bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Biology of
Vibrio vulnificus
Authors: Oliver James D. 
Published: June 2015

ABSTRACT

Vibrio vulnificus
, carrying a 50% fatality rate, is the most deadly of the foodborne pathogens. It occurs in estuarine and coastal waters and it is found in especially high numbers in oysters and other molluscan shellfish. The biology of
V. vulnificus
, including its ecology, pathogenesis, and molecular genetics, has been described in numerous reviews. This article provides a brief summary of some of the key aspects of this important human pathogen, including information on biotypes and genotypes, virulence factors, risk factor requirements and the role of iron in disease, association with oysters, geographic distribution, importance of salinity and water temperature, increasing incidence associated with global warming. This article includes some of our findings as presented at the “Vibrios in the Environment 2010” conference held in Biloxi, MS.
Effects of Global Warming onVibrioEcology
Authors: Vezzulli Luigi , Pezzati Elisabetta , Brettar Ingrid , Höfle Manfred , Pruzzo Carla 
Published: June 2015

ABSTRACTVibrio-related infections are increasing worldwide both in humans and aquatic animals. Rise in global sea surface temperature (SST), which is approximately 1°C higher now than 140 years ago and is one of the primary physical impacts of global warming, has been linked to such increases. In this chapter, major known effects of increasing SST on the biology and ecology of vibrios are described. They include the effects on bacterial growth rate, both in the field and in laboratory, culturability, expression of pathogenicity traits, and interactions with aquatic organisms and abiotic surfaces. Special emphasis is given to the effect of ocean warming onVibriointeractions with zooplankters, which represent one of the most important aquatic reservoirs for these bacteria. The reported findings highlight the biocomplexity of the interactions between vibrios and their natural environment in a climate change scenario, posing the need for interdisciplinary studies to properly understand the connection between ocean warming and persistence and spread of vibrios in sea waters and the epidemiology of the diseases they cause.
Genetics of Natural Competence in
Vibrio cholerae
and other Vibrios
Authors: Antonova Elena S. , Hammer Brian K. 
Published: June 2015

ABSTRACT

Many Gram-positive and Gram-negative bacteria can become naturally competent to take up extracellular DNA from the environment via a dedicated uptake apparatus. The genetic material that is acquired can (i) be used for nutrients, (ii) aid in genome repair, and (iii) promote horizontal gene transfer when incorporated onto the genome by homologous recombination, the process of “transformation.” Recent studies have identified multiple environmental cues sufficient to induce natural transformation in
Vibrio cholerae
and several other
Vibrio
species. In
V. cholerae
, nutrient limitation activates the cAMP receptor protein regulator, quorum-sensing signals promote synthesis of HapR-controlled QstR, chitin stimulates production of TfoX, and low extracellular nucleosides allow CytR to serve as an additional positive regulator. The network of signaling systems that trigger expression of each of these required regulators is well described, but the mechanisms by which each in turn controls competence apparatus genes is poorly understood. Recent work has defined a minimal set of genes that encode apparatus components and begun to characterize the architecture of the machinery by fluorescence microscopy. While studies with a small set of
V. cholerae
reference isolates have identified regulatory and competence genes required for DNA uptake, future studies may identify additional genes and regulatory connections, as well as revealing how common natural competence is among diverse
V. cholerae
isolates and other
Vibrio
species.
Knowledge and attitudes of school teachers, preschool teachers and students in teacher training about epilepsy and emergency management of seizures
Authors: Dumeier Henriette K , Neininger Martina P , Bernhard Matthias K , Syrbe Steffen , Merkenschlager Andreas , Zabel Jörg , Kiess Wieland , Bertsche Thilo , Bertsche Astrid 
Published: June 2015

ProblemSchool and preschool teachers play a key role in the care of children with epilepsy. Yet, data about their knowledge on epilepsy are scarce.MethodsAssessment of knowledge and attitudes towards epilepsy in teachers by conducting a questionnaire survey in Leipzig and Blankenburg, Germany, from August 2013 to January 2014.Results1243 questionnaires were completed by 302 school teachers, 883 preschool teachers, 56 students and two unclassified participants. Of the respondents, 140 (11%) stated to have already been actively involved in an epilepsy emergency situation, another 148 (12%) as observers. Only 214 (17%) of respondents felt sufficiently prepared for an emergency. A rescue medication had already been applied by 79 (6%) of respondents; only 186 respondents (15%) stated they would be willing to administer a prescribed rescue medication under any circumstances. In response to an open-ended question about the most common fatal outcomes of a seizure, status epilepticus and drowning were rarely mentioned. 233 (19%) of respondents assumed that epileptic seizures cannot result in death. 606 (49%) of respondents were concerned about the legal repercussions to an incorrect response to a seizure.129/403 (32%) of teachers with >20 years of professional experience claimed never to have had a child suffering from epilepsy in their care, even though the prevalence of childhood epilepsy indicates that they should. In total, 1066 (86%) respondents expressed a desire to gain more knowledge on epilepsy.ConclusionsTraining programmes for teachers should be established. Furthermore, a clear legal regulatory framework needs to be set up.
Lessons learnt from a cluster-randomised trial evaluating the effectiveness of Self-Management Support (SMS) delivered by practice nurses in routine diabetes care
Authors: van Dijk-de Vries Anneke , van Bokhoven Marloes A , Winkens Bjorn , Terluin Berend , Knottnerus J André , van der Weijden Trudy , van Eijk Jacques Th M 
Published: June 2015

ObjectiveTo evaluate the effectiveness of biopsychosocial Self-Management Support (SMS) delivered by practice nurses in routine diabetes care.DesignA pragmatic cluster-randomised controlled trial within a hybrid effectiveness-implementation study design. Practice nurses were cluster-randomised.SettingA regional care group in the Netherlands consisting of 77 family practices. The study involved practice nurses (n=40) providing care to approximately 4000 patients with diabetes.ParticipantsPatients with type 2 diabetes (n=264) selected by a self-administered questionnaire aimed at measuring emotional distress and diabetes-related reduced daily functioning.InterventionPractice nurses in the intervention arm (n=19) were trained to integrate SMS into their routine consultations. SMS included detection of patients with emotional distress and reduced daily functioning, and supporting them when needed through problem solving and reattribution techniques. Practice nurses in the control arm (n=21) provided usual care.Main outcome measuresThe primary outcome measure was a dichotomised score on a Visual Analogue Scale that measured the perceived effect of diabetes on daily functioning. Secondary measures included patients’ diabetes-related distress, quality of life, autonomy and participation, self-efficacy, self-management and glycaemic control. Outcomes were measured at baseline and at 4-month and 12-month follow-ups.ResultsOnly 16 of the 117 patients in the intervention arm (14%) who were found eligible by the posted research-driven screening questionnaire were detected by their practice nurses. Extra consultations for the self-management support were delivered to only 11 study participants. In the control arm, 147 patients received usual care. Multilevel analyses showed no significant differences in outcomes between the intervention and control arms.ConclusionsSMS in its present form was not effective. The research-driven screening to select trial participants appeared to be inconsistent with nurse-led detection in routine practice. Adequate follow-up moments need to be built in to overcome barriers resulting from tension between the implementation and effectiveness parts of hybrid studies.Trial registration numberCurrent Controlled Trials NTR2764.
Prayer or spiritual healing as adjuncts to conventional care: a cross sectional analysis of prevalence and characteristics of use among women
Authors: Rao Angela , Sibbritt David , Phillips Jane L , Hickman Louise D 
Published: June 2015

ObjectivesTo determine the prevalence and characteristics of users of prayer or spiritual healing among women.Design and settingThis cross sectional study was conducted as a part of the Australian Longitudinal Study on Women's Health (ALSWH), a 20-year study that examines various factors affecting women's health and well-being.ParticipantsThe sample used in the current study were women from the 1946–1951 cohort (n=9965) (59–64 years) who were surveyed in 2010.Outcome measuresUse of prayer or spiritual healing; demographic factors and measures of health status. χ2Tests, analyses of variance (to determine associations) and a stepwise backward logistic regression model (for the most significant predictors) using a likelihood ratio test were used to determine the outcome measures.ResultsIt is estimated that 26% of Australian women from the 1946–1951 cohort (aged 59–64 years) use prayer or spiritual healing on a regular basis. Women were significantly more likely to use prayer or spiritual healing if they were non-smokers, non-drinkers or low-risk drinkers, had symptoms of severe tiredness (OR 1.25; 95% CI 1.12 to 1.40), depression, (OR 1.30; 95% CI 1.11 to 1.53), anxiety (OR 1.33; 95% CI 1.15 to 1.53), diagnosed cancer (OR 1.84; 95% CI 1.28 to 2.65) or other major illnesses (OR 1.43; 95% CI 1.18 to 1.75) and used other complementary therapies.ConclusionsA significant proportion of adult women are using prayer or spiritual healing. Given that prayer or spiritual healing was significantly associated with health symptoms, chronic illnesses and positive health seeking behaviours, respect for prayer or spiritual healing practices is required within health care settings. Future research is recommended around specific populations using prayer or spiritual healing, reasons for their use and potential benefits on health related outcomes and general well-being.
A pilot randomised controlled trial of personalised care after treatment for prostate cancer (TOPCAT-P): nurse-led holistic-needs assessment and individualised psychoeducational intervention: study protocol
Authors: Stanciu Marian Andrei , Morris Caroline , Makin Matt , Watson Eila , Bulger Jenna , Evans Richard , Hiscock Julia , Hoare Zoë , Edwards Rhiannon Tudor , Neal Richard David , Wilkinson Clare 
Published: June 2015

IntroductionProstate cancer is common and the incidence is increasing, but more men are living longer after diagnosis, and die with their disease rather than of it. Nonetheless, specific and substantial physical, sexual, emotional and mental health problems often lead to a poor quality of life. Urology services increasingly struggle to cope with the demands of follow-up care, and primary care is likely to play the central role in long-term follow-up. The present phase II trial will evaluate the feasibility and acceptability of a nurse-led, person-centred psychoeducational intervention, delivered in community or primary care settings.Methods and analysisProstate cancer survivors diagnosed in the past 9–48 months and currently biochemically stable will be identified from hospital records by their treating clinician. Eligible men would have either completed radical treatment, or would be followed up with prostate specific antigen monitoring and symptom reporting. We will recruit 120 patients who will be randomised to receive either an augmented form of usual care, or an additional nurse-led intervention for a period of 36 weeks. Following the health policy in Wales, the intervention is offered by a key worker, is promoting prudent healthcare and is using a holistic needs assessment. Outcome measures will assess physical symptoms, psychological well-being, confidence in managing own health and quality of life. Healthcare service use will be measured over 36 weeks. Feedback interviews with patients and clinicians will further inform the acceptability of the intervention. Recruitment, attrition, questionnaire completion rates and outcome measures variability will be assessed, and results will inform the design of a future phase III trial and accompanying economic evaluation.Ethics and disseminationEthics approval was granted by Bangor University and North Wales REC (13/WA/0291). Results will be reported in peer-reviewed publications, at scientific conferences, and directly through national cancer and primary care networks.Trial registration numberISRCTN 34516019.
Activation-Induced Cytidine Deaminase Contributes to Pancreatic Tumorigenesis by Inducing Tumor-Related Gene Mutations
Authors: Sawai Yugo , Kodama Yuzo , Shimizu Takahiro , Ota Yuji , Maruno Takahisa , Eso Yuji , Kurita Akira , Shiokawa Masahiro , Tsuji Yoshihisa , Uza Norimitsu , Matsumoto Yuko , Masui Toshihiko , Uemoto Shinji , Marusawa Hiroyuki , Chiba Tsutomu 
Published: June 2015

Abstract
Pancreatic ductal adenocarcinoma (PDAC) develops via an accumulation of various gene mutations. The mechanism underlying the mutations in PDAC development, however, is not fully understood. Recent insight into the close association between the mutation pattern of various cancers and specific mutagens led us to investigate the possible involvement of activation-induced cytidine deaminase (AID), a DNA editing enzyme, in pancreatic tumorigenesis. Our immunohistochemical findings revealed AID protein expression in human acinar ductal metaplasia, pancreatic intraepithelial neoplasia, and PDAC. Both the amount and intensity of the AID protein expression increased with the progression from precancerous to cancerous lesions in human PDAC tissues. To further assess the significance of ectopic epithelial AID expression in pancreatic tumorigenesis, we analyzed the phenotype of AID transgenic (AID Tg) mice. Consistent with our hypothesis that AID is involved in the mechanism of the mutations underlying pancreatic tumorigenesis, we found precancerous lesions developing in the pancreas of AID Tg mice. Using deep sequencing, we also detected Kras and c-Myc mutations in our analysis of the whole pancreas of AID Tg mice. In addition, Sanger sequencing confirmed the presence of Kras, c-Myc, and Smad4 mutations, with the typical mutational footprint of AID in precancerous lesions in AID Tg mice separated by laser capture microdissection. Taken together, our findings suggest that AID contributes to the development of pancreatic precancerous lesions by inducing tumor-related gene mutations. Our new mouse model without intentional manipulation of specific tumor-related genes provides a powerful system for analyzing the mutations involved in PDAC. Cancer Res; 75(16); 3292–301. ©2015 AACR.
A Polymer-Based Antibody–Vinca Drug Conjugate Platform: Characterization and Preclinical Efficacy
Authors: Yurkovetskiy Alexander V. , Yin Mao , Bodyak Natalya , Stevenson Cheri A. , Thomas Joshua D. , Hammond Charles E. , Qin LiuLiang , Zhu Bangmin , Gumerov Dmitry R. , Ter-Ovanesyan Elena , Uttard Alex , Lowinger Timothy B. 
Published: June 2015

Abstract
Antibody–drug conjugates (ADC) are an emerging drug class that uses antibodies to improve cytotoxic drug targeting for cancer treatment. ADCs in current clinical trials achieve a compromise between potency and physicochemical/pharmacokinetic properties by conjugating potent cytotoxins directly to an antibody at a 4:1 or less stoichiometric ratio. Herein, we report a novel, polyacetal polymer-based platform for creating ADC that use poly-1-hydroxymethylethylene hydroxymethyl-formal (PHF), also known as Fleximer. The high hydrophilicity and polyvalency properties of the Fleximer polymer can be used to produce ADC with high drug loading without compromising physicochemical and pharmacokinetic properties. Using trastuzumab and a vinca drug derivative to demonstrate the utility of this platform, a novel Fleximer-based ADC was prepared and characterized in vivo. The ADC prepared had a vinca-antibody ratio of 20:1. It exhibited a high antigen-binding affinity, an excellent pharmacokinetic profile and antigen-dependent efficacy, and tumor accumulation in multiple tumor xenograft models. Our findings illustrate the robust utility of the Fleximer platform as a highly differentiated alternative to the conjugation platforms used to create ADC currently in clinical development. Cancer Res; 75(16); 3365–72. ©2015 AACR.
Tumor Suppressor Activity of Klotho in Breast Cancer Is Revealed by Structure–Function Analysis
Authors: Ligumsky Hagai , Rubinek Tami , Merenbakh-Lamin Keren , Yeheskel Adva , Sertchook Rotem , Shahmoon Shiri , Aviel-Ronen Sarit , Wolf Ido 
Published: June 2015

Abstract
Klotho is a transmembrane protein containing two internal repeats, KL1 and KL2, both displaying significant homology to members of the β-glycosidase family. Klotho is expressed in the kidney, brain, and various endocrine tissues, but can also be cleaved and act as a circulating hormone. Klotho is an essential cofactor for binding of fibroblast growth factor 23 (FGF23) to the FGF receptor and can also inhibit the insulin-like growth factor-1 (IGF-1) pathway. Data from a wide array of malignancies indicate klotho as a tumor suppressor; however, the structure–function relationships governing its tumor suppressor activities have not been deciphered. Here, the tumor suppressor activities of the KL1 and KL2 domains were examined. Overexpression of either klotho or KL1, but not of KL2, inhibited colony formation by MCF-7 and MDA-MB-231 cells. Moreover, in vivo administration of KL1 was not only well tolerated but significantly slowed tumor formation in nude mice. Further studies indicated that KL1, but not KL2, interacted with the IGF-1R and inhibited the IGF-1 pathway. Based on computerized structural modeling, klotho constructs were generated in which critical amino acids have been mutated. Interestingly, the mutated proteins retained their tumor suppressor activity but showed reduced ability to modulate FGF23 signaling. These data indicate differential activity of the klotho domains, KL1 and KL2, in breast cancer and reveal that the tumor suppressor activities of klotho can be dissected from its physiologic activities.
Implications: These findings pave the way for a rational design of safe klotho-based molecules for the treatment of breast cancer. Mol Cancer Res; 13(10); 1398–407. ©2015 AACR.
Extracellular Vesicles Present in Human Ovarian Tumor Microenvironments Induce a Phosphatidylserine-Dependent Arrest in the T-cell Signaling Cascade
Authors: Kelleher Raymond J. , Balu-Iyer Sathy , Loyall Jenni , Sacca Anthony J. , Shenoy Gautam N. , Peng Peng , Iyer Vandana , Fathallah Anas M. , Berenson Charles S. , Wallace Paul K. , Tario Joseph , Odunsi Kunle , Bankert Richard B. 
Published: June 2015

AbstractThe identification of immunosuppressive factors within human tumor microenvironments, and the ability to block these factors, would be expected to enhance patients' antitumor immune responses. We previously established that an unidentified factor, or factors, present in ovarian tumor ascites fluids reversibly inhibited the activation of T cells by arresting the T-cell signaling cascade. Ultracentrifugation of the tumor ascites fluid has now revealed a pellet that contains small extracellular vesicles (EV) with an average diameter of 80 nm. The T-cell arrest was determined to be causally linked to phosphatidylserine (PS) that is present on the outer leaflet of the vesicle bilayer, as a depletion of PS-expressing EV or a blockade of PS with anti-PS antibody significantly inhibits the vesicle-induced signaling arrest. The inhibitory EV were also isolated from solid tumor tissues. The presence of immunosuppressive vesicles in the microenvironments of ovarian tumors and our ability to block their inhibition of T-cell function represent a potential therapeutic target for patients with ovarian cancer. Cancer Immunol Res; 3(11); 1269–78. ©2015 AACR.
Diagnosis of Stroke-Associated Pneumonia
Authors: Smith Craig J. , Kishore Amit K. , Vail Andy , Chamorro Angel , Garau Javier , Hopkins Stephen J. , Di Napoli Mario , Kalra Lalit , Langhorne Peter , Montaner Joan , Roffe Christine , Rudd Anthony G. , Tyrrell Pippa J. , van de Beek Diederik , Woodhead Mark , Meisel Andreas 
Published: June 2015

Background and Purpose—
Lower respiratory tract infections frequently complicate stroke and adversely affect outcome. There is currently no agreed terminology or gold-standard diagnostic criteria for the spectrum of lower respiratory tract infections complicating stroke, which has implications for clinical practice and research. The aim of this consensus was to propose standardized terminology and operational diagnostic criteria for lower respiratory tract infections complicating acute stroke.

Methods—
Systematic literature searches of multiple electronic databases were undertaken. An evidence review and 2 rounds of consensus consultation were completed before a final consensus meeting in September 2014, held in Manchester, United Kingdom. Consensus was defined a priori as ≥75% agreement between the consensus group members.

Results—
Consensus was reached for the following: (1) stroke-associated pneumonia (SAP) is the recommended terminology for the spectrum of lower respiratory tract infections within the first 7 days after stroke onset; (2) modified Centers for Disease Control and Prevention (CDC) criteria are proposed for SAP as follows—probable SAP: CDC criteria met, but typical chest x-ray changes absent even after repeat or serial chest x-ray; definite SAP: CDC criteria met, including typical chest x-ray changes; (3) there is limited evidence for a diagnostic role of white blood cell count or C-reactive protein in SAP; and (4) there is insufficient evidence for the use of other biomarkers (eg, procalcitonin).

Conclusions—
Consensus operational criteria for the terminology and diagnosis of SAP are proposed based on the CDC criteria. These require prospective evaluation in patients with stroke to determine their reliability, validity, impact on clinician behaviors (including antibiotic prescribing), and clinical outcomes.
Retrobulbar Spot Sign Predicts Thrombolytic Treatment Effects and Etiology in Central Retinal Artery Occlusion
Authors: Nedelmann Max , Graef Michael , Weinand Frank , Wassill Klaus-Heiko , Kaps Manfred , Lorenz Birgit , Tanislav Christian 
Published: June 2015

Background and Purpose—
Transorbital sonography may help establish diagnosis of central retinal artery occlusion (CRAO). Next to Doppler sonographic proof of CRAO, an intra-arterial spot sign can be detected in some cases. We hypothesized that it reflects calcified components. It may be associated with embolization from atherosclerotic plaques and may negatively influence thrombolysis.

Methods—
Prospective monocenter study of 46 patients with ophthalmologically confirmed CRAO. Systemic tissue-type plasminogen activator thrombolysis was performed when appropriate. All patients received etiologic workup.

Results—

CRAO was confirmed by Doppler in all patients. Fifty-nine percent of patients with arterio-arterial embolization were spot sign–positive compared with 20% from cardiac source (
P
<0.05) and none with vasculitis. Eleven patients underwent thrombolysis. Clinically relevant visual improvement was only found in absence of a spot sign (
P
<0.05).

Conclusions—
Transbulbar ultrasound is valuable for initial diagnosis and diagnostic workup of CRAO. In the light of inconsistent results of previous thrombolysis trials, ultrasound may identify patients more likely to benefit from thrombolytic treatment.