bluuebunny/crossref_metadata_2025_split huggingface dataset:
Clinical Studies of
Escherichia coli
O157:H7 Conjugate Vaccines in Adults and Young Children
Authors: Szu Shousun Chen , Ahmed Amina 
Published: November 2014

ABSTRACT

Pediatric immunization has been the most effective measure to prevent and reduce the burden of infectious diseases in children. The recent inclusion of pneumococcal and meningococcal polysaccharide conjugates in infant immunization further reinforces their importance. Currently there is no human vaccine against enterohemorrhagic
Escherichia coli
(EHEC) infections. This review focuses on the human EHEC vaccine that has been studied clinically, in particular, the polysaccharide conjugate against
E. coli O
157. The surface polysaccharide antigen, O-specific polysaccharide, was linked to rEPA, recombinant exotoxin A of
Pseudomonas aeruginosa
. In adults and children 2 to 5 years old, O157-rEPA conjugates, shown to be safe, induced high levels of antilipopolysaccharide immunoglobulin G with bactericidal activities against
E. coli
O157, a functional bioassay that mimics the killing of inoculum in vivo. A similar construct using the B subunit of Shiga toxin (Stx) 1 as the carrier protein elicited both bactericidal and toxin-neutralizing antibodies in mice.

So far there is no clinical study of Stx-based human vaccine. Passive immunization of Stx-specific antibodies with humanized, chimeric, or human monoclonal antibodies, produced in transgenic mice, showed promising data in animal models and offered high prospects. Demonstrations of their safety and effectiveness in treating hemolytic-uremic syndrome or patients with EHEC infections are under way, and results are much anticipated.

For future development, other virulence factors such as the nontoxic Stx B subunit or intimin should be included, either as carrier protein in conjugates or as independent components. The additional antigens from O157 may provide broader coverage to non-O157 Stx-producing
E. coli
and facilitate both preventive and therapeutic treatment.
The association of statin use with reduced incidence of venous thromboembolism: a population-based cohort study
Authors: Lassila Riitta , Jula Antti , Pitkäniemi Janne , Haukka Jari 
Published: November 2014

ObjectivesVenous thromboembolism (VTE) continues to be a frequent medical emergency requiring rapid recognition so as to reach diagnosis and initiate anticoagulation therapy. The use of statins in addition to reducing the incidence of arterial thrombosis for decreasing the incidence and reoccurrence of VTE is reported. The aim of our study was to explore the association between statin usage and the incidence of new VTE at the population level during a 10-year follow-up.DesignPopulation-based historic cohort.SettingThe Health 2000 Survey was based on a nationally representative sample.Participants8028 individuals aged 30 years or over in Finland.Primary and secondary outcome measuresThe primary end point event was the first ever hospitalisation due to one of the following causes: pulmonary embolism (International Classification of Diseases-10 I26), cerebral venous non-pyogenic thrombosis (I63.6), or venous thrombosis (I80.9–189).ResultsThe preselected explanatory variables applied to the Poisson regression model were statin usage (no/yes) during follow-up (2000–2011) and several baseline data (age, sex; usage of blood glucose lowering drugs, vitamin K antagonists and antiplatelet agents). We observed 136 VTE events, the incidence of 1.72 (95% CI 1.44 to 2.04) per 1000 person-years. Current statin usage did not associate with the incidence of VTE according to the univariate model (rate ratio (RR) 0.93, 0.56 to 1.52), but when adjusted with baseline variables (age, sex, medications) the RR declined to 0.60 (0.36 to 1.00, p=0.04).ConclusionsStatin use offers protection against first ever VTE events and appears as a primary prevention tool in patients without anticoagulation or antiplatelet medication.
Increasing antimicrobial resistance in clinical isolates ofStaphylococcus intermediusgroup bacteria and emergence of MRSP in the UK
Authors: Beever L. , Bond R. , Graham P. A. , Jackson B. , Lloyd D. H. , Loeffler A. 
Published: November 2014

Frequencies of antimicrobial resistance were determined amongst 14,555 clinicalStaphylococcus intermediusgroup (SIG) isolates from UK dogs and cats to estimate resistance trends and quantify the occurrence of meticillin‐resistantStaphylococcus pseudintermedius(MRSP). Reports from two diagnostic laboratories (13,313 general submissions, 1242 referral centre only submissions) were analysed retrospectively (2003/2006–2012). MRSP were defined by phenotypic resistance to meticillin and concurrent broad β‐lactam resistance; a subset was confirmed genetically (SIG‐specificnucandmecA). Trends were analysed by Cochran‐Armitage test. Resistance remained below 10 per cent for cefalexin, amoxicillin‐clavulanic acid and the fluoroquinolones. Increasing resistance trends were seen in both laboratories for ampicillin/amoxicillin (both P<0.001), cefovecin (both P<0.046) and enrofloxacin (both P<0.02). Resistance to cefalexin increased over time in referral hospital isolates (P<0.001) to clindamycin (P=0.01) and trimethoprim‐sulfamethoxazole (P=0.001) amongst general laboratory submissions. Overall, 106 MRSP were isolated (0.7 per cent of submissions) including 32 (2.6 per cent of submissions, all genetically confirmed) from the referral centre population (inter‐laboratory difference P<0.001). Against a background of widely susceptible SIG isolates, a new trend of increasing resistance to important antimicrobials was identified overtime and the emergence of MRSP from UK clinical cases was confirmed. Attention to responsible use of antibacterial therapy in small animal practice is urgently needed.
PELP1 Overexpression in the Mouse Mammary Gland Results in the Development of Hyperplasia and Carcinoma
Authors: Cortez Valerie , Samayoa Cathy , Zamora Andrea , Martinez Lizatte , Tekmal Rajeshwar R. , Vadlamudi Ratna K. 
Published: November 2014

Abstract
Estrogen receptor (ER) coregulator overexpression promotes carcinogenesis and/or progression of endocrine related-cancers in which steroid hormones are powerful mitogenic agents. Recent studies in our laboratory, as well as others, demonstrated that the estrogen receptor coregulator PELP1 is a proto-oncogene. PELP1 interactions with histone demethylase KDM1 play a critical role in its oncogenic functions and PELP1 is a prognostic indicator of decreased survival in patients with breast cancer. However, the in vivo significance of PELP1 deregulation during initiation and progression of breast cancer remains unknown. We generated an inducible, mammary gland-specific PELP1-expressing transgenic (Tg) mouse (MMTVrtTA-TetOPELP1). We found more proliferation, extensive side branching, and precocious differentiation in PELP1-overexpressing mammary glands than in control glands. Aged MMTVrtTA-TetOPELP1 Tg mice had hyperplasia and preneoplastic changes as early as 12 weeks, and ER-positive mammary tumors occurred at a latency of 14 to 16 months. Mechanistic studies revealed that PELP1 deregulation altered expression of a number of known ER target genes involved in cellular proliferation (cyclin D1, CDKs) and morphogenesis (EGFR, MMPs) and such changes facilitated altered mammary gland morphogenesis and tumor progression. Furthermore, PELP1 was hyper-phosphorylated at its CDK phosphorylation site, suggesting an autocrine loop involving the CDK–cyclin D1–PELP1 axis in promoting mammary tumorigenesis. Treatment of PELP1 Tg mice with a KDM1 inhibitor significantly reduced PELP1-driven hyperbranching, reversed alterations in cyclin D1 expression levels, and reduced CDK-driven PELP1 phosphorylation. These results further support the hypothesis that PELP1 deregulation has the potential to promote breast tumorigenesis in vivo and represent a novel model for future investigation into molecular mechanisms of PELP1-mediated tumorigenesis. Cancer Res; 74(24); 7395–405. ©2014 AACR.
Changes in BAI1 and Nestin Expression Are Prognostic Indicators for Survival and Metastases in Breast Cancer and Provide Opportunities for Dual Targeted Therapies
Authors: Meisen Walter Hans , Dubin Samuel , Sizemore Steven T. , Mathsyaraja Haritha , Thies Katie , Lehman Norman L. , Boyer Peter , Jaime-Ramirez Alena Cristina , Elder J. Bradley , Powell Kimerly , Chakravarti Arnab , Ostrowski Michael C. , Kaur Balveen 
Published: November 2014

Abstract
The 2-year survival rate of patients with breast cancer brain metastases is less than 2%. Treatment options for breast cancer brain metastases are limited, and there is an unmet need to identify novel therapies for this disease. Brain angiogenesis inhibitor 1 (BAI1) is a GPCR involved in tumor angiogenesis, invasion, phagocytosis, and synaptogenesis. For the first time, we identify that BAI1 expression is significantly reduced in breast cancer and higher expression is associated with better patient survival. Nestin is an intermediate filament whose expression is upregulated in several cancers. We found that higher Nestin expression significantly correlated with breast cancer lung and brain metastases, suggesting both BAI1 and Nestin can be therapeutic targets for this disease. Here, we demonstrate the ability of an oncolytic virus, 34.5ENVE, to target and kill high Nestin-expressing cells and deliver Vstat120 (extracellular fragment of BAI1). Finally, we created two orthotopic immune-competent murine models of breast cancer brain metastases and demonstrated 34.5ENVE extended the survival of immune-competent mice bearing intracranial breast cancer tumors. Mol Cancer Ther; 14(1); 307–14. ©2014 AACR.
Repurposing the Antihelmintic Mebendazole as a Hedgehog Inhibitor
Authors: Larsen Andrew R. , Bai Ren-Yuan , Chung Jon H. , Borodovsky Alexandra , Rudin Charles M. , Riggins Gregory J. , Bunz Fred 
Published: November 2014

Abstract
The hedgehog (Hh) signaling pathway is activated in many types of cancer and therefore presents an attractive target for new anticancer agents. Here, we show that mebendazole, a benzamidazole with a long history of safe use against nematode infestations and hydatid disease, potently inhibited Hh signaling and slowed the growth of Hh-driven human medulloblastoma cells at clinically attainable concentrations. As an antiparasitic, mebendazole avidly binds nematode tubulin and causes inhibition of intestinal microtubule synthesis. In human cells, mebendazole suppressed the formation of the primary cilium, a microtubule-based organelle that functions as a signaling hub for Hh pathway activation. The inhibition of Hh signaling by mebendazole was unaffected by mutants in the gene that encodes human Smoothened (SMO), which are selectively propagated in cell clones that survive treatment with the Hh inhibitor vismodegib. Combination of vismodegib and mebendazole resulted in additive Hh signaling inhibition. Because mebendazole can be safely administered to adults and children at high doses over extended time periods, we propose that mebendazole could be rapidly repurposed and clinically tested as a prospective therapeutic agent for many tumors that are dependent on Hh signaling. Mol Cancer Ther; 14(1); 3–13. ©2014 AACR.
Inflammasome Activation by Mitochondrial Oxidative Stress in Macrophages Leads to the Development of Angiotensin II–Induced Aortic Aneurysm
Authors: Usui Fumitake , Shirasuna Koumei , Kimura Hiroaki , Tatsumi Kazuki , Kawashima Akira , Karasawa Tadayoshi , Yoshimura Koichi , Aoki Hiroki , Tsutsui Hiroko , Noda Tetsuo , Sagara Junji , Taniguchi Shun’ichiro , Takahashi Masafumi 
Published: November 2014

Objective—
Abdominal aortic aneurysm (AAA) is considered a chronic inflammatory disease; however, the molecular basis underlying the sterile inflammatory response involved in the process of AAA remains unclear. We previously showed that the inflammasome, which regulates the caspase-1–dependent interleukin-1β production, mediates the sterile cardiovascular inflammatory responses. Therefore, we hypothesized that the inflammasome is a key mediator of initial inflammation in AAA formation.

Approach and Results—

Apoptosis-associated speck-like protein containing a caspase recruitment domain is highly expressed in adventitial macrophages in human and murine AAA tissues. Using an established mouse model of AAA induced by continuous infusion of angiotensin II in
Apoe
–/–
mice, NLR family pyrin domain containing 3 (NLRP3), apoptosis-associated speck-like protein containing a caspase recruitment domain, and caspase-1 deficiency in
Apoe
–/–
mice were shown to decrease the incidence, maximal diameter, and severity of AAA along with adventitial fibrosis and inflammatory responses significantly, such as inflammatory cell infiltration and cytokine expression in the vessel wall. NLRP3, apoptosis-associated speck-like protein containing a caspase recruitment domain, and caspase-1 deficiency in
Apoe
–/–
mice also reduced elastic lamina degradation and metalloproteinase activation in the early phase of AAA formation. Furthermore, angiotensin II stimulated generation of mitochondria-derived reactive oxygen species in the adventitial macrophages, and this mitochondria-derived reactive oxygen species generation was inhibited by NLRP3, apoptosis-associated speck-like protein containing a caspase recruitment domain, and caspase-1 deficiency. In vitro experiments revealed that angiotensin II stimulated the NLRP3 inflammasome activation and subsequent interleukin-1β release in macrophages, and this activation was mediated through an angiotensin type I receptor/mitochondria-derived reactive oxygen species–dependent pathway.

Conclusions—
Our results demonstrate the importance of the NLRP3 inflammasome in the initial inflammatory responses in AAA formation, indicating its potential as a novel therapeutic target for preventing AAA progression.
Intravenous Autologous Bone Marrow Mononuclear Stem Cell Therapy for Ischemic Stroke
Authors: Prasad Kameshwar , Sharma Alka , Garg Ajay , Mohanty Sujata , Bhatnagar Shinjini , Johri Sharat , Singh Kunwar Karni , Nair Velu , Sarkar Ravi Shankar , Gorthi Sankar Prasad , Hassan Kaukab Maqbool , Prabhakar Sudesh , Marwaha Neelam , Khandelwal Niranjan , Misra Usha Kant , Kalita Jayantee , Nityanand Soniya 
Published: November 2014

Background and Purpose—
Pilot studies have suggested benefit from intravenous administration of bone marrow mononuclear stem cells (BMSCs) in stroke. We explored the efficacy and safety of autologous BMSCs in subacute ischemic stroke.

Methods—

This was a phase II, multicenter, parallel group, randomized trial with blinded outcome assessment that included 120 patients. Patients with subacute ischemic stroke were randomly assigned to the arm that received intravenous infusion of autologous BMSCs or to control arm. Coprimary clinical efficacy outcomes were Barthel Index score and modified Rankin scale at day 180. Secondary outcomes were change in infarct volume, National Institute of Health Stroke Scale (NIHSS) at day 90 and 180. Main safety outcomes were adverse events, any new area of
18
fluorodeoxyglucose positron emission tomography uptake in any body part over 365 days.

Results—

Fifty-eight patients received a mean of 280.75 million BMSCs at median of 18.5 days after stroke onset. There was no significant difference between BMSCs arm and control arm in the Barthel Index score (63.1 versus 63.6;
P
=0.92), modified Rankin scale shift analysis (
P
=0.53) or score >3 (47.5% versus 49.2%;
P
=0.85), NIHSS score (6.3 versus 7.0;
P
=0.53), change in infarct volume (−11.1 versus −7.36;
P
=0.63) at day 180. Adverse events were also similar in the 2 arms, and no patient showed any new area of
18
fluorodeoxyglucose uptake.

Conclusions—
With the methods used, results of this hitherto first randomized controlled trial indicate that intravenous infusion of BMSCs is safe, but there is no beneficial effect of treatment on stroke outcome.

Clinical Trial Registration—

URLs:
http://ctri.nic.in/Clinicaltrials
and
http://www.clinicaltrials.gov
. Unique identifiers: CTRI-ROVCTRI/2008/091/0004 and NCT0150177.
Cool-Season Precipitation Patterns Associated with Teleconnection Interactions in the United States
Authors: Wise Erika K. , Wrzesien Melissa L. , Dannenberg Matthew P. , McGinnis David L. 
Published: November 2014

AbstractSeasonal climate forecasts are regularly published to provide decision makers with insights on upcoming climate conditions. Precipitation forecasts, in particular, are useful for fields such as agriculture and water resources. Projections frequently cite a single climate oscillation such as El Niño–Southern Oscillation (ENSO) or the North Atlantic Oscillation (NAO) when suggesting whether a region will be wetter or drier than normal. The complex climate system is composed of a multitude of simultaneous oceanic and atmospheric oscillations, however. Through the study of five atmospheric-pressure-based oscillations, their interactions, and associated precipitation values, this research demonstrates the wide variety of precipitation patterns that can arise when different phases of prominent climate modes occur. Results show that incorporating other Northern Hemisphere teleconnections can dampen or shift expected ENSO and NAO impact patterns. These results indicate that seasonal precipitation projections may be improved by incorporating multiple, regionally important teleconnection indices into the forecast.
Video methodologies in research: Unlocking the complexities of occupation
Authors: Bailliard Antoine L. 
Published: November 2014

Background. Video methods are used by numerous academic disciplines researching human action. Occupational therapists and scientists have primarily employed video data to enumerate subcomponents of occupational behaviour, to conduct reliability tests, and to study clinical reasoning. There is a gap in the literature using video data to explore complex dimensions of typical occupational behaviour. Purpose. This paper aims to encourage the use of video methodology beyond its current state in research on occupation. Key Issues. Drawing on recent theoretical developments in the literature and empirical illustrations from a video-based project with migrants, this paper demonstrates the potential contributions of video data to understandings of identity, the physical environment, the stream of occupations, and collective occupations. The paper also discusses the unique advantages and richness of collecting video data in comparison to interviews and traditional observations. The challenges in employing video methodologies are discussed. Implications. Video research offers unprecedented opportunities to study human occupation in incommensurable detail as it unfolds through sociocultural and physical environments.
Using the mouse grimace scale to assess pain associated with routine ear notching and the effect of analgesia in laboratory mice
Authors: Miller AL , Leach MC 
Published: November 2014

Social housing is recommended where possible for laboratory mice. In order to achieve this, mice must be individually identifiable. Although, various methods are available, permanent identification is often required, such as ear notching. This method is likely to be painful and to date there is limited literature on pain assessment and alleviation for this routine husbandry practice. Here we aimed to determine if the mouse grimace scale (MGS) could be used to assess pain in C57BL/6 mice following routine ear notching. Langford et al. found that very acute noxious stimuli (i.e. < 10 min in duration) did not produce a change in MGS score in comparison to baseline. Here, no significant difference was found between MGS scores at baseline and immediately post ear notching, potentially indicating that the pain associated with ear notching is either too acute to assess using the MGS tool or the practice is not painful. Studies in other species indicate that ear notching is painful, therefore, unless we can confidently conclude that the process of ear notching is not painful, we should err on the side of caution and assume it is painful due to the large number of mice ear-notched and potential welfare consequences. Alternative methods of assessing pain following this routine practice should be used in order to assess both the potential pain in mice, and the effectiveness of analgesics or local anaesthetics to relieve any associated pain.
Inferior Results of Salvage Arthrodesis After Failed Ankle Replacement Compared to Primary Arthrodesis
Authors: Rahm Stefan , Klammer Georg , Benninger Emanuel , Gerber Fabienne , Farshad Mazda , Espinosa Norman 
Published: November 2014

Background: Up to now, there has been no evidence that salvage arthrodesis would perform inferior when compared with primary ankle arthrodesis. The purpose of this study was to compare their clinical and radiographic results. Methods: A retrospective analysis was performed using 2 validated scores and assessment of radiographic union by comparing 23 patients who underwent salvage ankle arthrodesis (group SA = salvage arthrodesis) after failed total ankle replacement with 23 matched patients who received primary ankle arthrodesis (group PA = primary arthrodesis). The mean follow-up period was 38 (range 16-92) months in group SA and 56 (23-94) months in group PA. Results: Complete union was achieved in 17 patients (74%) after a mean time of 50 (13- 114) weeks in group SA and in 16 patients (70%) after a mean time of 23 (10-115) weeks in group PA. The SF-36 score averaged 48 points (7-80) in SA and 66 points (14-94; P = .006) in group PA. In group SA the mean FFI was 57% (22-82) for pain and 71% (44-98) for function. In group PA significantly better results for pain with 34% (0-88; P = .002) and function with 48% (1-92; P = .002) were found. Conclusion: Salvage arthrodesis led to impaired life quality and reduced function combined with significantly higher pain when compared with primary ankle arthrodesis. These findings can be used to counsel our patients preoperatively. Level of Evidence: Level III, retrospective case series.
Abdominal ultrasonographic findings in acromegalic cats
Authors: Lourenço Bianca N , Randall Elissa , Seiler Gabriela , Lunn Katharine F 
Published: November 2014

Objectives Acromegaly is increasingly recognized as a cause of insulin resistance in cats with diabetes mellitus (DM). The objective of this study was to determine if ultrasonographic changes in selected abdominal organs of acromegalic cats could be used to raise the index of suspicion for this condition. Methods In this retrospective case-control study, medical records of cats presenting to North Carolina State University or Colorado State University from January 2002 to October 2012 were reviewed. Cats were included in the acromegaly group if they had insulin-resistant DM with increased serum insulin-like growth factor (IGF-1) concentrations and had an abdominal ultrasound examination performed with report available. A control group included age-matched cats that had abdominal ultrasound examination performed for investigation of disease unlikely to involve the kidneys, adrenal glands, pancreas or liver. Results Twenty-four cats were included in each group. IGF-1 concentrations in the acromegaly group ranged from >148 to 638 nmol/l. When compared with age-matched controls, cats with acromegaly demonstrated significantly increased median left and right kidney length, significantly increased median left and right adrenal gland thickness, and significantly increased median pancreatic thickness. Hepatomegaly and bilateral adrenomegaly were reported in 63% and 53% of acromegalic cats, respectively, and in none of the controls. Pancreatic abnormalities were described in 88% of the acromegalic cats and 8% of the controls. Conclusions and relevance These findings indicate that compared with non-acromegalic cats, age-matched acromegalic patients have measurably larger kidneys, adrenal glands and pancreas. Diagnostic testing for acromegaly should be considered in poorly regulated diabetic cats exhibiting organomegaly on abdominal ultrasound examination.