bluuebunny/crossref_metadata_2025 huggingface dataset:
Adenosine triphosphate is a critical determinant for VEGFR signal during hypoxia
Authors: Al Mamun Abdullah , Hayashi Hisaki , Sakima Miho , Sato Motohiko
Published: November 2016

Hypoxia induces angiogenesis through the VEGF signaling pathway; however, signal propagation of VEGF in hypoxia is not fully understood. In this study, we examined alterations in VEGF signaling during hypoxia conditions and its determinant in endothelial cells. To analyze VEGF signaling during hypoxia, human umbilical vein endothelial cells (HUVECs) were exposed to 3 h of hypoxia (1% O2) followed by 3 h of reoxygenation or 12 h of hypoxia. Hypoxia induced expression of VEGF mRNA, but it was not associated with an increase in tube formation by HUVECs. During 3 h of hypoxia, VEGF-induced phosphorylation of VEGF receptor-2 (VEGFR-2) and downstream molecules were significantly inhibited without a change in VEGFR-2 expression, but it was completely restored after reoxygenation. VEGF-mediated VEGFR-2 phosphorylation is associated with a reduction in cellular ATP in hypoxia conditions (65.93 ± 8.32% of normoxia, means ± SE, P < 0.01). Interestingly, attenuation of VEGFR-2 phosphorylation was restored by addition of ATP to prepared membranes from cells that underwent 3 h of hypoxia. In contrast to 3 h of hypoxia, exposure of cells to 12 h of hypoxia decreased VEGFR-2 expression and VEGF-mediated VEGFR-2 phosphorylation. The magnitude of VEGFR-2 phosphorylation was not fully restored by addition of ATP to prepared membranes from cells exposed to 12 h of hypoxia. These data indicate that ATP is an important determinant of VEGF signaling in hypoxia and suggest that the activation process of VEGFR-2 was modified by sustained hypoxia. These observations contribute to our understanding of signal alterations in VEGF in endothelial cells during hypoxia.
Altered muscle satellite cell activation following 16 wk of resistance training in young men
Authors: Nederveen Joshua P. , Snijders Tim , Joanisse Sophie , Wavell Christopher G. , Mitchell Cameron J. , Johnston Leeann M. , Baker Steven K. , Phillips Stuart M. , Parise Gianni
Published: November 2016

Skeletal muscle satellite cells (SC) play an important role in muscle adaptation. In untrained individuals, SC content and activation status have been observed to increase in response to a single bout of exercise. Muscle fiber characteristics change considerably when resistance exercise is performed chronically, but whether training status affects the activity of SC in response to a single bout of exercise remains unknown. We examined the changes in SC content and activation status following a single bout of resistance exercise, before and following a 16-wk progressive resistance training (RT) program in 14 young (25 ± 3 yr) men. Before and after RT, percutaneous biopsies from the vastus lateralis muscle were taken before a single bout of resistance exercise and after 24 and 72 h of postexercise recovery. Muscle fiber size, capillarization, and SC response were determined by immunohistochemistry. Following RT, there was a greater activation of SC after 24 h in response to a single bout of resistance exercise (Pre, 1.4 ± 0.3; 24 h, 3.1 ± 0.3 Pax7+/MyoD+cells per 100 fibers) compared with before RT (Pre, 1.4 ± 0.3; 24 h, 2.2 ± 0.3 Pax7+/MyoD+cells per 100 fibers, P < 0.05); no difference was observed 72 h postexercise. Following 16 wk of RT, MyoD mRNA expression increased from basal to 24 h after the single bout of exercise ( P < 0.05); this change was not observed before training. Individual capillary-to-fiber ratio (C/F i) increased in both type I (1.8 ± 0.3 to 2.0 ± 0.3 C/F i, P < 0.05) and type II (1.7 ± 0.3 to 2.2 ± 0.3 C/F i, P < 0.05) fibers in response to RT. After RT, enhanced activation of SC in response to resistance exercise is accompanied by increases in muscle fiber capillarization.
Endoplasmic reticulum stress inhibition limits the progression of chronic kidney disease in the Dahl salt-sensitive rat
Authors: Yum Victoria , Carlisle Rachel E. , Lu Chao , Brimble Elise , Chahal Jasmine , Upagupta Chandak , Ask Kjetil , Dickhout Jeffrey G.
Published: November 2016

Proteinuria is one of the primary risk factors for the progression of chronic kidney disease (CKD) and has been implicated in the induction of endoplasmic reticulum (ER) stress. We hypothesized that the suppression of ER stress with a low molecular weight chemical chaperone, 4-phenylbutyric acid (4-PBA), would reduce the severity of CKD and proteinuria in the Dahl salt-sensitive (SS) hypertensive rat. To induce hypertension and CKD, 12-wk-old male rats were placed on a high-salt (HS) diet for 4 wk with or without 4-PBA treatment. We assessed blood pressure and markers of CKD, including proteinuria, albuminuria, and renal pathology. Furthermore, we determined if HS feeding resulted in an impaired myogenic response, subsequent to ER stress. 4-PBA treatment reduced salt-induced hypertension, proteinuria, and albuminuria and preserved myogenic constriction. Furthermore, renal pathology was reduced with 4-PBA treatment, as indicated by lowered expression of profibrotic markers and fewer intratubular protein casts. In addition, ER stress in the glomerulus was reduced, and the integrity of the glomerular filtration barrier was preserved. These results suggest that 4-PBA treatment protects against proteinuria in the SS rat by preserving the myogenic response and by preventing ER stress, which led to a breakdown in the glomerular filtration barrier. As such, alleviating ER stress serves as a viable therapeutic strategy to preserve kidney function and to delay the progression of CKD in the animal model under study.
Antioxidant treatment attenuates lactate production in diabetic nephropathy
Authors: Laustsen Christoffer , Nielsen Per Mose , Nørlinger Thomas Stokholm , Qi Haiyun , Pedersen Uffe Kjærgaard , Bertelsen Lotte Bonde , Østergaard Jakob Appel , Flyvbjerg Allan , Ardenkjær-Larsen Jan Henrik , Palm Fredrik , Stødkilde-Jørgensen Hans
Published: November 2016

The early progression of diabetic nephropathy is notoriously difficult to detect and quantify before the occurrence of substantial histological damage. Recently, hyperpolarized [1-13C]pyruvate has demonstrated increased lactate production in the kidney early after the onset of diabetes, implying increased lactate dehydrogenase activity as a consequence of increased nicotinamide adenine dinucleotide substrate availability due to upregulation of the polyol pathway, i.e., pseudohypoxia. In this study, we investigated the role of oxidative stress in mediating these metabolic alterations using state-of-the-art hyperpolarized magnetic resonance (MR) imaging. Ten-week-old female Wistar rats were randomly divided into three groups: healthy controls, untreated diabetic (streptozotocin treatment to induce insulinopenic diabetes), and diabetic, receiving chronic antioxidant treatment with TEMPOL (4-hydroxy-2,2,6,6-tetramethylpiperidin-1-oxyl) via the drinking water. Examinations were performed 2, 3, and 4 wk after the induction of diabetes by using a 3T Clinical MR system equipped with a dual tuned 13C/1H-volume rat coil. The rats received intravenous hyperpolarized [1-13C]pyruvate and were imaged using a slice-selective 13C-IDEAL spiral sequence. Untreated diabetic rats showed increased renal lactate production compared with that shown by the controls. However, chronic TEMPOL treatment significantly attenuated diabetes-induced lactate production. No significant effects of diabetes or TEMPOL were observed on [13C]alanine levels, indicating an intact glucose-alanine cycle, or [13C]bicarbonate, indicating normal flux through the Krebs cycle. In conclusion, this study demonstrates that diabetes-induced pseudohypoxia, as indicated by an increased lactate-to-pyruvate ratio, is significantly attenuated by antioxidant treatment. This demonstrates a pivotal role of oxidative stress in renal metabolic alterations occurring in early diabetes.
Hydrogen peroxide suppresses TRPM4 trafficking to the apical membrane in mouse cortical collecting duct principal cells
Authors: Wu Ming-Ming , Zhai Yu-Jia , Li Yu-Xia , Hu Qing-Qing , Wang Zhi-Rui , Wei Shi-Peng , Zou Li , Alli Abdel A. , Thai Tiffany L. , Zhang Zhi-Ren , Ma He-Ping
Published: November 2016

A Ca2+-activated nonselective cation channel (NSCCa) is found in principal cells of the mouse cortical collecting duct (CCD). However, the molecular identity of this channel remains unclear. We used mpkCCDc14cells, a mouse CCD principal cell line, to determine whether NSCCarepresents the transient receptor potential (TRP) channel, the melastatin subfamily 4 (TRPM4). A Ca2+-sensitive single-channel current was observed in inside-out patches excised from the apical membrane of mpkCCDc14cells. Like TRPM4 channels found in other cell types, this channel has an equal permeability for Na+and K+and has a linear current-voltage relationship with a slope conductance of ~23 pS. The channel was inhibited by a specific TRPM4 inhibitor, 9-phenanthrol. Moreover, the frequency of observing this channel was dramatically decreased in TRPM4 knockdown mpkCCDc14cells. Unlike those previously reported in other cell types, the TRPM4 in mpkCCDc14cells was unable to be activated by hydrogen peroxide (H2O2). Conversely, after treatment with H2O2, TRPM4 density in the apical membrane of mpkCCDc14cells was significantly decreased. The channel in intact cell-attached patches was activated by ionomycin (a Ca2+ionophore), but not by ATP (a purinergic P2receptor agonist). These data suggest that the NSCCacurrent previously described in CCD principal cells is actually carried through TRPM4 channels. However, the physiological role of this channel in the CCD remains to be further determined.
Analysis of Antimicrobial and Antioxidant Activities of Chenopodium ambrosioides: An Ethnomedicinal Plant
Authors: Ajaib Muhammad , Hussain Tanveer , Farooq Saleha , Ashiq Mehrban
Published: November 2016

The antimicrobial and antioxidant potential of Chenopodium ambrosioides L. was explored. Antimicrobial potential was investigated through zone of inhibition and minimum inhibition concentration whereas antioxidant potential of selected plant was evaluated through different techniques, that is, total phenolic contents, total flavonoids content, DPPH assay, ABTS assay, and metal chelating. It is concluded that both parts showed good to satisfactory antimicrobial and antioxidant results. The maximum antibacterial potential is exhibited by bark macerated in petroleum ether against Bacillus subtilis (33±1.5 mm) and maximum antifungal potential exhibited by methanol extracts of fruit against Aspergillus niger (16±1.5 mm). Aqueous extracts failed to show any activity against selected organisms. The minimum (significant) MIC value exhibited by fruit extract against Staphylococcus aureus was 0.009±0.02 at 0.7 mg/mL. Aqueous extracts of bark and fruit exhibited maximum antioxidant potential in all assays except DPPH assay. Petroleum ether bark extract showed maximum % DPPH value.
Investigation on the Combined Effect of Fibers and Cement on the Mechanical Performance of Foamed Bitumen Mixtures Containing 100% RAP
Authors: Taziani Ehsan Ashouri , Toraldo Emanuele , Giustozzi Filippo , Crispino Maurizio
Published: November 2016

Concerns about virgin aggregate sources and increasing demands for construction materials of transport infrastructures as the key parameters in development are the most important reasons, which convinced pavement engineers to develop new methods in order to use higher amount of recycled asphalt pavement (RAP). One of the common methodologies to produce mixtures containing RAP is foamed bitumen mix (FBM). In addition, according to previous research studies, incorporating various types of fibers and hydraulic binders such as cement could significantly improve the mechanical performance of mixtures. The present research study evaluated FBM containing 100% RAP and two types of fiber and Portland cement. Dynamic modulus, unconfined dynamic creep compression, and indirect tensile strength were evaluated in the laboratory at optimum moisture content, which was investigated in this research. Both types of fiber and cement proved to enhance specific properties of mixtures.
Body Composition in Adult Patients with Thalassemia Major
Authors: Vlychou Marianna , Alexiou Evangelos , Thriskos Paschalis , Fezoulidis Ioannis , Vassiou Katerina
Published: November 2016

Objective. To assess body composition in adult male and female patients with thalassemia major by dual-energy X-ray absorptiometry (DXA) and to compare the findings with a group of healthy age-matched controls. Methods. Our study group included sixty-two patients (27 males, mean age 36 years, and 35 females, mean age 36.4 years) and fifteen age-matched healthy controls. All patients had an established diagnosis of thalassemia major and followed a regular blood transfusion scheme since childhood and chelation treatment. Fat, lean, and bone mineral density (BMD) were assessed with dual-energy X-ray absorptiometry. Ferritin levels and body mass index of all patients and controls were also recorded. Student t-test and Wilcoxon test were performed and statistical significance was set at p<0.05. Results. BMD and whole body lean mass are lower in both male and female adult patients compared with controls (p<0.01 in both groups), whereas whole body fat mass was found to have no statistically significant difference compared to controls. Regional trunk fat around the abdomen was found to be lower in male patients compared to controls (p=0.02). Conclusion. Severe bone loss and diminished lean mass are expected in adult male and female patients with thalassemia major. Fat changes seem to affect mainly male patients.
An IFPI Temperature Sensor Fabricated in an Unstriped Optical Fiber with Self-Strain-Compensation Function
Authors: Song Yang , Hua Liwei , Lei Jincheng , Zhang Qi , Liu Jie , Ye Lingyun , Xiao Hai
Published: November 2016

This paper describes an intrinsic Fabry-Perot interferometer (IFPI) temperature sensor with self-strain-compensation function. The sensor was fabricated on a buffer-intact optical fiber using a femtosecond (fs) laser system. The use of fs laser allows the sensor to be fabricated in an optical fiber without the necessity of removing the polymer buffer coating, thus not compromising its mechanical property. The sensor is composed of two cascaded IFPIs in different cavity length of 100 μm and 500 μm, respectively. The shorter IFPI serves as the temperature sensor, while the second IFPI serves as a compensation sensor, which is used to decouple the strain from the raw signal collected by the shorter FPI. The reflection spectrum of sensor, containing both sensory information and compensation information, is collected in wavelength domain and demultiplexed in the Fourier domain of reflection spectrum. An algorithm was developed and successfully implemented to compensate the strain influence on the proposed temperature sensor. The results showed that the proposed sensor structure holds a constant temperature sensitivity of 11.33 pm/°C when strained differently.
Structural Prediction of Bis{(di-p-anisole)-1,4-azabutadiene}-bis[triphenylphosphine]ruthenium(II) Using 31P NMR Spectroscopy
Authors: Tay Meng Guan , Lokanathan Thareni , Ong Kok Tong , Abu Talip Ruwaida Asyikin , Chia Ying Ying
Published: November 2016

The present paper reports the use of 31P NMR spectroscopy to predict the isomer structures of [bis{4-methoxy-phenyl-[3-(4-methoxy-phenyl)-allylidene]-amino}]-bis[triphenylphosphine]ruthenium(II), also known as bis{(di-p-anisole)-1,4-azabutadiene}-bis[triphenylphosphine]ruthenium(II), complexes. The complexation reaction was carried out under refluxing condition of (di-p-anisole)-1,4-azabutadiene (compound 1), triphenylphosphine (PPh3), and ruthenium chloride in the ratio of 2 : 2 : 1 for five hours. In addition, ruthenium(II) complexes were also characterized using FTIR and UV-Vis spectroscopy to support the formation of ruthenium(II) complexes. 31P NMR spectroscopic study on ruthenium(II) complexes suggested that there are three isomers present after the complexation reaction and all the ruthenium complexes demonstrate octahedral geometry.
Oxidative Stress and Liver Cancer: Etiology and Therapeutic Targets
Authors: Wang Zhanpeng , Li Zhuonan , Ye Yanshuo , Xie Lijuan , Li Wei
Published: November 2016

Accumulating evidence has indicated that oxidative stress (OS) is associated with the development of hepatocellular carcinoma (HCC). However, the mechanisms remain largely unknown. Normally, OS occurs when the body receives any danger signal—from either an internal or external source—and further induces DNA oxidative damage and abnormal protein expression, placing the body into a state of vulnerability to the development of various diseases such as cancer. There are many factors involved in liver carcinogenesis, including hepatitis B virus (HBV) and hepatitis C virus (HCV) infection, alcohol abuse, and nonalcoholic fatty liver disease (NAFLD). The relationship between OS and HCC has recently been attracting increasing attention. Therefore, elucidation of the impact of OS on the development of liver carcinogenesis is very important for the prevention and treatment of liver cancer. This review focuses mainly on the relationship between OS and the development of HCC from the perspective of cellular and molecular mechanisms and the etiology and therapeutic targets of HCC.
BAI1 Orchestrates Macrophage Inflammatory Response to HSV Infection—Implications for Oncolytic Viral Therapy
Authors: Bolyard Chelsea , Meisen W. Hans , Banasavadi-Siddegowda Yeshavanth , Hardcastle Jayson , Yoo Ji Young , Wohleb Eric S. , Wojton Jeffrey , Yu Jun-Ge , Dubin Samuel , Khosla Maninder , Xu Bo , Smith Jonathan , Alvarez-Breckenridge Christopher , Pow-anpongkul Pete , Pichiorri Flavia , Zhang Jianying , Old Matthew , Zhu Dan , Van Meir Erwin G. , Godbout Jonathan P. , Caligiuri Michael A. , Yu Jianhua , Kaur Balveen
Published: November 2016

Purpose: Brain angiogenesis inhibitor (BAI1) facilitates phagocytosis and bacterial pathogen clearance by macrophages; however, its role in viral infections is unknown. Here, we examined the role of BAI1, and its N-terminal cleavage fragment (Vstat120) in antiviral macrophage responses to oncolytic herpes simplex virus (oHSV).

Experimental Design: Changes in infiltration and activation of monocytic and microglial cells after treatment of glioma-bearing mice brains with a control (rHSVQ1) or Vstat120-expressing (RAMBO) oHSV was analyzed using flow cytometry. Co-culture of infected glioma cells with macrophages or microglia was used to examine antiviral signaling. Cytokine array gene expression and Ingenuity Pathway Analysis (IPA) helped evaluate changes in macrophage signaling in response to viral infection. TNFα-blocking antibodies and macrophages derived from Bai1−/− mice were used.

Results: RAMBO treatment of mice reduced recruitment and activation of macrophages/microglia in mice with brain tumors, and showed increased virus replication compared with rHSVQ1. Cytokine gene expression array revealed that RAMBO significantly altered the macrophage inflammatory response to infected glioma cells via altered secretion of TNFα. Furthermore, we showed that BAI1 mediated macrophage TNFα induction in response to oHSV therapy. Intracranial inoculation of wild-type/RAMBO virus in Bai1−/− or wild-type non–tumor-bearing mice revealed the safety of this approach.

Conclusions: We have uncovered a new role for BAI1 in facilitating macrophage anti-viral responses. We show that arming oHSV with antiangiogenic Vstat120 also shields them from inflammatory macrophage antiviral response, without reducing safety. Clin Cancer Res; 23(7); 1809–19. ©2016 AACR.
Optimization of a PEGylated Glucuronide-Monomethylauristatin E Linker for Antibody–Drug Conjugates
Authors: Burke Patrick J. , Hamilton Joseph Z. , Jeffrey Scott C. , Hunter Joshua H. , Doronina Svetlana O. , Okeley Nicole M. , Miyamoto Jamie B. , Anderson Martha E. , Stone Ivan J. , Ulrich Michelle L. , Simmons Jessica K. , McKinney Erica E. , Senter Peter D. , Lyon Robert P.
Published: November 2016

The emergence of antibody–drug conjugates (ADC), such as brentuximab vedotin and ado-trastuzumab emtansine, has led to increased efforts to identify new payloads and develop improved drug-linker technologies. Most antibody payloads impart significant hydrophobicity to the ADC, resulting in accelerated plasma clearance and suboptimal in vivo activity, particularly for conjugates with high drug-to-antibody ratios (DAR). We recently reported on the incorporation of a discrete PEG24 polymer as a side chain in a β-glucuronidase-cleavable monomethylauristatin E (MMAE) linker to provide homogeneous DAR 8 conjugates with decreased plasma clearance and increased antitumor activity in xenograft models relative to a non-PEGylated control. In this work, we optimized the drug-linker by minimizing the size of the PEG side chain and incorporating a self-stabilizing maleimide to prevent payload de-conjugation in vivo. Multiple PEG-glucuronide-MMAE linkers were prepared with PEG size up to 24 ethylene oxide units, and homogeneous DAR 8 ADCs were evaluated. A clear relationship was observed between PEG length and conjugate pharmacology when tested in vivo. Longer PEG chains resulted in slower clearance, with a threshold length of PEG8 beyond which clearance was not impacted. Conjugates bearing PEG of sufficient length to minimize plasma clearance provided a wider therapeutic window relative to faster clearing conjugates bearing shorter PEGs. A lead PEGylated glucuronide-MMAE linker was identified incorporating a self-stabilizing maleimide and a PEG12 side chain emerged from these efforts, enabling highly potent, homogeneous DAR 8 conjugates and is under consideration for future ADC programs. Mol Cancer Ther; 16(1); 116–23. ©2016 AACR.
Comparing the Effectiveness of Electroacupuncture with Different Grades of Knee Osteoarthritis: A Prospective Study
Authors: Qi Li , Tang Yonggang , You Yong , Qin Fengling , Zhai Lijuan , Peng Hongxia , Nie Rongrong
Published: November 2016

Background: The electroacupuncture (EA) with different number of points significantly affected its efficacy on knee osteoarthritis (KOA), and the severity of KOA also influenced its response to treatments. Hence, we prospectively compared the clinical efficacy of EA on KOA with different severities. Methods: A total of 132 KOA patients recruited from 181st Central Hospital of The Chinese People's Liberation Army between March 2014 and March 2015 were classified into 4 KOA stages according to Kellgren Lawrence grading scale. They were allocated into three treatment groups, including two-point group, four-point group and six-point group. Patients in the six-point group received treatment at six-points including ST34, SP10, SP9, ST36, ST35 and EX-LE4. Patients in the four-point group received treatment at ST34, SP10, ST35 and EX-LE5, while patients in the two-point group received treatment at ST35 and EX-LE4. Visual Analog Scale (VAS), McMaster Universities Osteoarthritis Index (WOMAC) and self-assessment questionnaire of patients were assessed after treatment. Results: Three kinds of EA treatments all have significant clinical effects on KOA patients with down-regulated scores of VAS and WOMAC. Regarding post-treatment efficacy, the six point group exhibited lower VAS score and higher WOMAC score compared with the other two groups. For patients with different KOA grades, patients with higher KOA grades were associated with lower grade of treatment efficacy. Conclusions: Patients with KOA, especially those with lower KOA stages, could gain beneficial efficacies from EA treatments with two, four and six points, respectively.
ABO-Incompatible Living Donor Liver Transplantation in Focus of Antibody Rebound
Authors: Rummler Silke , Bauschke Astrid , Baerthel Erik , Juette Heike , Maier Katrin , Malessa Christina , Barz Dagmar , Settmacher Utz
Published: November 2016

Background: Living donor liver transplantation (LDLT) is an option to expand the donor organ pool for patients with life-threatening diseases who cannot be supplied with a cadaver organ. Next to the donor risks, complications after ABO-incompatible LDLT (ABOi LDLT) in the recipient are subject to controversial discussion. Improvement in ABOi graft survival rates have been achieved with plasma treatment procedures (PTP) and immunosuppression but antibody-mediated rejection (AMR) and graft loss still occur. Methods: Since 2008, we have prepared 10 patients for ABOi LDLT. Seven of the 10 patients for transplantation had hepatocellular carcinoma (HCC). Results: All patients underwent PTP before and after ABOi LDLT as well as immunosuppression according to the treatment schedule. We did not use anti-CD20 monoclonal antibodies in the transplant setting. We transplanted 6 of 10 preconditioned patients. After 3 years, 5 of the 6 transplanted patients were still alive. Conclusion: Even if B-cell depletion with anti-CD 20 treatment in the setting of ABOi LDLT is commonly accepted, our center successfully administered only quadruple drug immunosuppression combined with PTP. Especially patients with HCC had a high titer increment also pre-transplantation and were at high risk for arterial thrombosis and graft loss.
‘Head Invasion' Is Not a Metastasis-Free Condition in Pedunculated T1 Colorectal Carcinomas Based on the Precise Histopathological Assessment
Authors: Kimura Yui Jennifer , Kudo Shin-ei , Miyachi Hideyuki , Ichimasa Katsuro , Kouyama Yuta , Misawa Masashi , Sato Yuta , Matsudaira Shingo , Oikawa Hiromasa , Hisayuki Tomokazu , Mori Yuichi , Kudo Toyoki , Ogata Noriyuki , Kodama Kenta , Wakamura Kunihiko , Hayashi Takemasa , Katagiri Atsushi , Baba Toshiyuki , Hidaka Eiji , Ishida Fumio , Hamatani Shigeharu
Published: November 2016

Background/Aim: Previous reports stated that pedunculated T1 colorectal carcinomas with ‘head invasion' showed almost no nodal metastasis, requiring endoscopic treatment alone. However, clinically, some lesions develop nodal metastasis. We aimed to validate the necessity of distinguishing between ‘pedunculated' and ‘non-pedunculated' lesions, and also between ‘head' and ‘stalk' invasions. Methods: Initial or additional surgery with lymph node dissection was performed in 76 pedunculated and 594 non-pedunculated cases. Among pedunculated lesions, the baseline was defined as the junction line between normal and neoplastic epithelium (Haggitt's level 2). The degree of invasion was classified as ‘head invasion' (above the baseline) or ‘stalk invasion' (beyond the baseline). Clinicopathological factors were analyzed with respect to nodal metastasis. Results: Nine of 76 (11.8%) pedunculated cases and 52/594 (8.8%) non-pedunculated cases developed nodal metastasis (p = 0.40). No significant differences were found in the rate of nodal metastasis between ‘head invasion' (4/30, 13.3%) and ‘stalk invasion' (5/46, 10.9%). All the 4 cases with ‘head invasion' had at least one pathological factor. Conclusions: ‘Head invasion' was not a metastasis-free condition. Even for pedunculated T1 cancers with ‘head invasion', additional surgery with lymph node dissection should be considered if these have pathological risk factors.
Bile Acids and the Potential Role in Primary Biliary Cirrhosis
Authors: Yang Hang , Duan Zhijun
Published: November 2016

Background: Bile acids (BAs) play a potential role in regulating the whole-body metabolic homeostasis via the interaction with gut microbiome and the signal transduction as messengers, which establish a link between the primary biliary cirrhosis (PBC) and gut microbiome in many aspects, particularly with regard to the immune system of the body. PBC, as a chronic cholestatic liver disease characterised by the destruction of small intrahepatic bile ducts, causes fibrosis and potential cirrhosis without efficient therapies. Summary: Recent researches show BAs can induce the differentiation of hepatic stellate cells, suggesting that it may serve as a novel therapy to resist, even changeover the irreversible liver cirrhosis in PBC. Key Messages: In this review, we conclude and provide information on the possible mechanism of pleiotropic BAs in homeostasis of the gut microbiome and liver regeneration, and hope to broaden the therapy of PBC and promote the relevant drugs' development.
Adherence to oral anticoagulant therapy in patients with atrial fibrillation
Authors: Raparelli Valeria , Proietti Marco , Cangemi Roberto , Lip Gregory Y. H. , Lane Deirdre A. , Basili Stefania
Published: November 2016

Oral anticoagulation is pivotal in the management of thromboembolic risk in non-valvular atrial fibrillation (NVAF) patients. Effective anticoagulation is important to avoid major adverse events and medication adherence is central to achieve good anticoagulation control. Non-vitamin K antagonist oral anticoagulants (NOACs) are as effective and safe as vitamin K antagonist (VKAs) in NVAF patients. Due to the absence of routine anticoagulation monitoring with NOACs treatment, concerns have been raised about patient’s adherence to NOACs and real-life data demonstrates variability in adherence and persistence. A multi-level approach, including patients’ preferences, factors determining physicians’ prescribing habits and healthcare system infrastructure and support, is warranted to improve initiation and adherence of anticoagulants. Adherence to NOACs is paramount to achieve a clinical benefit. Implementation of educational programs and easy-to-use tools to identify patients most likely to be non-adherent to NOACs, are central issues in improving the quality of NVAF anticoagulation management.

Note: The review process for this manuscript was fully handled by C. Weber, Editor in Chief.
Differentiated Smooth Muscle Cells Generate a Subpopulation of Resident Vascular Progenitor Cells in the Adventitia Regulated by Klf4
Authors: Majesky Mark W. , Horita Henrick , Ostriker Allison , Lu Sizhao , Regan Jenna N. , Bagchi Ashim , Dong Xiu Rong , Poczobutt Joanna , Nemenoff Raphael A. , Weiser-Evans Mary C.M.
Published: November 2016

Rationale:

The vascular adventitia is a complex layer of the vessel wall consisting of vasa vasorum microvessels, nerves, fibroblasts, immune cells, and resident progenitor cells. Adventitial progenitors express the stem cell markers, Sca1 and CD34 (adventitial sca1-positive progenitor cells [AdvSca1]), have the potential to differentiate in vitro into multiple lineages, and potentially contribute to intimal lesions in vivo.

Objective:

Although emerging data support the existence of AdvSca1 cells, the goal of this study was to determine their origin, degree of multipotency and heterogeneity, and contribution to vessel remodeling.

Methods and Results:

Using 2 in vivo fate-mapping approaches combined with a smooth muscle cell (SMC) epigenetic lineage mark, we report that a subpopulation of AdvSca1 cells is generated in situ from differentiated SMCs. Our data establish that the vascular adventitia contains phenotypically distinct subpopulations of progenitor cells expressing SMC, myeloid, and hematopoietic progenitor-like properties and that differentiated SMCs are a source to varying degrees of each subpopulation. SMC-derived AdvSca1 cells exhibit a multipotent phenotype capable of differentiating in vivo into mature SMCs, resident macrophages, and endothelial-like cells. After vascular injury, SMC-derived AdvSca1 cells expand in number and are major contributors to adventitial remodeling. Induction of the transcription factor Klf4 in differentiated SMCs is essential for SMC reprogramming in vivo, whereas in vitro approaches demonstrate that Klf4 is essential for the maintenance of the AdvSca1 progenitor phenotype.

Conclusions:

We propose that generation of resident vascular progenitor cells from differentiated SMCs is a normal physiological process that contributes to the vascular stem cell pool and plays important roles in arterial homeostasis and disease.
Ultimatum Concession Bargaining
Authors: Felli Chiara , Güth Werner , Mata-Pérez Esther , Ponti Giovanni
Published: November 2016

We collect experimental evidence on a modified version of the standard ultimatum game in which the responder states an acceptance threshold below which the offer is rejected and both players, proposer and responder, are allowed several attempts to reach an agreement by conceding. Proposers concede by increasing offers and responders concede by decreasing acceptance thresholds. Treatments differ in whether a further attempt requires that at least one party should have conceded. A further condition varies the number of possible negotiating attempts, namely, 3 versus 5. Behavior in the lab diverges significantly from the theoretical solution in which the proposer is expected to get nearly the whole pie in each treatment. Proposers (responders) initially offer less (ask more) and concede more across negotiation attempts in the treatment in which concessions are required. Moreover, compulsory concessions weaken the bargaining position of the proposer, who eventually gets significantly less. Finally, although concessions significantly improve the likelihood of an agreement compared to standard ultimatum game experiments, the longer negotiation horizon (five attempts instead of three) delays the agreement without enhancing it, even when no concessions are needed.
Birth Weight, Breastfeeding, Maternal Smoking and Caries Trajectories
Authors: Bernabé E. , MacRitchie H. , Longbottom C. , Pitts N.B. , Sabbah W.
Published: November 2016

Evidence for the effects of low birth weight, breastfeeding and maternal smoking on childhood caries is mainly cross-sectional. We examined the association of these 3 putative early life factors with caries increment over a 4-y period among young children. We used data from a 4-y longitudinal caries-risk assessment study carried out among Scottish children. Early life factors were measured when children were aged 1 y (baseline). Caries assessment was repeated annually from ages 1 to 4, and the number of decayed, missing and filled primary tooth surfaces (dmfs) were used as a repeated outcome measure. The associations of low birth weight, breastfeeding and maternal smoking with dmfs at baseline and over time (trajectories) were assessed in linear mixed models. A total of 1,102 children were included in this analysis. Birth weight, breastfeeding and maternal smoking were not associated with dmfs at baseline. However, low birth weight and maternal smoking were associated with the rate of change in dmfs. By wave 4, the predicted mean difference in dmfs was 1.86 between children with low and normal birth weight, and 1.66 between children of smoking and non-smoking mothers. Children with low birth weight and smoking mothers had greater caries increments than those with normal weight and non-smoking mothers, respectively. There was no association between breastfeeding duration and childhood caries, either at baseline or over time.
Modeling of human behavior in crowds using a cognitive feedback approach
Authors: Papelis YE , Kady RA , Bair LJ , Weisel E
Published: November 2016

We present an agent-based approach to modeling crowd behavior that is based on complementary psychological and engineering principles. The application focus is for developing realistic models that address not only the physical but also the psychological aspects of crowd behavior. Our approach to modeling the psychology of a crowd is based on the principle of emotional reflection. According to this principle, human emotions are evoked in response to the perception of other people’s emotions, implying that emotions propagate in a crowd as a result of each person’s perception of other crowd members’ emotions in addition to external factors. We demonstrate that when incorporating an emotional component into a crowd simulation, there is enough sensitivity between the outcomes and emotion-based responses to provide a rich and powerful test-bed for assessing possible effects of emotionally driven responses in crowds. The emotional model is coupled with a movement model that is based on the social forces formulation, but with parameters that vary according to the current emotional state of each crowd member. We present the model along with results of how different emotional levels can affect the movement dynamics of crowds.
Traffic congestion, accessibility to employment, and housing prices: A study of single-family housing market in Los Angeles County
Authors: Hou Yuting
Published: November 2016

This study mainly addresses two main questions: (1) whether traffic congestion negatively affects single-family house price by constraining accessibility to jobs; (2) whether congestion effects and accessibility effects vary by income groups within a metropolitan area. This study uses a multilevel hedonic price model to estimate the marginal price of accessibility while controlling for other neighbourhood attributes and the correlation of proximal housing sales. The congestion effects are identified by comparing the implicit price of accessibility between congested-flow and free-flow. The results show that the accessibility measured with congested time yields higher marginal price, suggesting that households are willing to pay more to avoid locations with high congestion delays and accessibility loss. The results also suggest that accessibility effects are more valued by homebuyers in middle-income neighbourhoods, compared with those in the lowest or highest income neighbourhoods.
Development of X-ray protective garments from rare earth-modified natural rubber composites
Authors: Sambhudevan Sreedha , Shankar Balakrishnan , Saritha A , Joseph Kuruvilla , Philip John , Saravanan T
Published: November 2016

Commonly used shielding materials while X-ray imaging by clinical persons is based on lead but incessant contact with this toxic material can pave way to severe health problems. Polymer composites, embedded with lead-free additives, especially based on natural rubber can be chosen as a suitable alternative candidate due to its lightweight, cost-effectiveness and capability to absorb regular energy region of X-ray used in medical imaging. Rubber composites were prepared with modified rare earth oxides at different filler loadings. The characterization of the filler reveals that their size falls in the nanoregime, which, in turn, supplemented to the superior properties of the composites. Mechanical properties were found to increase with filler content. X-ray shielding studies were done at different tube voltages and thicknesses and the results prove the efficacy of materials to be considered as a promising shielding resource.
The Eighth Industrial Fluids Properties Simulation Challenge
Authors: Schultz Nathan E , Ahmad Riaz , Brennan John K , Frankel Kevin A , Moore Jonathan D , Moore Joshua D , Mountain Raymond D , Ross Richard B , Thommes Matthias , Shen Vincent K , Siderius Daniel W , Smith Kenneth D
Published: November 2016

The goal of the eighth industrial fluid properties simulation challenge was to test the ability of molecular simulation methods to predict the adsorption of organic adsorbates in activated carbon materials. In particular, the eighth challenge focused on the adsorption of perfluorohexane in the activated carbon BAM-P109. Entrants were challenged to predict the adsorption in the carbon at 273 K and relative pressures of 0.1, 0.3, and 0.6. The predictions were judged by comparison with a benchmark set of experimentally determined values. Overall, good agreement and consistency were found between the predictions of most entrants.
Predicting the adsorption of n-perfluorohexane in BAM-P109 standard activated carbon by molecular simulation using SAFT-γ Mie coarse-grained force fields
Authors: Herdes Carmelo , Forte Esther , Jackson George , Müller Erich A
Published: November 2016

This work is framed within the Eighth Industrial Fluid Properties Simulation Challenge, with the aim of assessing the capability of molecular simulation methods and force fields to accurately predict adsorption in porous media for systems of relevant practical interest. The current challenge focuses on predicting adsorption isotherms of n-perfluorohexane in the certified reference material BAM-P109 standard activated carbon. A temperature of [Formula: see text] K and pressures of [Formula: see text], 0.3, and 0.6 relative to the bulk saturation pressure p0 (as predicted by the model) are the conditions selected in this challenge. In our methodology we use coarse-grained intermolecular models and a top-down technique where an accurate equation of state is used to link the experimental macroscopic properties of a fluid to the force-field parameters. The state-of-the-art version of the statistical associating fluid theory (SAFT) for potentials of variable range as reformulated in the Mie group contribution incarnation (SAFT- γ Mie) is employed here. The parameters of the SAFT- γ Mie force field are estimated directly from the vapour pressure and saturated liquid density data of the pure fluids using the equation of state, and further validated by molecular dynamic simulations. The coarse-grained intermolecular potential models are then used to obtain the adsorption isotherm kernels for argon, carbon dioxide, and n-perfluorohexane in graphite slit pores of various widths using Grand Canonical Monte Carlo simulations. A unique and fluid-independent pore size distribution curve with total micropore volume of 0.5802 cm3/g is proposed for the BAM-P109. The pore size distribution is obtained by applying a non-linear regression procedure over the adsorption integral equation to minimise the quadratic error between the available experimental adsorption isotherms for argon and carbon dioxide and purpose-built Grand Canonical Monte Carlo kernels. The predicted adsorption levels of n-perfluorohexane at 273 K in BAM-P109 are 72.75 ± 0.01, 73.82 ± 0.01, and 75.44 ± 0.05 cm3/g at Standard Temperature and Pressure (STP) conditions for [Formula: see text], 0.3, and 0.6, respectively.
8th Industrial Fluid Properties Simulation Challenge: n-Perfluorohexane adsorption prediction on activated carbon BAM-P109 by molecular simulation
Authors: Gonciaruk Aleksandra , Runcieman Louis , Avendaño Carlos , Siperstein Flor R
Published: November 2016

We combine two approaches to describe an activated carbon which contains micro- and mesopores. We propose a simple approach of packing individual three-dimensional rigid structures to represent microporous region of commercially available BAM-P109 activated carbon. Mesopores are represented by planar walls interacting via the standard Steele 10-4-3 potential assuming experimental pore-size distribution. The models are used to predict n-perfluorohexane adsorption at 273 K temperature. We used uncharged united atom model for n-perfluorohexane molecule. The non-bonded interactions were described by the Gordon potential model, with parameters adjusted to reproduce the Mie force field potential, which was designed to accurately represent vapour pressure of alkanes and perfluoroalkanes. Adsorption isotherm was calculated using Grand Canonical Monte Carlo method implemented in MCCCS Towhee. We show that predicted n-perfluorohexane loading at relative pressures of interest are significantly lower than the experimental ones. The underprediction is attributed to the low aromatic carbon interaction strength and sensitive calculations of chemical potential. Adjusted interaction parameter of aromatic carbon and chemical potential led to n-perfluorohexane adsorption that agreed well with the reported experimental values.
Effect of antipsychotic pharmacotherapy on clinical outcomes of intermittent theta-burst stimulation for refractory depression
Authors: Schulze Laura , Remington Gary , Giacobbe Peter , Kennedy Sidney H , Blumberger Daniel M , Daskalakis Zafiris J , Downar Jonathan
Published: November 2016

Theta-burst stimulation is an emerging protocol for repetitive transcranial magnetic stimulation that takes 1–3 min to administer, yet offers equal/superior potency to conventional protocols lasting 30–60 min. However, preclinical evidence suggests that D2 receptor blockade may abolish the acute effects of theta-burst stimulation on synaptic facilitation or inhibition. As many patients presenting for repetitive transcranial magnetic stimulation are taking antipsychotic medications as augmentation for treatment-resistant depression, this finding is potentially concerning for the implementation of theta-burst stimulation in clinical settings. Here, we examined whether treatment-resistant depression patients taking antipsychotics have worse outcomes after a course of intermittent theta-burst stimulation. A chart review identified 105 treatment-resistant depression patients who underwent dorsomedial prefrontal-intermittent theta-burst stimulation; clinical outcomes on Hamilton Depression Rating Scale and Beck Depression Inventory were compared for those taking and not taking antipsychotics. The 29 of 105 patients who were taking antipsychotics showed non-significantly better response and remission rates, and non-significantly larger percentage improvements on both scales, with a positive but non-significant correlation between higher antipsychotic dose and larger percentage improvement. Contrary to expectations, outcomes were not significantly worse, and in some analyses trended towards being better, in patients taking antipsychotics. Future randomized controlled studies of repetitive transcranial magnetic stimulation combined with standardized dopaminergic manipulations may be justified and warranted.
The effect of the amount of peritumoral adipose tissue in the detection of additional tumors with digital breast tomosynthesis and ultrasound
Authors: García-Barquín Paula , Páramo María , Elizalde Arlette , Pina Luis , Etxano Jon , Fernandez-Montero Alejandro , Caballeros Meylin
Published: November 2016

Background

Digital breast tomosynthesis (DBT) and ultrasound (US) can detect additional cancers after negative mammography. However, not all cancers are visible by both techniques.

Purpose

To study the role of the amount of peritumoral fat in the detection of additional cancers with DBT or US.

Material and Methods

One reader retrospectively reviewed 142 breast cancers in 109 women who underwent mammography, DBT, US, and magnetic resonance imaging (MRI). Two readers in consensus evaluated the additional cancers detected by US, DBT, or MRI, and classified them into four groups according to the amount of peritumoral adipose tissue: group I, >75% of peritumoral fat; group II, 50–74%; group III, 25–49%, and group IV, 0–24%. The detection of additional cancers by US and DBT with respect to the other imaging techniques was evaluated.

Results

Seventy-eight cancers were detected by mammography and the remaining 64 cancers were detected by DBT, US, or MRI. US and DBT detected 46 (71.8%) and 25 (39.06%) additional tumors, respectively. Statistical significance was only found in group IV ( P < 0.01).

Conclusion

US detected more tumors than DBT in lesions surrounded by a small amount of fat. No significant differences were found between US and DBT in the detection of additional cancers in the other groups.