bluuebunny/crossref_metadata_2025_split huggingface dataset:
First magenetic resonance imaging studies on aluminium maltolate‐treated aged New Zealand rabbits: an Alzheimer's animal model
Authors: Magisetty Obulesu , Dowlathabad Muralidhara Rao , Raichurkar Keshav P. , Mannar Shamasundar N. 
Published: September 2015

AbstractBackgroundAlzheimer's disease is a devastative neurodegenerative disorder. To date, there has been no animal model that could unravel the complete disease pathology. Magnetic resonance imaging has played a pivotal role in the quantitative assessment of brain tissue atrophy for a few decades. In particular, temporal lobe atrophy and ventricular dilatation have been found to be sensitive in Alzheimer's disease.MethodsThe present study focused on the replication of these crucial pathological events to enable disease progression to be diagnosed at an early stage and stopped through the use of potential therapeutic strategies.ResultThe objective of this study was to show temporal lobe atrophy and ventricular dilatation in aluminium maltolate‐treated aged New Zealand rabbit, and our study was able to demonstrate this for the first time.ConclusionThe present study makes this animal model a substantial one for further molecular level studies and opens up new targets for potential therapeutic strategies.
TRPM2 protects against tissue damage following oxidative stress and ischaemia–reperfusion
Authors: Miller Barbara A. , Cheung Joseph Y. 
Published: September 2015

AbstractTRPM channels are a subgroup of the transient receptor potential (TRP) channel superfamily whose members have important roles in cell proliferation and survival. TRPM2, the second subfamily member to be cloned, is expressed in many tissues including brain, heart, vasculature and haematopoietic cells. TRPM2 is activated by oxidative stress and several other extracellular signals including tumour necrosis factor α (TNF‐α) and amyloid β‐peptide, which increase production of ADP‐ribose (ADPR). ADPR binds to the TRPM2 C‐terminal NUDT9‐H domain, activating the channel. Early studies support the paradigm that TRPM2 activation induces cell death by sustained Ca2+ influx or by enhancing cytokine production, aggravating inflammation and tissue injury. However, more recent data show that for a number of physiological processes, TRPM2 is protective. TRPM2 protects lungs from endotoxin‐induced injury by reducing reactive oxygen species (ROS) production by phagocytes. It protects hearts from oxidative damage after ischaemia–reperfusion or hypoxia–reoxygenation by maintaining better mitochondrial bioenergetics and by decreasing ROS. Sustained Ca2+ entry through TRPM2 is required to maintain cellular bioenergetics and protect against hypoxia–reoxygenation injury. TRPM2 also protects neuroblastoma from moderate oxidative stress by decreasing ROS through increased levels of forkhead box transcription factor 3a (FOXO3a) and a downstream effector, superoxide dismutase 2. TRPM2 is important for tumour growth and cell survival through modulation of hypoxia‐inducible transcription factor expression, mitochondrial function and mitophagy. These findings in cardiac ischaemia and in neuroblastoma suggest that TRPM2 has a basic role in sustaining mitochondrial function and in cell survival that applies to a number of physiological systems and pathophysiological processes including ischaemia–reperfusion injury.
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Technical Note: MRI only prostate radiotherapy planning using the statistical decomposition algorithm
Authors: Siversson Carl , Nordström Fredrik , Nilsson Terese , Nyholm Tufve , Jonsson Joakim , Gunnlaugsson Adalsteinn , Olsson Lars E. 
Published: September 2015

Purpose:In order to enable a magnetic resonance imaging (MRI) only workflow in radiotherapy treatment planning, methods are required for generating Hounsfield unit (HU) maps (i.e., synthetic computed tomography, sCT) for dose calculations, directly from MRI. The Statistical Decomposition Algorithm (SDA) is a method for automatically generating sCT images from a single MR image volume, based on automatic tissue classification in combination with a model trained using a multimodal template material. This study compares dose calculations between sCT generated by the SDA and conventional CT in the male pelvic region.Methods:The study comprised ten prostate cancer patients, for whom a 3D T2 weighted MRI and a conventional planning CT were acquired. For each patient, sCT images were generated from the acquired MRI using the SDA. In order to decouple the effect of variations in patient geometry between imaging modalities from the effect of uncertainties in the SDA, the conventional CT was nonrigidly registered to the MRI to assure that their geometries were well aligned. For each patient, a volumetric modulated arc therapy plan was created for the registered CT (rCT) and recalculated for both the sCT and the conventional CT. The results were evaluated using several methods, including mean average error (MAE), a set of dose‐volume histogram parameters, and a restrictive gamma criterion (2% local dose/1 mm).Results:The MAE within the body contour was 36.5 ± 4.1 (1 s.d.) HU between sCT and rCT. Average mean absorbed dose difference to target was 0.0% ± 0.2% (1 s.d.) between sCT and rCT, whereas it was −0.3% ± 0.3% (1 s.d.) between CT and rCT. The average gamma pass rate was 99.9% for sCT vs rCT, whereas it was 90.3% for CT vs rCT.Conclusions:The SDA enables a highly accurate MRI only workflow in prostate radiotherapy planning. The dosimetric uncertainties originating from the SDA appear negligible and are notably lower than the uncertainties introduced by variations in patient geometry between imaging sessions.
A Phase-Variable Surface Layer from the Gut Symbiont Bacteroides thetaiotaomicron
Authors: Taketani Mao , Donia Mohamed S. , Jacobson Amy N. , Lambris John D. , Fischbach Michael A. 
Published: September 2015

ABSTRACT

The capsule from
Bacteroides
, a common gut symbiont, has long been a model system for studying the molecular mechanisms of host-symbiont interactions. The
Bacteroides
capsule is thought to consist of an array of phase-variable polysaccharides that give rise to subpopulations with distinct cell surface structures. Here, we report the serendipitous discovery of a previously unknown surface structure in
Bacteroides thetaiotaomicron
: a surface layer composed of a protein of unknown function, BT1927. BT1927, which is expressed in a phase-variable manner by ~1:1,000 cells in a wild-type culture, forms a hexagonally tessellated surface layer. The BT1927-expressing subpopulation is profoundly resistant to complement-mediated killing, due in part to the BT1927-mediated blockade of C3b deposition. Our results show that the
Bacteroides
surface structure is capable of a far greater degree of structural variation than previously known, and they suggest that structural variation within a
Bacteroides
species is important for productive gut colonization.

IMPORTANCE
Many bacterial species elaborate a capsule, a structure that resides outside the cell wall and mediates microbe-microbe and microbe-host interactions. Species of
Bacteroides
, the most abundant genus in the human gut, produce a capsule that consists of an array of polysaccharides, some of which are known to mediate interactions with the host immune system. Here, we report the discovery of a previously unknown surface structure in
Bacteroides thetaiotaomicron
. We show that this protein-based structure is expressed by a subset of cells in a population and protects
Bacteroides
from killing by complement, a component of the innate immune system. This novel surface layer protein is conserved across many species of the genus
Bacteroides
, suggesting an important role in colonization and host immune modulation.
Live Imaging of Host-Parasite Interactions in a Zebrafish Infection Model Reveals Cryptococcal Determinants of Virulence and Central Nervous System Invasion
Authors: Tenor Jennifer L. , Oehlers Stefan H. , Yang Jialu L. , Tobin David M. , Perfect John R. 
Published: September 2015

ABSTRACT

The human fungal pathogen
Cryptococcus neoformans
is capable of infecting a broad range of hosts, from invertebrates like amoebas and nematodes to standard vertebrate models such as mice and rabbits. Here we have taken advantage of a zebrafish model to investigate host-pathogen interactions of
Cryptococcus
with the zebrafish innate immune system, which shares a highly conserved framework with that of mammals. Through live-imaging observations and genetic knockdown, we establish that macrophages are the primary immune cells responsible for responding to and containing acute cryptococcal infections. By interrogating survival and cryptococcal burden following infection with a panel of
Cryptococcus
mutants, we find that virulence factors initially identified as important in causing disease in mice are also necessary for pathogenesis in zebrafish larvae. Live imaging of the cranial blood vessels of infected larvae reveals that
C. neoformans
is able to penetrate the zebrafish brain following intravenous infection. By studying a
C. neoformans
FNX1 gene mutant, we find that blood-brain barrier invasion is dependent on a known cryptococcal invasion-promoting pathway previously identified in a murine model of central nervous system invasion. The zebrafish-
C. neoformans
platform provides a visually and genetically accessible vertebrate model system for cryptococcal pathogenesis with many of the advantages of small invertebrates. This model is well suited for higher-throughput screening of mutants, mechanistic dissection of cryptococcal pathogenesis in live animals, and use in the evaluation of therapeutic agents.

IMPORTANCE
Cryptococcus neoformans
is an important opportunistic pathogen that is estimated to be responsible for more than 600,000 deaths worldwide annually. Existing mammalian models of cryptococcal pathogenesis are costly, and the analysis of important pathogenic processes such as meningitis is laborious and remains a challenge to visualize. Conversely, although invertebrate models of cryptococcal infection allow high-throughput assays, they fail to replicate the anatomical complexity found in vertebrates and, specifically, cryptococcal stages of disease. Here we have utilized larval zebrafish as a platform that overcomes many of these limitations. We demonstrate that the pathogenesis of
C. neoformans
infection in zebrafish involves factors identical to those in mammalian and invertebrate infections. We then utilize the live-imaging capacity of zebrafish larvae to follow the progression of cryptococcal infection in real time and establish a relevant model of the critical central nervous system infection phase of disease in a nonmammalian model.
Assessing risk factors for early hip osteoarthritis in activity-related hip pain: a Delphi study
Authors: Jackson K A , Glyn-Jones S , Batt M E , Arden N K , Newton J L 
Published: September 2015

ObjectiveHip pain and injury as a result of activity can lead to the development of early hip osteoarthritis (OA) in susceptible individuals. Our understanding of the factors that increase susceptibility continues to evolve. The ability to clearly identify individuals (and cohorts) with activity-related hip pain who are at risk of early hip OA is currently lacking. The purpose of this study was to gain expert consensus on which key clinical measures might help predict the risk of early hip OA in individuals presenting with activity-related hip pain. The agreed measures would constitute a standardised approach to initial clinical assessment to help identify these individuals.MethodsThis Dephi study used online surveys to gain concordance of expert opinion in a structured process of ‘rounds’. In this study, we asked ‘What outcome measures are useful in predicting hip OA in activity-related hip pain?’ The Delphi panel consisted of experts from sport and exercise medicine, orthopaedics, rheumatology, physiotherapy and OA research.ResultsThe study identified key clinical measures in the history, examination and investigations (plain anteroposterior radiograph and femoroacetabular impingement views) that the panel agreed would be useful in predicting future risk of hip OA when assessing activity-related hip pain. The panel also agreed that certain investigations and tests (eg, MR angiography) did not currently have a role in routine assessment. There was a lack of consensus regarding the role of MRI, patient-reported outcome measures (PROMs) and certain biomechanical and functional assessments.ConclusionsWe provide a standardised approach to the clinical assessment of patients with activity-related hip pain. Assessment measures rejected by the Delphi panel were newer, more expensive investigations that currently lack evidence. Assessment measures that did not reach consensus include MRI and PROMs. Their role remains ambiguous and would benefit from further research.
Cost-effectiveness and budget impact of Empirical vitamin D therapy on unintentional falls in older adults in the UK
Authors: Poole C D , Smith J , Davies J S 
Published: September 2015

ObjectivesTo evaluate the health outcomes and economics associated with the current guidance relating to the prevention of falls in the elderly through vitamin D supplementation.SettingUK.ParticipantsUK population aged 60 years and above.InterventionsA Markov health state transition model simulated patient transitions between key fall-related outcomes using a 5-year horizon and annual cycles to assess the costs and benefits of empirical treatment with colecalciferol 800 iu daily.Primary and secondary outcome measuresCosts and health outcomes attributable to fall prevention following vitamin D supplementation.ResultsOur model shows that treating the UK population aged 60 years and above with 800 iu colecalciferol would, over a 5-year period: (1) prevent in excess of 430 000 minor falls; (2) avoid 190 000 major falls; (3) prevent 1579 acute deaths; (4) avoid 84 000 person-years of long-term care and (5) prevent 8300 deaths associated with increased mortality in long-term care. The greatest gains are seen among those 75 years and older. Based on reduction in falls alone, the intervention in all adults aged 65+ is cost-saving and leads to increased quality adjusted life years. Treating all adults aged 60+ incurs an intervention cost of £2.70bn over 5 years, yet produces a −£3.12bn reduction in fall-related costs; a net saving of £420M. Increasing the lower bound age limit by 5-year increments increases budget impact to −£1.17bn, −£1.75bn, and −£2.06bn for adults 65+, 70+ and 75+, respectively.ConclusionsThis study shows that treatment of the elderly UK population with colecalciferol 800 iu daily would be associated with reductions in mortality and substantial cost-savings through fall prevention.
The challenge of vaccinating adults: attitudes and beliefs of the Canadian public and healthcare providers
Authors: MacDougall D M , Halperin B A , MacKinnon-Cameron D , Li Li , McNeil S A , Langley J M , Halperin S A 
Published: September 2015

ObjectivesVaccine coverage for recommended vaccines is low among adults. The objective of this study was to assess the knowledge, attitudes, beliefs and behaviours of adults and healthcare providers related to four vaccine-preventable diseases and vaccines (diphtheria-tetanus-pertussis, zoster, pneumococcus and influenza).DesignWe undertook a survey and focus groups of Canadian adults and healthcare providers (doctors, nurses, pharmacists). A total of 4023 adults completed the survey and 62 participated in the focus groups; 1167 providers completed the survey and 45 participated in the focus groups.ResultsOnly 46.3% of adults thought they were up-to-date on their vaccines; 30% did not know. In contrast, 75.6% of providers reported being up-to-date. Only 57.5% of adults thought it was important to receive all recommended vaccines (compared to 87.1–91.5% of providers). Positive attitudes towards vaccines paralleled concern about the burden of illness and confidence in the vaccines, with providers being more aware of disease burden and confident in vaccine effectiveness than the public. Between 55.0% and 59.7% of adults reported willingness to be vaccinated if recommended by their healthcare provider. However, such recommendations were variable; while 77.4% of the public reported being offered and 52.8% reported being recommended the influenza vaccine by their provider, only 10.8% were offered and 5.6% recommended pertussis vaccine. Barriers and facilitators to improved vaccine coverage in adults, such as trust-mistrust of health authorities, pharmaceutical companies and national recommendations, autonomy versus the public good and logistical issues (such as insufficient time and lack of vaccination status tracking), were identified by both the public and providers.ConclusionsDespite guidelines for adult vaccination, there are substantial gaps in knowledge and attitudes and beliefs among both the public and healthcare providers that lead to low vaccine coverage. A systematic approach that involves education, elimination of barriers and establishing and improving infrastructure for adult immunisation is required.
A retrospective evaluation of the intrauterine device in a patient population in Buenos Aires, Argentina
Authors: Jagroep Sherani R , Pichardo Margaret S , Arribas Lia , Heredia Graciela , Coccio Elina , Palermo Tia M 
Published: September 2015

BackgroundThe intrauterine device (IUD) is a long-acting reversible contraceptive method that is safe for a wide range of women, including adolescents and nulliparous women. Globally, it is often underutilised due to misperceptions among patients. Examination of characteristics associated with IUD discontinuation including adverse effects and IUD expulsion can inform provider practices to improve contraception success and patient satisfaction with this method. We studied IUD performance at a public family planning clinic in Buenos Aires, Argentina, serving a predominantly immigrant, low-income population.MethodsWe conducted a retrospective evaluation of 1047 IUD insertions between 2002 and 2007 with 5 years of follow-up data. We performed bivariate and survival analysis to examine characteristics associated with IUD discontinuation: adverse outcomes including pain, bleeding, and IUD expulsion, and time to removal.FindingsOf 1047 patients, only 188 (18%) had their IUD removed within 5 years. The main causes of IUD discontinuation were involuntary (38%) reasons such as an IUD expulsion and personal choice (34%) such as desiring pregnancy.ConclusionsFindings suggest overall good long-term performance with IUD insertion, with minimal complaints or adverse outcomes. These findings may help to support providers serving similar populations in promoting this method.
3D automatic segmentation method for retinal optical coherence tomography volume data using boundary surface enhancement
Authors: Sun Yankui , Zhang Tian , Zhao Yue , He Yufan 
Published: September 2015

With the introduction of spectral-domain optical coherence tomography (SD-OCT), much larger image datasets are routinely acquired compared to what was possible using the previous generation of time-domain OCT. Thus, there is a critical need for the development of three-dimensional (3D) segmentation methods for processing these data. We present here a novel 3D automatic segmentation method for retinal OCT volume data. Briefly, to segment a boundary surface, two OCT volume datasets are obtained by using a 3D smoothing filter and a 3D differential filter. Their linear combination is then calculated to generate new volume data with an enhanced boundary surface, where pixel intensity, boundary position information, and intensity changes on both sides of the boundary surface are used simultaneously. Next, preliminary discrete boundary points are detected from the A-Scans of the volume data. Finally, surface smoothness constraints and a dynamic threshold are applied to obtain a smoothed boundary surface by correcting a small number of error points. Our method can extract retinal layer boundary surfaces sequentially with a decreasing search region of volume data. We performed automatic segmentation on eight human OCT volume datasets acquired from a commercial Spectralis OCT system, where each volume of datasets contains 97 OCT B-Scan images with a resolution of [Formula: see text] (each B-Scan comprising 512 A-Scans containing 496 pixels); experimental results show that this method can accurately segment seven layer boundary surfaces in normal as well as some abnormal eyes.
An Imbalance in TAZ and YAP Expression in Hepatocellular Carcinoma Confers Cancer Stem Cell–like Behaviors Contributing to Disease Progression
Authors: Hayashi Hiromitsu , Higashi Takaaki , Yokoyama Naomi , Kaida Takayoshi , Sakamoto Keita , Fukushima Yukiko , Ishimoto Takatsugu , Kuroki Hideyuki , Nitta Hidetoshi , Hashimoto Daisuke , Chikamoto Akira , Oki Eiji , Beppu Toru , Baba Hideo 
Published: September 2015

Abstract
Transcriptional coactivator with PDZ-binding motif (TAZ) and yes-associated protein (YAP) are equivalently placed downstream effectors of the Hippo pathway with oncogenic roles in human cancers. However, the expression profiles of TAZ/YAP differ depending on the cancer cell type, suggesting that these proteins have different roles during cancer progression, yet no studies have examined the biologic significance of the balance between TAZ and YAP expression levels. Here we examined the functional roles of TAZ/YAP in hepatocellular carcinoma progression. We found that TAZ, but not YAP, was predominantly expressed in HCC. TAZ knockdown under normal conditions attenuated cell growth in HCC cells; however, TAZ knockdown combined with 5-fluorouracil treatment significantly increased chemoresistance compared with control cells. Notably, TAZ knockdown induced compensatory YAP expression and was accompanied by upregulation of CD90, a HCC–specific cancer stem cell marker. Continuous treatment with 5-fluorouracil also induced YAP expression and promoted tumor formation in vivo. Conversely, double knockdown of TAZ/YAP reduced chemoresistance and tumorigenicity. Moreover, YAP knockdown aggravated HCC cell growth to a greater degree than TAZ knockdown, and YAP overexpression was strongly associated with poor prognoses in patients with HCC. Collectively, these studies demonstrate that TAZ and YAP exhibit different functional roles in cancer progression, and a shift to predominant YAP expression upon TAZ depletion conferred cancer stem cell–like properties including chemoresistance and tumorigenicity in HCC. Therefore, targeting of both TAZ/YAP will be required for a complete antitumor response in HCC. Cancer Res; 75(22); 4985–97. ©2015 AACR.