MDS.
Moving and being moved through time: Autoethnographic Reflections on first‐person research and its development over 30 years
Authors: Cotter Angela
Published: November 2016

Background

The research and practice divide is the subject of much debate in clinical disciplines. The movement towards autoethnography and first person research can illustrate the ways that the connection may be lived out in individual experience, contribute to bridging the divide and address deeper levels of experience that have not often been addressed in research or practice.

Aim

The article aims to contribute to furthering practitioner research and first person research through describing how research and practice have been interwoven in the author's experience as a psychotherapist and nurse. It also explicitly aims to include the non‐rational and transpersonal aspects which form a key part of the author's experience.

Methodology

Data is drawn from a range of written material including both personal journals, published and unpublished research and creative writing.

Findings

The findings are presented in narrative format reflecting the way that memory moves back and forth in present experience. The paper interweaves thirty years experience of research and practice, highlighting areas about which there was an experienced silence.

Implications

The article highlights the contribution that first person research can make in addressing deeper levels of experience that may not be disclosed in other forms of research because they contain non‐rational elements, that however do form an important part of some cultural perspectives and indivdual experience.
TWEAK increases SIRT1 expression and promotes p53 deacetylation affecting human hepatic stellate cell senescence
Authors: Zhang Feng , Zhang Ming , Wang Aixiu , Xu Mingcui , Wang Chen , Xu Guifang , Zhang Bin , Zou Xiaoping , Zhuge Yuzheng
Published: November 2016

To detect the effects of tumor necrosis factor‐like weak inducer of apoptosis (TWEAK) on SIRT1 expression and p53 deacetylation, involving cell senescence, in activated human hepatic stellate cell (HSC) in vitro, human HSC LX‐2 was cultured with TWEAK for 24 h. The result showed that the expression of membrane receptor Fn14 was remarkably increased by TWEAK, which upregulated SIRT1 in LX‐2 cells, detected by Western blotting and real‐time PCR. The expression of p53 was not significantly altered; however, the ac‐p53 was decreased. Furthermore, the viability of LX‐2 cells was significantly enhanced by TWEAK. The activity of SA‐β‐Gal was notably inhibited, showing a suppressing effect of TWEAK on the senescence of activated HSC. Primary cultured HSC on days 7 and 11 was used to examine the expression of TWEAK, Fn14, SIRT1, and the activity of SA‐β‐Gal. The result indicated that the mRNA of TWEAK, SIRT1, and Fn14 was all decreased on day 11 compared to that on day 7, and the activity of SA‐β‐Gal was higher on day 11 than that on day 7. The present study suggested that TWEAK enhanced the expression of SIRT1 and decreased the acetylation of p53, probably inhibiting the senescence of activated HSC in vitro, which provides a molecular basis for TWEAK as a potential target in the therapy of liver fibrosis.
Specific N‐glycan alterations are coupled in epithelial–mesenchymal transition induced by EGF in GE11 epithelial cells
Authors: Xu Qingsong , Qu Chen , Wang Wenjing , Gu Jianguo , Du Yuguang , Song Linsheng
Published: November 2016

Epithelial–mesenchymal transition (EMT) is a phenomenon in cancer progression during which cancer cells undergo remarkable alteration acquiring highly invasive property. The aim of this study was to evaluate specific N‐glycan alterations during EMT induced by epidermal growth factor (EGF) in GE11 epithelial cells. Herein, we demonstrated that EGF activated epidermal growth factor receptor (EGFR)/Akt/extracellular signal‐regulated kinase (ERK) phosphorylation and promoted GE11 cell proliferation. Meanwhile, EGF stimulated the epithelial cells to undergo morphological alteration, destroying cell–cell inter‐contact and exhibiting mesenchymal cells higher metastatic potential. A wound‐healing assay showed the migratory ability increased 1.5‐fold after EGF treatment. Moreover, the relative intensity of N‐cadherin versus E‐cadherin increased 2.6‐fold, and the E‐cadherin distribution in cell–cell junctions became jagged and faint after EGF incubation for 72 h. Interestingly, the amounts of bisecting GlcNAc structure were dramatically declined, by contrast, the formation of β1,6 GlcNAc branches on cell surface was upregulated during EMT induced by EGF. To understand the roles of N‐glycans in EGF‐induced EMT, the cells were stably transfected with N‐acetylglucosaminyltransferase III (GnT‐III), which catalyzes the bisecting GlcNAc structure formation. As the markers for EMT, EGF‐induced E‐cadherin decrease and fibronectin increase were delayed in GnT‐III‐overexpressing cells. Taken together, these results demonstrated that specific N‐glycan alterations were coupled in EMT induced by EGF, which might be contributed to diagnosis and therapy of tumor metastasis.
Conditioned medium: a new alternative for cryopreservation of equine umbilical cord mesenchymal stem cells
Authors: Maia Leandro , Dias Marianne Camargos , de Moraes Carolina Nogueira , de Paula Freitas‐Dell'Aqua Camila , da Mota Ligia S.L. Silveira , Santiloni Valquíria , da Cruz Landim‐Alvarenga Fernanda
Published: November 2016

Cryopreservation is a feasible alternative to maintaining several cell lines, particularly for immediate therapeutic use, transportation of samples, and implementation of new in vitro studies. This work parts from the hypothesis that the medium of cryopreservation composed by 90% of conditioned medium (CM) supports cryopreservation of equine umbilical cord intervascular matrix mesenchymal stem cells (UCIM‐MSCs), allowing the maintenance of the biological properties for the establishment of cell banks intended for therapeutic use and in vitro studies. Thus, we evaluated the viability, apoptosis/necrosis rates, immunophenotypic profile (IP), chromosomal stability, clonicity, and differentiation potential of UCIM‐MSCs cryopreserved with four different mediums (with FBS: M1, M3, M4 and without FBS: M2). After 3 months of cryopreservation, samples were thawed and analyzed. The potential of differentiation in the mesodermal lineages, clonicity, and the chromosomal stability were maintained after cryopreservation of UCIM‐MSCs with medium containing FBS. Changes (P < 0.05) at IP for some markers were observed at cells cryopreserved with medium M1–M3. Only the UCIM‐MSCs cryopreserved with the CM (M4) had similar viability post‐thaw (P = 0.23) when compared with fresh cells. We proved the hypothesis that the medium of cryopreservation containing CM supports the cryopreservation of UCIM‐MSCs, at the experimental conditions, being the medium that better maintains the biological characteristics observed at fresh cells. Thus, future studies of UCIM‐MSCs secretome should be conducted to better understand the beneficial and protective effects of the CM during the freezing process.
Functional expression of G protein‐coupled receptor 30 in immature rat epididymal epithelium
Authors: Cao Xiaonian , Huang Jiehong , Zhang Geng , Zuo Wulin , Lan Chongfeng , Sun Qing , Yang Dengliang , Gao Dongdong , Cheng Christopher H.K. , Zhou Wen‐Liang
Published: November 2016

The aim of this study is to investigate the functional role of G protein‐coupled receptor 30 (GPR30) in the epididymis. We found that GPR30 is expressed in the epithelium of the immature rat epididymis and is involved in chloride secretion into the caudal epididymis lumen. The short‐circuit current (Isc) experiments showed that in primary cultured caudal epididymis epithelium, activation of GPR30 by its specific agonist G1 induced a mono‐phasic current increase, and G15, the specific antagonist of GPR30, could completely inhibit the current induced by G1. The G1‐induced Isc was largely blocked by application of the non‐specific chloride channel inhibitor diphenylamine‐dicarboxylic acid (DPC), or by the cystic fibrosis transmembrane conductance regulator (CFTR) inhibitor CFTRinh‐172, suggesting that the current was mainly mediated through CFTR. In addition, after stimulating GPR30 by G1, the intracellular concentration of cAMP in the epithelium was significantly increased, indicating that the cAMP signal pathway is involved and could be responsible for the CFTR activation. Finally, to further investigate the function of GPR30 in vivo, G15 was administrated into rats subcutaneously. The osmotic pressure of the micro perfusion solution from epididymis was measured and the sperms were collected. Results showed that there was an osmotic pressure increase of the perfusion solution from G15 treated rats. When the GPR30 was inhibited by G15 endogenously, the motility of sperms decreased. Our data demonstrated that GPR30 is involved in the formation of caudal epididymis fluid micro‐environment thus affecting sperm motility.
Adoptive transfer of T regulatory cells inhibits lipopolysaccharide‐induced inflammation in fetal brain tissue in a late‐pregnancy preterm birth mouse model
Authors: Wang Fan , Xiao Mi , Chen Ru‐Juan , Lin Xiao‐Jie , Siddiq Muhammad , Liu Li
Published: November 2016

To evaluate the effect of regulatory T cells (Tregs) on the inflammation resulting from lipopolysaccharide (LPS) challenge in prenatal brain tissue, Tregs isolated from pregnant mice were transferred into model mice, and the expression levels of fork head family transcription factor (Foxp3), interleukin‐6 (IL‐6), CD68 (a marker of microglia), and toll‐like receptor 4 (TLR‐4) were assessed in the fetal brain tissue. Foxp3, IL‐6, and TLR‐4 expression were detected by polymerase chain reaction and Western blot; CD68 expression level was detected using immunochemical analysis. Foxp3, IL‐6, TLR‐4, and CD68 expressions in fetal brain were significantly induced by maternal LPS administration, and the increased expression levels were markedly reduced by adoptive transfer of Tregs. Maternal LPS exposure significantly induced inflammation in perinatal brain tissue, and Tregs negatively regulated this LPS‐induced inflammation.
Serenity, courage, and wisdom: The keys to successful coronary calcification treatment
Authors: Danek Barbara Anna , Brilakis Emmanouil S.
Published: November 2016

Key Points

Patients who undergo percutaneous coronary intervention of moderately or severely calcified coronary lesions have high risk for subsequent major adverse cardiac events.

Part of this risk is due to non‐modifiable clinical factors, such as advanced age and prior coronary artery bypass graft surgery that are commonly associated with coronary calcification.

Careful choice of revascularization strategy, meticulous attention to percutaneous coronary intervention technique, and optimal post‐intervention management are likely to improve the long‐term outcomes of patients with severely calcified coronary lesions.
Bifurcation stenting with bioresorbable scaffolds: Quo vadis?
Authors: Kornowski Ran
Published: November 2016

Key Points

Bioresorbable everolimus‐eluting vascular scaffold (BEEVS) provides a vascular support to prevent early recoil, but unlike metallic stents, it resorbs over time and leaves no foreign material in the coronary artery.

True bifurcation lesions were excluded from pivotal BEEVS trials since the consequence of the scaffold within coronary bifurcations is uncertain.

Feasibility and safety of bifurcation double‐stenting utilizing Absorb BEEVS in the main‐branch and either a BEEVS or metallic DES in the side‐branch has been demonstrated in the current preliminary study.
A toast to no sternotomy
Authors: Yadav Pradeep K. , Eng Marvin H.
Published: November 2016

Key Points

Short‐ and long‐term outcomes of alcohol septal ablation are comparable to surgical myectomy

With growing evidence, myectomy should not be considered as the frontline therapy

Unless a prospective randomized study is conducted, debate over preferred approach (surgical vs. ASA) will continue
You can't get there from here
Authors: Reilly John
Published: November 2016

Key Points

Iliac artery intervention can be safely and successfully performed from transradial or transulnar access.

Transradial coronary intervention is becoming increasingly common in the U.S., this report may spark interest in use of this alternate access for peripheral intervention.

Further research with direct comparison to femoral access in lieu of historical controls will bolster the case for transradial intervention.
To BAV or not to BAV, that is a TAVR question
Authors: Massumi Mehran , Krajcer Zvonimir
Published: November 2016

Key Points

TAVR without pre‐deployment BAV appears to be a safe alternative in non‐severely calcified aortic valves

Criteria to establish severity of aortic valvular calcium using CT data will aid in deciding whether a valve is a reasonable candidate for direct implantation

Prospective, randomized trials comparing TAVR with and without pre‐deployment BAV across all commercially available valve platforms are necessary to assess the safety of direct deployment of a TAVR valve
Efficacy and safety of dabigatran, rivaroxaban, and warfarin for stroke prevention in Chinese patients with atrial fibrillation: the Hong Kong Atrial Fibrillation Project
Authors: Li Wen‐Hua , Huang Duo , Chiang Chern‐En , Lau Chu‐Pak , Tse Hung‐Fat , Chan Esther W. , Wong Ian C.K. , Lip Gregory Y. H. , Chan Pak‐Hei , Siu Chung‐Wah
Published: November 2016

Background

Little is known about the comparative effectiveness and safety of non–vitamin K antagonist oral anticoagulants (NOAC) compared to warfarin in Chinese atrial fibrillation (AF) patients. Our aim was to compare the ischemic stroke risk reduction and incidence of intracranial hemorrhage (ICH) of warfarin in relation to quality of anticoagulation control (as reflected by time in therapeutic range [TTR]), and to dabigatran and rivaroxaban in a real‐world cohort of Chinese AF patients.

Hypothesis

NOAC, rather than warfarin, is preferred in Chinese AF patients.

Methods

Of 2099 patients studied (73.1 ± 12.3 years, female: 44.6%, CHA2DS2‐VASc 3.7 ± 1.9 and HAS‐BLED 2.0 ± 1.0) with nonvalvular AF, 963 patients (45.9%) were on warfarin (only 16.3% had TTR ≥65%), 669 patients were on rivaroxaban, and 467 patients were on dabigatran.

Results

After a mean follow‐up of 21.7 ± 13.4 months, there were 156 ischemic strokes (annual incidence of 4.10%/year), with the incidence of ischemic stroke being highest in patients on warfarin with TTR <65% (5.24%/year), followed by those on rivaroxaban (3.74%/year), and those on warfarin with TTR ≥65% (3.35%/year), whereas patients on dabigatran had the lowest incidence of ischemic stroke (1.89%/year). The incidence of ICH was lowest in patients on dabigatran (0.39%/year) compared with those on rivaroxaban (0.52%/year) and warfarin, with TTR <65% (0.95%/year) and TTR ≥65% (0.58%/year). Patients on rivaroxaban 20 mg daily had similar ischemic stroke risk (1.93%/year) and ICH risk (0.21%/year) compared to dabigatran.

Conclusions

In Chinese AF patients, the benefits of warfarin therapy for stroke prevention and ICH reduction depend on TTR. Of the treatments compared, dabigatran, as well as rivaroxaban 20 mg daily, was associated with lowest ischemic stroke and ICH rates.
Effect of the LIVESTRONG at the YMCA exercise program on physical activity, fitness, quality of life, and fatigue in cancer survivors
Authors: Irwin Melinda L. , Cartmel Brenda , Harrigan Maura , Li Fangyong , Sanft Tara , Shockro Laura , O'Connor Keelin , Campbell Nancy , Tolaney Sara M. , Mayer Erica L. , Yung Rachel , Freedman Rachel A. , Partridge Ann H. , Ligibel Jennifer A.
Published: November 2016

BACKGROUND

Physical activity (PA) has been linked to a lower risk of developing and dying of cancer, yet many cancer survivors do not exercise. In the current study, the authors evaluated the impact of the LIVESTRONG at the YMCA exercise program, available at Young Men's Christian Associations (YMCAs) across the United States, on PA, fitness, quality of life, fatigue, body composition, serum biomarkers, and program safety in cancer survivors.

METHODS

Cancer survivors were recruited through the Yale Cancer Center and the Dana‐Farber Cancer Institute and randomized to a 12‐week, twice‐weekly LIVESTRONG at the YMCA exercise program at YMCAs in Connecticut or Massachusetts or to a control group. Questionnaires, dual‐energy x‐ray absorptiometry scans, 6‐minute walk tests (6MWTs), and a fasting blood draw were completed at baseline and at 12 weeks. Intervention effects were evaluated using mixed model repeated measures analysis, with changes at 12 weeks in PA and 6MWT as the primary endpoints.

RESULTS

A total of 186 participants were randomized (95 to the exercise group and 91 to the control group). The majority of patients were diagnosed with AJCC stage I to II cancer and 53% had breast cancer. Participants randomized to the LIVESTRONG at the YMCA program experienced increases in PA (71% exercising at ≥ 150 minutes/week vs 26% of controls; P<.05) and improvements in the 6MWT (group difference: 28.9 meters [95% confidence interval, 0.3‐49.0; P = .004]) and quality of life (group difference: 2.6 [95% confidence interval, 0.1‐5.0; P = .04]). No adverse events were reported.

CONCLUSIONS

The LIVESTRONG at the YMCA exercise program has the potential to impact thousands of survivors across the YMCA network and could lead to improvements in disease and psychosocial outcomes in the growing population of cancer survivors. Cancer 2017;123:1249–1258. © 2016 American Cancer Society.
Light wavelengths of LEDs to improve the color discrimination in Ishihara test and Farnsworth Panel D‐15 test for deutans
Authors: Tamura Shigeharu , Okamoto Yosuke , Nakagawa Seiji , Sakamoto Takashi , Ando Masanori , Shigeri Yasushi
Published: November 2016

This study was performed to determine significant light wavelengths to improve color discrimination ability of subjects with deutan. We conducted both the Ishihara test and the Farnsworth Panel D‐15 test for subjects with deutan and normal color vision. Seven different LED lights from 450 to 660 nm and an additional D65 white lamp were utilized to change the lighting conditions, including the wavelength and intensity. The results of the Ishihara test and D‐15 test showed that color identification of deutans was markedly improved with the longer wavelength LEDs regardless of the intensity of the additional D65 lamp. Notably, the error rates of deutans in the Ishihara test were <25% for LED wavelengths of 630 and 660 nm. In the case of subjects with normal color vision, the D65 lamp abolished the errors in the Ishihara test, regardless of the LED wavelength. Addition of the D65 lamp also decreased the number of crossings in the D‐15 test. These results suggested that illumination by LED light with longer wavelengths, such as 630 and 660 nm, may provide deutans with greater red‐green discrimination ability in both the Ishihara test and the Farnsworth Panel D‐15 test. © 2016 Wiley Periodicals, Inc. Col Res Appl, 42, 424–430, 2017
Background luminance and subtense affects color appearance
Authors: Sun Pei‐Li , Li Hung‐Chung , Ronnier Luo M.
Published: November 2016

Two psychophysical experiments were conducted to investigate the color appearance under non‐uniform surround conditions with variation of stimulus luminance, surround luminance, background luminance, background orientation, and background size. The results show that the background size and surround luminance influence the appearance intensively, but that the orientation of background pattern has little effect. A method to determine optimal parameters for the CIECAM02 color appearance model in lighting applications is proposed. An UGR‐based model also is optimized for brightness estimation. The luminance of adapting field can be estimated by Gaussian‐like functions. © 2016 Wiley Periodicals, Inc. Col Res Appl, 42, 440–449, 2017
Role of Passive Diffusion, Transporters, and Membrane Trafficking‐Mediated Processes in Cellular Drug Transport
Authors: Cocucci E , Kim JY , Bai Y , Pabla N
Published: November 2016

Intracellular drug accumulation is thought to be dictated by two major processes, passive diffusion through the lipid membrane or membrane transporters. The relative role played by these distinct processes remains actively debated. Moreover, the role of membrane‐trafficking in drug transport remains underappreciated and unexplored. Here we discuss the distinct processes involved in cellular drug distribution and propose that better experimental models are required to elucidate the differential contributions of various processes in intracellular drug accumulation.
Cardiovascular Toxicities of Small Molecule Tyrosine Kinase Inhibitors: An Opportunity for Systems‐Based Approaches
Authors: Brown S‐A , Nhola L , Herrmann J
Published: November 2016

Once universally considered a rapidly fatal condition, cancer has increasingly become a chronic medical condition and comorbidities and adverse effects of cancer therapies have become increasingly significant. One of the leading advancements that has gained traction for the treatment of a variety of malignancies is the class of small molecule tyrosine kinase inhibitors (TKIs). Although, in many aspects revolutionary, TKIs have their own profile of side effects, including cardiovascular side effects, the most common being hypertension (HTN), congestive heart failure, corrected QT (QTc) prolongation, and instances of premature coronary heart disease. Herein, we describe the mechanisms of small TKI‐induced cardiovascular toxicity and related intracellular signaling. In particular, systems‐based approaches to the understanding of small TKI‐induced cardiovascular toxicity are addressed. The pathophysiology of synergic cardiovascular toxicity from TKIs, anthracyclines, and monoclonal antibodies (e.g., trastuzumab, bevacizumab) is illustrated. Finally, recommendations are made for implementing systems medicine in clinical practice, for individualized cardiovascular wellness after cancer therapy.
EBV‐associated but HHV8‐unrelated double‐hit effusion‐based lymphoma
Authors: Chen Bo‐Jung , Chen David Yen‐Ting , Kuo Chun‐Chi , Chuang Shih‐Sung
Published: November 2016

Effusion‐based lymphoma is a rare and unique type of large B‐cell lymphoma presenting in effusion without a mass lesion. It shares many clinicopathological features with primary effusion lymphoma (PEL), but is distinct from PEL by the absence of HHV8 association. Double hit lymphoma (DHL) is an aggressive B‐cell lymphoma, defined by concurrent rearrangement of MYC and BCL2 or BCL6. DHL often presents as lymphadenopathy or an extranodal mass, but rarely occurs in effusion. Here we report a 61‐year‐old male with alcoholic cirrhosis presenting as massive ascites and left pleural effusion. He has no HIV, HBV or HCV infection and no mass lesion by CT scans. Cytology of both pleural effusion and ascites show large lymphoma cells with plasmablastic morphology characterized by pleomorphic and eccentric nuclei, prominent nucleoli and frequent mitoses. Immunohistochemical study with cell block shows that the lymphoma cells express plasma cell‐related markers (CD138, MUM‐1 and EMA), but not CD3, CD30, CD45, B‐cell markers (CD19, CD20, CD79a, and PAX5), HHV8, ALK or cytokeratin. EBER is positive in most lymphoma cells. Fluorescence in situ hybridization reveals rearrangement at the IGH, BCL2, and MYC loci, but not at BCL6. It is diagnosed as an EBV‐associated but HHV8‐unrelated double hit effusion‐based lymphoma with plasmablastic features. The patient passed away soon after diagnosis without chemotherapy. This is the first reported case of double‐hit effusion‐based lymphoma with MYC and BCL2 rearrangement. This case illustrates the importance of integrating clinical, cytological, immunophenotypical, and molecular findings to reach a correct diagnosis. Diagn. Cytopathol. 2017;45:257–261. © 2016 Wiley Periodicals, Inc.
A case of composite classical and nodular lymphocyte predominant Hodgkin lymphoma with progression to diffuse large B‐cell non‐Hodgkin lymphoma: Diagnostic difficulty in fine‐needle aspiration cytology
Authors: Das Dilip K. , Sheikh Zafar A. , Al‐Shama'a Mariam H. , John Bency , Alawi Abdulla M. S. , Junaid Thamradeen A.
Published: November 2016

A small percentage of nodular lymphocytic predominant Hodgkin lymphoma (NLPHL) progresses to diffuse large B‐cell lymphoma (DLBCL). There have also been rare reports of gray zone lymphoma with features intermediate between classical Hodgkin lymphoma (CHL) and DLBCL. We report a very rare case of composite lymphoma (CHL and NLPHL) progressing to DLBCL, and highlight the diagnostic difficulty faced during its fine‐needle aspiration (FNA) cytology diagnosis. A 65‐year‐old woman presented with a right axillary swelling which was subjected to FNA cytology. The routine FNA cytology diagnosis was anaplastic large cell lymphoma (ALCL) but immunocytochemistry did not support this diagnosis completely. The histopathological diagnosis of the excised lymph node was NLPHL with progression to DLBCL in our hospital but in a hospital abroad where the patient was treated, the reviewed diagnosis was CHL. The patient had a rapid downhill course with development of terminal pleural effusion and died approximately one year from initial diagnosis.The review of the cyto‐histologic material along with additional immunocyto/histochemical studies and the clinical course of the disease support the diagnosis of a composite lymphoma (CHL and NLPHL) with progression to DLBCL. It is suggested that all the three lesions were clonally related. Diagn. Cytopathol. 2017;45:262–266. © 2016 Wiley Periodicals, Inc.
Breaking Sad: Unleashing the Breakthrough Potential of Ketamine's Rapid Antidepressant Effects
Authors: Feifel David
Published: November 2016

Preclinical Research

The surprising results of a small clinical trial on the effects of low dose ketamine, a 65‐year old anesthetic drug that is also used off‐label for chronic pain and recreationally as a club drug, in eight depressed subjects unleashed the most significant advance in antidepressant drug development in decades. That study and subsequent ones have demonstrated that low dose, infused ketamine is able to induce a remission of depression in patients who have failed conventional medications, within 24 h. The apparent increased efficacy and rapid onset of effect of ketamine distinguish it from all other current antidepressant treatments. However, a single infusion of subanesthetic doses of ketamine produces benefits that typically last <3 weeks. The infusions are associated with a transient “psychedelic” experience and increased blood pressure that requires monitoring. There is also a theoretical potential to induce ketamine addiction. These features limit ketamine's ability to be a widely used treatment for depression and thus limit is ability to have a meaningful impact on the heavy morbidity and mortality associated with this disorder, despite its “breakthrough” rate of efficacy and speed of action. While growing numbers of clinicians are using ketamine to treat treatment resistant depression, many in the depression field believe that the aforementioned limiting aspects need to be separated from its remarkable therapeutic effects in order to unlock the breakthrough potential of this agent. To that end, drug development efforts have focused on various features of ketamine as targets for optimization including its modulation of the NMDA receptor, its pharmacokinetics, its chirality and its active metabolites including HNK (2R, 6R)‐hyroxynorketamine. Drug Dev Res 77 : 489–494, 2016. © 2016 Wiley Periodicals, Inc.
Association between body mass index and salivary uric acid among Mexican‐origin infants, youth and adults: Gender and developmental differences
Authors: Martínez Airín D. , Ruelas Lillian , Granger Douglas A.
Published: November 2016

Uric acid (UA) is the end product of the metabolic breakdown of purine nucleotides. Recent studies have measured UA in saliva in relation to obesity and chronic disease risk. Given the increasing prevalence of metabolic syndrome among Latino youth, we examined gender and age differences in salivary uric acid (sUA) and weight in a sample of Mexican‐origin children (n = 65, 2 months to 18 years, 49% female) and adults (n = 46, 19–58 years, 72% female). We measured weight, height, waist, and hip circumference and collected saliva samples (later assayed for sUA). Structural equation models estimated the relationship between age, developmental stage, and weight outcomes in relation to sUA levels between genders, while controlling for race. Results demonstrate that increased sUA levels were related to higher BMI percentiles in females of all ages (β = 0.43, p < .001). There were significant differences in sUA levels between developmental stages for girls, with female toddlers having the highest sUA levels (β = .28, p = .02). In an interaction between BMI z‐score and gender between youth and adults, BMI has a larger effect on increasing sUA levels among younger girls (β = 0.27, p < .03) and adult women (β = 0.33, p = .02). Levels of sUA may be gender‐specific in relation to BMI and developmental stage.
Human pDCs display sex‐specific differences in type I interferon subtypes and interferon α/β receptor expression
Authors: Ziegler Susanne M. , Beisel Claudia , Sutter Kathrin , Griesbeck Morgane , Hildebrandt Heike , Hagen Sven H. , Dittmer Ulf , Altfeld Marcus
Published: November 2016

The outcomes of many diseases differ between women and men, with women experiencing a higher incidence and more severe pathogenesis of autoimmune and some infectious diseases. It has been suggested that this is partially due to activation of plasmacytoid dendritic cells (pDCs), the main producers of interferon (IFN)‐α, in response to toll‐like receptor (TLR)7 stimulation. We investigated the induction of type I IFN (IFN‐I) subtypes upon TLR7 stimulation on isolated pDCs. Our data revealed a sex‐specific differential expression of IFN‐Is, with pDCs from females showing a significantly higher mRNA expression of all 13 IFN‐α subtypes. In addition, pDCs from females had higher levels of IFN‐β mRNA after stimulation, indicating that sex differences in IFN‐I production by pDCs were mediated by a signaling event upstream of the first loop of IFN‐I mRNA transcription. Furthermore, the surface expression levels of the common IFN‐α/β receptor subunit 2 were significantly higher on pDCs from females in comparison to males. These data indicate that higher IFN‐α production is already established at the mRNA level and propose a contribution of higher IFN‐α/β receptor 2 expression on pDCs to the immunological differences in IFN‐I production observed between females and males.
Stochastic model for simulation of near‐fault ground motions
Authors: Dabaghi Mayssa , Der Kiureghian Armen
Published: November 2016

A parameterized stochastic model of near‐fault ground motion in two orthogonal horizontal directions is developed. The major characteristics of recorded near‐fault ground motions are represented. These include near‐fault effects of directivity and fling step; temporal and spectral non‐stationarity; intensity, duration, and frequency content characteristics; directionality of components; and the natural variability of ground motions. Not all near‐fault ground motions contain a forward directivity pulse, even when the conditions for such a pulse are favorable. The proposed model accounts for both pulse‐like and non‐pulse‐like cases. The model is fitted to recorded near‐fault ground motions by matching important characteristics, thus generating an ‘observed’ set of model parameters for different earthquake source and site characteristics. A method to generate and post‐process synthetic motions for specified model parameters is also presented. Synthetic ground motion time series are generated using fitted parameter values. They are compared with corresponding recorded motions to validate the proposed model and simulation procedure. The use of synthetic motions in addition to or in place of recorded motions is desirable in performance‐based earthquake engineering applications, particularly when recorded motions are scarce or when they are unavailable for a specified design scenario. Copyright © 2016 John Wiley & Sons, Ltd.
Wall building stiffness and strength effect on content sliding in Wellington seismic conditions
Authors: Yeow Trevor Z. , MacRae Gregory A. , Dhakal Rajesh P.
Published: November 2016

A numerical study of unobstructed content sliding within several low‐to‐midrise reinforced concrete cantilever wall buildings designed to Wellington conditions in New Zealand is performed to validate the belief that increasing a building's strength and/or stiffness would result in more severe sliding response. It was shown that contents within stronger buildings experienced larger sliding response. If the building was designed to be strong, the sliding response of contents with a friction coefficient of 0.1 was smaller in stiffer buildings compared with those in flexible buildings. However, the trends start reversing with an increase in friction coefficient or a decrease in building strength. Overall, content sliding is not necessarily more severe in stiffer buildings, and in many cases, the opposite is true. This study's findings were compared against an existing parametric equation for estimating the maximum sliding displacement. This equation, which was originally derived for contents located within elastic frame buildings, was found to be more efficient than considering total floor accelerations alone but was underconservative by a mean of 17% for yielding multistorey buildings. A design procedure considering content sliding using the parametric equation and an example are provided. Copyright © 2016 John Wiley & Sons, Ltd.
Fate of microglia during HIV‐1 infection: From activation to senescence?
Authors: Chen Natalie C. , Partridge Andrea T. , Sell Christian , Torres Claudio , Martín‐García Julio
Published: November 2016

Microglia support productive human immunodeficiency virus type 1 (HIV‐1) infection and disturbed microglial function could contribute to the development of HIV‐associated neurocognitive disorders (HAND). Better understanding of how HIV‐1 infection and viral protein exposure modulate microglial function during the course of infection could lead to the identification of novel therapeutic targets for both the eradication of HIV‐1 reservoir and treatment of neurocognitive deficits. This review first describes microglial origins and function in the normal central nervous system (CNS), and the changes that occur during aging. We then critically discuss how HIV‐1 infection and exposure to viral proteins such as Tat and gp120 affect various aspects of microglial homeostasis including activation, cellular metabolism and cell cycle regulation, through pathways implicated in cellular stress responses including p38 mitogen‐activated protein kinase (MAPK) and nuclear factor κB (NF‐κB). We thus propose that the functions of human microglia evolve during both healthy and pathological aging. Aging‐associated dysfunction of microglia comprises phenotypes resembling cellular senescence, which could contribute to cognitive impairments observed in various neurodegenerative diseases. In addition, microglia seems to develop characteristics that could be related to cellular senescence post‐HIV‐1 infection and after exposure to HIV‐1 viral proteins. However, despite its potential role as a component of HAND and likely other neurocognitive disorders, microglia senescence has not been well characterized and should be the focus of future studies, which could have high translational relevance. GLIA 2017;65:431–446