bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cause‐specific mortality in a Chinese chrysotile textile worker cohort
Authors: Wang Xiaorong , Lin Sihao , Yu Ignatius , Qiu Hong , Lan Yajia , Yano Eiji 
Published: November 2012

Chrysotile asbestos has continued to be mined and used in China, but its health effects on exposed workers have not been well documented. This study was conducted to give a complete picture about cause‐specific mortality in Chinese asbestos workers. A cohort of 586 males and 279 females from a chrysotile textile factory were prospectively followed for 37 years. Their vital status was identified, and the date and underlying cause of death were verified from death registry. Cause‐specific standardized mortality ratios by gender were computed with nationwide gender‐ and cause‐specific mortality rates as reference. Male workers were 11 years older, and had 6 years longer exposure duration than females; 79% in males and 1% in females smoked. In males, the mortality rate of all cancers doubled; both larynx and lung cancer were four‐fold, and mesothelioma was 33‐fold. In females, there was slightly excess mortality from lung cancer and all cancers, and significant increase in mesothelioma and ovarian cancer. Other significantly increased mortality was seen from cancers of thymus, small intestine and penis in males, and cancers of bone and bladder in females. In addition to asbestosis, mortality from pulmonary heart disease was significantly elevated in both genders. The data confirmed significantly excess mortality from mesothelioma in either gender, lung and larynx cancers in males, and ovarian cancer in females. A gender difference in mortality from lung cancer and all cancers could be mainly due to the discrepancies in age, exposure duration and smoking between the male and female workers.
The role of obesity and type 2 diabetes mellitus in the development of male obesity‐associated secondary hypogonadism
Authors: Saboor Aftab S. A. , Kumar S. , Barber T. M. 
Published: November 2012

SummaryObesity, secondary (hypogonadotrophic) hypogonadism (SH), sleep disorders [such as obstructive sleep apnoea (OSA)] and type 2 diabetes mellitus (T2DM) in men have complex interlinks both with respect to mutual aetiopathogenesis as well as therapeutics. Correction of the attendant hypogonadism in obese men may serve to break this link and have beneficial effects beyond restoration of normal sexual function. Male obesity‐associated secondary hypogonadism (MOSH) should be regarded as a distinct clinical entity and subtype of SH. A high index of suspicion for the presence of MOSH must be maintained by clinicians when assessing obese men. The pathogenesis of MOSH remains incompletely understood. Furthermore, the optimal management of MOSH and its associated sequelae will require long‐term prospective studies that in turn will inform the development of future clinical guidelines for this important and prevalent condition.
Acoustic rhinometry, rhinomanometry and visual analogue scale before and after septal surgery: a prospective 10‐year follow‐up
Authors: Haavisto L.E. , Sipilä J.I. 
Published: November 2012

ObjectivesThe aim of the study was to compare rhinomanometry, acoustic rhinometry and subjective estimation of the nasal obstruction before and after septoplasty and to evaluate the long‐term results of septal surgery.DesignProspective long‐term follow‐up, before and after septoplasty.SettingUniversity tertiary‐care hospital, referral centre.ParticipantsThe study included 30 adult patients who were operated on because of septal deviation.Main outcome measuresPre‐operatively, acoustic rhinometry and active anterior rhinomanometry were performed on each subject after decongestion of the nose. A visual analogue scale for unilateral nasal obstruction was filled in by the patients. The measurements were repeated both 6 months and 10 years post‐operatively.ResultsA significant change in acoustic values was found during the long‐term follow‐up of 10 years. The mean minimal cross‐sectional area on the more obstructive side was 0.35 cm2 pre‐operatively. Six months after operation, it was 0.52 cm2, and 10 years after operation, it was 0.68 cm2. The mean resistance fell from pre‐operative 1.16 Pa/mL/s to 0.41 Pa/mL/s during the first 6 months, but rose again to 1.21 Pa/mL/s after 10 years. Despite a tendency of improvement, no statistically significant change was found between pre‐operative and postoperative values in VAS. Six months after operation 69% of the patients were satisfied with the result, and after ten years the amount of satisfied patients was 83%.ConclusionsWe found an increase in acoustic values, but an increase in nasal resistance in the long‐term follow‐up. Other factors than nasal area may have an impact on nasal resistance and the feeling of nasal obstruction. The small size on the sample interfered with the results.
Neural Computation and the Computational Theory of Cognition
Authors: Piccinini Gualtiero , Bahar Sonya 
Published: November 2012

AbstractWe begin by distinguishing computationalism from a number of other theses that are sometimes conflated with it. We also distinguish between several important kinds of computation: computation in a generic sense, digital computation, and analog computation. Then, we defend a weak version of computationalism—neural processes are computations in the generic sense. After that, we reject on empirical grounds the common assimilation of neural computation to either analog or digital computation, concluding that neural computation is sui generis. Analog computation requires continuous signals; digital computation requires strings of digits. But current neuroscientific evidence indicates that typical neural signals, such as spike trains, are graded like continuous signals but are constituted by discrete functional elements (spikes); thus, typical neural signals are neither continuous signals nor strings of digits. It follows that neural computation is sui generis. Finally, we highlight three important consequences of a proper understanding of neural computation for the theory of cognition. First, understanding neural computation requires a specially designed mathematical theory (or theories) rather than the mathematical theories of analog or digital computation. Second, several popular views about neural computation turn out to be incorrect. Third, computational theories of cognition that rely on non‐neural notions of computation ought to be replaced or reinterpreted in terms of neural computation.
Grafting of functional motifs onto protein scaffolds identified by PDB screening – an efficient route to design optimizable protein binders
Authors: Tlatli Rym , Nozach Hervé , Collet Guillaume , Beau Fabrice , Vera Laura , Stura Enrico , Dive Vincent , Cuniasse Philippe 
Published: November 2012

Artificial miniproteins that are able to target catalytic sites of matrix metalloproteinases (MMPs) were designed using a functional motif‐grafting approach. The motif corresponded to the four N‐terminal residues of TIMP‐2, a broad‐spectrum protein inhibitor of MMPs. Scaffolds that are able to reproduce the functional topology of this motif were obtained by exhaustive screening of the Protein Data Bank (PDB) using stamps software (search for three‐dimensional atom motifs in protein structures). Ten artificial protein binders were produced. The designed proteins bind catalytic sites of MMPs with affinities ranging from 450 nm to 450 μm prior to optimization. The crystal structure of one artificial binder in complex with the catalytic domain of MMP‐12 showed that the inter‐molecular interactions established by the functional motif in the artificial binder corresponded to those found in the MMP‐14–TIMP‐2 complex, albeit with some differences in geometry. Molecular dynamics simulations of the ten binders in complex with MMP‐14 suggested that these scaffolds may allow partial reproduction of native inter‐molecular interactions, but differences in geometry and stability may contribute to the lower affinity of the artificial protein binders compared to the natural protein binder. Nevertheless, these results show that the in silico design method used provides sets of protein binders that target a specific binding site with a good rate of success. This approach may constitute the first step of an efficient hybrid computational/experimental approach to protein binder design.
Pre‐existing central nervous system lesions negate cytokine requirements for regional experimental autoimmune encephalomyelitis development
Authors: Li Xin , Lees Jason R. 
Published: November 2012

SummaryIn region‐specific forms of experimental autoimmune encephalomyelitis (EAE), lesion initiation is regulated by T‐cell‐produced interferon‐γ (IFN‐γ) resulting in spinal cord disease in the presence of IFN‐γ and cerebellar disease in the absence of IFN‐γ. Although this role for IFN‐γ in regional disease initiation is well defined, little is known about the consequences of previous tissue inflammation on subsequent regional disease, information vital to the development of therapeutics in established disease states. This study addressed the hypothesis that previous establishment of regional EAE would determine subsequent tissue localization of new T‐cell invasion and associated symptoms regardless of the presence or absence of IFN‐γ production. Serial transfer of optimal or suboptimal doses of encephalitogenic IFN‐γ‐sufficient or ‐deficient T‐cell lines was used to examine the development of new clinical responses associated with the spinal cord and cerebellum at various times after EAE initiation. Previous inflammation within either cerebellum or spinal cord allowed subsequent T‐cell driven inflammation within that tissue regardless of IFN‐γ presence. Further, T‐cell IFN‐γ production after initial lesion formation exacerbated disease within the cerebellum, suggesting that IFN‐γ plays different roles at different stages of cerebellar disease. For the spinal cord, IFN‐γ‐deficient cells (that are ordinarily cerebellum disease initiators) were capable of driving new spinal‐cord‐associated clinical symptoms more than 60 days after the initial acute EAE resolution. These data suggest that previous inflammation modulates the molecular requirements for new neuroinflammation development.
A Measure of Competition Based on 10‐K Filings
Authors: LI FENG , LUNDHOLM RUSSELL , MINNIS MICHAEL 
Published: November 2012

ABSTRACTIn this paper we develop a measure of competition based on management's disclosures in their 10‐K filing and find that firms’ rates of diminishing marginal returns on new and existing investment vary significantly with our measure. We show that these firm‐level disclosures are related to existing industry‐level measures of disclosure (e.g., Herfindahl index), but capture something distinctly new. In particular, we show that the measure has both across‐industry variation and within‐industry variation, and each is related to the firm's future rates of diminishing marginal returns. As such, our measure is a useful complement to existing measures of competition. We present a battery of specification tests designed to explore the boundaries of our measure and how it varies with the definition of industry and the presence of other measures of competition.
Histopathologic staining of low temperature cutaneous burns: Comparing biomarkers of epithelial and vascular injury reveals utility of HMGB1 and hematoxylin phloxine saffron
Authors: Hirth Douglas A. , Singer Adam J. , Clark Richard A. F. , McClain Steve A. 
Published: November 2012

AbstractHistopathology remains the gold standard for evaluation of burn depth, progression, and healing, but burn literature offers little guidance on the best stains for analysis of these complex and evolving injuries. A battery of histochemical and immunohistochemical stains was compared on adjacent sections to determine the best stains for histopathologic study and imaging of burns. Using a validated porcine model of vertical burn progression, full‐thickness cutaneous biopsies were stained using hematoxylin and eosin, Hematoxylin phloxine saffron (HPS), Masson Trichrome, Elastin Von Gieson, Movatt's Pentachrome, vimentin, CD31, KI‐67, caspase 3a, and high mobility group box 1. Depth of collagen degeneration, cellular necrosis, apoptosis, and vascular occlusion; and reparative processes of cellular hyperplasia, reepithelialization, and new collagen deposition were measured by ocular microscopy. High mobility group box 1 was superior for necrosis between 1 and 24 hours postburn. Vimentin underestimated necrosis until 48 hours postburn. For overall assessment, hematoxylin and eosin and HPS were comparable, except for analysis of thermally injured collagen, vessel occlusion, erythrocyte extravasation, and polariscopic study of collagen deposition, where HPS was superior. HPS stain offers specific advantages in histopathologic burn analysis. Inexpensive and rapid to produce, HPS allows users to analyze eosinophilic components more precisely than standard hematoxylin and eosin.
Food and Drug Administration (FDA) drug approval end points for chronic cutaneous ulcer studies
Authors: Eaglstein William H. , Kirsner Robert S. , Robson Martin C. 
Published: November 2012

AbstractThe rising costs of caring for chronic cutaneous ulcers (CCUs) and recent appreciation of the mortality of CCUs have led to consideration of the reasons for the failure to have new drug therapies. No new chemical entities to heal CCUs have been approved by the Food and Drug Administration (FDA) in over a decade, in part due to an inability to reach the FDA accepted end point of “complete wound closure.” The frequent failure to reach the complete closure end point brings forward the question of the relevance of other healing end points such as improved quality of life, or partial healing. Because CCUs carry a prognosis and mortality rate worse than many cancers, it is reasonable to compare the FDA trial end points for cancer drug approval with those for CCUs. And the difference is quite striking. While there is only one end point for CCUs, there are five surrogate and three direct end points for cancers. In contrast to cancer, surrogate end points and partial healing are not acceptable for therapies aimed at CCUs. For example, making tumors smaller is an acceptable end point, but making CCUs smaller is not and improvement in the signs and symptoms of cancer is an acceptable end point for cancers but not CCUs. As CCUs carry a prognosis and mortality rate worse than many cancers, we believe a reconsideration of end points for CCUs is highly warranted.
Microwave‐Assisted Hydrothermal Synthesis of Submicrometer Willemite Phase Zinc Silicate and Its Zinc Ion Release Behavior
Authors: Xiong Kun , Liu Jingqun , Li Jiyan , Ye Jiandong 
Published: November 2012

As an important trace element in human bone, zinc (Zn) has a great influence on bone metabolism. The aim of this work was to prepare a Zn‐containing material that can release Zn ions. For this purpose, submicrometer willemite phase zinc silicate (Zn2SiO4, ZS) with poor crystallinity was synthesized at 110°C via the microwave‐assisted hydrothermal (MH) method. Under the MH condition, the growth of ZS was consistent with “multi‐core growth” mechanism. Moreover, the influences of the reaction temperature and the reactant concentration on the final products were investigated in detail. The inductively coupled plasma atomic emission spectroscopy (ICP) data indicated that the poor crystallinity ZS could successfully release Zn for at least 28 d as soaking in the simulated body fluid (SBF). Without the replenishment of SBF, ~333 μM Zn was released from ZS synthesized at 110°C (ZS‐110). If SBF was periodically replenished once a day, more Zn was released from ZS‐110, and the parascholzite phase calcium zinc phosphate hydrate (CaZn2(PO4)2·2H2O) formed during the soaking process of ZS‐110. Under the concentration of 6.25 mg/mL, the extract of ZS‐110 was proved to be nontoxic by assessing with mouse osteoblast cells (MC3T3). Therefore, the poor crystallinity ZS has potential to be incorporated into the orthopedic reconstructive materials as a source of Zn ions, which can improve the bioactivity of the materials.
Do wild fish species contribute to the transmission of koi herpesvirus to carp in hatchery ponds?
Authors: Fabian M , Baumer A , Steinhagen D 
Published: November 2012

AbstractThe koi herpesvirus (KHV) has spread worldwide since its discovery in 1998 and causes disease and mortality in koi and common carp populations with a high impact on the carp production industry. Many investigations have been conducted to examine ways of distribution and to identify possible transmission vectors. The answers, however, raise many new questions. In the present study, different wild fish species taken from carp ponds with a history of KHV infection were examined for their susceptibility to the virus. In the tissue of these fish, the virus load was determined and it was tested whether a release of the virus could be induced by stress and the virus then could be transferred to naive carp. Wild fish were gathered from carp ponds during acute outbreaks of virus‐induced mortality in summer and from ponds stocked with carp carrying a latent KHV infection. From these ponds, wild fish were collected during the harvesting process in autumn or spring when the ponds were drained. We found that regardless of season, temperature variation, age and infection status of the carp stock, wild fish from carp ponds and its outlets could be tested positive for the KHV genome using real‐time PCR with a low prevalence and virus load. Furthermore, virus transfer to naive carp was observed after a period of cohabitation. Cyprinid and non‐cyprinid wild fish can therefore be considered as an epidemiological risk for pond carp farms.
Vinpocetine and α‐tocopherol prevent the increase in DA and oxidative stress induced by 3‐NPA in striatum isolated nerve endings
Authors: Herrera‐Mundo Nieves , Sitges María 
Published: November 2012

AbstractVinpocetine is a neuroprotective drug that exerts beneficial effects on neurological symptoms and cerebrovascular disease. 3‐nitropropionic acid (3‐NPA) is a toxin that irreversibly inhibits succinate dehydrogenase, the mitochondrial enzyme that acts in the electron transport chain at complex II. In previous studies in striatum‐isolated nerve endings (synaptosomes), we found that vinpocetine decreased dopamine (DA) at expense of its main metabolite 3,4‐dihydroxyphenylacetic acid (DOPAC), and that 3‐NPA increased DA, reactive oxygen species (ROS), DA‐quinone products formation, and decreased DOPAC. Therefore, in this study, the possible effect of vinpocetine on 3‐NPA‐induced increase in DA, ROS, lipid peroxidation, and DA‐quinone products formation in striatum synaptosomes were investigated, and compared with the effects of the antioxidant α‐tocopherol. Results show that the increase in DA induced by 3‐NPA was inhibited by both 25 μM vinpocetine and 50 μM α‐tocopherol. Vinpocetine, as α‐tocopherol, also inhibited 3‐NPA‐induced increase in ROS (as judged by DCF fluorescence), lipid peroxidation (as judged by TBA‐RS formation), and DA‐quinone products formation (as judged by the nitroblue tetrazolium reduction method). As in addition to the inhibition of complex II exerted by 3‐NPA, 3‐NPA increases DA‐oxidation products that in turn can inhibit other sites of the respiratory chain, the drop in DA produced by vinpocetine and α‐tocopherol may importantly contribute to their protective action from oxidative damage, particularly in DA‐rich structures.
Rosuvastatin ameliorates high‐fat and high‐cholesterol diet‐induced nonalcoholic steatohepatitis in rats
Authors: Okada Yoshihisa , Yamaguchi Kanji , Nakajima Tomoki , Nishikawa Taichiro , Jo Masayasu , Mitsumoto Yasuhide , Kimura Hiroyuki , Nishimura Takeshi , Tochiki Nozomi , Yasui Kohichiroh , Mitsuyoshi Hironori , Minami Masahito , Kagawa Keizo , Okanoue Takeshi , Itoh Yoshito 
Published: November 2012

AbstractBackground/AimsStatins, which are inhibitors of 3‐hydroxy‐3‐methylglutaryl coenzyme A reductase and inhibit endogenous cholesterol synthesis, possess pleiotropic activities, such as anti‐inflammatory, anti‐oxidative and antifibrotic effects. Here, we investigated whether statins ameliorate steatohepatitis using a high‐fat and high‐cholesterol (HFHC) diet‐induced rat model.MethodsEight‐week‐old male Sprague–Dawley rats were fed control chow or HFHC diet. Half of the HFHC diet‐fed rats were orally administered 2 mg/kg/day rosuvastatin for 12 weeks. Hepatic injury, steatosis, fibrosis and markers of lipid peroxidation/oxidant stress were evaluated.ResultsAs previously reported, HFHC diet induced steatohepatitis in rat livers with hypercholesterolaemia. Rosuvastatin decreased Oil Red O stained‐positive areas, liver/body weight ratio, serum total cholesterol levels and hepatic free fatty acid contents in HFHC diet‐fed rats. Further study revealed that rosuvastatin significantly decreased hepatic mRNA expression of tumour necrosis factor‐α and interleukin‐6, serum alanine aminotransferase levels and hepatic lobular inflammation grade. Hepatic fibrosis was also ameliorated by rosuvastatin with decreases in hepatic mRNA expression of transforming growth factor‐β, connective tissue growth factor and type‐1 procollagen. Similarly, hepatic Sirius red stained or α‐smooth muscle actin stained‐positive areas and expression of markers of lipid peroxidation/oxidant stress [hepatic 8‐hydroxy‐oxyguanosine and hepatic 4‐hydroxy‐2‐nonenal] were decreased. Interestingly, whereas the expression of carnitine palmitoyltransferase‐1 and long‐chain acyl‐CoA dehydrogenase was not affected, that of catalase and acyl‐coA oxidase was restored.ConclusionsThese data suggest that rosuvastatin improved not only hepatic steatosis but also hepatic injury and fibrosis via improved peroxisomal β‐oxidation in this rat HFHC model.
Genotype matching in a parasitoid–host genotypic food web: an approach for measuring effects of environmental change
Authors: Lavandero Blas , Tylianakis Jason M. 
Published: November 2012

AbstractFood webs typically quantify interactions between species, whereas evolution operates through the success of alleles within populations of a single species. To bridge this gap, we quantify genotypic interaction networks among individuals of a single specialized parasitoid species and its obligate to cyclically parthenogenetic aphid host along a climatic gradient. As a case study for the kinds of questions genotype food webs could be used to answer, we show that genetically similar parasitoids became more likely to attack genetically similar hosts in warmer sites (i.e. there was network‐wide congruence between the within‐species shared allelic distance of the parasitoid and that of its host). Narrowing of host‐genotype‐niche breadth by parasitoids could reduce resilience of the network to changes in host genetic structure or invasion by novel host genotypes and inhibit biological control. Thus, our approach can be easily used to detect changes to sub‐species‐level food webs, which may have important ecological and evolutionary implications, such as promoting host‐race specialization or the accelerated loss of functional diversity following extinctions of closely related genotypes.