bluuebunny/crossref_metadata_2025 huggingface dataset:
Taxonomy and distribution of the genus Quillaja Molina (Quillajaceae)
Authors: Luebert Federico
Published: December 2014

The taxonomy and distribution of the genus Quillaja (Quillajaceae) is examined and two species, Q. brasiliensis and Q. saponaria, are recognised and keyed out. Quillaja bra‐ siliensis is distributed in southern Brazil, northern Uruguay, northeastern Argentina and eastern Paraguay. The presence of Q. brasiliensis in Peru, indicated in some sources, is not confirmed with herbarium specimens. Quillaja saponaria is distributed in central Chile, besides one doubtful collection from Andean Bolivia. The mention of its presence in Peru is likewise unjustified. A distribution map of the species is provided and two names are lectotypified here.

Se examina la taxonomía y distribución del género Quillaja (Quillajaceae), donde dos especies, Q. brasiliensis y Q. saponaria, se reconocen y diferencian mediante una clave. Quillaja brasiliensis se distribuye en el sur de Brasil, norte de Uruguay, noreste de Argentina y este de Paraguay. La presencia de Q. brasiliensis en Perú, indicada en algunas fuentes, no se ve respaldada por ejemplares de herbario. Quillaja saponaria se distrbuye en Chile central, más una colección dudosa proveniente de los Andes de Bolivia. La mención de Q. saponaria para Perú tampoco se justifica. Se presenta un mapa de distribución de las especies y se lectotipifican dos nombres. (© 2013 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Hydration properties and texture fingerprints of easy‐ and hard‐to‐cook bean varieties
Authors: Kinyanjui Peter K. , Njoroge Daniel M. , Makokha Anselimo O. , Christiaens Stefanie , Ndaka Daniel S. , Hendrickx Marc
Published: December 2014

The objective of this study was to understand the factors that affect the hydration and cooking profiles of different bean varieties. During this study, nine bean varieties were classified as either easy‐to‐cook (ETC) or hard‐to‐cook (HTC) based on a subjective finger pressing test and an objective cutting test. Rose coco, Red haricot, and Zebra beans were classified as ETC, while Canadian wonder, Soya fupi, Pinto, non‐nodulating, Mwezi moja, Gwaku, and New mwezi moja were HTC. The effect of different soaking (pre)‐treatments on the cooking behavior and/or water absorption of whole or dehulled beans was investigated. Dehulling, soaking in high pH and monovalent salt solutions reduced the cooking time of beans, while soaking in low pH and CaCl2 solutions increased the cooking time. Moisture uptake was faster in ETC and dehulled beans. Soaking at high temperatures also increased the hydration rate. The results point to pectin‐related aspects and the rate of water uptake as possible factors that influence the cooking rate of beans.
Association of sialolithiasis with cholelithiasis: A population‐based study
Authors: Hung Shih‐Han , Lin Herng‐Ching , Su Chin‐Hui , Chung Shiu‐Dong
Published: December 2014

Background

The purpose of this study was to evaluate the association between cholelithiasis and developing sialolithiasis using a population‐based coverage database.

Methods

The data for this study were sourced from the Taiwan Longitudinal Health Insurance Database. We included 745 subjects with sialolithiasis as cases and 3725 sex‐matched and age‐matched subjects without sialolithiasis as controls.

Results

Chi‐square test revealed a significant difference in the prevalence of prior cholelithiasis between the cases and controls (8.6% vs 4.1%; p < .001). Furthermore, conditional logistic regression analysis indicated that the odds ratio (OR) of prior cholelithiasis for the cases was 2.19 (95% confidence interval [CI] = 1.62–2.98) when compared with the controls after adjusting for monthly income, geographic location, urbanization level, and tobacco use disorder. The adjusted OR of prior cholelithiasis for cases was 2.20 (95% CI = 1.46–3.33) and 2.15 (95% CI = 1.38–3.42) than controls for men and women, respectively.

Conclusion

This study demonstrates an association between sialolithiasis and cholelithiasis. © 2015 Wiley Periodicals, Inc. Head Neck 38: 560–563, 2016
Multimodal imaging analysis of an orthotopic head and neck cancer mouse model and application of anti‐CD137 tumor immune therapy
Authors: Vahle Anne‐Kristin , Hermann Sven , Schäfers Michael , Wildner Michael , Kerem Alexander , Öztürk Ender , Jure–Kunkel Maria , Franklin Cindy , Lang Stephan , Brandau Sven
Published: December 2014

Background

Recent technical progress makes sophisticated noninvasive imaging methods available for murine models. For the first time, in this study, we applied fluorodeoxyglucose (FDG)‐positron emission tomography (PET)‐CT and FDG‐PET‐MRI to a murine orthotopic model of head and neck cancer immunotherapy.

Methods

Tumor growth of floor of the mouth tumors was evaluated by multimodal small‐animal imaging using FDG‐PET‐CT and FDG‐PET‐MRI. The immunotherapeutic effects of anti‐CD137 antibody therapy were examined on body weight, tumor growth, and tumor‐infiltrating immune cells in longitudinal imaging studies and immunohistochemical analyses.

Results

Imaging revealed aggressive, fast‐growing tumors without evidence of local or distant metastases. CD137 immunotherapy decreased tumor take and growth and stabilized body weight over time. A clear case of tumor regression was demonstrated by longitudinal PET‐CT.

Conclusion

The murine model mimics the characteristics of head and neck cancer in humans and offers excellent opportunities to investigate immunomodulatory anticancer drugs. The CD137 antibody showed antitumor effects in some therapy‐responsive mice. © 2015 Wiley Periodicals, Inc. Head Neck 38: 542–549, 2016
Readability and quality assessment of internet‐based patient education materials related to laryngeal cancer
Authors: Narwani Vishal , Nalamada Keerthana , Lee Michael , Kothari Prasad , Lakhani Raj
Published: December 2014

Background

Patients are increasingly using the internet to access health‐related information. The purpose of this study was to assess the readability and quality of laryngeal cancer‐related websites.

Methods

Patient education materials were identified by performing an internet search using 3 search engines. Readability was assessed using Flesch Reading Ease Score (FRES), Flesch–Kincaid Grade Level (FKGL), and Gunning Fog Index (GFI). The DISCERN instrument was utilized to assess quality of health information.

Results

A total of 54 websites were included in the analysis. The mean readability scores were as follows: FRES, 48.2 (95% confidence interval [CI] = 44.8–51.6); FKGL, 10.9 (95% CI = 10.3–11.5); and GFI, 13.8 (95% CI = 11.3–16.3). These scores suggest that, on average, online information about patients with laryngeal cancer is written at an advanced level. The mean DISCERN score was 49.8 (95% CI = 45.4–54.2), suggesting that online information is of variable quality.

Conclusion

Our study suggests much of the laryngeal cancer information available online is of suboptimal quality and written at a level too difficult for the average adult to read comfortably. © 2015 Wiley Periodicals, Inc. Head Neck 38: 601–605, 2016
Minimum target prices for production of direct‐acting antivirals and associated diagnostics to combat hepatitis C virus
Authors: van de Ven Nikolien , Fortunak Joe , Simmons Bryony , Ford Nathan , Cooke Graham S. , Khoo Saye , Hill Andrew
Published: December 2014

Combinations of direct‐acting antivirals (DAAs) can cure hepatitis C virus (HCV) in the majority of treatment‐naïve patients. Mass treatment programs to cure HCV in developing countries are only feasible if the costs of treatment and laboratory diagnostics are very low. This analysis aimed to estimate minimum costs of DAA treatment and associated diagnostic monitoring. Clinical trials of HCV DAAs were reviewed to identify combinations with consistently high rates of sustained virological response across hepatitis C genotypes. For each DAA, molecular structures, doses, treatment duration, and components of retrosynthesis were used to estimate costs of large‐scale, generic production. Manufacturing costs per gram of DAA were based upon treating at least 5 million patients per year and a 40% margin for formulation. Costs of diagnostic support were estimated based on published minimum prices of genotyping, HCV antigen tests plus full blood count/clinical chemistry tests. Predicted minimum costs for 12‐week courses of combination DAAs with the most consistent efficacy results were: US$122 per person for sofosbuvir+daclatasvir; US$152 for sofosbuvir+ribavirin; US$192 for sofosbuvir+ledipasvir; and US$115 for MK‐8742+MK‐5172. Diagnostic testing costs were estimated at US$90 for genotyping US$34 for two HCV antigen tests and US$22 for two full blood count/clinical chemistry tests. Conclusions: Minimum costs of treatment and diagnostics to cure hepatitis C virus infection were estimated at US$171‐360 per person without genotyping or US$261‐450 per person with genotyping. These cost estimates assume that existing large‐scale treatment programs can be established. (Hepatology 2015;61:1174–1182)
Liver X receptors balance lipid stores in hepatic stellate cells through Rab18, a retinoid responsive lipid droplet protein
Authors: O'Mahony Fiona , Wroblewski Kevin , O'Byrne Sheila M. , Jiang Hongfeng , Clerkin Kara , Benhammou Jihane , Blaner William S. , Beaven Simon W.
Published: December 2014

Liver X receptors (LXRs) are determinants of hepatic stellate cell (HSC) activation and liver fibrosis. Freshly isolated HSCs from Lxrαβ−/− mice have increased lipid droplet (LD) size, but the functional consequences of this are unknown. Our aim was to determine whether LXRs link cholesterol to retinoid storage in HSCs and how this impacts activation. Primary HSCs from Lxrαβ−/− and wild‐type mice were profiled by gene array during in vitro activation. Lipid content was quantified by high‐performance liquid chromatography and mass spectroscopy. Primary HSCs were treated with nuclear receptor ligands, transfected with small interfering RNA and plasmid constructs, and analyzed by immunocytochemistry. Lxrαβ−/− HSCs have increased cholesterol and retinyl esters. The retinoid increase drives intrinsic retinoic acid receptor signaling, and activation occurs more rapidly in Lxrαβ−/− HSCs. We identify Rab18 as a novel retinoic acid‐responsive, LD‐associated protein that helps mediate stellate cell activation. Rab18 mRNA, protein, and membrane insertion increase during activation. Both Rab18 guanosine triphosphatase activity and isoprenylation are required for stellate cell LD loss and induction of activation markers. These phenomena are accelerated in Lxrαβ−/− HSCs, where there is greater retinoic acid flux. Conversely, Rab18 knockdown retards LD loss in culture and blocks activation, just like the functional mutants. Rab18 is also induced with acute liver injury in vivo. Conclusion: Retinoid and cholesterol metabolism are linked in stellate cells by the LD‐associated protein Rab18. Retinoid overload helps explain the profibrotic phenotype of Lxrαβ−/− mice, and we establish a pivotal role for Rab18 GTPase activity and membrane insertion in wild‐type stellate cell activation. Interference with Rab18 may have significant therapeutic benefit in ameliorating liver fibrosis. (Hepatology 2015;62:615–626
Ezetimibe for the treatment of nonalcoholic steatohepatitis: Assessment by novel magnetic resonance imaging and magnetic resonance elastography in a randomized trial (MOZART trial)
Authors: Loomba Rohit , Sirlin Claude B. , Ang Brandon , Bettencourt Ricki , Jain Rashmi , Salotti Joanie , Soaft Linda , Hooker Jonathan , Kono Yuko , Bhatt Archana , Hernandez Laura , Nguyen Phirum , Noureddin Mazen , Haufe William , Hooker Catherine , Yin Meng , Ehman Richard , Lin Grace Y. , Valasek Mark A. , Brenner David A. , Richards Lisa ,   for the San Diego Integrated NAFLD Research Consortium (SINC)
Published: December 2014

Ezetimibe inhibits intestinal cholesterol absorption and lowers low‐density lipoprotein cholesterol. Uncontrolled studies have suggested that it reduces liver fat as estimated by ultrasound in nonalcoholic steatohepatitis (NASH). Therefore, we aimed to examine the efficacy of ezetimibe versus placebo in reducing liver fat by the magnetic resonance imaging‐derived proton density‐fat fraction (MRI‐PDFF) and liver histology in patients with biopsy‐proven NASH. In this randomized, double‐blind, placebo‐controlled trial, 50 patients with biopsy‐proven NASH were randomized to either ezetimibe 10 mg orally daily or placebo for 24 weeks. The primary outcome was a change in liver fat as measured by MRI‐PDFF in colocalized regions of interest within each of the nine liver segments. Novel assessment by two‐dimensional and three‐dimensional magnetic resonance elastography was also performed. Ezetimibe was not significantly better than placebo at reducing liver fat as measured by MRI‐PDFF (mean difference between the ezetimibe and placebo arms ‐1.3%, P = 0.4). Compared to baseline, however, end‐of‐treatment MRI‐PDFF was significantly lower in the ezetimibe arm (15%‐11.6%, P < 0.016) but not in the placebo arm (18.5%‐16.4%, P = 0.15). There were no significant differences in histologic response rates, serum alanine aminotransferase and aspartate aminotransferase levels, or longitudinal changes in two‐dimensional and three‐dimensional magnetic resonance elastography‐derived liver stiffness between the ezetimibe and placebo arms. Compared to histologic nonresponders (25/35), histologic responders (10/35) had a significantly greater reduction in MRI‐PDFF (‐4.35 ± 4.9% versus ‐0.30 ± 4.1%, P < 0.019). Conclusions: Ezetimibe did not significantly reduce liver fat in NASH. This trial demonstrates the application of colocalization of MRI‐PDFF‐derived fat maps and magnetic resonance elastography‐derived stiffness maps of the liver before and after treatment to noninvasively assess treatment response in NASH. (Hepatology 2015;61:1239–1250)
Primary human papillomavirus DNA screening for cervical cancer prevention: Can the screening interval be safely extended?
Authors: Vink Margaretha A. , Bogaards Johannes A. , Meijer Chris J.L.M. , Berkhof Johannes
Published: December 2014

Cytological screening has substantially decreased the cervical cancer incidence, but even better protection may be achieved by primary high‐risk human papillomavirus (hrHPV) screening. In the Netherlands, five‐yearly cytological screening for women aged 30–60 years will be replaced by primary hrHPV screening in 2016. The new screening guidelines involve an extension of the screening interval from 5 to 10 years for hrHPV‐negative women aged 40 or 50 years. We investigated the impact of this program change on the lifetime cancer risks in women without an hrHPV infection at age 30, 35, 40, 45 or 50 years. The time to cancer was estimated using 14‐year follow‐up data from a population‐based screening intervention trial and the nationwide database of histopathology reports. The new screening guidelines are expected to lead to a reduced cervical cancer risk for all age groups. The average risk reduction was 34% and was smallest (25%) among women aged 35 years. The impact of hrHPV screening on the cancer risk was sensitive to the duration from cervical intraepithelial neoplasia grade 2/3 (CIN2/3) to cancer; a small increase in the cancer risk was estimated for women aged 35 or 40 years in case a substantial proportion of CIN2/3 showed fast progression to cancer. Our results indicate that primary hrHPV screening with a ten‐yearly interval for hrHPV‐negative women of age 40 and beyond will lead to a further reduction in lifetime cancer risk compared to five‐yearly cytology, provided that precancerous lesions progress slowly to cancer.
Effects of resistance exercise on fatigue and quality of life in breast cancer patients undergoing adjuvant chemotherapy: A randomized controlled trial
Authors: Schmidt Martina E. , Wiskemann Joachim , Armbrust Petra , Schneeweiss Andreas , Ulrich Cornelia M. , Steindorf Karen
Published: December 2014

Multiple exercise interventions have shown beneficial effects on fatigue and quality of life (QoL) in cancer patients, but various psychosocial interventions as well. It is unclear to what extent the observed effects of exercise interventions are based on physical adaptations or rather on psychosocial factors associated with supervised, group‐based programs. It needs to be determined which aspects of exercise programs are truly effective. Therefore, we aimed to investigate whether resistance exercise during chemotherapy provides benefits on fatigue and QoL beyond potential psychosocial effects of group‐based interventions. One‐hundred‐one breast cancer patients starting chemotherapy were randomly assigned to resistance exercise (EX) or a relaxation control (RC) group. Both interventions were supervised, group‐based, 2/week over 12 weeks. The primary endpoint fatigue was assessed with a 20‐item multidimensional questionnaire, QoL with the EORTC QLQ‐C30/BR23. Analyses of covariance for individual changes from baseline to Week 13 were calculated. In RC, total and physical fatigue worsened during chemotherapy, whereas EX showed no such impairments (between‐group p = 0.098 and 0.052 overall, and p = 0.038 and 0.034 among patients without severe baseline depression). Differences regarding affective or cognitive fatigue were not significant. Benefits of EX were also seen to affect role and social function. Effect sizes were between 0.43 and 0.48. Explorative analyses indicated significant effect modification by thyroxin use (p‐interaction = 0.044). In conclusion, resistance exercise appeared to mitigate physical fatigue and maintain QoL during chemotherapy beyond psychosocial effects inherent to supervised group‐based settings. Thus, resistance exercise could be an integral part of supportive care for breast cancer patients undergoing chemotherapy.
PTH(1-34) Treatment Increases Bisphosphonate Turnover in Fracture Repair in Rats
Authors: Murphy Ciara M , Schindeler Aaron , Cantrill Laurence C , Mikulec Kathy , Peacock Lauren , Little David G
Published: December 2014

Bisphosphonates (BP) are antiresorptive drugs with a high affinity for bone. Despite the therapeutic success in treating osteoporosis and metabolic bone diseases, chronic BP usage has been associated with reduced repair of microdamage and atypical femoral fracture (AFF). The latter has a poor prognosis, and although anabolic interventions such as teriparatide (PTH(1–34)) have been suggested as treatment options, there is a limited evidence base in support of their efficacy. Because PTH(1–34) acts to increase bone turnover, we hypothesized that it may be able to increase BP in turnover in the skeleton, which, in turn, may improve bone healing. To test this, we employed a mixture of fluorescent Alexa647-labelled pamidronate (Pam) and radiolabeled 14C-ZA (zoledronic acid). These traceable BPs were dosed to Wistar rats in models of normal growth and closed fracture repair. Rats were cotreated with saline or 25 μg/kg/d PTH(1–34), and the effects on BP liberation and bone healing were examined by X-ray, micro-CT, autoradiography, and fluorescent confocal microscopy. Consistent with increased BP remobilization with PTH(1–34), there was a significant decrease in fluorescence in both the long bones and in the fracture callus in treated animals compared with controls. This was further confirmed by autoradiography for 14C-ZA. In this model of acute BP treatment, callus bone volume (BV) was significantly increased in fractured limbs, and although we noted significant decreases in callus-bound BP with PTH(1–34), these were not sufficient to alter this BV. However, increased intracellular BP was noted in resorbing osteoclasts, confirming that, in principle, PTH(1–34) increases bone turnover as well as BP turnover. © 2015 American Society for Bone and Mineral Research.
Osteoblast-Specific Expression of the Fibrous Dysplasia (FD)–Causing Mutation GsαR201C Produces a High Bone Mass Phenotype but Does Not Reproduce FD in the Mouse
Authors: Remoli Cristina , Michienzi Stefano , Sacchetti Benedetto , Consiglio Alberto Di , Cersosimo Stefania , Spica Emanuela , Robey Pamela G , Holmbeck Kenn , Cumano Ana , Boyde Alan , Davis Graham , Saggio Isabella , Riminucci Mara , Bianco Paolo
Published: December 2014

We recently reported the generation and initial characterization of the first direct model of human fibrous dysplasia (FD; OMIM #174800), obtained through the constitutive systemic expression of one of the disease-causing mutations, GsαR201C, in the mouse. To define the specific pathogenetic role(s) of individual cell types within the stromal/osteogenic system in FD, we generated mice expressing GsαR201C selectively in mature osteoblasts using the 2.3kb Col1a1 promoter. We show here that this results in a striking high bone mass phenotype but not in a mimicry of human FD. The high bone mass phenotype involves specifically a deforming excess of cortical bone and prolonged and ectopic cortical bone remodeling. Expression of genes characteristic of late stages of bone cell differentiation/maturation is profoundly altered as a result of expression of GsαR201C in osteoblasts, and expression of the Wnt inhibitor Sost is reduced. Although high bone mass is, in fact, a feature of some types/stages of FD lesions in humans, it is marrow fibrosis, localized loss of adipocytes and hematopoietic tissue, osteomalacia, and osteolytic changes that together represent the characteristic pathological profile of FD, as well as the sources of specific morbidity. None of these features are reproduced in mice with osteoblast-specific expression of GsαR201C. We further show that hematopoietic progenitor/stem cells, as well as more mature cell compartments, and adipocyte development are normal in these mice. These data demonstrate that effects of Gsα mutations underpinning FD-defining tissue changes and morbidity do not reflect the effects of the mutations on osteoblasts proper. © 2015 American Society for Bone and Mineral Research. © 2014 American Society for Bone and Mineral Research
Surface Plasmon Resonance‐based Inhibitive Immunoassay Coupled with Dummy Template Molecularly Imprinted Polymer Solid Phase Extraction for On‐line Analysis of Trace Clenbuterol
Authors: Tang Pingping , Huo Jichuan , Zhang Hongping , Lei Hong , Lin Xiaoyan
Published: December 2014

A new indirect inhibitive immunoassay using surface plasmon resonance (SPR) coupled with molecularly imprinted polymer (MIP) was developed and applied for the analysis of trace clenbuterol (CL). A MIP coating using phenylephrine as the dummy template was synthesized in a flexible quartz capillary (30 cm×0.25 mm i.d.) by in situ polymerization technique, which then was used as the online solid phase extraction (SPE) tube before SPR detection. The thickness of the coating was 198 nm on average, illustrated by scanning electron microscope (SEM) image. The mechanism for adsorption of CL on dummy template MIP was found to be a Freundlich isotherm and pseudo‐second‐order model. The immunoassay was conducted on BIAcore 3000 biosensor automatically without pre‐treatment. The calibration curve was generated by linear fit in the range of 0.1–10 ng L‐1 and 10–100 ng L‐1. The detection limit was 0.1 ng L–1, which is super sensitive. This method was directly applied for the analysis of real‐world samples without pretreatment.
Synthesis of uniformly deuterated n‐dodecyl‐β‐d‐maltoside (d39‐DDM) for solubilization of membrane proteins in TROSY NMR experiments
Authors: Hiruma‐Shimizu Kazumi , Kalverda Arnout P. , Henderson Peter J. F. , Homans Steve W. , Patching Simon G.
Published: December 2014

This work reports the first synthesis of uniformly deuterated n‐dodecyl‐β‐d‐maltoside (d39‐DDM). DDM is a mild non‐ionic detergent often used in the extraction and purification of membrane proteins and for solubilizing them in experimental studies of their structure, dynamics and binding of ligands. We required d39‐DDM for solubilizing large α‐helical membrane proteins in samples for [15N–1H]TROSY (transverse relaxation‐optimized spectroscopy) NMR experiments to achieve the highest sensitivity and best resolved spectra possible. Our synthesis of d39‐DDM used d7‐d‐glucose and d25‐n‐dodecanol to introduce deuterium labelling into both the maltoside and dodecyl moieties, respectively. Two glucose molecules, one converted to a glycosyl acceptor with a free C4 hydroxyl group and one converted to a glycosyl donor substituted at C1 with a bromine in the α‐configuration, were coupled together with an α(1 → 4) glycosidic bond to give maltose, which was then coupled with n‐dodecanol by its substitution of a C1 bromine in the α‐configuration to give DDM. 1H NMR spectra were used to confirm a high level of deuteration in the synthesized d39‐DDM and to demonstrate its use in eliminating interfering signals from TROSY NMR spectra of a 52‐kDa sugar transport protein solubilized in DDM.
Seroepidemiology and occult hepatitis B virus infection in young adults in Banjarmasin, Indonesia
Authors: Darmawan Erica , Turyadi  , El‐Khobar Korri E. , Nursanty Ni Ketut Dias , Thedja Meta D. , Muljono David Handojo
Published: December 2014

Hepatitis B virus (HBV) infection remains a public health problem in Indonesia. There has been limited data regarding HBV infection in young adult population. This study aimed to evaluate the seroepidemiology of HBV infection and characterize occult HBV variants in healthy young adults in Banjarmasin, Indonesia, who were born before the implementation of the universal infant hepatitis B vaccination. Serum samples of 195 healthy young adults were tested for HBsAg, anti‐HBc, and anti‐HBs. The prevalence of HBsAg, anti‐HBc, and anti‐HBs was 9 (4.6%), 62 (31.8%), and 96 (49.2%), respectively. Seventy four (37.9%) samples were seronegative for all three parameters, indicating the susceptibility to HBV infection. Among 66 samples positive for HBsAg and/or anti‐HBc, 13 (19.7%) were HBV DNA positive; of these, four were HBsAg positive and nine were HBsAg negative, and categorized as occult HBV infection. Most occult HBV cases had high‐level anti‐HBs (>100 IU/l), suggesting that blood with positive anti‐HBs and anti‐HBc could not be regarded as noninfectious. Thirteen amino acid substitutions were identified: T126S, P127S, Q129R, T131N, M133T, and Y161S in the HBsAg‐positive group; P120T, T126I, G145S, Y161F, E164V, and V168F in the occult‐HBV group; and T143S in both groups. More studies are required to provide data on the prevalence and characteristics of mutants to ensure reliable diagnosis. The occult HBV infection, combined with the HBsAg prevalence, could indicate the high HBV carriage among young adults in this area. The high percentage of individuals susceptible to HBV infection reiterates the need for catch‐up immunization strategies targeted at young adults. J. Med. Virol. 87:199–207, 2015. © 2014 Wiley Periodicals, Inc.
High prevalence and genetic diversity of noroviruses among children with sporadic acute gastroenteritis in Nanning City, China, 2010–2011
Authors: Tan Dongmei , Deng Lili , Wang Mingliu , Li Xiugui , Ma Yuyan , Liu Wei
Published: December 2014

A molecular epidemiological study of Norovirus (NoV) infections in children aged <5 years was conducted in the outpatient department of a hospital between January 2010 and December 2011 in Nanning City, Guangxi Zhuang Autonomous Region of China. Fecal samples were collected from 354 pediatric patients with acute gastroenteritis, and were screened for the presence of NoV with one‐step real‐time reverse‐transcription polymerase chain reaction (RT‐PCR). NoV genogroup II (GII) was detected in 28.5% (101/342) of samples, but no NoV GI was found. Eighty‐four of the NoV GII strains were successfully sequenced, and they were clustered into seven genotypes: GII.4 (77.4%), GII.2 (8.3%), GII.14 (4.8%), GII.7 (3.6%), GII.3 (2.4%), GII.6 (2.4%), and GII.12 (1.2%). The predominant GII.4 variant in circulation was variant 2006b (92.3%). Importantly, the emergence of variant GII.4 2010 was detected. NoV was detected throughout the year, but mainly during the cold months. The highest prevalence of NoV was detected in young children aged <2 years. The NoV detection rates did not differ significantly in males and females. This is the first report to demonstrate the high prevalence and genetic diversity of NoVs in children with sporadic acute gastroenteritis in Nanning. Our study findings indicate the need for continual surveillance to monitor epidemiological changes and potential new variants of these viruses. J. Med. Virol. 87:498–503, 2015. © 2014 Wiley Periodicals, Inc.
The impact of stress in decision making in the context of uncertainty
Authors: Morgado P. , Sousa N. , Cerqueira J.J.
Published: December 2014

For a number of decades, different fields of knowledge, including psychology, economics, and neurosciences, have focused their research efforts on a better understanding of the decision‐making process. Making decisions based on the probability of future events is routine in everyday life; it occurs whenever individuals select an option from several alternatives, each one associated with a specific value. Sometimes subjects decide knowing the precise outcomes of each option, but commonly they have to decide without knowing the consequences (because either ambiguity or risk is involved). Stress has a broad impact on animal behaviors, affects brain regions involved in decision‐making processes, and, when maladaptive, is a trigger for neuropsychiatric disorders. This Mini‐Review provides a comprehensive overview on how stress impacts decision‐making processes, particularly under uncertain conditions. Understanding this can prove to be useful for intervention related to impairments to decision‐making processes that present in several stress‐triggered neuropsychiatric disorders. © 2014 Wiley Periodicals, Inc.
Outcomes following splenectomy in patients with myeloid neoplasms
Authors: Rialon Kristy L. , Speicher Paul J. , Ceppa Eugene P. , Rendell Victoria R. , Vaslef Steven N. , Beaven Anne , Tyler Douglas S. , Blazer Dan G.
Published: December 2014

Background and Objectives

Myeloid neoplasms are classified into five major categories. These patients may develop splenomegaly and require splenectomy to alleviate mechanical symptoms, to ameliorate transfusion‐dependent cytopenias, or to enhance stem cell transplantation. The objective of this study was to determine which clinical variables significantly impacted morbidity, mortality, and survival in patients with myeloid neoplasms undergoing splenectomy, and to determine if operative outcomes have improved over time.

Methods

The records of all patients with myeloid neoplasms undergoing splenectomy from 1993 to 2010 were retrospectively reviewed.

Results

Eighty‐nine patients (n = 89) underwent splenectomy for myeloid neoplasms. Over half of patients who had symptoms preoperatively had resolution of their symptoms post‐splenectomy. The morbidity rate was 38%, with the most common complications being bleeding (14%) or infection (20%). Thirty‐day mortality rate was 18% and median survival after splenectomy was 278 days. Decreased survival was associated with a diagnosis of myelodysplastic syndrome/myeloproliferative neoplasm, anemia, abnormal white blood cell count, and hypoalbuminemia. Patients who underwent stem cell transplantation did not show an increased risk for morbidity or mortality.

Conclusions

Patients with myeloid neoplasms have a poor prognosis after splenectomy and the decision to operate is a difficult one, associated with high morbidity and mortality. J. Surg. Oncol. 2015 111:389–395. © 2014 Wiley Periodicals, Inc.
Soft tissue sarcomas: Staging principles and prognostic nomograms
Authors: Massarweh Nader N. , Dickson Paxton V. , Anaya Daniel A.
Published: December 2014

Soft tissue sarcomas (STS) are a rare and heterogenous group of tumors that often represent a management challenge. The American Joint Committee on Cancer system is currently used to stage tumors and direct treatment. Limitations of the current STS staging system, future potential direction for pre‐operative staging, as well as the benefit of predictive nomograms for filling current knowledge gaps are all discussed. J. Surg. Oncol. 2015 111:532–539. Published 2014. This article has been contributed to by US Government employees and their work is in the public domain in the USA.
Determination of four acidic nonsteroidal anti‐inflammatory drugs in wastewater samples by dispersive liquid–liquid microextraction based on solidification of floating organic droplet and high‐performance liquid chromatography
Authors: Beldean‐Galea Mihail Simion , Coman Virginia , Thiébaut Didier , Vial Jérome
Published: December 2014

A simple, environmentally friendly, and sensitive dispersive liquid–liquid microextraction based on solidification of floating organic droplet for the extraction of four acidic nonsteroidal anti‐inflammatory drugs (ketoprofen, naproxen, ibuprofen, and diclofenac) from wastewater samples subsequent by high‐performance liquid chromatography analysis was developed. The influence of extraction parameters such as pH, the effect of solution ionic strength, type of extraction solvent, disperser solvent, and extraction solvent volume were studied. High enrichment factors (283–302) were obtained through the developed method. The method provides good linearity (r > 0.999) in a concentration range of 1–100 μg/L, good intra‐ and inter‐day precision (relative standard deviation < 7%) and low limits of quantification. The relative recoveries of the selected compounds were situated over 80% both in synthetic and real water samples. The developed method has been successfully applied for the analysis of the selected compounds in wastewater samples.
Liquid chromatography under limiting conditions of desorption 6: Separation of a four‐component polymer blend
Authors: Berek Dušan , Macová Eva
Published: December 2014

Baseline separation was achieved of a model four‐component polymer blend of polystyrene‐poly(methyl methacrylate)‐poly(ethylene oxide)‐poly(2‐vinyl pyridine) in a single chromatographic run with help of the unconventional method of liquid chromatography under limiting conditions of desorption. Narrow barriers of liquids were employed, which selectively decelerated elution of particular kinds of macromolecules. Bare silica gel was the column packing, and the eluent was a mixture of dimethylformamide/tetrahydrofuran/toluene 30:50:20 w/w/w. Barrier compositions were neat toluene, B#1, neat tetrahydrofuran, B#2, and dimethylformamide/tetrahydrofuran/toluene 15:55:30, B#3. Minor blend constituents (∼1%) could be identified, as well. The result represents a step toward the separation and molecular characterization of triblock‐copolymers, many of which are expected to contain besides both parent homopolymers also the diblock chains and thus they are in fact four‐component polymer blends.
In vivo molecular mapping of the tumor microenvironment in an azoxymethane‐treated mouse model of colon carcinogenesis
Authors: Leung Sarah J. , Rice Photini S. , Barton Jennifer K.
Published: December 2014

Background and Objective

Development of miniaturized imaging systems with molecular probes enables examination of molecular changes leading to initiation and progression of colorectal cancer in an azoxymethane (AOM)‐induced mouse model of the disease. Through improved and novel studies of animal disease models, more effective diagnostic and treatment strategies may be developed for clinical translation. We introduce use of a miniaturized multimodal endoscope with lavage‐delivered fluorescent probes to examine dynamic microenvironment changes in an AOM‐treated mouse model.

Study Design/Materials and Methods

The endoscope is equipped with optical coherence tomography (OCT) and laser induced fluorescence (LIF) imaging modalities. It is used with Cy5.5‐conjugated antibodies to create time‐resolved molecular maps of colon carcinogenesis. We monitored in vivo changes in molecular expression over a five month period for four biomarkers: epithelial growth factor receptor (EGFR), transferrin receptor (TfR), transforming growth factor beta 1 (TGFβ1), and chemokine (C‐X‐C motif) receptor 2 (CXCR2). In vivo OCT and LIF images were compared over multiple time points to correlate increases in biomarker expression with adenoma development.

Results

This system is uniquely capable of tracking in vivo changes in molecular expression over time. Increased expression of the biomarker panel corresponded to sites of disease and offered predictive utility in highlighting sites of disease prior to detectable structural changes. Biomarker expression also tended to increase with higher tumor burden and growth rate in the colon.

Conclusion

We can use miniaturized dual modality endoscopes with fluorescent probes to study the tumor microenvironment in developmental animal models of cancer and supplement findings from biopsy and tissue harvesting. Lasers Surg. Med. 47:40–49, 2015. © 2014 Wiley Periodicals, Inc.
Noninvasive 3‐dimensional imaging of liver regeneration in a mouse model of hereditary tyrosinemia type 1 using the sodium iodide symporter gene
Authors: Hickey Raymond D. , Mao Shennen A. , Amiot Bruce , Suksanpaisan Lukkana , Miller Amber , Nace Rebecca , Glorioso Jaime , O'Connor Michael K. , Peng Kah Whye , Ikeda Yasuhiro , Russell Stephen J. , Nyberg Scott L.
Published: December 2014

Cell transplantation is a potential treatment for the many liver disorders that are currently only curable by organ transplantation. However, one of the major limitations of hepatocyte (HC) transplantation is an inability to monitor cells longitudinally after injection. We hypothesized that the thyroidal sodium iodide symporter (NIS) gene could be used to visualize transplanted HCs in a rodent model of inherited liver disease: hereditary tyrosinemia type 1. Wild‐type C57Bl/6J mouse HCs were transduced ex vivo with a lentiviral vector containing the mouse Slc5a5 (NIS) gene controlled by the thyroxine‐binding globulin promoter. NIS‐transduced cells could robustly concentrate radiolabeled iodine in vitro, with lentiviral transduction efficiencies greater than 80% achieved in the presence of dexamethasone. Next, NIS‐transduced HCs were transplanted into congenic fumarylacetoacetate hydrolase knockout mice, and this resulted in the prevention of liver failure. NIS‐transduced HCs were readily imaged in vivo by single‐photon emission computed tomography, and this demonstrated for the first time noninvasive 3‐dimensional imaging of regenerating tissue in individual animals over time. We also tested the efficacy of primary HC spheroids engrafted in the liver. With the NIS reporter, robust spheroid engraftment and survival could be detected longitudinally after direct parenchymal injection, and this thereby demonstrated a novel strategy for HC transplantation. This work is the first to demonstrate the efficacy of NIS imaging in the field of HC transplantation. We anticipate that NIS labeling will allow noninvasive and longitudinal identification of HCs and stem cells in future studies related to liver regeneration in small and large preclinical animal models. Liver Transpl 21:442–453, 2015. © 2015 AASLD.
MINDFUL LEADERS HAVE MOXIE
Authors: Baldoni John
Published: December 2014

The financial crash of 2008 continues to leave side effects, one being diminished confidence in leaders. Baldoni contends that today's leaders in the post‐crash world need greater levels of resilience. He borrows the 1930s‐era term “moxie” to describe this new sense of resilience. “Those who have steered their companies back to prosperity,” he writes, “did it by making tougher, wiser choices, and moving forward in hard times.” Think of moxie also as an acronym, representing mindfulness, opportunity, X‐factor, innovation, and engagement. If you lead with moxie, you will be prepared for constant change and will be a source of inspiration to others.
CREATING A PERSONAL LEADERSHIP STRATEGY
Authors: Lidow Derek
Published: December 2014

Lidow guides those who want to be considered entrepreneurial leaders, with an assertion that it is entrepreneurs who lead their enterprises to success, not just their ideas. He says they “must master five skills: self‐awareness, the basics of enterprises, relationship building, motivation, and change leadership.” The vehicle for accomplishing this is the personal leadership strategy. He details five steps: tapping into core motivations, finding objective mentors, inventorying your traits, assessing your skills, and, finally, drafting your strategy. An important feature for decision making is asking yourself what is the best and worst that could happen if you choose to do or not do a particular activity.
Silibinin and its 2,3‐dehydro‐derivative inhibit basal cell carcinoma growth via suppression of mitogenic signaling and transcription factors activation
Authors: Tilley Cynthia , Deep Gagan , Agarwal Chapla , Wempe Michael F. , Biedermann David , Valentová Kateřina , Kren Vladimir , Agarwal Rajesh
Published: December 2014

Basal cell carcinoma (BCC) is the most common cancer worldwide, and its current treatment options are insufficient and toxic. Surprisingly, unlike several other malignancies, chemopreventive efforts against BCC are almost lacking. Silibinin, a natural agent from milk thistle seeds, has shown strong efficacy against several cancers including ultraviolet radiation‐induced skin (squamous) cancer; however, its potential activity against BCC is not yet examined. Herein, for the first time, we report the efficacy of silibinin and its oxidation product 2,3‐dehydrosilibinin (DHS) against BCC both in vitro and in vivo using ASZ (p53 mutated) and BSZ (p53 deleted) cell lines derived from murine BCC tumors. Both silibinin and DHS significantly inhibited cell growth and clonogenicity while inducing apoptosis in a dose‐ and time‐dependent manner, with DHS showing higher activity at lower concentrations. Both agents also inhibited the mitogenic signaling by reducing EGFR, ERK1/2, Akt, and STAT3 phosphorylation and suppressed the activation of transcription factors NF‐κB and AP‐1. More importantly, in an ectopic allograft model, oral administration of silibinin and DHS (200 mg/kg body weight) strongly inhibited the ASZ tumor growth by 44% and 71% (P < 0.05), respectively, and decreased the expression of proliferation biomarkers (PCNA and cyclin D1) as well as NF‐κB p50 and c‐Fos in the tumor tissues. Taken together, these results provide the first evidence for the efficacy and usefulness of silibinin and its derivative DHS against BCC, and suggest the need for additional studies with these agents in pre‐clinical and clinical BCC chemoprevention and therapy models. © 2014 Wiley Periodicals, Inc.
Motor phenotype of LRRK2‐associated Parkinson's disease: A tunisian longitudinal study
Authors: Nabli Fatma , Ben Sassi Samia , Amouri Rim , Duda John E. , Farrer Matthew J. , Hentati Fayçal
Published: December 2014

Mutations in the leucine‐rich repeat kinase 2 gene (LRRK2) were found to be a significant cause of late‐onset autosomal dominant forms of Parkinson's disease (PD). To determine the motor characteristics of LRRK2‐related disease, we conducted a longitudinal study of 58 G2019S LRRK2‐associated PD patients and compared them with genetically undefined (GU) PD patients. Fifty‐eight patients diagnosed with PD‐related LRRK2 G2019S mutation were included in the study and compared with 54 sporadic PD patients with negative tests for LRRK2 G2019S, PINK1, SNCA, PRKN, and DJ1 mutations. Patients were assessed at baseline and after a follow‐up period of 6 years. The Movement Disorder Society–Unified Parkinson's Disease Rating Scale (MDS‐UPDRS), the Hoehn and Yahr, and the Schwab and England scores were determined. Logistic regression was used to examine associations of G2019S mutation status with motor phenotype and rate of motor decline. The LRRK2‐associated PD patients had a mean age of onset of 56.25 ± 12.05 years and in most cases (58.6%) a postural instability gait difficulty (PIGD) phenotype. The mean annual decline in the MDS‐UDRS III motor score and the Hoehn and Yahr staging was of 1.3% and 2%, respectively. The PIGD phenotype predicted a more rapid progression of motor impairment. The PD motor phenotype and motor scores were similar in the LRRK2‐associated PD group and in the GU PD group, with no significant differences in the progression rate of motor impairment. Motor phenotype seems to be similar in LRRK2‐related PD and idiopathic PD. © 2014 International Parkinson and Movement Disorder Society
Behavioral effects of levodopa
Authors: Beaulieu‐Boire Isabelle , Lang Anthony E.
Published: December 2014

In recent years, levodopa‐induced behavioral changes have received increased attention in the medical literature and in clinical practice. The spectrum of these symptoms includes non‐motor fluctuations with neuropsychiatric symptoms, compulsive behaviors such as punding, dopamine dysregulation syndrome, and impulse control disorders, psychosis and hallucinations, as well as hypomania and mania. Despite knowledge of the clinical features associated with these behaviors, many of them are probably underdiagnosed. Although the mechanisms underlying behavioral symptoms are still incompletely understood, recent data from imaging and pathological studies have increased our understanding and guided new treatment strategies. Appropriate management remains challenging, because reduction of levodopa (l‐dopa) and dopaminergic treatment is often recommended; however, doses required for control of motor symptoms may still induce behavioral changes. Newer modes of delivery of dopaminergic treatment, deep brain stimulation, and nondopaminergic agents may either provide alternatives for treatment of these behavioral problems or permit treatment of parkinsonism with less risk of these behavioral disorders. © 2014 International Parkinson and Movement Disorder Society
Clinical spectrum of levodopa‐induced complications
Authors: Aquino Camila Catherine , Fox Susan H.
Published: December 2014

The first years of Parkinson disease (PD) treatment are marked by good and sustained responses to dopaminergic therapy. With disease progression and longer exposure to levodopa (l‐dopa), patients develop a range of l‐dopa–induced complications that include motor and non‐motor symptoms. Motor complications include motor fluctuations, characterized by periods of reduced benefit from the medication, and l‐dopa–induced dyskinesia, characterized by emergence of hyperkinetic involuntary movements. Dyskinesia can occur at peak effect of l‐dopa, at the beginning and end of dose, or between doses. These motor complications are often associated with fluctuations in non‐motor symptoms, particularly fluctuations in neuropsychiatric, autonomic, and sensory symptoms. Recognizing such complications and understanding their relationship with the timing of l‐dopa doses is essential for adequate diagnosis and management. © 2014 International Parkinson and Movement Disorder Society
On an initial‐boundary value problem for the p‐Ginzburg–Landau system
Authors: Lei Yutian
Published: December 2014

This paper is concerned with the asymptotic behavior of the decreasing energy solution uε to a p‐Ginzburg–Landau system with the initial‐boundary data for p > 4/3. It is proved that the zeros of uε in the parabolic domain G × (0,T] are located near finite lines {ai}×(0,T]. In particular, all the zeros converge to these lines when the parameter ε goes to zero. In addition, the author also considers the uniform energy estimation on a domain far away from the zeros. At last, the Hölder convergence of uε to a heat flow of p‐harmonic map on this domain is proved when p > 2. Copyright © 2014 John Wiley & Sons, Ltd.