bluuebunny/crossref_metadata_2025 huggingface dataset:
Blockade of MK2 is protective in inflammation‐associated colorectal cancer development
Authors: Ray Anita L. , Castillo Eliseo F. , Morris Katherine T. , Nofchissey Robert A. , Weston Lea L. , Samedi Von G. , Hanson Joshua A. , Gaestel Matthias , Pinchuk Irina V. , Beswick Ellen J.
Published: August 2015

Chronic inflammation is a risk factor for colorectal cancer. The MAPK‐activated protein kinase 2 (MK2) pathway controls multiple cellular processes including p38‐dependent inflammation. This is the first study to investigate the role of MK2 in development of colitis‐associated colon cancer (CAC). Herein, we demonstrate that MK2−/− mice are highly resistant to neoplasm development when exposed to AOM/DSS, while wild type (WT) C57BL/6 develop multiple neoplasms with the same treatment. MK2‐specific cytokines IL‐1, IL‐6 and TNF‐α were substantially decreased in AOM/DSS treated MK2−/− mouse colon tissues compared with WT mice, which coincided with a marked decrease in macrophage influx. Restoring MK2‐competent macrophages by injecting WT bone marrow derived macrophages into MK2−/− mice led to partial restoration of inflammatory cytokine production with AOM/DSS treatment; however, macrophages were not sufficient to induce neoplasm development. These results indicate that MK2 functions as an inflammatory regulator to promote colonic neoplasm development and may be a potential target for CAC.
Impact of CYP24A1 overexpression on growth of colorectal tumour xenografts in mice fed with vitamin D and soy
Authors: Höbaus Julia , Tennakoon Samawansha , Heffeter Petra , Groeschel Charlotte , Aggarwal Abhishek , Hummel Doris M. , Thiem Ursula , Marculescu Rodrig , Berger Walter , Kállay Enikö
Published: August 2015

Our previous studies showed that the 1,25‐dihydroxyvitamin D (1,25‐D3) catabolizing enzyme, 1,25‐dihydoxyvitamin D 24 hydroxylase (CYP24A1) was overexpressed in colorectal tumours and its level correlated with increased proliferation. We hypothesised that cells overexpressing CYP24A1 have growth advantage and a diet rich in vitamin D and soy would restore sensitivity to the anti‐tumourigenic effects of vitamin D. Soy contains genistein, a natural CYP24A1 inhibitor. To determine causality between CYP24A1 and tumour growth, we established xenografts in male SCID mice with HT29 cells stably overexpressing either GFP‐tagged CYP24A1 or GFP. Mice were fed with either high (2500 IU D3/kg) or low vitamin D (100 IU D3/kg) diet in the presence or absence of soy (20% diet). In vitro, cells overexpressing CYP24A1 grew faster than controls. 1,25‐D3, the active vitamin D metabolite, reduced cell number only in the presence of the CYP24A1 inhibitor VID400. Regardless of the amount of vitamin D in the diet, xenografts overexpressing CYP24A1 grew faster, were heavier and more aggressive. Soy reduced tumour volume only in the control xenografts, while the tumours overexpressing CYP24A1 were larger in the presence of dietary soy. In conclusion, we demonstrate that CYP24A1 overexpression results in increased aggressiveness and proliferative potential of colorectal tumours. Irrespective of the dietary vitamin D3, dietary soy is able to increase tumour volume when tumours overexpress CYP24A1, suggesting that combination of vitamin D3 and soy could have an anti‐tumourigenic effect only if CYP24A1 levels are normal.
Alteration of amino acid and biogenic amine metabolism in hepatobiliary cancers: Findings from a prospective cohort study
Authors: Stepien Magdalena , Duarte‐Salles Talita , Fedirko Veronika , Floegel Anne , Barupal Dinesh Kumar , Rinaldi Sabina , Achaintre David , Assi Nada , Tjønneland Anne , Overvad Kim , Bastide Nadia , Boutron‐Ruault Marie‐Christine , Severi Gianluca , Kühn Tilman , Kaaks Rudolf , Aleksandrova Krasimira , Boeing Heiner , Trichopoulou Antonia , Bamia Christina , Lagiou Pagona , Saieva Calogero , Agnoli Claudia , Panico Salvatore , Tumino Rosario , Naccarati Alessio , Bueno‐de‐Mesquita H. B(as). , Peeters Petra H. , Weiderpass Elisabete , Quirós J. Ramón , Agudo Antonio , Sánchez María‐José , Dorronsoro Miren , Gavrila Diana , Barricarte Aurelio , Ohlsson Bodil , Sjöberg Klas , Werner Mårten , Sund Malin , Wareham Nick , Khaw Kay‐Tee , Travis Ruth C. , Schmidt Julie A. , Gunter Marc , Cross Amanda , Vineis Paolo , Romieu Isabelle , Scalbert Augustin , Jenab Mazda
Published: August 2015

Perturbations in levels of amino acids (AA) and their derivatives are observed in hepatocellular carcinoma (HCC). Yet, it is unclear whether these alterations precede or are a consequence of the disease, nor whether they pertain to anatomically related cancers of the intrahepatic bile duct (IHBC), and gallbladder and extrahepatic biliary tract (GBTC). Circulating standard AA, biogenic amines and hexoses were measured (Biocrates AbsoluteIDQ‐p180Kit) in a case‐control study nested within a large prospective cohort (147 HCC, 43 IHBC and 134 GBTC cases). Liver function and hepatitis status biomarkers were determined separately. Multivariable conditional logistic regression was used to calculate odds ratios and 95% confidence intervals (OR; 95%CI) for log‐transformed standardised (mean = 0, SD = 1) serum metabolite levels and relevant ratios in relation to HCC, IHBC or GBTC risk. Fourteen metabolites were significantly associated with HCC risk, of which seven metabolites and four ratios were the strongest predictors in continuous models. Leucine, lysine, glutamine and the ratio of branched chain to aromatic AA (Fischer's ratio) were inversely, while phenylalanine, tyrosine and their ratio, glutamate, glutamate/glutamine ratio, kynurenine and its ratio to tryptophan were positively associated with HCC risk. Confounding by hepatitis status and liver enzyme levels was observed. For the other cancers no significant associations were observed. In conclusion, imbalances of specific AA and biogenic amines may be involved in HCC development.
Factors associated with type‐specific persistence of high‐risk human papillomavirus infection: A population‐based study
Authors: Stensen Signe , Kjaer Susanne K. , Jensen Signe M. , Frederiksen Kirsten , Junge Jette , Iftner Thomas , Munk Christian
Published: August 2015

Persistent genital infection with high‐risk (HR) human papillomavirus (HPV) is a prerequisite for cervical cancer development. The aim of this study was to identify factors associated with type‐specific persistence of HR HPV infections. From a population‐based cohort of 40,399 women participating in cervical cancer screening established during 2002–2005, we selected all HR HPV‐positive women (N = 7,778). During follow‐up (2005–2008), we collected cervical samples from these women and tested them for HPV DNA to determine type‐specific HR HPV persistence in the interval 1–4.5 years after enrolment. Data on hospitalisations, prescriptions and socioeconomic factors were obtained from nationwide registers. Women with abnormal cytology at baseline or who had undergone conisation during follow‐up were excluded. Factors associated with persistence were identified by logistic regression analysis. The overall rate of HR HPV persistence was 31.4%. The risk for persistence was significantly increased among women with a previous episode of genital warts (OR, 1.35; 95% CI, 1.04–1.74), current use of oral contraceptives (OR, 1.35; 95% CI, 1.13–1.63) or use of systemic glucocorticoids (OR, 2.04; 95% CI, 1.16–3.56). The number of pregnancies or births or use of a hormonal intrauterine device, hormonal therapy or nonsteroidal anti‐inflammatory drugs was not associated with risk for HR HPV persistence. A history of genital warts and current use of oral contraceptives or systemic glucocorticoids increased the risk, potentially indicating a decreased immune response to HPV infection. These findings suggest that host immune response characteristics are important in HR HPV persistence and consequently in cervical cancer development.
Perfluorinated chemicals, PFOS and PFOA, enhance the estrogenic effects of 17β‐estradiol in T47D human breast cancer cells
Authors: Sonthithai Pacharapan , Suriyo Tawit , Thiantanawat Apinya , Watcharasit Piyajit , Ruchirawat Mathuros , Satayavivad Jutamaad
Published: August 2015

Perfluorooctane sulfonate (PFOS) and perfluorooctanoic acid (PFOA) are the two most popular surfactants among perfluorinated compounds (PFCs), with a wide range of uses. Growing evidence suggests that PFCs have the potential to interfere with estrogen homeostasis, posing a risk of endocrine‐disrupting effects. This in vitro study aimed to investigate the estrogenic effect of these compounds on T47D hormone‐dependent breast cancer cells. PFOS and PFOA (10−12 to 10−4 M) were not able to induce estrogen response element (ERE) activation in the ERE luciferase reporter assay. The ERE activation was induced when the cells were co‐incubated with PFOS (10−10 to 10−7 M) or PFOA (10−9 to 10−7 M) and 1 nM of 17β‐estradiol (E2). PFOS and PFOA did not modulate the expression of estrogen‐responsive genes, including progesterone (PR) and trefoil factor (pS2), but these compounds enhanced the effect of E2‐induced pS2 gene expression. Neither PFOS nor PFOA affected T47D cell viability at any of the tested concentrations. In contrast, co‐exposure with PFOS or PFOA and E2 resulted in an increase of E2‐induced cell viability, but no effect was found with 10 ng ml−1 EGF co‐exposure. Both compounds also intensified E2‐dependent growth in the proliferation assay. ERK1/2 phosphorylation was increased by co‐exposure with PFOS or PFOA and E2, but not with EGF. Collectively, this study shows that PFOS and PFOA did not possess estrogenic activity, but they enhanced the effects of E2 on estrogen‐responsive gene expression, ERK1/2 activation and the growth of the hormone‐deprived T47D cells. Copyright © 2015 John Wiley & Sons, Ltd.
Combining bone morphogenetic proteins‐2 and ‐6 has additive effects on osteoblastic differentiation in vitro and accelerates bone formation in vivo
Authors: Visser Rick , Bodnarova Kristina , Arrabal Pilar M. , Cifuentes Manuel , Becerra Jose
Published: August 2015

While only two members of the bone morphogenetic protein subfamily (BMP‐2 and ‐7) are approved to be used in combination with collagen type I in orthopaedic surgery, other BMPs are known to also be highly osteoinductive. Although all the osteogenic BMPs signal through Smad‐1/‐5/‐8 phosphorylation, they show different preferences for the available BMP receptors. In this work we studied the effect of combining two osteogenic BMPs (‐2 and ‐6), which belong to different groups within the subfamily and have different affinities to the existing BMP receptors. Both the growth and in vitro differentiation of MC3T3‐E1 mouse preosteoblasts and rat bone marrow‐derived mesenchymal stem cells (MSCs) were studied, as well as in vivo ectopic bone formation when the BMPs were intramuscularly implanted in rats with collagen type I sponges as carriers. The results show that these two growth factors have additive effects on the osteoblastic differentiation of cells in vitro and that their combination might be helpful to accelerate in vivo osteogenesis while reducing the amount of each individual BMP used. © 2015 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 178–185, 2016.
Advances in the Treatment of Borderline Personality Disorder: An Introduction to the Special Issue
Authors: McMain Shelley F.
Published: August 2015

The past few decades have seen major progress in the treatment of borderline personality disorder (BPD), a condition that historically has been viewed as difficult to treat. Currently, several evidence‐based psychotherapies are available that have generated excitement and hope, yet these developments have also raised new problems that must be addressed. In this special issue, experts in the field of BPD have been invited to share their ideas on some viable directions in the treatment field. This commentary reviews the challenges we currently face and describes the treatment directions presented by the contributors.
Fucoidan Suppresses the Growth of Human Acute Promyelocytic Leukemia Cells In Vitro and In Vivo
Authors: Atashrazm Farzaneh , Lowenthal Ray M. , Woods Gregory M. , Holloway Adele F. , Karpiniec Samuel S. , Dickinson Joanne L.
Published: August 2015

Fucoidan, a natural component of seaweeds, is reported to have immunomodulatory and anti‐tumor effects. The mechanisms underpinning these activities remain poorly understood. In this study, the cytotoxicity and anti‐tumor activities of fucoidan were investigated in acute myeloid leukemia (AML) cells. The human AML cell lines NB4, KG1a, HL60, and K562 were treated with fucoidan and cell cycle, cell proliferation, and expression of apoptotic pathways molecules were analyzed. Fucoidan suppressed the proliferation and induced apoptosis through the intrinsic and extrinsic pathways in the acute promyelocytic leukemia (APL) cell lines NB4 and HL60, but not in KG1a and K562 cells. In NB4 cells, apoptosis was caspase‐dependent as it was significantly attenuated by pre‐treatment with a pan‐caspase inhibitor. P21/WAF1/CIP1 was significantly up‐regulated leading to cell cycle arrest. Fucoidan decreased the activation of ERK1/2 and down‐regulated the activation of AKT through hypo‐phosphorylation of Thr(308) residue but not Ser(473). In vivo, a xenograft model using the NB4 cells was employed. Mice were fed with fucoidan and tumor growth was measured following inoculation with NB4 cells. Subsequently, splenic natural killer (NK) cell cytotoxic activity was also examined. Oral doses of fucoidan significantly delayed tumor growth in the xenograft model and increased cytolytic activity of NK cells. Taken together, these data suggest that the selective inhibitory effect of fucoidan on APL cells and its protective effect against APL development in mice warrant further investigation of fucoidan as a useful agent in treatment of certain types of leukemia. J. Cell. Physiol. 231: 688–697, 2016. © 2015 Wiley Periodicals, Inc.
Impaired Hematopoiesis and Disrupted Monocyte/Macrophage Homeostasis in Mucopolysaccharidosis Type I Mice
Authors: Viana Gustavo Monteiro , Buri Marcus Vinícius , Paredes‐Gamero Edgar Julian , Martins Ana Maria , D'Almeida Vânia
Published: August 2015

Mucopolysaccharidosis type I (MPS I) is a rare autosomal recessive disease caused by alpha‐L‐iduronidase deficiency in which heparan and dermatan sulfate degradation is compromised. Besides primary lysosomal glycosaminoglycan accumulation, further changes in cellular functions have also been described in several murine MPS models. Herein, we evaluated alterations in hematopoiesis and its implications on the production of mature progeny in a MPS I murine model. Despite the significant increase in hematopoietic stem cells, a reduction in common myeloid progenitors and granulocyte‐macrophage progenitor cells was observed in Idua −/− mice bone marrow. Furthermore, no alterations in number, viability nor activation of cell death mechanisms were observed in Idua −/− mice mature macrophages but they presented higher sensitivity to apoptotic induction after staurosporine treatment. In addition, changes in Ca2+ signaling and a reduction in phagocytosis ability were also found. In summary, our results revealed significant intracellular changes in mature Idua −/− macrophages related to alterations in Idua −/− mice hematopoiesis, revealing a disruption in cell homeostasis. These results provide new insights into physiopathology of MPS I. J. Cell. Physiol. 231: 698–707, 2016. © 2015 Wiley Periodicals, Inc.
Synthesis and Antioxidant Activity of Bis‐oxazolyl/thiazolyl/imidazolyl 1,3,4‐Oxadiazoles and 1,3,4‐Thiadiazoles
Authors: Basha Nabhubygari Mahaboob , Reddy Putta Ramachandra , Padmaja Adivireddy , Padmavathi Venkatapuram
Published: August 2015

A variety of symmetrical trisheterocycles bis‐oxazolyl/thiazolyl/imidazolylacetamido‐sulfonylmethyl 1,3,4‐oxadiazoles and 1,3,4‐thiadiazoles was prepared, and their antioxidant activity was studied. The compounds bisoxazolyl oxadiazole and bisoxazolyl thiadiazole having methyl substituent on the aromatic ring exhibited greater antioxidant activity than the standard ascorbic acid.
Quantitative Correlation Between Cross‐Linking Degrees and Mechanical Properties of Protein Films Modified With Polycarboxylic Acids
Authors: Shen Li , Xu Helan , Yang Yiqi
Published: August 2015

For the first time, mechanical properties of cross‐linked protein products were quantitatively correlated with cross‐linking degrees and molecular structures of polycarboxylic acids. Non‐toxic polycarboxylic acids could effectively improve performance properties of multiple protein products via cross‐linking. However, the reaction mechanism and relationship between reaction and performance properties remained unclear. In this study, the cross‐linking reaction between gliadin, and polycarboxylic acids was verified. Natural logarithm relationship was found between the cross‐linking degree and tensile strength of protein films. The polycarboxylic acids with more carboxyl groups and shorter backbones could more effectively increase the tensile strength of gliadin films.
Tips and tricks for DIEP flap breast reconstruction in patients with previous abdominal scar
Authors: Laporta Rosaria , Longo Benedetto , Sorotos Michail , Santanelli di Pompeo Fabio
Published: August 2015

The aim of this study was to analyze outcomes of patients who had prior abdominal operations and underwent DIEP flap breast reconstruction and to describe technical strategies to insure well‐vascularized flap‐harvest minimizing abdominal donor‐site complications. All patients who underwent DIEP flap breast reconstruction between 2004 and 2014 were reviewed and divided into a control group (CG) and a scar group (SG). Patient demographics, operative details, flap and donor‐site complications were analyzed and compared. For all of the scars, DIEP flap design was not modified, but a standardized approach was developed according to the type and location of the scar, available vascular pedicle, perforator locations, and the required flap tissue for breast reconstruction. Two hundred and eighty patients underwent 292 flaps in CG and 107 underwent 111 flaps in SG. Pfannenstiel, McBurney, laparoscopic, midline and subcostal were the most common previous incisions. There were no significant differences between groups regarding demographics, flap and mastectomy weight, active smoking, or radiation status (P > 0.05). No significant differences were observed in DIEP flap loss (P = 0.909), partial flap loss (P=0.799), or fat necrosis (P=0.871) and in the rate of abdominal donor‐site complications between groups (P > 0.05). SG had a significantly higher mean operative time than CG (P=0.034). Medial raw was a negative risk‐factor for flap complications, while BMI (>25.1 kg/m2) and smoking‐history were significant predictors for donor‐site complications. With careful preoperative planning and appropriate technical strategies, successfully DIEP flap breast reconstruction can be performed without increased flap and donor‐site complications in patients with preexisting abdominal scars. © 2015 Wiley Periodicals, Inc. Microsurgery 37:282–292, 2017.
A perforator from the ulnar artery and cutaneous nerve of the hypothenar area: An anatomical study for clinical application
Authors: Han Hyun Ho , Choi Yong Seong , Kim In Beom , Kim Sang Hyun , Jun Young‐Joon
Published: August 2015

Purpose

The hypothenar perforator flap is a recently introduced method for fingertip reconstruction, which offers excellent results but lacks adequate anatomic studies. The present study is aimed to clarify the anatomic characteristics of the hypothenar area to analyze the potential clinical application of sensate flaps and to access the reliability of hypothenar perforator arteries.

Materials and Methods

A total of 26 amputated forearms were used, and a percentage scattergram using an x‐y‐axis was created. The y‐axis was a vertical line from the midpoint of pisiform base (0%) to the midvolar crease of the metacarpophalangeal joint (100%). The x‐axis was a line perpendicular to the y‐axis, and was quantified as a percentage value. We then studied the number of perforators, the diameter and length of the pedicle, and evaluated the differences between the zones and sexes.

Results

A reliable region for the hypothenar perforator flap, including more than two perforator arteries with an average diameter of over 1 mm, was mapped as 5%–20% on the x‐axis and 10%–50% on the y‐axis. The nerves appeared to occur more densely than the arteries, with 5%–15% on the x‐axis and 25%–60% on the y‐axis.

Conclusion

The most consistent area for sensate flap elevation was the region around 5%–15% on the x‐axis and 25%–50% on the y‐axis. We expect that our data concerning perforator artery and cutaneous nerve branches in the hypothenar area of the hand will aid in establishing appropriate clinical usage of the hypothenar perforator flap. © 2014 Wiley Periodicals, Inc. Microsurgery 37:49–56, 2017.
Low‐rise scar deep inferior epigastric artery perforator flap for breast reconstruction
Authors: Akita Shinsuke , Mitsukawa Nobuyuki , Tokumoto Hideki , Kuriyama Motone , Kubota Yoshitaka , Kira Tomoe , Sasahara Yoshitaro , Sakakibara Masahiro , Nagashima Takeshi , Satoh Kaneshige
Published: August 2015

Background

To achieve an unnoticeable postoperative scar in patients with little abdominal skin laxity for breast reconstruction by deep inferior epigastric artery perforator (DIEP) flap, we devised a new design called the low‐rise scar DIEP flap; the skin paddle of this flap is located lower with a smaller vertical width, and more adipose tissue is elevated to obtain enough volume. The purpose of this report is to evaluate the utility of the low‐rise scar DIEP flap compared with that of the conventionally designed flap.

Methods

Twelve patients who underwent low‐rise scar DIEP flaps (study group) and 11 patients who underwent conventionally‐designed DIEP flaps (control group) were included in the present study. The distance from the umbilicus to horizontal scar was divided by the patient's height. The length of the scar was divided by the abdominal circumference. These ratios were compared between groups.

Results

All flaps survived completely and no recipient site complication was observed, except for one case in the control group with small‐range fat necrosis. No donor site complication was observed in either group. The distance ratio was significantly larger in study group (<0.01, 0.049 ± 0.004, and 0.028 ± 0.005, respectively). The length ratio was significantly smaller in the study group <0.01, 0.42 ± 0.02 and 0.36 ± 0.02, respectively). The weight of the flap used for reconstruction was 338.8 ± 127.7 g in the study group and 320.5 ± 63.0 g in the control group

Conclusions

A low‐rise scar DIEP flap leaves a lower and shorter postoperative scar. © 2015 Wiley Periodicals, Inc. Microsurgery 35:451–456, 2015.
A posteriori error estimation for elliptic partial differential equations with small uncertainties
Authors: Guignard Diane , Nobile Fabio , Picasso Marco
Published: August 2015

In this article, a finite element error analysis is performed on a class of linear and nonlinear elliptic problems with small uncertain input. Using a perturbation approach, the exact (random) solution is expanded up to a certain order with respect to a parameter that controls the amount of randomness in the input and discretized by finite elements. We start by studying a diffusion (linear) model problem with a random coefficient characterized via a finite number of random variables. The main focus of the article is the derivation of a priori and a posteriori error estimates of the error between the exact and approximate solution in various norms, including goal‐oriented error estimation. The analysis is then extended to a class of nonlinear problems. We finally illustrate the theoretical results through numerical examples, along with a comparison with the Stochastic Collocation method in terms of computational costs. © 2015 Wiley Periodicals, Inc. Numer Methods Partial Differential Eq 32: 175–212, 2016
Convergence of goal‐oriented adaptive finite element methods for nonsymmetric problems
Authors: Holst Michael , Pollock Sara
Published: August 2015

In this article, we develop convergence theory for a class of goal‐oriented adaptive finite element algorithms for second‐order nonsymmetric linear elliptic equations. In particular, we establish contraction results for a method of this type for Dirichlet problems involving the elliptic operator
with A Lipschitz, symmetric positive definite, with b divergence‐free, and with
. We first describe the problem class and review some standard facts concerning conforming finite element discretization and error‐estimate‐driven adaptive finite element methods (AFEM). We then describe a goal‐oriented variation of standard AFEM. Following the recent work of Mommer and Stevenson for symmetric problems, we establish contraction and convergence of the goal‐oriented method in the sense of the goal function. Our analysis approach is signficantly different from that of Mommer and Stevenson, combining the recent contraction frameworks developed by Cascon, Kreuzer, Nochetto, and Siebert; by Nochetto, Siebert, and Veeser; and by Holst, Tsogtgerel, and Zhu. We include numerical results, demonstrating performance of our method with standard goal‐oriented strategies on a convection problem. © 2015 Wiley Periodicals, Inc. Numer Methods Partial Differential Eq 32: 479–509, 2016
Efficacy of water preloading before main meals as a strategy for weight loss in primary care patients with obesity: RCT
Authors: Parretti Helen M. , Aveyard Paul , Blannin Andrew , Clifford Susan J. , Coleman Sarah J. , Roalfe Andrea , Daley Amanda J.
Published: August 2015

Objective

To investigate the efficacy of water preloading before meals as a weight loss strategy for adults with obesity.

Methods

A two‐group randomized controlled trial was conducted in Birmingham, England. Eighty‐four adults with obesity were recruited from general practices. All participants were given a face‐to‐face weight management consultation at baseline (30 min) and a follow‐up telephone consultation at 2 weeks (10 min). At baseline, participants were randomized to either drinking 500 ml of water 30 min before their main meals or an attention control group where participants were asked to imagine their stomach was full before meals. The primary outcome was weight change at 12‐week follow‐up. Several measures of adherence were also used, including 24 h total urine collections.

Results

41 participants were randomized to the intervention group and 43 to the comparator group. The water preloading group lost −1.3 kg (95% CI −2.4 to −0.1, P = 0.028) more than comparators at follow up. Adjusting for ethnicity, deprivation, age, and gender resulted in the intervention group losing −1.2 kg (95% CI −2.4 to 0.07, P = 0.063) more than the comparator.

Conclusions

There is preliminary evidence that water preloading before main meals leads to a moderate weight loss at follow up. ISRCTN33238158
Serotonin promotes acinar dedifferentiation following pancreatitis‐induced regeneration in the adult pancreas
Authors: Saponara Enrica , Grabliauskaite Kamile , Bombardo Marta , Buzzi Raphael , Silva Alberto B , Malagola Ermanno , Tian Yinghua , Hehl Adrian B , Schraner Elisabeth M , Seleznik Gitta M , Zabel Anja , Reding Theresia , Sonda Sabrina , Graf Rolf
Published: August 2015

The exocrine pancreas exhibits a distinctive capacity for tissue regeneration and renewal following injury. This regenerative ability has important implications for a variety of disorders, including pancreatitis and pancreatic cancer, diseases associated with high morbidity and mortality. Thus, understanding its underlying mechanisms may help in developing therapeutic interventions. Serotonin has been recognized as a potent mitogen for a variety of cells and tissues. Here we investigated whether serotonin exerts a mitogenic effect in pancreatic acinar cells in three regenerative models, inflammatory tissue injury following pancreatitis, tissue loss following partial pancreatectomy, and thyroid hormone‐stimulated acinar proliferation. Genetic and pharmacological techniques were used to modulate serotonin levels in vivo. Acinar dedifferentiation and cell cycle progression during the regenerative phase were investigated over the course of 2 weeks. By comparing acinar proliferation in the different murine models of regeneration, we found that serotonin did not affect the clonal regeneration of mature acinar cells. Serotonin was, however, required for acinar dedifferentiation following inflammation‐mediated tissue injury. Specifically, lack of serotonin resulted in delayed up‐regulation of progenitor genes and delayed the formation of acinar‐to‐ductal metaplasia and defective acinar cell proliferation. We identified serotonin‐dependent acinar secretion as a key step in progenitor‐based regeneration, as it promoted acinar cell dedifferentiation and the recruitment of type 2 macrophages. Finally, we identified a regulatory Hes1–Ptfa axis in the uninjured adult pancreas, activated by zymogen secretion. Our findings indicated that serotonin plays a critical role in the regeneration of the adult pancreas following pancreatitis by promoting the dedifferentiation of acinar cells. Copyright © 2015 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Evaluation of a Weight‐based Rabbit Anti‐thymocyte Globulin Induction Dosing Regimen for Kidney Transplant Recipients
Authors: Pennington Catherine A. , Tischer Sarah M. , Lee Eliza , Lee Sun , Sindelar James , Park Jeong M.
Published: August 2015

Study Objective

Although rabbit anti‐thymocyte globulin (rATG) is commonly used as induction therapy for kidney transplantation, dosing is not standardized. Recently available findings suggest that even subtle differences in the cumulative dose of rATG induction may have an impact on acute rejection rates for patients receiving steroid‐minimization maintenance immunosuppression. This investigation evaluated the potential consequences of rounding and capping rATG doses in patients receiving steroid‐containing maintenance immunosuppression when calculating the dose based on actual body weight.

Design

Single‐center retrospective cohort study.

Setting

A large academic medical center.

Patients

A total of 261 adult kidney transplant recipients between July 1, 2010, and December 31, 2012, who received rATG induction and were maintained on tacrolimus, mycophenolate, and prednisone.

Methods and Measurements

Incidences of biopsy‐confirmed acute rejection, opportunistic infections and hematologic effects within 12 months posttransplant were assessed for patients receiving a cumulative rATG dose of 5 mg/kg or higher (5.2 ± 0.2 mg/kg, n=138) compared with those who received a cumulative rATG dose lower than  5 mg/kg (4.5 ± 0.6 mg/kg, n=123). The groups had similar baseline characteristics, immunologic risk, and indications for rATG induction. The incidence of clinically relevant biopsy‐confirmed acute rejection was low and similar between the groups (8.7% for rATG of 5 mg/kg or higher vs 8.9% for rATG lower than  5 mg/kg, p=0.944). Patient survival, all‐cause graft survival, and graft function did not differ between the groups. Incidences of cytomegalovirus and BK virus infection as well as the extent and duration of lymphopenia were also similar between the groups.

Conclusions

In combination with triple maintenance immunosuppression consisting of tacrolimus, mycophenolate, and prednisone, modest differences in the cumulative rATG dose were not associated with increased risk of acute rejection. Measures to optimize rATG utilization present opportunities for cost‐saving without sacrificing efficacy in this patient population.
Synthesis of optically active conjugated polymers containing platinum in the main chain: Control of the higher‐order structures by substituents and solvents
Authors: Miyagi Yu , Hirao Takehiro , Haino Takeharu , Sanda Fumio
Published: August 2015

The Sonogashira–Hagihara coupling polymerization of d‐hydroxyphenylglycine‐derived diiodo monomers 1–4 and platinum‐containing diethynyl monomer 5 gave the corresponding polymers [poly(1–5)–(2–5)] with number‐average molecular weights of 19,000–25,000 quantitatively. The polymers were soluble in CHCl3, CH2Cl2, THF, and DMF. CD and UV–vis spectroscopic analysis revealed that amide‐substituted polymers [poly(1–5) and poly(2–5)] formed chiral higher‐order structures in solution, while ester‐substituted polymers [poly(3–5) and poly(4–5)] did not. Poly(1–5) formed one‐handed helices in THF/toluene mixtures, while it formed chiral aggregates in THF/MeOH mixtures. Poly(1–5) emitted fluorescence with quantum yields ranging from 0.8 to 1.3%. The polymers usually aggregated in the solid state. © 2015 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2015, 53, 2452–2461
Effect of side chain conjugation lengths on photovoltaic performance of two‐dimensional conjugated copolymers that contain diketopyrrolopyrrole and thiophene with side chains
Authors: Liu You‐Ren , Chan Li‐Hsin , Tang Horng‐Yi
Published: August 2015

Two new two‐dimensional conjugated copolymers that contain diketopyrrolopyrrole and thiophene with different π conjugation lengths as side chains, called PDPPMTD and PDPPBTD, were designed and synthesized for use in polymer solar cells (PSCs). The resulting copolymers in the thin film state displayed broad absorption in the visible range with an absorption edge at over 1000 nm, and both had relatively low‐lying HOMO levels, at −5.20 and −5.18 eV for PDPPMTD and PDPPBTD, respectively. The power conversion efficiency (PCE) of the PSC that was based on PDPPBTD/PC61BM (w/w = 1:2) reached 4.10 % with a Jsc of 14.5 mA/cm2, a Voc of 0.59 V and an FF of 48%, while PDPPMTD/PC61BM (w/w = 1:2) had a PCE of 2.96% with a Jsc of 12.6 mA/cm2, a Voc of 0.60 V, and an FF of 39%. These results indicate that subtle tuning of the chemical structure can significantly influence Jsc and FF. © 2015 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2015, 53, 2878–2889
Effect of limonene on the frontal ring opening metathesis polymerization of dicyclopentadiene
Authors: Alzari Valeria , Nuvoli Daniele , Sanna Davide , Ruiu Andrea , Mariani Alberto
Published: August 2015

The frontal ring opening metathesis polymerization (FROMP) of dicyclopentadiene (DCPD) in the presence of limonene, using second generation Grubbs’ catalysts, is reported. The effect of limonene on the amount of catalyst and the typical frontal polymerization parameters, as maximum temperature (Tmax) and velocity of the front (Vf), is studied. In addition, the influence of limonene on the mechanical properties of the polymeric samples is reported. Finally, a deep study on the swelling properties of polymers is done. It has been demonstrated that limonene acts as both inhibitor and solvent of the catalyst. The Tmax, Vf, Tg, and Young modulus values decrease as the amount of limonene increases, and the polymer samples swell in THF depending on the amount of limonene. All results indicate that the limonene addition on FROMP of results in advantages on the polymerization reaction and its parameters and on the final polymer properties. © 2015 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2016, 54, 63–68
Encapsulating Tin Dioxide@Porous Carbon in Carbon Tubes: A Fiber‐in‐Tube Hierarchical Nanostructure for Superior Capacity and Long‐Life Lithium Storage
Authors: Liu Yuan , Lan Jin‐Le , Cai Qing , Yu Yun‐Hua , Lin Yuan‐Hua , Yang Xiao‐Ping
Published: August 2015

A novel fiber‐in‐tube hierarchical nanostructure of SnO2@porous carbon in carbon tubes (SnO2@PC/CTs) is creatively designed and synthesized though a carbon coating on scalable electrospun hybrid nanofibers template and a post‐etching technique. This 1D nanoarchitecture consists of double carbon‐buffering matrixes, i.e., the external carbon tubular shell and the internal porous carbon skeleton, which can work synergistically to address the various issues of SnO2 nanoanode operation, such as pulverization, particle aggregation, and vulnerable electrical contacts between the SnO2 nanoparticles and the carbon conductors. Thus, the as‐obtained SnO2@PC/CTs nanohybrids used as a lithium‐ion‐battery anode exhibits a higher reversible capacity of 1045 mA h g−1 at 0.5 A g−1 after 300 cycles as well as a high‐rate cycling stability after 1000 cycles. The enhanced performance can be attributed to the wonderful merits of the external carbon protective shell for preserving the integrity of the overall electrode, and the internal porous carbon skeleton for inhibiting the aggregation and electrical isolation of the active particles during cycling.
Energy coupling mechanisms of MFS transporters
Authors: Zhang Xuejun C. , Zhao Yan , Heng Jie , Jiang Daohua
Published: August 2015

Major facilitator superfamily (MFS) is a large class of secondary active transporters widely expressed across all life kingdoms. Although a common 12‐transmembrane helix‐bundle architecture is found in most MFS crystal structures available, a common mechanism of energy coupling remains to be elucidated. Here, we discuss several models for energy‐coupling in the transport process of the transporters, largely based on currently available structures and the results of their biochemical analyses. Special attention is paid to the interaction between protonation and the negative‐inside membrane potential. Also, functional roles of the conserved sequence motifs are discussed in the context of the 3D structures. We anticipate that in the near future, a unified picture of the functions of MFS transporters will emerge from the insights gained from studies of the common architectures and conserved motifs.
Protein structure refinement via molecular‐dynamics simulations: What works and what does not?
Authors: Feig Michael , Mirjalili Vahid
Published: August 2015

Protein structure refinement during CASP11 by the Feig group was described. Molecular dynamics simulations were used in combination with an improved selection and averaging protocol. On average, modest refinement was achieved with some targets improved significantly. Analysis of the CASP submission from our group focused on refinement success versus amount of sampling, refinement of different secondary structure elements and whether refinement varied as a function of which group provided initial models. The refinement of local stereochemical features was examined via the MolProbity score and an updated protocol was developed that can generate high‐quality structures with very low MolProbity scores for most starting structures with modest computational effort. Proteins 2016; 84(Suppl 1):282–292. © 2015 Wiley Periodicals, Inc.
Heat dissipation and its relation to molecular orbital energies in single‐molecule junctions
Authors: Naimi Yaghoob , Vahedi Javad
Published: August 2015

We present a theoretical study of the heat dissipation in single‐molecule junctions. In order to investigate the heat dissipation in the electrodes and the relationship between the transmission spectra and the electronic structures, we consider a toy model in which electrodes are linked by a two‐level molecular bridge. By using the Landauer approach, we show how heat dissipation in the electrodes of a molecular junction is related to its transmission characteristics. We show that in general, heat is not equally dissipated in the left and right electrodes of the junction and it depends on the bias polarity and the positions of the molecule's energy levels with respect to the Fermi level. Also, we exploit the molecule as a junction and the results show a good agreement with the toy model. Our results for the heat dissipation are remarkable in the sense that they can be used to detect which energy levels of a junction are dominated in the transport process.
Importance of coordination number and bond length in titanium revealed by electronic structure investigations
Authors: Huang Liang‐Feng , Grabowski Blazej , McEniry Eunan , Trinkle Dallas R. , Neugebauer Jörg
Published: August 2015

We study the influence of coordination number and bond length on the phase stability and orbital occupation in Ti using density functional theory. In particular, Ti under a wide range of conditions (equilibrium state, hydrostatic pressure, anisotropic strain, and phase transformations) is systematically investigated allowing us to derive generic energetic and electronic trends. Our analysis of the correlations between electronic structure and the atomic geometry reveals that the most suitable descriptors of the system are an effective coordination number and an effective bond length. Utilizing these descriptors, we show that (i) the phase stability of Ti increases with coordination number, because of the increased number of interatomic bonds; (ii) the occupation number of the d (s and p) orbital decreases (increases) with increasing the bond length, because of the localized (delocalized) character of the d (p and s) orbital. These dependencies are particularly evident after applying a simple harmonic strain correction to the energy and an electron‐transfer correction within the phase. The physical picture derived from pure Ti is used to explain the phase stability and orbital occupation of Ti–Nb and Ti–Zr alloys, which reveals the underlying mechanisms for various experimental phenomena in Ti alloys.
Electronic structure and magnetic properties of an iron‐ and tantalum‐based double perovskite
Authors: He Ying‐Fang , Shao Bin
Published: August 2015

Based on density functional theory, the dynamic stability, electronic structure, and magnetic properties of a LiNbO3 ‐type double perovskite (A2BB′O6), Zn2 FeTaO6, have been studied. Results show that the experimental structure is dynamic stabilized with a spontaneous polarization of 57C cm−2 along the c‐axis. By using GGA+U method, the system is predicted to be a charge transfer type insulator with 4.3 magnetic moment on Fe ion. The easy axis is in the ab‐plane. Calculations on exchange integrals indicate that the magnetic coupling between Fe ions of the Fe–O–Ta–O–Fe bridge is very weak. However, the AFM coupling of the Fe–O–Fe bridge is much stronger, which suggests a potential way to design magnetoelectric materials in ferrimagnetic phase with 3d and 5d ions at B‐ and ‐site in the LiNbO3 double perovskite system.
Mechanistic Evidence of Viscum schimperi (Viscaceae) Antihyperglycemic Activity: From a Bioactivity‐guided Approach to Comprehensive Metabolite Profiling
Authors: Abdallah Hossam M. , Farag Mohamed A. , Abdel‐Naim Ashraf B. , Ghareib Salah A. , Abdel‐Sattar Essam A.
Published: August 2015

Diabetes mellitus is possibly the world's largest growing metabolic disorder. Effective treatment of diabetes is increasingly dependent on active constituents of medicinal plants capable of controlling hyperglycemia as well as its secondary complications. Viscum schimperi Engl. is a plant growing in Saudi Arabia and known for its antidiabetic activity. The potential antidiabetic activity of its methanol extract as well as its chloroform, n‐butanol, and the remaining water fractions was evaluated in streptozotocin‐induced diabetic rats at two dose levels. The antidiabetic activity was assessed through the determination of fasting blood glucose level, insulin levels, area under the curve (AUC) in oral glucose tolerance test, glucose absorption in isolated rat gut assay, and glucose uptake by psoas muscle. Moreover, large‐scale untargeted metabolite profiling of methanol extract was performed via UPLC‐PDA and qTOF‐MS (ultra‐performance liquid chromatography photodiode array detection and quadrupole time‐of‐flight mass spectrometry) respectively, to explore its chemical composition and standardization of its extract. Multivariate statistical analysis including principal component analysis and orthogonal projection to latent structures discriminant analysis was used to determine bioactives in its fractions. In conclusion, oleanane triterpenes and O‐caffeoyl quinic acid conjugates were the major compounds that might account for antihyperglycemic effect of the plant. Copyright © 2015 John Wiley & Sons, Ltd.
Specification of Flows for Flushing Surficial Sand from Cobble Riffles
Authors: James C. S.
Published: August 2015

Maintenance of habitat for benthic organisms and fish spawning may require flushing of sand from gravel or cobble river beds. An approach is proposed for specifying both the magnitude and duration of flow necessary to scour sand to a desired depth over a specified length of riffle bed. Scour is assumed to begin at the upstream end of the reach to be flushed and to progress downstream. The flow magnitude necessary for scour to an equilibrium depth was found from previously published laboratory data to be related to the median sand grain size and its movability number (the ratio of shear velocity to settling velocity). The required flow duration is determined by the time for scour to progress over the specified distance. The progression rate was determined through new laboratory experiments to be related to the flow velocity and depth, the distance advanced, the sand movability number and the channel slope. Application of the approach is illustrated by example. Copyright © 2015 John Wiley & Sons, Ltd.
Learning to collaborate through collaboration: How allying with expert firms influences collaborative innovation within novice firms
Authors: Howard Michael , Steensma H. Kevin , Lyles Marjorie , Dhanaraj Charles
Published: August 2015

Research summary: Strategic alliances have been recognized as a means for firms to learn their partners' proprietary knowledge; such alliances are also valuable opportunities for partner firms to learn tacit organizational routines from their counterparts. We consider how relatively novice technology firms can learn intraorganizational collaborative routines from more experienced alliance partners and then deploy them independently for their own innovative pursuits. We examine the alliance relationships between Eli Lilly & Co. (Lilly), a recognized expert in collaborative innovation, and 55 small biotech partner firms. Using three levels of analysis (firm, patent, and inventor dyad), we find that greater social interaction between the partner firm and Lilly subsequently increases internal collaboration among the partner firm's inventors.

Managerial summary: Can collaborating externally advance internal collaboration? Yes. Our research found that collaboration among scientists at small, early‐stage biotechnology firms significantly increased after these firms formed highly interactive R&D alliances with a large pharmaceutical company known for its expertise in such collaboration. It is well known that alliances help new firms learn specific new technologies and commercialize innovations. Our study broadens the scope of potential benefits of alliances. New firms can also learn collaboration techniques, deploying them internally to enhance their own abilities in collaborative innovation. Managers should take this additional benefit into consideration in developing their alliance strategies. Pursuing alliance partners with expertise in collaboration and keeping a high level of mutual interactions with partner firm personnel should be important considerations to extract this value. Copyright © 2015 John Wiley & Sons, Ltd.