bluuebunny/crossref_metadata_2025_split huggingface dataset:
Identification of an old antibiotic clofoctol as a novel activator of unfolded protein response pathways and an inhibitor of prostate cancer
Authors: Wang Minghua , Shim Joong Sup , Li Ruo‐Jing , Dang Yongjun , He Qingli , Das Manisha , Liu Jun O 
Published: June 2014

Background and PurposeFinding new indications for existing drugs, also known as drug repositioning or repurposing, is a powerful approach to accelerate drug discovery and development. The unfolded protein response pathways have been proposed to be a viable target for developing new anticancer drugs.Experimental ApproachWe screened the Johns Hopkins Drug Library for inhibitors of prostate cancer cell proliferation to identify new antiprostate cancer treatments among known drugs. We systematically investigated the mechanism underlying the anticancer activity of a hit and assessed its efficacy in blocking prostate tumour growth in a mouse model.Key ResultsThe antibacterial drug clofoctol was identified as a novel inhibitor of prostate cancer cell proliferation. Morphologically, cells treated with clofoctol were found to undergo massive vacuolization, reminiscent of endoplasmic reticulum stress. Indeed, all three unfolded protein response pathways including inositol requiring enzyme 1, double‐stranded RNA‐activated PK‐like ER kinase and activating transcription factor 6 were found to be activated by clofoctol. Activation of unfolded protein response pathways by clofoctol led to the inhibition of protein translation in cells and the induction of G1 cell cycle arrest in prostate cancer cells. Clofoctol also inhibited prostate cancer xenograft growth in vivo without apparent toxicity.Conclusion and ImplicationsOur findings revealed clofoctol as a novel activator of the unfolded protein response pathways and a promising inhibitor of prostate cancer. As clofoctol has been used in the clinic for years, it is ready for clinical evaluation as a novel antiprostate cancer drug candidate.
Partners in clime: Public‐private partnerships andBritishColumbia's capacity to pursue climate policy objectives
Authors: Newman Joshua , Perl Anthony 
Published: June 2014

AbstractGovernments are increasingly using public‐private partnerships (P3s) to draw the private sector into more active participation in infrastructure development. Climate action initiatives have not typically yielded profitable results for the private sector, and might therefore constrain the placing of conditions by governments onP3arrangements. This article investigates a majorP3infrastructure project in BritishColumbia – theCanada Line extension to Vancouver's urban rail transit network – and concludes that theP3organization did not constrain the government's capacity to pursue policy objectives for climate action. This counterintuitive result occurred because public sector leadership enabled an effective engagement with environmental policy priorities.
Making the invisible public service visible? Exploring data on the supply of policy and management consultancies inCanada
Authors: Howlett Michael , Migone Andrea 
Published: June 2014

AbstractThe use of external policy and management consultants in government has been receiving increasing attention in many countries, includingCanada. We explore new data on management consulting compiled from information released since the creation of theFederalAccountabilityAct to address the supply side of contracting. We find several large multi‐year contracts have taken up a larger percentage of contracting activity while the number of smaller contracts has declined. The data suggest a pattern of oligopsonic demand concentrated mostly in a handful of very heavy users and an increasingly oligopolistic supply pattern where less than 5% of companies accounted for 80% of total contract values and where repeat contracts are the norm. Measures of accountability and transparency need to extend to the “invisible” public service of contract consultants.
Digital dilemmas: Values, ethics and information technology
Authors: Kernaghan Kenneth 
Published: June 2014

AbstractIn writings on public administration, the subject areas of values and ethics and of information technology (IT) have received substantial, but largely separate, attention. The public administration community can benefit by drawing on scholarship in the field of information and computer ethics and developing its own body of research with a view to sensitizing public servants to the effects of changes in IT on values and ethics. This article focuses on developments in the use of IT (for example, self‐service technologies, Big Data, the Internet of Things) as a basis for assessing their implications for public sector values and ethics. Research is needed on the extent to which the values and ethics regimes of public organizations take account of the impact of changes in IT; the degree to which the various components of these regimes can foster sensitivity to the implications of these changes; and the significance for the public sector of such emerging ethical issues as robot ethics. Value conflicts and dilemmas arising from advances in digital technologies argue for vigorous measures to alert public servants to the technologies' impact.
Design, Synthesis, and Pharmacological Evaluation of Novel 2‐(4‐substituted piperazin‐1‐yl)1, 8 Naphthyridine 3‐Carboxylic Acids as 5‐HT3 Receptor Antagonists for the Management of Depression
Authors: Dhar Arghya K. , Mahesh Radhakrishnan , Jindal Ankur , Devadoss Thangaraj , Bhatt Shvetank 
Published: June 2014

1, 8‐naphthyridine‐3‐carboxylic acid analogs were synthesized and found to possess potential 5‐HT3 receptor antagonism as well as antidepressant‐like activity. Initially, 5‐HT3 receptor antagonism of all the compounds was determined in the form of pA2 value against agonist 2‐methyl 5‐HT in longitudinal muscle–myenteric plexus preparation from guinea‐pig ileum. Among all the compounds tested, compound 7a demonstrated most promising pA2 value of 7.6. Subsequently, all the compounds were evaluated for antidepressant activity using forced swim test and tail suspension test in mice. Compounds 7a, 7d, 7f, 7h, and 7i exhibited significant (p < 0.05) antidepressant‐like activity as compound to vehicle‐treated group. Importantly, none of the tested compound affected locomotor activity of mice at tested dose levels.
Narrow‐Diameter versus Standard‐Diameter Implants and Their Effect on the Need for Guided Bone Regeneration: A Virtual Three‐Dimensional Study
Authors: Papadimitriou Dimitrios E.V. , Friedland Bernard , Gannam Camille , Salari Samira , Gallucci German O. 
Published: June 2014

AbstractPurposeNarrow‐diameter implants (NDIs) are proven treatment options for completely edentulous patients with severely resorbed alveolar ridges. The aim of this study was to evaluate virtually whether or not the implant diameter affects the need for ridge augmentation in edentulous patients, using a 3D planning software program.Materials and MethodsExisting cone beam CT scans of 200 outpatients (100 maxillae, 100 mandibles) were selected, and treatment was planned in a virtual 3D planning software program with either 3.3 mm–diameter implants (test group) or 4.1 mm–diameter implants (control group). Statistical analysis was performed.ResultsA total of 1,760 implants were virtually planned (880 implants each for test and control groups). Overall, significantly associated with the absence or need for ridge augmentation as compared with need for ridge augmentation (p < .0001). Use of the 3.3 mm–diameter implants increased the odds ratio for ridge augmentation being unnecessary by 2.2 (95% confidence interval) relative to the 4.1 mm–diameter implants.ConclusionsUse of NDIs was able to provide a statistically significant reduction in need for bone grafting among completely edentulous patients. More clinical longitudinal studies are necessary to confirm the long‐term success of their use.
Relation between Spongy Bone Density in the Maxilla and Skeletal Bone Density
Authors: Merheb Joe , Temmerman Andy , Coucke Wim , Rasmusson Lars , Kübler Alexander , Thor Andreas , Quirynen Marc 
Published: June 2014

AbstractBackground and PurposeOsteoporosis is a disease affecting more than 300 million people worldwide and is responsible for numerous medical complications. This study aimed to investigate the relation between skeletal and maxillary bone density.Materials and MethodsSeventy‐three patients were recruited and divided between group A (osteoporosis), group B (healthy, control), and group C (osteopenia) on the basis of a dual‐energy x‐ray absorptiomery (DXA) scan. These patients also received a CT scan on which bone density measurements were performed at five sites: maxilla midline, retromolar tuberosities, incisor, premolars, and molar regions.ResultsThe bone density was lower in osteoporotic patients compared with the control patients. The bone mineral density (BMD) of the tuberosities showed the strongest correlations with the BMD of the hip and the spine (respectively, r = 0.50 and r = 0.61). The midline region showed moderate correlations with the hip (r = 0.47) and the spine (r = 0.46). For potential implant sites, the correlations with the BMD of the hip and spine were, however, small to insignificant. Based on measurements of bone density of the maxilla, it was possible to predict if the patient was osteoporotic or not with a sensitivity of 65% and a specificity of 83%.ConclusionsThe maxillary bone density of subjects with osteoporosis is significantly lower than that of healthy patients. Moreover, there is a direct correlation between the density of the skeleton and the density of some sites of the maxilla. Using measurements of maxillary bone density in order to predict skeletal bone density might be a useful tool for the screening of osteoporosis.
Clinical and Histomorphometric Evaluation of Fresh Frozen Bone Allograft in Sinus Lift Surgery
Authors: de Castilho Tatiana Regina Ramos Nantes , Tortamano Pedro , Marotti Juliana , de Andrade José Carlos Silva , Chilvarquer Israel , Ximenez Michel Eli Lipiec , Alves Maria Teresa de Seixas 
Published: June 2014

AbstractPurposeThe aim of this prospective clinical study was to evaluate the clinical and histomorphometric data of newly formed bone tissue from fresh frozen human allograft in sinus lift surgery.Patients and MethodsThirty‐three sinus lift procedures were performed in 20 patients, divided into two groups. The control group (n = 8) received autogenous bone from the mandibular ramus, and the experimental group (n = 12) received fresh frozen bone (FFB) allograft in chips. After 6 months, 52 implants were placed and 50 biopsies were collected for histomorphometric analysis. Cone beam computed tomography scans were performed at preoperative, immediate postoperative, and delayed postoperative time intervals to assess the degree of graft volume loss.ResultsThere was no statistically significant difference between groups as regards degree of graft volume loss (p = .983), total bone area (p = .191), remaining particles (p = .348), and proportion of active osteoblasts (p = .867). There was a statistically significant difference in the vitality rate between the groups (p = .043). In both groups, all implants were clinically osseointegrated after 4 months.ConclusionFFB allograft was shown to be a feasible substitute for autogenous bone graft in sinus lift surgery.
The Interaction of Implant Luting Cements and Oral Bacteria Linked to Peri‐Implant Disease: An In Vitro Analysis of Planktonic and Biofilm Growth – A Preliminary Study
Authors: Raval Neal C. , Wadhwani Chandur P.K. , Jain Sumita , Darveau Richard P. 
Published: June 2014

AbstractBackgroundThere is little consensus on the most appropriate cement to use when restoring a cement‐retained, implant‐supported restoration. One consideration should be the interaction of pathogenic oral bacteria with restorative cements.PurposeTo determine how oral bacteria associated with peri‐implant disease grow in the presence of implant cements.Materials and MethodsFive test cements with varying composition (zinc oxide–eugenol [TBO], eugenol‐free zinc oxide [TBNE], zinc orthophosphate [FL], and two resin cements [PIC and ML]) were used to fabricate specimen disks. The disks were submerged in bacterial suspensions of either Aggregatibacter actinomycetemcomitans, Fusobacterium nucleatum, or Porphyromonas gingivalis. Planktonic bacterial growth within the test media was measured by determining the optical density of the cultures (OD600). Positive controls (media and bacteria without cement disks) and negative controls (media alone) were similarly evaluated. The mean and standard deviations (SD) were calculated for planktonic growth from three separate experiments. ANOVA statistical analysis with post hoc Tukey tests was performed where differences existed (p < .05). Selected cement disks (TBO and ML) were further examined for bacterial biofilm growth. Surface bacteria were removed and grown on agar media, and colony‐forming units (CFUs) were quantified.ResultsPlanktonic growth for both A. actinomycetemcomitans and P. gingivalis was significantly inhibited (p < .05) when grown in the presence of cement disks consisting of TBNE, PIC, FL, and TBO. In contrast, neither of these bacteria displayed growth inhibition in the presence of ML cement disks. F. nucleatum growth was also significantly inhibited by PIC, FL. and TBO (p < .05), but not by ML and TBNE cement disks. CFU counts for the biofilm study for TBO gave minimal and, in some instances, no bacterial adherence and growth, in contrast to ML, which supported substantially greater bacterial biofilm growth.ConclusionCements display differing abilities to inhibit both planktonic and biofilm bacterial growth. Cements with the ability to reduce planktonic or biofilm growth of the test bacteria may be advantageous in reducing peri‐implant disease. Understanding the microbial growth–inhibiting characteristics of different cement types should be considered important in the selection criteria.
Reduced cerebral oxygen–carbohydrate index during endotracheal intubation in vascular surgical patients
Authors: Fabricius‐Bjerre Andreas , Overgaard Anders , Winther‐Olesen Marie , Lönn Lars , Secher Niels H. , Nielsen Henning B. 
Published: June 2014

SummaryBrain activation reduces balance between cerebral consumption of oxygen versus carbohydrate as expressed by the so‐called cerebral oxygen‐carbohydrate‐index (OCI). We evaluated whether preparation for surgery, anaesthesia including tracheal intubation and surgery affect OCI. In patients undergoing aortic surgery, arterial to internal jugular venous (a‐v) concentration differences for oxygen versus lactate and glucose were determined from before anaesthesia to when the patient left the recovery room. Intravenous anaesthesia was supplemented with thoracic epidural anaesthesia for open aortic surgery (n = 5) and infiltration with bupivacaine for endovascular procedures (n = 14). The a‐v difference for O2 decreased throughout anaesthesia and in the recovery room (1·6 ± 1·9 versus 3·2 ± 0·8 mmol l−1, mean ± SD), and while a‐v glucose decreased during surgery and into the recovery (0·4 ± 0·2 versus 0·7 ± 0·2 mmol l−1, P<0·05), a‐v lactate did not change significantly (0·03 ± 0·16 versus −0·03 ± 0·09 mmol l−1). Thus, OCI decreased from 5·2 ± 1·8 before induction of anaesthesia to 3·2 ± 1·0 following tracheal intubation (P<0·05) because of the decrease in a‐v O2 with a recovery for OCI to 4·6 ± 1·4 during surgery and to 5·6 ± 1·7 in the recovery room. In conclusion, preparation for surgery and tracheal intubation decrease OCI that recovers during surgery under the influence of sensory blockade.
Diffuse alveolar haemorrhage and severe hypoxemia from Strongyloides stercoralis hyperinfection syndrome
Authors: El‐Sameed Yaser Abu , Beejay Nigel , Al Maashari Rehab 
Published: June 2014

AbstractStrongyloides stercoralis hyperinfection syndrome is a rare, yet highly fatal disorder. It occurs most commonly in immunocompromised patients. We report a case of a 36‐year‐old Ethiopian female who presented with abdominal pain and hypotension. Shortly thereafter, she developed acute respiratory failure and progressed to acute respiratory distress syndrome and septic shock. She was found to have diffuse alveolar hemorrhage due to disseminated strongyloidiasis. We discuss the clinical condition of Strongyloides hyperinfection syndrome presenting with severe hypoxemia and complicated by severe diffuse alveolar hemorrhage leading to death. Similar cases in the literature are also describe.
Some behavioural and ecological factors affecting distribution, biomass and production of juvenile Atlantic salmon
Authors: Gibson R. John 
Published: June 2014

AbstractObservations were made in an experimental stream tank (total area 14.7 m2) on juvenile Atlantic salmon, Salmo salar L (parr), relating experimental observations to field observations, including the reported diurnal fasting behaviour of juvenile salmon at water temperatures <10 °C. Densities in the tank ranged from five to twenty parr, at water temperatures ranging from 4.6 °C to 15.8 °C. The wide channel of the stream tank, with mean water velocity of 18.8 cm·s−1, was the preferred section, where territorial behaviour was observed. Biomass was regulated in the wide channel by territorial mosaics or by dominance hierarchies. Dominance hierarchies were reflected in coloration of the fish. Dominant salmon were generally in the wide channel. Densities of salmon parr (of mean fork length 10.2 cm) in the channel ranged from 0.84 m−2 to 1.73 m−2, with an average biomass of 14.2 g·m−2. Growth was least at the 5.9 °C temperature treatment. In experiments at temperatures below 10 °C, feeding, dominance hierarchy and territorial behaviour were observed in daylight hours, contrary to the published literature. Interactions with other species may affect behaviour. Some observations were made on a closely related species, brown trout (Salmo trutta L.), a commonly cohabiting species in many systems. Trout displaced salmon from their preferred locations in the tank and were more aggressive than the salmon, reducing agonistic behaviour by the salmon. The commonest agonistic act shown by salmon was ‘charge’ and that by the trout was ‘approach’. Some field observations affecting behaviour and production are discussed.
Posterior hypothalamic modulation of ocular‐responsive trigeminal subnucleus caudalis neurons is mediated by Orexin‐A and Orexin1 receptors
Authors: Katagiri Ayano , Okamoto Keiichiro , Thompson Randall , Rahman Mostafeezur , Bereiter David A. 
Published: June 2014

AbstractOrexin‐A (OxA) is synthesized in posterior and lateral regions of the hypothalamus and contributes to homeostatic regulation of body functions including pain modulation. To determine if orexinergic mechanisms contribute to posterior hypothalamus (PH)‐induced modulation of ocular input to subnucleus caudalis/upper cervical (Vc/C1) neurons, the orexin‐1 receptor antagonist SB334867 was applied to the dorsal brainstem surface prior to PH disinhibition, by bicuculline methiodide, in male rats under isoflurane anesthesia. Ocular input to Vc/C1 units by bright light or hypertonic saline was markedly reduced by PH disinhibition and reversed completely by local Vc/C1 application of SB334867. OxA applied to the Vc/C1 surface mimicked the effects of PH disinhibition in a dose‐dependent manner. OxA‐induced inhibition was prevented by co‐application of SB334867, but not by the orexin‐2 receptor antagonist TCS Ox2 29. PH disinhibition and local OxA application also reduced the high threshold convergent cutaneous receptive field area of ocular units, suggesting widespread effects on somatic input to Vc/C1 ocular units. Vc/C1 application of OxA or SB334867 alone did not affect the background discharge of ocular units and suggested that the PH–OxA influence on ocular unit activity was not tonically active. Vc/C1 application of OxA or SB334867 alone also did not alter mean arterial pressure, whereas PH disinhibition evoked prompt and sustained increases. These results suggest that stimulus‐evoked increases in PH outflow acts through OxA and orexin‐1 receptors to alter the encoding properties of trigeminal brainstem neurons responsive to input from the ocular surface and deep tissues of the eye.
Effect of amiloride on endoplasmic reticulum stress response in the injured spinal cord of rats
Authors: Kuroiwa Masahiro , Watanabe Masahiko , Katoh Hiroyuki , Suyama Kaori , Matsuyama Daisuke , Imai Takeshi , Mochida Joji 
Published: June 2014

AbstractAfter traumatic spinal cord injury (SCI), endoplasmic reticulum (ER) stress exacerbates secondary injury, leading to expansion of demyelination and reduced remyelination due to oligodendrocyte precursor cell (OPC) apoptosis. Although recent studies have revealed that amiloride controls ER stress and leads to improvement in several neurological disorders including SCI, its mechanism is not completely understood. Here, we used a rat SCI model to assess the effects of amiloride on functional recovery, secondary damage expansion, ER stress‐induced cell death and OPC survival. Hindlimb function in rats with spinal cord contusion significantly improved after amiloride administration. Amiloride significantly decreased the expression of the pro‐apoptotic transcription factor CHOP in the injured spinal cord and significantly increased the expression of the ER chaperone GRP78, which protects cells against ER stress. In addition, amiloride treatment led to a significant decrease in ER stress‐induced apoptosis and a significant increase of NG2‐positive OPCs in the injured spinal cord. Furthermore, in vitro experiments performed to investigate the direct effect of amiloride on OPCs revealed that amiloride reduced CHOP expression in OPCs cultured under ER stress. These results suggest that amiloride controls ER stress in SCI and inhibits cellular apoptosis, contributing to OPC survival. The present study suggests that amiloride may be an effective treatment to reduce ER stress‐induced cell death in the acute phase of SCI.
Leucine‐rich glioma inactivated 3 is a melanogenic cytokine in human skin
Authors: Jeong Hyo‐Soon , Jeong Yun‐Mi , Kim Jandi , Lee Seung Hoon , Choi Hye‐Ryung , Park Kyoung‐Chan , Kim Beom Joon , Baek Kwang Jin , Kwon Nyoun Soo , Yun Hye‐Young , Kim Dong‐Seok 
Published: June 2014

AbstractRecently, we demonstrated that leucine‐rich glioma inactivated 3 (LGI3) is expressed in human skin. However, the effects of LGI3 on melanocytes remain unknown. The present study demonstrated that LGI3 can serve to stimulate melanogenesis without affecting cell viability. To determine the effects of LGI3 on melanin synthesis, normal human melanocytes and Mel‐Ab cells were treated with recombinant LGI3 and melanin content was measured. Our results showed that LGI3 promoted melanin synthesis in both cell types. Moreover, upregulation of microphthalmia‐associated transcription factor (MITF) and tyrosinase was observed at both the mRNA and protein levels via RT‐PCR and Western blotting, respectively. Furthermore, immunohistochemical staining showed that the expression of LGI3 increased in the basal layer of melasma skin samples, whereas it decreased slightly in vitiligo samples. These results suggest that LGI3 may play a role as a melanogenic cytokine in human skin.