bluuebunny/crossref_metadata_2025_split huggingface dataset:
Integrated clinical coding in urology – a novel way of working
Authors: Misra S , Chetwood A , Dixon G , Coker C , Thomas P 
Published: July 2014

Objectives: The objective of this article is to report a completed cycle of audit of coding co-morbidities for bladder outlet surgery. We also present a novel way of working to achieve better accuracy in capturing admitted patient care data and coding in urology. Materials and methods: We undertook a retrospective case note and coding review of all bladder outlet surgeries performed in a single month. After initiating several measures to improve data recording and capture, we re-audited our results prospectively and analysed the results. Results: The initial accuracy of coding co-morbidities was 73%. This improved to 100% at re-audit. However, we found that procedure coding errors remained. We have devised a novel working model to improve all coding issues related to urology. Conclusion: It is possible to improve accuracy of coding by educating clinicians working alongside our integrated model of a team of a clinician with an interest in coding with coding and finance personnel.
A critical role of autocrine sonic hedgehog signaling in human CD138+ myeloma cell survival and drug resistance
Authors: Liu Zhiqiang , Xu Jingda , He Jin , Zheng Yuhuan , Li Haiyan , Lu Yong , Qian Jianfei , Lin Pei , Weber Donna M. , Yang Jing , Yi Qing 
Published: July 2014

Key Points
CD138+ MM cells are a major source of SHH. Autocrine SHH enhances MM drug resistance.
Platelet bioreactor-on-a-chip
Authors: Thon Jonathan N. , Mazutis Linas , Wu Stephen , Sylman Joanna L. , Ehrlicher Allen , Machlus Kellie R. , Feng Qiang , Lu Shijiang , Lanza Robert , Neeves Keith B. , Weitz David A. , Italiano Joseph E. 
Published: July 2014

Key PointsWe have developed a biomimetic microfluidic platelet bioreactor that recapitulates bone marrow and blood vessel microenvironments. Application of shear stress in this bioreactor triggers physiological proplatelet production, and platelet release.
Defining minimal residual disease in acute myeloid leukemia: which platforms are ready for “prime time”?
Authors: Grimwade David , Freeman Sylvie D. 
Published: July 2014

Abstract
The past 40 years have witnessed major advances in defining the cytogenetic aberrations, mutational landscape, epigenetic profiles, and expression changes underlying hematological malignancies. Although it has become apparent that acute myeloid leukemia (AML) is highly heterogeneous at the molecular level, the standard framework for risk stratification guiding transplant practice in this disease remains largely based on pretreatment assessment of cytogenetics and a limited panel of molecular genetic markers, coupled with morphological assessment of bone marrow (BM) blast percentage after induction. However, application of more objective methodology such as multiparameter flow cytometry (MFC) has highlighted the limitations of morphology for reliable determination of remission status. Moreover, there is a growing body of evidence that detection of subclinical levels of leukemia (ie, minimal residual disease, MRD) using MFC or molecular-based approaches provides powerful independent prognostic information. Consequently, there is increasing interest in the use of MRD detection to provide early end points in clinical trials and to inform patient management. However, implementation of MRD assessment into clinical practice remains a major challenge, hampered by differences in the assays and preferred analytical methods employed between routine laboratories. Although this should be addressed through adoption of standardized assays with external quality control, it is clear that the molecular heterogeneity of AML coupled with increasing understanding of its clonal architecture dictates that a “one size fits all” approach to MRD detection in this disease is not feasible. However, with the range of platforms now available, there is considerable scope to realistically track treatment response in every patient.
Approaches for the design of reduced toxicant emission cigarettes
Authors: Dittrich David J , Fieblekorn Richard T , Bevan Michael J , Rushforth David , Murphy James J , Ashley Madeleine , McAdam Kevin G , Liu Chuan , Proctor Christopher J 
Published: July 2014

Abstract
Cigarette smoking causes serious diseases through frequent and prolonged exposure to toxicants. Technologies are being developed to reduce smokers’ toxicant exposure, including filter adsorbents, tobacco treatments and substitutes. This study examined the effect of modifications to filter ventilation, variations in cigarette circumference and active charcoal filter length and loading, as well as combinations of these features in a reduced-toxicant prototype (RTP) cigarette, on the yields of toxicants in cigarette smoke. An air-dilution mechanism, called split-tipping, was developed in which a band of porous paper in the centre of the filter tipping functions to minimise the loss of effective filter ventilation that occurs at the high flow rates encountered during human-smoking, and to facilitate the diffusional loss of volatile toxicants. As compared with conventional filter ventilation cigarettes, split-tipping reduced tar and volatile smoke constituent emissions under high flow rate machine-smoking conditions, most notably for products with a 1-mg ISO tar yield. Furthermore, mouth level exposure (MLE) to tar and nicotine was reduced among smokers of 1-mg ISO tar cigarettes in comparison to smokers of cigarettes with traditional filter ventilation. For higher ISO tar level cigarettes, however, there were no significant reductions in MLE. Smaller cigarette circumferences reduced sidestream toxicant yields and modified the balance of mainstream smoke chemistry with reduced levels of aromatic amines and benzo[a]pyrene but increased yields of formaldehyde. Smaller circumference cigarettes also had lower mainstream yields of volatile toxicants. Longer cigarette filters containing increased levels of high-activity carbon (HAC) showed reduced machine-smoking yields of volatile toxicants: with up to 97% removal for some volatile toxicants at higher HAC loadings. Split-tipping was combined with optimal filter length and cigarette circumference in an RTP cigarette that gave significantly lower mainstream (up to ~90%) and sidestream (predominately 20%–60%) smoke yields of numerous toxicants as compared with a commercial comparator cigarette under machine-smoking conditions. Significantly lower mainstream and sidestream smoke toxicant yields were observed for an RTP cigarette comprising several toxicant reducing technologies; these observations warrant further evaluation in clinical studies where real-world relevance can be tested using biomarkers of exposure and physiological effect.
Short term treatment versus long term management of neck and back disability in older adults utilizing spinal manipulative therapy and supervised exercise: a parallel-group randomized clinical trial evaluating relative effectiveness and harms
Authors: Vihstadt Corrie , Maiers Michele , Westrom Kristine , Bronfort Gert , Evans Roni , Hartvigsen Jan , Schulz Craig 
Published: July 2014

Abstract
Background
Back and neck disability are frequent in older adults resulting in loss of function and independence. Exercise therapy and manual therapy, like spinal manipulative therapy (SMT), have evidence of short and intermediate term effectiveness for spinal disability in the general population and growing evidence in older adults. For older populations experiencing chronic spinal conditions, long term management may be more appropriate to maintain improvement and minimize the impact of future exacerbations. Research is limited comparing short courses of treatment to long term management of spinal disability.
The primary aim is to compare the relative effectiveness of 12 weeks versus 36 weeks of SMT and supervised rehabilitative exercise (SRE) in older adults with back and neck disability.

Methods/Design
Randomized, mixed-methods, comparative effectiveness trial conducted at a university-affiliated research clinic in the Minneapolis/St. Paul, Minnesota metropolitan area.

Participants
Independently ambulatory community dwelling adults ≥ 65 years of age with back and neck disability of minimum 12 weeks duration (n = 200).

Interventions
12 weeks SMT + SRE or 36 weeks SMT + SRE.

Randomization
Blocked 1:1 allocation; computer generated scheme, concealed in sequentially numbered, opaque, sealed envelopes.

Blinding
Functional outcome examiners are blinded to treatment allocation; physical nature of the treatments prevents blinding of participants and providers to treatment assignment.

Primary endpoint
36 weeks post-randomization.

Data collection
Self-report questionnaires administered at 2 baseline visits and 4, 12, 24, 36, 52, and 78 weeks post-randomization. Primary outcomes include back and neck disability, measured by the Oswestry Disability Index and Neck Disability Index. Secondary outcomes include pain, general health status, improvement, self-efficacy, kinesiophobia, satisfaction, and medication use. Functional outcome assessment occurs at baseline and week 37 for hand grip strength, short physical performance battery, and accelerometry. Individual qualitative interviews are conducted when treatment ends. Data on expectations, falls, side effects, and adverse events are systematically collected.

Primary analysis
Linear mixed-model method for repeated measures to test for between-group differences with baseline values as covariates.

Discussion
Treatments that address the management of spinal disability in older adults may have far reaching implications for patient outcomes, clinical guidelines, and healthcare policy.

Trial registry
www.ClinicalTrials.gov; Identifier: NCT01057706.
A study protocol for the profile of pain in older women: assessing the multi dimensional nature of the experience of pain in arthritis
Authors: de Luca Katie , Parkinson Lynne , Byles Julie 
Published: July 2014

Abstract
Background
Arthritis is a significant contributor to illness, pain and disability and imposes a considerable burden upon the community. Pain is a cardinal symptom of arthritis and has significant implications on biopsychosocial wellbeing. The multidimensional nature of the experience of pain in arthritis has not been well defined in community-based samples.

Aims
The two aims of this study are to generate profiles of pain from a community sample of older women and to compare profiles for women with and without arthritis.

Methods
The sub study is a cross-sectional postal survey of 700 Australian community-based women. The survey includes a range of measures on health, arthritis and pain that will be used to examine the multidimensional nature of the experience of pain in arthritis and generate profiles of pain.

Discussion
With no core set of measures for the evaluation of arthritis pain, this survey was created from an amalgamation of measures to capture multiple dimensions of pain. Findings from this study will assist in defining the symptom of pain in arthritis and may lead to further research in evidence-based treatment options for people with arthritis.
Corset: enabling differential gene expression analysis for de novoassembled transcriptomes
Authors: Davidson Nadia M , Oshlack Alicia 
Published: July 2014

AbstractNext generation sequencing has made it possible to perform differential gene expression studies in non-model organisms. For these studies, the need for a reference genome is circumvented by performing de novo assembly on the RNA-seq data. However, transcriptome assembly produces a multitude of contigs, which must be clustered into genes prior to differential gene expression detection. Here we present Corset, a method that hierarchically clusters contigs using shared reads and expression, then summarizes read counts to clusters, ready for statistical testing. Using a range of metrics, we demonstrate that Corset out-performs alternative methods. Corset is available from https://code.google.com/p/corset-project/.
Molecularly and clinically related drugs and diseases are enriched in phenotypically similar drug-disease pairs
Authors: Vogt Ingo , Prinz Jeanette , Campillos Mónica 
Published: July 2014

Abstract
Background
The incomplete understanding of disease causes and drug mechanisms of action often leads to ineffective drug therapies or side effects. Therefore, new approaches are needed to improve treatment decisions and to elucidate molecular mechanisms underlying pathologies and unwanted drug effects.

Methods
We present here the first analysis of phenotypically related drug-disease pairs. The phenotypic similarity between 4,869 human diseases and 1,667 drugs was evaluated using an ontology-based semantic similarity approach to compare disease symptoms with drug side effects. We assessed and visualized the enrichment over random of clinical and molecular relationships among drug-disease pairs that share phenotypes using lift plots. To determine the associations between drug and disease classes enriched among phenotypically related pairs we employed a network-based approach combined with Fisher's exact test.

Results
We observed that molecularly and clinically related (for example, indication or contraindication) drugs and diseases are likely to share phenotypes. An analysis of the relations between drug mechanisms of action (MoAs) and disease classes among highly similar pairs revealed known and suspected MoA-disease relationships. Interestingly, we found that contraindications associated with high phenotypic similarity often involve diseases that have been reported as side effects of the drug, probably due to common mechanisms. Based on this, we propose a list of 752 precautions or potential contraindications for 486 drugs.

Conclusions
Phenotypic similarity between drugs and diseases facilitates the proposal of contraindications and the mechanistic understanding of diseases and drug side effects.
Parathyroid Hormone-Related Protein: Potential Therapeutic Target for Melanoma Invasion and Metastasis
Authors: Huang Dao Chao , Yang Xian Fang , Ochietti Benoît , Fadhil Ibtihal , Camirand Anne , Kremer Richard 
Published: July 2014

AbstractThe role of PTHrP in the highly metastatic human melanoma disease is not known. This study investigates the mechanisms of action of this secreted factor through homozygous inactivation of the Pthrp gene in A375 human melanoma cells. In vitro, Pthrp-ablated cells (knockout [KO]-A375, −/−) showed decreased motility and anchorage-independent growth, rounder morphology, and a significant reduction in invasion capacity compared with nonablated A375 cells (wild-type [WT]-A375, +/+). PTHrP peptide 1–34 and conditioned medium from WT-A375 cells partially restored the invasive phenotype in KO-A375. Pthrp ablation substantially decreased actin polymerization, matrix metallopeptidase 9 expression and focal adhesion kinase phosphorylation. In vivo, green fluorescent protein-transduced ablated and nonablated A375 cells were injected intracardially or sc into nude mice to study proliferation and multiorgan metastasis. Dissemination of injected Pthrp-ablated cells to lung and liver was reduced by 85% and 50%, respectively, compared with nonablated controls (120 hours after injection). The number of metastatic lesions and the percentage of animals with metastasis were markedly lower in mice injected with Pthrp-ablated A375, and 45% of these animals survived a 7-week period compared with 15% of mice injected with nonablated WT-A375. When mice injected with WT-A375 were treated with our blocking anti-PTHrP monoclonal antibody raised against the first 33 amino acids of human PTHrP, tumor size was decreased by more than 80% over 4 weeks and survival was significantly improved over 8 months. This study provides direct evidence of the major role for PTHrP in melanoma invasion and metastasis and suggests that agents that suppress PTHrP may be beneficial against melanoma progression.
Estrogen Receptor (ER) Agonists Differentially Regulate Neuroangiogenesis in Peritoneal Endometriosis via the Repellent Factor SLIT3
Authors: Greaves Erin , Collins Frances , Esnal-Zufiaurre Arantza , Giakoumelou Sevasti , Horne Andrew W. , Saunders Philippa T. K. 
Published: July 2014

Abstract
Endometriosis is an estrogen-dependent neurovascular disorder characterized by growth of endometrial tissue (lesions) outside the uterine cavity. Patients suffer chronic pelvic pain, and it has been proposed that co-recruitment of nerves/blood vessels (neuroangiogenesis) into the lesions is fundamental to the development of painful symptoms. We hypothesized that estrogen-dependent regulation of axonal guidance molecules of the SLIT/ROBO (Roundabout) family could play a role in neuroangiogenesis occurring in endometriosis lesions found on the peritoneal wall. In tissue samples from human patients and a mouse model of endometriosis, concentrations of mRNA encoded by SLIT3 were significantly higher in lesions than normal peritoneum. Estrogen regulation of SLIT3 was investigated using 17β-estradiol and selective agonists for each subtype of estrogen receptor (ER) (ERα agonist, 4,4′,4″-(4-propyl-(1H)-pyrazole-1,3,5-tryl) trisphenol; ERβ agonist, 2,3-bis(4-hydroxy-phenyl)-propionitrile [DPN]). In mice, DPN (EC50 0.85) increased Slit3 mRNA concentrations compared with hormone-depleted and 17β-estradiol-treated (EC50 0.1) animals and decreased the density of nerves but not vessels in endometriosis lesions. SLIT3 mRNA concentrations were increased in DPN-treated human endometrial endothelial cells and in 4,4′,4″-(4-propyl-(1H)-pyrazole-1,3,5-tryl) trisphenol-treated (EC50 200) rat dorsal root ganglia neurons. Functional assays (neurite outgrowth, network formation) revealed that SLIT3 promotes angiogenesis but decreases neurogenesis. In conclusion, these data suggest that estrogen-dependent expression of SLIT3 may play a key role in regulating nerve-vessel interactions within the complex microenvironment of endometriosis lesions.
5-HT Obesity Medication Efficacy via POMC Activation is Maintained During Aging
Authors: Burke Luke K. , Doslikova Barbora , D'Agostino Giuseppe , Garfield Alastair S. , Farooq Gala , Burdakov Denis , Low Malcolm J. , Rubinstein Marcelo , Evans Mark L. , Billups Brian , Heisler Lora K. 
Published: July 2014

Abstract
The phenomenon commonly described as the middle-age spread is the result of elevated adiposity accumulation throughout adulthood until late middle-age. It is a clinical imperative to gain a greater understanding of the underpinnings of age-dependent obesity and, in turn, how these mechanisms may impact the efficacy of obesity treatments. In particular, both obesity and aging are associated with rewiring of a principal brain pathway modulating energy homeostasis, promoting reduced activity of satiety pro-opiomelanocortin (POMC) neurons within the arcuate nucleus of the hypothalamus (ARC). Using a selective ARC-deficient POMC mouse line, here we report that former obesity medications augmenting endogenous 5-hydroxytryptamine (5-HT) activity d-fenfluramine and sibutramine require ARC POMC neurons to elicit therapeutic appetite-suppressive effects. We next investigated whether age-related diminished ARC POMC activity therefore impacts the potency of 5-HT obesity pharmacotherapies, lorcaserin, d-fenfluramine, and sibutramine and report that all compounds reduced food intake to a comparable extent in both chow-fed young lean (3–5 months old) and middle-aged obese (12–14 months old) male and female mice. We provide a mechanism through which 5-HT anorectic potency is maintained with age, via preserved 5-HT–POMC appetitive anatomical machinery. Specifically, the abundance and signaling of the primary 5-HT receptor influencing appetite via POMC activation, the 5-HT2CR, is not perturbed with age. These data reveal that although 5-HT obesity medications require ARC POMC neurons to achieve appetitive effects, the anorectic efficacy is maintained with aging, findings of clinical significance to the global aging obese population.
A Novel Model for Neuroendocrine Toxicology: Neurobehavioral Effects of BPA Exposure in a Prosocial Species, the Prairie Vole (Microtus ochrogaster)
Authors: Sullivan Alana W. , Beach Elsworth C. , Stetzik Lucas A. , Perry Amy , D'Addezio Alyssa S. , Cushing Bruce S. , Patisaul Heather B. 
Published: July 2014

Abstract
Impacts on brain and behavior have been reported in laboratory rodents after developmental exposure to bisphenol A (BPA), raising concerns about possible human effects. Epidemiological data suggest links between prenatal BPA exposure and altered affective behaviors in children, but potential mechanisms are unclear. Disruption of mesolimbic oxytocin (OT)/vasopressin (AVP) pathways have been proposed, but supporting evidence is minimal. To address these data gaps, we employed a novel animal model for neuroendocrine toxicology: the prairie vole (Microtus ochrogaster), which are more prosocial than lab rats or mice. Male and female prairie vole pups were orally exposed to 5-μg/kg body weight (bw)/d, 50-μg/kg bw/d, or 50-mg/kg bw/d BPA or vehicle over postnatal days 8–14. Subjects were tested as juveniles in open field and novel social tests and for partner preference as adults. Brains were then collected and assessed for immunoreactive (ir) tyrosine hydroxylase (TH) (a dopamine marker) neurons in the principal bed nucleus of the stria terminalis (pBNST) and TH-ir, OT-ir, and AVP-ir neurons in the paraventricular nucleus of the hypothalamus (PVN). Female open field activity indicated hyperactivity at the lowest dose and anxiety at the highest dose. Effects on social interactions were also observed, and partner preference formation was mildly inhibited at all dose levels. BPA masculinized principal bed nucleus of the stria terminalis TH-ir neuron numbers in females. Additionally, 50-mg/kg bw BPA-exposed females had more AVP-ir neurons in the anterior PVN and fewer OT-ir neurons in the posterior PVN. At the 2 lowest doses, BPA eliminated sex differences in PVN TH-ir neuron numbers and reversed this sex difference at the highest dose. Minimal behavioral effects were observed in BPA-exposed males. These data support the hypothesis that BPA alters affective behaviors, potentially via disruption of OT/AVP pathways.
Maternal Diet-induced Obesity Programs Cardiovascular Dysfunction in Adult Male Mouse Offspring Independent of Current Body Weight
Authors: Blackmore Heather L. , Niu Youguo , Fernandez-Twinn Denise S. , Tarry-Adkins Jane L. , Giussani Dino A. , Ozanne Susan E. 
Published: July 2014

Abstract
Obese pregnancies are not only associated with adverse consequences for the mother but also the long-term health of her child. Human studies have shown that individuals from obese mothers are at increased risk of premature death from cardiovascular disease (CVD), but are unable to define causality. This study aimed to determine causality using a mouse model of maternal diet–induced obesity. Obesity was induced in female C57BL/6 mice by feeding a diet rich in simple sugars and saturated fat 6 weeks prior to pregnancy and throughout pregnancy and lactation. Control females were fed laboratory chow. Male offspring from both groups were weaned onto chow and studied at 3, 5, 8, and 12 weeks of age for gross cardiac morphometry using stereology, cardiomyocyte cell area by histology, and cardiac fetal gene expression using qRT-PCR. Cardiac function was assessed by isolated Langendorff technology at 12 weeks of age and hearts were analyzed at the protein level for the expression of the β1 adrenergic receptor, muscarinic type-2 acetylcholine receptor, and proteins involved in cardiac contraction. Offspring from obese mothers develop pathologic cardiac hypertrophy associated with re-expression of cardiac fetal genes. By young adulthood these offspring developed severe systolic and diastolic dysfunction and cardiac sympathetic dominance. Importantly, cardiac dysfunction occurred in the absence of any change in corresponding body weight and despite the offspring eating a healthy low-fat diet. These findings provide a causal link to explain human observations relating maternal obesity with premature death from CVD in her offspring.