bluuebunny/crossref_metadata_2025_split huggingface dataset:
Proposed mechanisms for homeopathy are physically impossible
Authors: Grimes David Robert 
Published: August 2012

AbstractBackground  Homeopathy is a system of complementary and alternative medicine based on a belief that a malady can be treated by the administration of an extreme dilution of an agent thought to cause the physical signs of that malady. Homeopathy enjoys popular support from the general public and advocates of alternative medicine, but most large‐scale clinical trials show no homeopathy to be no more effective than placebo treatment.Objectives  To explore the chemical and physical plausibility of homeopathic treatments.Methods  Homeopathic claims were put into a physical context and analysed using the laws of basic physics and chemistry.Results  Through the laws of physics, homeopathic medicines appear to have zero chance of containing any biologically active component. Evidence from physical chemistry also rules out the plausibility of mechanisms such as water memory.Conclusions  The proposed mechanisms of homeopathy are shown to be implausible when analysed from a physical and chemical perspective, and thus it is of no surprise that the biological effects of homeopathy cannot be measured in large‐scale clinical trials.
Homeopathy is as effective as fluoxetine in depression
Authors: Fisher P 
Published: August 2012

Adler UC, Paiva NMP, Cesar AT, Adler MS, Molina A, Padula AE, Calil HM.Homeopathic individualized Q‐potencies versus fluoxetine for moderate to severe depression: double‐blind, randomized non‐inferiority trial.Evid Based Complement Altern Med 2011: 20182.
Benefits of early systemic antibiotics in localized aggressive periodontitis: a retrospective study
Authors: Beliveau Dennis , Magnusson Ingvar , Bidwell John A. , Zapert Edward F. , Aukhil Ikramuddin , Wallet Shannon M. , Shaddox Luciana M. 
Published: August 2012

AbstractBackgroundTreatment of localized aggressive periodontitis (LAP) may include systemic antibiotics, yet it is unclear at what stage of treatment planning antibiotics are most effective.AimThis retrospective analysis compared immediate versus delayed antibiotic therapy on clinical parameters and gingival crevicular fluid (GCF) inflammatory mediators.Material and MethodsAt baseline, 3 months and 6 months after treatment, clinical parameters [probing depth (PD), clinical attachment level (CAL), bleeding on probing (BoP) and plaque] and GCF were collected from LAP participants, who received a 7‐day antibiotic regimen immediately (ImA) or 3 months following (DelA) mechanical therapy.ResultsAlthough both groups presented significant CAL reductions at 6 months, only ImA resulted in a reduction in mean PD at both 3 and 6 months, along with reductions in CAL and BoP at 3 months following therapy. In addition, GCF mediators were higher in DelA group at 3 months post mechanical treatment, but were significantly reduced 6 months following antibiotic therapy.ConclusionsImA and DelA regimens were both effective in improving CAL by 6 months post therapy. However, ImA allowed for better improvement in overall clinical parameters early in the course of treatment, concomitant with lower levels of inflammatory mediators within the GCF.
Treatment results of CO2 laser vaporisation in a cohort of 35 patients with oral leukoplakia
Authors: Brouns EREA , Baart JA , Karagozoglu KH , Aartman IHA , Bloemena E , van der Waal I 
Published: August 2012

ObjectivesThe aim of the present study was to evaluate the treatment results of CO2 laser vaporisation in a well‐defined cohort of patients with oral leukoplakia (OL).Material and methodsThe group consisted of 35 patients. Before treatment, a clinical photograph and an incisional biopsy were performed in all cases. Also posttreatment results were documented with clinical photographs. The assessment of the treatment results was performed by an independent clinician who had not performed the treatment. The mean follow‐up period was 61.9 months (range 12–179 months).ResultsIn 14/35 patients, there was a recurrence between 1 and 43 months (mean 18.7 months), the annual recurrence rate being approximately 8%. In three of these patients, malignant transformation occurred at a later stage. In two other patients, a malignancy occurred without a prior recurrence. In altogether 5 of 35 patients, malignant transformation occurred in a mean period of 54 months, the annual malignant transformation rate being approximately 3%.ConclusionsThe results in the present study are worse than those reported in the literature, perhaps owing to the use of different diagnostic criteria for OL, differences in the employed laser technique and assessment of possible recurrences by an independent clinician.
Manassantin B inhibits melanosome transport in melanocytes by disrupting the melanophilin–myosin Va interaction
Authors: Chang Huikyoung , Choi Hyunjung , Joo Kyung‐Mi , Kim Daegun , Lee Tae Ryong 
Published: August 2012

SummaryHuman skin hyperpigmentation disorders occur when the synthesis and/or distribution of melanin increases. The distribution of melanin in the skin is achieved by melanosome transport and transfer. The transport of melanosomes, the organelles where melanin is made, in a melanocyte precedes the transfer of the melanosomes to a keratinocyte. Therefore, hyperpigmentation can be regulated by decreasing melanosome transport. In this study, we found that an extract of Saururus chinensis Baill (ESCB) and one of its components, manassantin B, inhibited melanosome transport in Melan‐a melanocytes and normal human melanocytes (NHMs). Manassantin B disturbed melanosome transport by disrupting the interaction between melanophilin and myosin Va. Manassantin B is neither a direct nor an indirect inhibitor of tyrosinase. The total melanin content was not reduced when melanosome transport was inhibited in a Melan‐a melanocyte monoculture by manassantin B. Manassantin B decreased melanin content only when Melan‐a melanocytes were co‐cultured with SP‐1 keratinocytes or stimulated by α‐MSH. Therefore, we propose that specific inhibitors of melanosome transport, such as manassantin B, are potential candidate or lead compounds for the development of agents to treat undesirable hyperpigmentation of the skin.
Prognostic impact of β-2-microglobulin expression in colorectal cancers stratified by mismatch repair status
Authors: Koelzer Viktor Hendrik , Baker Kristi , Kassahn Daniela , Baumhoer Daniel , Zlobec Inti 
Published: August 2012

Backgroundβ-2-microglobulin (B2M) is essential for antigen presentation, yet may also possess proto-oncogenic properties.AimTo determine the prognostic impact of B2M in patients with mismatch repair (MMR) proficient and deficient colorectal cancer (CRC) and to investigate whether this effect on outcome is dependent on the local immune response.MethodsB2M protein expression and tumour-infiltrating immune cells (CD3, CD16, CD163, CD20, CD4, CD45RO, CD56, CD68, CD8, FoxP3, GranzymeB, iNOS, mast cell tryptase, MUM1, PD1, TIA-1) were evaluated in a well characterised tissue microarray of 408 CRCs. The predictive value for clinicopathological features and the prognostic significance of B2M expression were analysed, stratified by MMR status and the immunohistological characteristics of immune cell infiltrates.ResultsInterobserver agreement for B2M staining was high (intra-class correlation coefficient=0.91). Complete B2M loss was more frequent in MMR-deficient (19.4%) compared to MMR-proficient (7.1%) tumours (p<0.001). In MMR-deficient cases, B2M loss predicted rare local recurrence (p=0.034), infrequent nodal-positivity (p=0.035), absence of distant metastasis (p=0.048; sensitivity=100%) and a trend towards favourable survival (p=0.124) independent of immune infiltrates. No associations between B2M and clinicopathological features were observed in MMR-proficient cases.ConclusionsOur data show for the first time that absence of B2M protein expression identifies MMR-deficient cancers with a favourable clinical course and absence of metastatic disease. Validation of B2M protein expression for sub-classification of MMR-deficient CRC is recommended for future clinical trials.
Diagnostic accuracy of icteric index to detect abnormal total bilirubin values
Authors: Salinas Maria , López-Garrigós Maite , Lugo Javier , Gutiérrez Mercedes , Flors Lucia , Leiva-Salinas Carlos 
Published: August 2012

AimsTotal bilirubin tests are individually inexpensive but can result in huge costs to healthcare systems worldwide, because they are very commonly requested. The main objective of this study was to evaluate the diagnostic accuracy of the icteric index, a test with zero reagent cost, as a preliminary biomarker to decide when total bilirubin measurement is necessary.MethodsWe retrospectively reviewed all the requested total bilirubin values and their corresponding icteric index results in a 2-year period (2010–11). Receiver operating characteristic (ROC) curve analysis was used to determine the optimal icteric index cut-off value to discriminate between normal and abnormal bilirubin values (>20.5 μmol/l; >1.2 mg/dl).ResultsThe study included total bilirubin and icteric index results of 100 207 patients. The ROC curve analysis suggested 34.2 μmol/l (2 mg/dl) as the optimal icteric index threshold to identify abnormal bilirubin values. The area under the curve was 0.981. Regardless of the patient population studied (primary care, hospital and different individual hospital departments), sensitivity was greater than 94% and specificity was over 98%. Likelihood ratio values provided strong evidence that total bilirubin is less than 20.5 μmol/l (<1.2 mg/dl) when the icteric index is less than 34.2 μmol/l (<2 mg/dl).ConclusionsThis study supports the use of the icteric index to identify patients with abnormal total bilirubin values. Considerable economic savings can be achieved if this strategy is applied on a clinical daily basis. Its implementation and report should be discussed and planned by laboratory professionals together with requesting physicians.
Identification of Galanin and Its Receptor GalR1 as Novel Determinants of Resistance to Chemotherapy and Potential Biomarkers in Colorectal Cancer
Authors: Stevenson Leanne , Allen Wendy L. , Turkington Richard , Jithesh Puthen V. , Proutski Irina , Stewart Gail , Lenz Heinz-Josef , Van Schaeybroeck Sandra , Longley Daniel B. , Johnston Patrick G. 
Published: August 2012

Abstract
Purpose: A major factor limiting the effective clinical management of colorectal cancer (CRC) is resistance to chemotherapy. Therefore, the identification of novel, therapeutically targetable mediators of resistance is vital.
Experimental design: We used a CRC disease-focused microarray platform to transcriptionally profile chemotherapy-responsive and nonresponsive pretreatment metastatic CRC liver biopsies and in vitro samples, both sensitive and resistant to clinically relevant chemotherapeutic drugs (5-FU and oxaliplatin). Pathway and gene set enrichment analyses identified candidate genes within key pathways mediating drug resistance. Functional RNAi screening identified regulators of drug resistance.
Results: Mitogen-activated protein kinase signaling, focal adhesion, cell cycle, insulin signaling, and apoptosis were identified as key pathways involved in mediating drug resistance. The G-protein–coupled receptor galanin receptor 1 (GalR1) was identified as a novel regulator of drug resistance. Notably, silencing either GalR1 or its ligand galanin induced apoptosis in drug-sensitive and resistant cell lines and synergistically enhanced the effects of chemotherapy. Mechanistically, GalR1/galanin silencing resulted in downregulation of the endogenous caspase-8 inhibitor FLIPL, resulting in induction of caspase-8–dependent apoptosis. Galanin mRNA was found to be overexpressed in colorectal tumors, and importantly, high galanin expression correlated with poor disease-free survival of patients with early-stage CRC.
Conclusion: This study shows the power of systems biology approaches to identify key pathways and genes that are functionally involved in mediating chemotherapy resistance. Moreover, we have identified a novel role for the GalR1/galanin receptor–ligand axis in chemoresistance, providing evidence to support its further evaluation as a potential therapeutic target and biomarker in CRC. Clin Cancer Res; 18(19); 5412–26. ©2012 AACR.
Inhibition of the Hedgehog Pathway Targets the Tumor-Associated Stroma in Pancreatic Cancer
Authors: Hwang Rosa F. , Moore Todd T. , Hattersley Maureen Mertens , Scarpitti Meghan , Yang Bin , Devereaux Erik , Ramachandran Vijaya , Arumugam Thiruvengadam , Ji Baoan , Logsdon Craig D. , Brown Jeffrey L. , Godin Robert 
Published: August 2012

Abstract
Purpose: The Hedgehog (Hh) pathway has emerged as an important pathway in multiple tumor types and is thought to be dependent on a paracrine signaling mechanism. The purpose of this study was to determine the role of pancreatic cancer-associated fibroblasts (human pancreatic stellate cells, HPSCs) in Hh signaling. In addition, we evaluated the efficacy of a novel Hh antagonist, AZD8542, on tumor progression with an emphasis on the role of the stroma compartment.
Experimental Design: Expression of Hh pathway members and activation of the Hh pathway were analyzed in both HPSCs and pancreatic cancer cells. We tested the effects of Smoothened (SMO) inhibition with AZD8542 on tumor growth in vivo using an orthotopic model of pancreatic cancer containing varying amounts of stroma.
Results: HPSCs expressed high levels of SMO receptor and low levels of Hh ligands, whereas cancer cells showed the converse expression pattern. HPSC proliferation was stimulated by Sonic Hedgehog with upregulation of downstream GLI1 mRNA. These effects were abrogated by AZD8542 treatment. In an orthotopic model of pancreatic cancer, AZD8542 inhibited tumor growth only when HPSCs were present, implicating a paracrine signaling mechanism dependent on stroma. Further evidence of paracrine signaling of the Hh pathway in prostate and colon cancer models is provided, demonstrating the broader applicability of our findings.
Conclusion: Based on the use of our novel human-derived pancreatic cancer stellate cells, our results suggest that Hh-targeted therapies primarily affect the tumor-associated stroma, rather than the epithelial compartment. Mol Cancer Res; 10(9); 1147–57. ©2012 AACR.
Activity of the Estrogen-Metabolizing Enzyme Cytochrome P450 1B1 Influences the Development of Pulmonary Arterial Hypertension
Authors: White Kevin , Johansen Anne Katrine , Nilsen Margaret , Ciuclan Loredana , Wallace Emma , Paton Leigh , Campbell Annabel , Morecroft Ian , Loughlin Lynn , McClure John D. , Thomas Matthew , Mair Kirsty M. , MacLean Margaret R. 
Published: August 2012

Background—
Pulmonary arterial hypertension (PAH) is a hyperproliferative vascular disorder observed predominantly in women. Estrogen is a potent mitogen in human pulmonary artery smooth muscle cells and contributes to PAH in vivo; however, the mechanisms attributed to this causation remain obscure. Curiously, heightened expression of the estrogen-metabolizing enzyme cytochrome P450 1B1 (CYP1B1) is reported in idiopathic PAH and murine models of PAH.

Methods and Results—

Here, we investigated the putative pathogenic role of CYP1B1 in PAH. Quantitative reverse transcription–polymerase chain reaction, immunoblotting, and in situ analysis revealed that pulmonary CYP1B1 is increased in hypoxic PAH, hypoxic+SU5416 PAH, and human PAH and is highly expressed within the pulmonary vascular wall. PAH was assessed in mice via measurement of right ventricular hypertrophy, pulmonary vascular remodeling, and right ventricular systolic pressure. Hypoxic PAH was attenuated in CYP1B1
−/−
mice, and the potent CYP1B1 inhibitor 2,3′,4,5′-tetramethoxystilbene (TMS; 3 mg · kg
−1
· d
−1
IP) significantly attenuated hypoxic PAH and hypoxic+SU5416 PAH in vivo. TMS also abolished estrogen-induced proliferation in human pulmonary artery smooth muscle cells and PAH–pulmonary artery smooth muscle cells. The estrogen metabolite 16α-hydroxyestrone provoked human pulmonary artery smooth muscle cell proliferation, and this mitogenic effect was greatly pronounced in PAH–pulmonary artery smooth muscle cells. ELISA analysis revealed that 16α-hydroxyestrone concentration was elevated in PAH, consistent with CYP1B1 overexpression and activity. Finally, administration of the CYP1B1 metabolite 16α-hydroxyestrone (1.5 mg · kg
−1
· d
−1
IP) caused the development of PAH in mice.

Conclusions—
Increased CYP1B1-mediated estrogen metabolism promotes the development of PAH, likely via the formation of mitogens, including 16α-hydroxyestrone. Collectively, this study reveals a possible novel therapeutic target in clinical PAH.
A Millennial Proxy Record of ENSO and Eastern Australian Rainfall from the Law Dome Ice Core, East Antarctica
Authors: Vance Tessa R. , van Ommen Tas D. , Curran Mark A. J. , Plummer Chris T. , Moy Andrew D. 
Published: August 2012

Abstract
ENSO causes climate extremes across and beyond the Pacific basin; however, evidence of ENSO at high southern latitudes is generally restricted to the South Pacific and West Antarctica. Here, the authors report a statistically significant link between ENSO and sea salt deposition during summer from the Law Dome (LD) ice core in East Antarctica. ENSO-related atmospheric anomalies from the central-western equatorial Pacific (CWEP) propagate to the South Pacific and the circumpolar high latitudes. These anomalies modulate high-latitude zonal winds, with El Niño (La Niña) conditions causing reduced (enhanced) zonal wind speeds and subsequent reduced (enhanced) summer sea salt deposition at LD. Over the last 1010 yr, the LD summer sea salt (LDSSS) record has exhibited two below-average (El Niño–like) epochs, 1000–1260 ad and 1920–2009 ad, and a longer above-average (La Niña–like) epoch from 1260 to 1860 ad. Spectral analysis shows the below-average epochs are associated with enhanced ENSO-like variability around 2–5 yr, while the above-average epoch is associated more with variability around 6–7 yr. The LDSSS record is also significantly correlated with annual rainfall in eastern mainland Australia. While the correlation displays decadal-scale variability similar to changes in the interdecadal Pacific oscillation (IPO), the LDSSS record suggests rainfall in the modern instrumental era (1910–2009 ad) is below the long-term average. In addition, recent rainfall declines in some regions of eastern and southeastern Australia appear to be mirrored by a downward trend in the LDSSS record, suggesting current rainfall regimes are unusual though not unknown over the last millennium.
Influence of the Laurentian Great Lakes on Regional Climate*
Authors: Notaro Michael , Holman Kathleen , Zarrin Azar , Fluck Elody , Vavrus Steve , Bennington Val 
Published: August 2012

Abstract
The influence of the Laurentian Great Lakes on climate is assessed by comparing two decade-long simulations, with the lakes either included or excluded, using the Abdus Salam International Centre for Theoretical Physics Regional Climate Model, version 4. The Great Lakes dampen the variability in near-surface air temperature across the surrounding region while reducing the amplitude of the diurnal cycle and annual cycle of air temperature. The impacts of the Great Lakes on the regional surface energy budget include an increase (decrease) in turbulent fluxes during the cold (warm) season and an increase in surface downward shortwave radiation flux during summer due to diminished atmospheric moisture and convective cloud amount. Changes in the hydrologic budget due to the presence of the Great Lakes include increases in evaporation and precipitation during October–March and decreases during May–August, along with springtime reductions in snowmelt-related runoff. Circulation responses consist of a regionwide decrease in sea level pressure in autumn–winter and an increase in summer, with enhanced ascent and descent in the two seasons, respectively. The most pronounced simulated impact of the Great Lakes on synoptic systems traversing the basin is a weakening of cold-season anticyclones.
Training Intuitive Decision Making in a Simulated Real-World Environment
Authors: Patterson Robert Earl , Pierce Byron J. , Boydstun Alan S. , Ramsey Lisa M. , Shannan Jodi , Tripp Lisa , Bell Herb 
Published: August 2012

Objective: We investigated whether naturalistic, intuitive (pattern recognition–based) decision making can be developed via implicit statistical learning in a simulated real-world environment. Background: To our knowledge, no definitive studies have actually shown that implicit learning plays a causal role in the development of intuitive decision making when the latter is defined as pattern recognition of real-world, or simulated real-world, environmental situations. Method: The simulated environment was presented dynamically so as to induce a sense of simulated locomotion through the scene and over sequences of objects on the ground. During training, participants passively viewed the objects sequences; during test, participants made intuitive decisions about related or unrelated sequences. Results: Intuitive decision making can be developed via implicit learning. Articulatory suppression, which affects working memory, exerted a significant inhibitory effect on the training of intuitive decision making. Intuitive decision making trained in the simulated environment fully transferred to a flat display (but not vice versa). Conclusion: Intuitive decision making is developed by an implicit learning process that is engaged by the meaning inherent in naturalistic scenes. Application: Implicit learning can be used for training intuitive decision making.
Prognostic Significance of the Containment and Location of Osteochondral Lesions of the Talus
Authors: Choi Woo Jin , Choi Gi Won , Kim Jun Shik , Lee Jin Woo 
Published: August 2012

Background: Uncontained osteochondral lesions of the talar shoulder are associated with an increased risk of clinical failure in patients treated with current cylindrical osteochondral autograft techniques. Whether the same holds true in patients undergoing arthroscopic treatment is unknown. Purpose: To determine the relative prognostic significance of the containment (shoulder vs nonshoulder type) and location (medial vs lateral) of an osteochondral lesion of the talus (OLT). Hypothesis: Arthroscopic treatment may not be ideal for uncontained lesions of the talar shoulder due to a lack of structural support. Study Design: Cohort study; Level of evidence, 3. Methods: Arthroscopic treatment for OLT was performed on the ankles of 399 patients between 2001 and 2009. Analyses were performed by grouping the patients according to type of containment (shoulder, n = 181; nonshoulder, n = 218), location (medial, n = 274; lateral, n = 125), and both type of containment and location (medial shoulder, n = 129; medial nonshoulder, n = 145; lateral shoulder, n = 52; lateral nonshoulder, n = 73). To evaluate the role of containment and location independently of OLT size, patients were grouped according to quartile of defect size, and outcomes were analyzed within each group. Results: Patients with shoulder-type OLT had a substantially worse clinical outcome than did those with nonshoulder-type OLT, even after adjustment for OLT size ( P < .05). However, there was no significant difference in clinical outcome between patients with medial OLT and those with lateral OLT, and the clinical failure rates of the 2 groups were similar ( P > .05). A Cox proportional hazards regression model demonstrated that OLT containment, but not location, exerted an independent prognostic effect. Conclusion: Patients with uncontained OLT of the talar shoulder experienced a more complicated clinical outcome than did those with contained, nonshoulder-type OLT even after adjustment for OLT size and regardless of location.