bluuebunny/crossref_metadata_2025_split huggingface dataset:
Integrative genomics identifies candidate microRNAs for pathogenesis of experimental biliary atresia
Authors: Bessho Kazuhiko , Shanmukhappa Kumar , Sheridan Rachel , Shivakumar Pranavkumar , Mourya Reena , Walters Stephanie , Kaimal Vivek , Dilbone Eric , Jegga Anil G , Bezerra Jorge A 
Published: October 2013

Abstract

Background
Biliary atresia is a fibroinflammatory obstruction of extrahepatic bile duct that leads to end-stage liver disease in children. Despite advances in understanding the pathogenesis of biliary atresia, very little is known about the role of microRNAs (miRNAs) in onset and progression of the disease. In this study, we aimed to investigate the entire biliary transcriptome to identify miRNAs with potential role in the pathogenesis of bile duct obstruction.

Results
By profiling the expression levels of miRNA in extrahepatic bile ducts and gallbladder (EHBDs) from a murine model of biliary atresia, we identified 14 miRNAs whose expression was suppressed at the times of duct obstruction and atresia (≥2 fold suppression, P < 0.05, FDR 5%). Next, we obtained 2,216 putative target genes of the 14 miRNAs using in silico target prediction algorithms. By integrating this result with a genome-wide gene expression analysis of the same tissue (≥2 fold increase, P < 0.05, FDR 5%), we identified 26 potential target genes with coordinate expression by the 14 miRNAs. Functional analysis of these target genes revealed a significant relevance of miR-30b/c, -133a/b, -195, -200a, -320 and −365 based on increases in expression of at least 3 target genes in the same tissue and 1st-to-3rd tier links with genes and gene-groups regulating organogenesis and immune response. These miRNAs showed higher expression in EHBDs above livers, a unique expression in cholangiocytes and the subepithelial compartment, and were downregulated in a cholangiocyte cell line after RRV infection.

Conclusions
Integrative genomics reveals functional relevance of miR-30b/c, -133a/b, -195, -200a, -320 and −365. The coordinate expression of miRNAs and target genes in a temporal-spatial fashion suggests a regulatory role of these miRNAs in pathogenesis of experimental biliary atresia.
Comparative energetics and kinetics of autotrophic lipid and starch metabolism in chlorophytic microalgae: implications for biomass and biofuel production
Authors: Subramanian Sowmya , Barry Amanda N , Pieris Shayani , Sayre Richard T 
Published: October 2013

Abstract
Due to the growing need to provide alternatives to fossil fuels as efficiently, economically, and sustainably as possible there has been growing interest in improved biofuel production systems. Biofuels produced from microalgae are a particularly attractive option since microalgae have production potentials that exceed the best terrestrial crops by 2 to 10-fold. In addition, autotrophically grown microalgae can capture CO2 from point sources reducing direct atmospheric greenhouse gas emissions. The enhanced biomass production potential of algae is attributed in part to the fact that every cell is photosynthetic. Regardless, overall biological energy capture, conversion, and storage in microalgae are inefficient with less than 8% conversion of solar into chemical energy achieved. In this review, we examine the thermodynamic and kinetic constraints associated with the autotrophic conversion of inorganic carbon into storage carbohydrate and oil, the dominant energy storage products in Chlorophytic microalgae. We discuss how thermodynamic restrictions including the loss of fixed carbon during acetyl CoA synthesis reduce the efficiency of carbon accumulation in lipids. In addition, kinetic limitations, such as the coupling of proton to electron transfer during plastoquinone reduction and oxidation and the slow rates of CO2 fixation by Rubisco reduce photosynthetic efficiency. In some cases, these kinetic limitations have been overcome by massive increases in the numbers of effective catalytic sites, e.g. the high Rubisco levels (mM) in chloroplasts. But in other cases, including the slow rate of plastoquinol oxidation, there has been no compensatory increase in the abundance of catalytically limiting protein complexes. Significantly, we show that the energetic requirements for producing oil and starch relative to the recoverable energy stored in these molecules are very similar on a per carbon basis. Presently, the overall rates of starch and lipid synthesis in microalgae are very poorly characterized. Increased understanding of the kinetic constraints of lipid and starch synthesis, accumulation and turnover would facilitate the design of improved biomass production systems.
Hallux valgus and plantar pressure loading: the Framingham foot study
Authors: Galica Andrew M , Hagedorn Thomas J , Dufour Alyssa B , Riskowski Jody L , Hillstrom Howard J , Casey Virginia A , Hannan Marian T 
Published: October 2013

AbstractBackgroundHallux valgus (HV), a common structural foot deformity, can cause foot pain and lead to limited mobility. The purpose of this study was to evaluate differences in plantar pressure and force during gait by HV status in a large population‐based cohort of men and women.MethodsA trained examiner performed a validated physical examination on participants' feet and recorded the presence of hallux valgus and other specific foot disorders. Each foot was classified into one of four mutually exclusive groups based on the foot examination. Foot groups were: (i) HV only, (ii) HV and at least one additional foot disorder (FD), (iii) no HV but at least one other FD, and (iv) neither HV nor FD (referent). Biomechanical data for both feet were collected using Tekscan Matscan. Foot posture during quiet standing, using modified arch index (MAI), and foot function during gait, using center of pressure excursion index (CPEI), were calculated per foot. Further, walking scans were masked into eight sub‐regions using Novel Automask, and peak pressure and maximum force exerted in each region were calculated.ResultsThere were 3205 participants, contributing 6393 feet with complete foot exam data and valid biomechanical measurements. Participants with HV had lower hallucal loading and higher forces at lesser toes as well as higher MAI and lower CPEI values compared to the referent. Participants with HV and other FDs were also noted to have aberrant rearfoot forces and pressures.ConclusionsThese results suggest that HV alters foot loading patterns and pressure profiles. Future work should investigate how these changes affect the risk of other foot and lower extremity ailments.
Comparison of shear bond strength and adhesive remnant index between precoated and conventionally bonded orthodontic brackets
Authors: Guzman Ulises A , Jerrold Laurance , Vig Peter S , Abdelkarim Ahmad 
Published: October 2013

Abstract

Background
The purpose of this study was to compare the shear bond strength and adhesive remnant index (ARI) at the enamel-bonding interface of precoated and conventionally bonded brackets, utilizing standardized procedures.

Methods
The test sample consisted of 90 recently extracted bovine permanent mandibular incisors. The teeth were bonded using the same protocol and were tested in three different situations. A material testing systems machine was utilized for debonding, and the remaining adhesive on the tooth was recorded.

Results
Immediately after bonding, we found that the shear bond strength of the precoated brackets (6.27 MPa) was significantly higher than that of conventional brackets (5.37 MPa) (p < 0.05). However, no significant differences in bond strength were found between the two bracket systems after 24 h of bonding or after thermocycling. The conventional brackets had higher ARI scores than the precoated bracket systems immediately after bonding and after 24 h.

Conclusions
Since there were no significant differences in the bonding strength after 24 h, the immediate bonding strength of the precoated brackets during the first day does not appear to be a major advantage over the conventional bracket systems. However, less adhesive on the tooth after debonding is an advantage of precoated brackets.
Intra-articular CD1c-expressing myeloid dendritic cells from rheumatoid arthritis patients express a unique set of T cell-attracting chemokines and spontaneously induce Th1, Th17 and Th2 cell activity
Authors: Moret Frederique M , Hack Cornelis E , van der Wurff-Jacobs Kim MG , de Jager Wilco , Radstake Timothy RDJ , Lafeber Floris PJG , van Roon Joel AG 
Published: October 2013

Abstract
Introduction
Myeloid dendritic cells (mDCs) are potent T cell-activating antigen-presenting cells that have been suggested to play a crucial role in the regulation of immune responses in many disease states, including rheumatoid arthritis (RA). Despite this, studies that have reported on the capacity of naturally occurring circulating mDCs to regulate T cell activation in RA are still lacking. This study aimed to evaluate the phenotypic and functional properties of naturally occurring CD1c (BDCA-1)+ mDCs from synovial fluid (SF) compared to those from peripheral blood (PB) of RA patients.

Methods
CD1c+ mDC numbers and expression of costimulatory molecules were assessed by fluorescence-activated cell sorting (FACS) analysis in SF and PB from RA patients. Ex vivo secretion of 45 inflammatory mediators by mDCs from SF and PB of RA patients was determined by multiplex immunoassay. The capacity of mDCs from SF to activate autologous CD4+ T cells was measured.

Results
CD1c+ mDC numbers were significantly increased in SF versus PB of RA patients (mean 4.7% vs. 0.6%). mDCs from SF showed increased expression of antigen-presenting (human leukocyte antigen (HLA) class II, CD1c) and costimulatory molecules (CD80, CD86 and CD40). Numerous cytokines were equally abundantly produced by mDCs from both PB and SF (including IL-12, IL-23, IL-13, IL-21). SF mDCs secreted higher levels of interferon γ-inducible protein-10 (IP-10), monokine induced by interferon γ (MIG) and, thymus and activation-regulated chemokine (TARC), but lower macrophage-derived chemokine (MDC) levels compared to mDCs from PB. mDCs from SF displayed a strongly increased capacity to induce proliferation of CD4+ T cells associated with a strongly augmented IFNγ, IL-17, and IL-4 production.

Conclusions
This study suggests that increased numbers of CD1c+ mDCs in SF are involved in the inflammatory cascade intra-articularly by the secretion of specific T cell-attracting chemokines and the activation of self-reactive T cells.
Patient education, disease activity and physical function: can we be more targeted? A cross sectional study among people with rheumatoid arthritis, psoriatic arthritis and hand osteoarthritis
Authors: Drăgoi Răzvan G , Ndosi Mwidimi , Sadlonova Martina , Hill Jackie , Duer Mona , Graninger Winfried , Smolen Josef , Stamm Tanja A 
Published: October 2013

Abstract
Introduction
In order to target educational needs of patients more effectively, an Austrian-German educational needs assessment tool (OENAT) was developed, the educational needs of patients with rheumatoid arthritis (RA), psoriatic arthritis (PsA) and hand osteoarthritis (HOA) were described and the relationships between educational needs, gender, disease activity and function were explored.

Methods
The English ENAT was adapted into Austrian-German using Beaton's cross-cultural adaptation process. Internal construct validity was assessed by Rasch analysis. Educational needs across diagnostic groups and subgroups of patients were summarized descriptively and their relationship with disease activity and physical functioning explored.

Results
The sample comprised 130 RA, 125 PsA and 48 HOA patients. Their mean ages ± SD were 56 ± 14, 51 ± 11 and 64 ± 7 years for RA, PsA and HOA; disease duration was 11 ± 9, 11 ± 11 and 14 ± 9 years, respectively. More than 70% in each patient group expressed interest in receiving education about their disease.
The educational needs differed significantly between women and men in all 3 groups. In RA and PsA, female patients expressed significantly higher educational needs than men in 'movements’ and 'feelings’ domains (p=0.04 and p=0.03 for RA and p<0.01 and p=0.01 for PsA). Female patients in the HOA group had significantly higher scores on all domains except for the 'movements’. Older patients with PsA scored significantly higher than their younger counterparts in the 'pain’ domain (p=0.05). RA patients with disease duration >5 years), expressed higher educational needs in 'movements’ (p<0.01). Educational background had effects in the PsA group only, patients with basic education had greater scores than those with higher education on 'movements’ and 'arthritis process’ (p=0.01).
In the RA group, DAS28 correlated significantly with 'movements’ (r=0.24, p=0.01), 'feelings’ (r=0.22, p=0.02), and 'treatments’ (r=0.22, p=0.03). In the PsA group, all OENAT domains correlated with disease activity (DAPSA and CDAI).

Conclusions
This study showed that educational needs vary with personal characteristics. Patient education may be more targeted and effective, if gender, age, educational background and disease duration are taken into account. Correlations with disease activity and function suggest that the OENAT could enable identification of 'intervention points’, which can be ideal opportunities for effective patient education.
Diagnostic value and prognostic evaluation of Presepsin for sepsis in an emergency department
Authors: Liu Bo , Chen Yun-Xia , Yin Qin , Zhao Yun-Zhou , Li Chun-Sheng 
Published: October 2013

Abstract
Introduction
Presepsin levels are known to be increased in sepsis. The aim of this study was to evaluate the early diagnostic and prognostic value of Presepsin compared with procalcitonin (PCT), Mortality in Emergency Department Sepsis (MEDS) score and Acute Physiology and Chronic Health Evaluation II (APACHE II) score in septic patients in an emergency department (ED) and to investigate Presepsin as a new biomarker of sepsis.

Methods
This study enrolled 859 consecutive patients with at least two diagnostic criteria for systemic inflammatory response syndrome (SIRS) who were admitted to Beijing Chao-yang Hospital ED from December 2011 to October 2012, and 100 age-matched healthy controls. Patients were stratified into four groups: SIRS, sepsis, severe sepsis, and septic shock. Plasma Presepsin and serum PCT were measured, and MEDS score and APACHE II score were calculated at enrollment. Comparisons were analyzed using the Kruskal-Wallis and Mann–Whitney U tests.

Results
On admission, the median levels of plasma Presepsin increased with sepsis severity. The areas under the receiver operating characteristic (AUC) curves of Presepsin were greater than those of PCT in diagnosing sepsis, and predicting severe sepsis and septic shock. The AUC of Presepsin for predicting 28-day mortality in septic patients was slightly lower than that of PCT, MEDS score and APACHE II score. The AUC of a combination of Presepsin and MEDS score or APACHE II score was significantly higher than that of MEDS score or APACHE II score alone in predicting severe sepsis, and was markedly higher than that of Presepsin alone in predicting septic shock and 28-day mortality in septic patients, respectively. Plasma Presepsin levels in septic patients were significantly higher in non-survivors than in survivors at 28 days’ follow-up. Presepsin, MEDS score and APACHE II score were found to be independent predictors of severe sepsis, septic shock and 28-day mortality in septic patients. The levels of plasma Presepsin were positively correlated with PCT, MEDS score and APACHE II score in every septic group.

Conclusion
Presepsin is a valuable biomarker for early diagnosis of sepsis, risk stratification, and evaluation of prognosis in septic patients in the ED.
Role of calcium desensitization in the treatment of myocardial dysfunction after deep hypothermic circulatory arrest
Authors: Rungatscher Alessio , Hallström Seth , Giacomazzi Alice , Linardi Daniele , Milani Elisabetta , Tessari Maddalena , Luciani Giovanni Battista , Scarabelli Tiziano M , Mazzucco Alessandro , Faggian Giuseppe 
Published: October 2013

Abstract
Introduction
Rewarming from deep hypothermic circulatory arrest (DHCA) produces calcium desensitization by troponin I (cTnI) phosphorylation which results in myocardial dysfunction. This study investigated the acute overall hemodynamic and metabolic effects of epinephrine and levosimendan, a calcium sensitizer, on myocardial function after rewarming from DHCA.

Methods
Forty male Wistar rats (400 to 500 g) underwent cardiopulmonary bypass (CPB) through central cannulation and were cooled to a core temperature of 13°C to 15°C within 30 minutes. After DHCA (20 minutes) and CPB-assisted rewarming (60 minutes) rats were randomly assigned to 60 minute intravenous infusion with levosimendan (0.2 μg/kg/min; n = 15), epinephrine (0.1 μg/kg/min; n = 15) or saline (control; n = 10). Systolic and diastolic functions were evaluated at different preloads with a conductance catheter.

Results
The slope of left ventricular end-systolic pressure volume relationship (Ees) and preload recruitable stroke work (PRSW) recovered significantly better with levosimendan compared to epinephrine (Ees: 85 ± 9% vs 51 ± 11%, P<0.003 and PRSW: 78 ± 5% vs 48 ± 8%, P<0.005; baseline: 100%). Levosimendan but not epinephrine reduced left ventricular stiffness shown by the end-diastolic pressure-volume relationship and improved ventricular relaxation (Tau). Levosimendan preserved ATP myocardial content as well as energy charge and reduced plasma lactate concentrations. In normothermia experiments epinephrine in contrast to Levosimendan increased cTnI phosphorylation 3.5-fold. After rewarming from DHCA, cTnI phosphorylation increased 4.5-fold in the saline and epinephrine group compared to normothermia but remained unchanged with levosimendan.

Conclusions
Levosimendan due to prevention of calcium desensitization by cTnI phosphorylation is more effective than epinephrine for treatment of myocardial dysfunction after rewarming from DHCA.
Fluid balance and cardiac function in septic shock as predictors of hospital mortality
Authors: Micek Scott T , McEvoy Colleen , McKenzie Matthew , Hampton Nicholas , Doherty Joshua A , Kollef Marin H 
Published: October 2013

Abstract
Introduction
Septic shock is a major cause of morbidity and mortality throughout the world. Unfortunately, the optimal fluid management of septic shock is unknown and currently is empirical.

Methods
A retrospective analysis was performed at Barnes-Jewish Hospital (St. Louis, Missouri). Consecutive patients (n = 325) hospitalized with septic shock who had echocardiographic examinations performed within 24 hours of shock onset were enrolled.

Results
A total of 163 (50.2%) patients with septic shock died during hospitalization. Non-survivors had a significantly larger positive net fluid balance within the 24 hour window of septic shock onset (median (IQR): 4,374 ml (1,637 ml, 7,260 ml) vs. 2,959 ml (1,639.5 ml, 4,769.5 ml), P = 0.004). The greatest quartile of positive net fluid balance at 24 hours and eight days post-shock onset respectively were found to predict hospital mortality, and the greatest quartile of positive net fluid balance at eight days post-shock onset was an independent predictor of hospital mortality (adjusted odds ratio (AOR), 1.66; 95% CI, 1.39 to 1.98; P = 0.004). Survivors were significantly more likely to have mild left ventricular dysfunction as evaluated by bedside echocardiography and non-survivors had slightly elevated left ventricular ejection fraction, which was also found to be an independent predictor of outcome.

Conclusions
Our data confirms the importance of fluid balance and cardiac function as outcome predictors in patients with septic shock. A clinical trial to determine the optimal administration of intravenous fluids to patients with septic shock is needed.
FER-1/Dysferlin promotes cholinergic signaling at the neuromuscular junction in C. elegans and mice
Authors: Krajacic Predrag , Pistilli Emidio E. , Tanis Jessica E. , Khurana Tejvir S. , Lamitina S. Todd 
Published: October 2013

Summary
Dysferlin is a member of the evolutionarily conserved ferlin gene family. Mutations in Dysferlin lead to Limb Girdle Muscular Dystrophy 2B (LGMD2B), an inherited, progressive and incurable muscle disorder. However, the molecular mechanisms underlying disease pathogenesis are not fully understood. We found that both loss-of-function mutations and muscle-specific overexpression of C. elegans fer-1, the founding member of the Dysferlin gene family, caused defects in muscle cholinergic signaling. To determine if Dysferlin-dependent regulation of cholinergic signaling is evolutionarily conserved, we examined the in vivo physiological properties of skeletal muscle synaptic signaling in a mouse model of Dysferlin-deficiency. In addition to a loss in muscle strength, Dysferlin −/− mice also exhibited a cholinergic deficit manifested by a progressive, frequency-dependent decrement in their compound muscle action potentials following repetitive nerve stimulation, which was observed in another Dysferlin mouse model but not in a Dysferlin-independent mouse model of muscular dystrophy. Oral administration of Pyridostigmine bromide, a clinically used acetylcholinesterase inhibitor (AchE.I) known to increase synaptic efficacy, reversed the action potential defect and restored in vivo muscle strength to Dysferlin −/− mice without altering muscle pathophysiology. Our data demonstrate a previously unappreciated role for Dysferlin in the regulation of cholinergic signaling and suggest that such regulation may play a significant pathophysiological role in LGMD2B disease.
Par-complex aPKC and Par3 cross-talk with innate immunity NF-κB pathway in epithelial cells
Authors: Forteza Radia , Wald Flavia A. , Mashukova Anastasia , Kozhekbaeva Zhanna , Salas Pedro J. 
Published: October 2013

SummaryComponents of the Par-complex, atypical PKC and Par3, have been found to be downregulated upon activation of NF-κB in intestinal epithelial cells. To determine their possible role in pro-inflammatory responses we transduced Caco-2 human colon carcinoma cells with constitutively active (ca) PKCι or anti-Par3 shRNA-expressing lentiviral particles. Contrary to previous reports in other cell types, ca-PKCι did not activate, but rather decreased, baseline NF-κB activity in a luminiscence reporter assay. An identical observation applied to a PB1 domain deletion PKCι, which fails to localize to the tight-junction. Conversely, as expected, the same ca-PKCι activated NF-κB in non-polarized HEK293 cells. Likewise, knockdown of Par3 increased NF-κB activity and, surprisingly, greatly enhanced its response to TNFα, as shown by transcription of IL-8, GRO-1, GRO-2 and GRO-3. We conclude that aPKC and Par3 are inhibitors of the canonical NF-κB activation pathway, although perhaps acting through independent pathways, and may be involved in pro-inflammatory responses.