bluuebunny/crossref_metadata_2025_split huggingface dataset:
Oral intake of phenylbutyrate with or without vitamin D3upregulates the cathelicidin LL-37 in human macrophages: a dose finding study for treatment of tuberculosis
Authors: Mily Akhirunnesa , Rekha Rokeya Sultana , Kamal S M Mostafa , Akhtar Evana , Sarker Protim , Rahim Zeaur , Gudmundsson Gudmundur H , Agerberth Birgitta , Raqib Rubhana 
Published: April 2013

Abstract

Background
We earlier showed that 4-phenylbutyrate (PB) can induce cathelicidin LL-37 expression synergistically with 1,25-dihydroxyvitamin D3 in a lung epithelial cell line. We aimed to evaluate a therapeutic dose of PB alone or in combination with vitamin D3 for induction of LL-37 expression in immune cells and enhancement of antimycobacterial activity in monocyte-derived macrophages (MDM).

Methods
Healthy volunteers were enrolled in an 8-days open trial with three doses of PB [250 mg (Group-I), 500 mg (Group-II) or 1000 mg (Group-III)] twice daily (b.d.) together with vitamin D3 {5000 IU once daily (o.d.)}, PB (500 mg b.d.) (Group-IV) or vitamin D3 (5000 IU o.d.) (Group-V), given orally for 4 days. Blood was collected on day-0, day-4 and day-8; plasma was separated, peripheral blood mononuclear cells (PBMC), non-adherent lymphocytes (NAL) and MDM were cultured. LL-37 transcript in cells and peptide concentrations in supernatant were determined by qPCR and ELISA, respectively. In plasma, 25-hydorxyvitamin D3 levels were determined by ELISA. MDM-mediated killing of Mycobacterium tuberculosis (Mtb) (H37Rv) was performed by conventional culture method.

Results
MDM from Group-II had increased concentration of LL-37 peptide and transcript at day-4, while Group-I showed increased transcript at day-4 and day-8 compared to day-0 (p < 0.05). Both Group-I and -II exhibited higher levels of transcript on day-4 compared to Group-III and Group-V (p < 0.035). Increased induction of peptide was observed in lymphocytes from Group-II on day-4 compared to Group-I and Group-IV (p < 0.05), while Group-IV showed increased levels on day-8 compared to Group-I and Group-III (p < 0.04). Intracellular killing of Mtb on day-4 was significantly increased compared to day-0 in Group-I, -II and -V (p < 0.05).

Conclusion
The results demonstrate that 500 mg b.d. PB with 5000 IU o.d. vitamin D3 is the optimal dose for the induction of LL-37 in macrophages and lymphocytes and intracellular killing of Mtb by macrophages. Hence, this dose has potential application in the treatment of TB and is now being used in a clinical trial of adults with active pulmonary TB (NCT01580007).
Assessing the validity of a self-administered food-frequency questionnaire (FFQ) in the adult population of Newfoundland and Labrador, Canada
Authors: Liu Lin , Wang Peizhong Peter , Roebothan Barbara , Ryan Ann , Tucker Christina Sandra , Colbourne Jennifer , Baker Natasha , Cotterchio Michelle , Yi Yanqing , Sun Guang 
Published: April 2013

AbstractBackgroundThe Food- Frequency Questionnaire (FFQ) is a dietary assessment tool frequently used in large-scale nutritional epidemiology studies. The goal of the present study is to validate a self-administered version of the Hawaii FFQ modified for use in the general adult population of Newfoundland and Labrador (NL).MethodsOver a one year period, 195 randomly selected adults completed four 24-hour dietary recalls (24-HDRs) by telephone and one subsequent self-administered FFQ. Estimates of energy and nutrients derived from the 24-HDRs and FFQs were compared (protein, carbohydrate, fibre, fat, vitamin A, carotene, vitamin D, and calcium). Data were analyzed using the Pearson’s correlation coefficients, cross-classification method, and Bland–Altman plots.ResultsThe mean nutrient intake values of the 24-HDRs were lower than those of the FFQs, except for protein in men. Sex and energy-adjusted de-attenuated Pearson correlation coefficients for each nutrient varied from 0.13 to 0.61. Except for protein in men, all correlations were statistically significant with p < 0.05. Cross-classification analysis revealed that on average, 74% women and 78% men were classified in the same or adjacent quartile of nutrient intake when comparing data from the FFQ and 24-HDRs. Bland–Altman plots showed no serious systematic bias between the administration of the two instruments over the range of mean intakes.ConclusionThis 169-item FFQ developed specifically for the adult NL population had moderate relative validity and therefore can be used in studies to assess food consumption in the general adult population of NL. This tool can be used to classify individual energy and nutrient intakes into quartiles, which is useful in examining relationships between diet and chronic disease.
The infectious synapse formed between mature dendritic cells and CD4+T cells is independent of the presence of the HIV-1 envelope glycoprotein
Authors: Rodriguez-Plata Maria T , Puigdomènech Isabel , Izquierdo-Useros Nuria , Puertas Maria C , Carrillo Jorge , Erkizia Itziar , Clotet Bonaventura , Blanco Julià , Martinez-Picado Javier 
Published: April 2013

Abstract

Background
Since cell-mediated infection of human immunodeficiency virus type 1 (HIV-1) is more efficient than cell-free infection, cell-to-cell propagation plays a crucial role in the pathogenesis of HIV-1 infection. Transmission of HIV-1 is enabled by two types of cellular contacts, namely, virological synapses between productively infected cells and uninfected target cells and infectious synapses between uninfected dendritic cells (DC) harboring HIV-1 and uninfected target cells. While virological synapses are driven by expression of the viral envelope glycoprotein on the cell surface, little is known about the role of envelope glycoprotein during contact between DC and T cells. We explored the contribution of HIV-1 envelope glycoprotein, adhesion molecules, and antigen recognition in the formation of conjugates comprising mature DC (mDC) and CD4+ T cells in order to further evaluate their role in mDC-mediated HIV-1 transmission at the immunological synapse.

Results
Unlike virological synapse, HIV-1 did not modulate the formation of cell conjugates comprising mDC harboring HIV-1 and non-activated primary CD4+ T cells. Disruption of interactions between ICAM-1 and LFA-1, however, resulted in a 60% decrease in mDC-CD4+ T-cell conjugate formation and, consequently, in a significant reduction of mDC-mediated HIV-1 transmission to non-activated primary CD4+ T cells (p < 0.05). Antigen recognition or sustained MHC-TcR interaction did not enhance conjugate formation, but significantly boosted productive mDC-mediated transmission of HIV-1 (p < 0.05) by increasing T-cell activation and proliferation.

Conclusions
Formation of the infectious synapse is independent of the presence of the HIV-1 envelope glycoprotein, although it does require an interaction between ICAM-1 and LFA-1. This interaction is the main driving force behind the formation of mDC-CD4+ T-cell conjugates and enables transmission of HIV-1 to CD4+ T cells. Moreover, antigen recognition boosts HIV-1 replication without affecting the frequency of cellular conjugates. Our results suggest a determinant role for immune activation driven by mDC-CD4+ T-cell contacts in viral dissemination and that this activation likely contributes to the pathogenesis of HIV-1 infection.
Unrooted unordered homeomorphic subtree alignment of RNA trees
Authors: Milo Nimrod , Zakov Shay , Katzenelson Erez , Bachmat Eitan , Dinitz Yefim , Ziv-Ukelson Michal 
Published: April 2013

Abstract
We generalize some current approaches for RNA tree alignment, which are traditionally confined to ordered rooted mappings, to also consider unordered unrooted mappings. We define the Homeomorphic Subtree Alignment problem (HSA), and present a new algorithm which applies to several modes, combining global or local, ordered or unordered, and rooted or unrooted tree alignments. Our algorithm generalizes previous algorithms that either solved the problem in an asymmetric manner, or were restricted to the rooted and/or ordered cases. Focusing here on the most general unrooted unordered case, we show that for input trees T and S, our algorithm has an O(n

T

n

S
+ min(d

T
,d

S
)L

T

L

S
) time complexity, where n

T
,L

T
and d

T
are the number of nodes, the number of leaves, and the maximum node degree in T, respectively (satisfying d

T
≤ L

T
≤ n

T
), and similarly for n

S
,L

S
and d

S
with respect to the tree S. This improves the time complexity of previous algorithms for less general variants of the problem.
In order to obtain this time bound for HSA, we developed new algorithms for a generalized variant of the Min-Cost Bipartite Matching problem (MCM), as well as to two derivatives of this problem, entitled All-Cavity-MCM and All-Pairs-Cavity-MCM. For two input sets of size n and m, where n ≤ m, MCM and both its cavity derivatives are solved in O(n
3 + n
m) time, without the usage of priority queues (e.g. Fibonacci heaps) or other complex data structures. This gives the first cubic time algorithm for All-Pairs-Cavity-MCM, and improves the running times of MCM and All-Cavity-MCM problems in the unbalanced case where n ≪ m.
We implemented the algorithm (in all modes mentioned above) as a graphical software tool which computes and displays similarities between secondary structures of RNA given as input, and employed it to a preliminary experiment in which we ran all-against-all inter-family pairwise alignments of RNAse P and Hammerhead RNA family members, exposing new similarities which could not be detected by the traditional rooted ordered alignment approaches. The results demonstrate that our approach can be used to expose structural similarity between some RNAs with higher sensitivity than the traditional rooted ordered alignment approaches. Source code and web-interface for our tool can be found in http://www.cs.bgu.ac.il/\~negevcb/FRUUT.
Interstage mortality for functional single ventricle with heterotaxy syndrome: a retrospective study of the clinical experience of a single tertiary center
Authors: Song Jinyoung , Kang I-Seok , Huh June , Lee Ok Jeong , Kim Geena , Jun Tae Gook , Yang Ji Hyuk 
Published: April 2013

Abstract

Background
In spite of improved survival after palliation for single ventricle, interstage mortality for a single ventricle with heterotaxy syndrome is unknown. The purpose of this study was to quantify interstage mortality and influence mortality risk factors.

Methods
From November 1994 until February 2012, all patients that had a functional single ventricle and heterotaxy syndrome who underwent palliative operations at our center were included. Patients with hypoplastic left heart syndrome and operative mortality cases were excluded. The factors that influenced interstage mortality were determined by multivariate Cox analysis.

Results
There were 16 patients with interstage mortality (41.0%), much higher than the non-heterotaxy group (vs. 11.3%, P = 0.001, OR = 5.478). The major presumptive causes of death were infection or sepsis (37.5%) and unknown sudden death (31.3%). When we compared the survival group and the mortality group with heterotaxy syndrome, Blalock-Taussig shunt as a 1st palliation is most common for both groups but there were more for the mortality group (81.2% vs. 52.2%), and there were more with bidirectional cavo-pulmonary shunt as a 1st palliation in the survival group (10 patients vs. 2 patients). The existence of pulmonary vein stenosis at initial diagnosis was more common for the mortality group. In multivariate Cox analysis, however, the duration of hospitalization at palliation, the duration of intensive care unit stay after palliation and the existence of pulmonary vein stenosis at diagnosis were significant risk factors.

Conclusion
Interstage mortality for a functional single ventricle with heterotaxy syndrome is significantly higher than for non-heterotaxy syndrome. Therefore more attention should be given to the prevention of interstage mortality in these patients with risk factors.
Azacitidine might be beneficial in a subgroup of older AML patients compared to intensive chemotherapy: a single centre retrospective study of 227 consecutive patients
Authors: van der Helm Lieke H , Scheepers Ellen RM , Veeger Nic JGM , Daenen Simon MGJ , Mulder André B , van den Berg Eva , Vellenga Edo , Huls Gerwin 
Published: April 2013

AbstractBackgroundTreatment options in older acute myeloid leukaemia (AML) patients include intensive chemotherapy, best supportive care (BSC), and hypomethylating agents. Currently, limited data is available on hypomethylating agents in older AML patients in unselected patient populations.MethodsTo compare the effectiveness of azacitidine with conventional therapy, we collected data of 227 consecutive AML patients (≥60 years) who were treated with azacitidine (N = 26), intensive chemotherapy (N = 90), or BSC (N = 97).ResultsAzacitidine-treated patients were older and had more comorbidities, but lower white blood cell- and bone marrow blast counts compared with intensive chemotherapy patients. Complete or partial response was achieved in 42% of azacitidine-treated patients and in 73% of intensive chemotherapy patients (P = 0.005). However, the overall survival (OS) was similar (1-year-OS 57% versus 56%,P = 0.93; 2-year-OS 35% versus 35%,P = 0.92), and remained similar after correction for risk factors in a multivariate analysis. Patients treated with BSC had an inferior OS (1-year- and 2-year-OS 16% and 2%,P < 0.001). Compared to intensive chemotherapy, azacitidine-treated patients spent less days in the hospital (median in first three months 0.5 versus 56,P < 0.001), and needed less red blood cell and platelet transfusions (median per month 2.7 versus 7,P < 0.001 and 0.3 versus 5,P < 0.001) in the first three months.ConclusionsAzacitidine treatment is associated with a comparable OS but higher tolerability in a subgroup of older AML patients compared with intensive chemotherapy. Patients receiving BSC had a poor prognosis.
Training the next generation of clinical researchers: evaluation of a graduate podiatrist research internship in rheumatology
Authors: Naidoo Serena , Bowen Catherine , Arden Nigel , Redmond Anthony 
Published: April 2013

AbstractBackgroundThe aim of this study was to evaluate the effectiveness of the Arthritis Research UK funded graduate internship scheme for podiatrists and to explore the experiences of interns and mentors.MethodsNine new graduates completed the internship programme (July 2006–June 2010); six interns and two mentors participated in this study. The study was conducted in three phases. Phase 1: quantitative survey of career and research outcomes for interns. Phase 2 and 3: qualitative asynchronous interviews through email to explore the experiences of interns and mentors. Interpretive phenomenological analysis (IPA) of coded transcripts identified recurring themes.ResultsResearch outputs included ten peer reviewed publications with authorial contributions from interns, 23 conference abstract presentations and one subsequent ‘Jewel in the Crown’ award at the British Society for Rheumatology Conference. Career progression includes two National Institute for Health research (NIHR) PhD fellowships, two Arthritis Research UK PhD fellowships, one NIHR Master of Research fellowship and one specialist rheumatology clinical post. Two interns are members of NIHR and professional body committees.Seven important themes arose from the qualitative phases: perceptions of the internship pre‐application; internship values; maximising personal and professional development; psychosocial components of the internship; the role of mentoring and networking; access to research career pathways; perceptions of future developments for the internship programme. The role of mentorship and the peer support network have had benefits that have persisted beyond the formal period of the scheme.ConclusionsThe internship model appears to have been perceived to have been valuable to the interns' careers and may have contributed significantly to the broader building of capacity in clinical research in foot and ankle rheumatology. We believe the model has potential to be transferable across health disciplines and on national and international scales.
TEOS/PDMS-OH hybrid material for the consolidation of damaged pottery
Authors: Zhao Jing , Luo Hongjie , Wang Liqin , Li Weidong , Zhou Tie , Rong Bo 
Published: April 2013

Abstract
The use of organic–inorganic hybrid compounds containing tetraethoxysilane (TEOS) and hydroxyl-terminated polydimethylsiloxane (PDMS-OH) is one of the most promising approaches for using alkoxysilane-based formulations to improve the effectiveness of the consolidation of traditional silicate artifacts, such as ancient stone. Based on analysis of existing damaged potteries influenced by the crystallization of NaCl salt, the hybrid we prepared in this study provided a crack-free and homogeneous gel on the premise of appropriate PDMS-OH content. The consolidants were applied to samples prepared following procedures that simulate old pottery and the effect of the protective products was evaluated by characterizing the surface morphology, the determination of the consolidant uptake, color changes, water vapour permeability and several wet-dry cycles with salt. The best formulation found for the hybrid in the present work was made up of 10% PDMS-OH with TEOS, which showed a significant increase in compressive strength, with a value of 3.50 MPa at 3 mm depth of consolidation, similar to the sample treated with Primal SF(the commercial protective agents used for comparison purposes), which had 3.20 MPa in compressive strength at 2 mm depth of consolidation. Except for small color changes and excellent water vapor permeability, there was still no significant change, and the destructive effects from NaCl crystallization for the hydrophobic surface of the sample treated with hybrid material was different to what happened for the hydrophilic case in the original. Thus, this study has revealed, for the first time, the addition of an appropriate amount of PDMS-OH to TEOS helps to improve the mechanical properties, hydrophobic behavior and salt resistance of damaged pottery effloresced by the NaCl crystals; in addition small color changes and excellent water vapor permeability should also be taken into consideration.
Urinary angiotensinogen predicts adverse outcomes among acute kidney injury patients in the intensive care unit
Authors: Alge Joseph L , Karakala Nithin , Neely Benjamin A , Janech Michael G , Velez Juan Carlos Q , Arthur John M ,   The SAKInet Investigators
Published: April 2013

Abstract
Introduction
Acute kidney injury (AKI) is commonly observed in the intensive care unit (ICU), where it can be caused by a variety of factors. The objective of this study was to evaluate the prognostic value of urinary angiotensinogen, a candidate prognostic AKI biomarker identified in post-cardiac surgery patients, in this heterogeneous population.

Methods
Urinary angiotensinogen was measured by ELISA and corrected for urine creatinine in 45 patients who developed AKI in the ICU. Patients were grouped by AKI etiology, and the angiotensinogen-to-creatinine ratio (uAnCR) was compared among the groups using the Kruskal-Wallis test. The ability of uAnCR to predict the following endpoints was tested using the area under the ROC curve (AUC): the need for renal replacement therapy (RRT) or death, increased length of stay (defined as hospital discharge > 7 days or death ≤ 7 days from sample collection), and worsening AKI (defined as an increase in serum creatinine > 0.3 mg/dL after sample collection or RRT).

Results
uAnCR was significantly elevated in patients who met the composite outcome RRT or death (89.4 vs 25.4 ng/mg; P = 0.01), and it was a strong predictor of this outcome (AUC = 0.73). Patients with uAnCR values above the median for the cohort (55.21 ng/mg) had increased length of stay compared to patients with uAnCR ≤ 55.21 ng/mg (22 days vs 7 days after sample collection; P = 0.01). uAnCR was predictive of the outcome increased length of stay (AUC = 0.77). uAnCR was also a strong predictor of worsening of AKI (AUC = 0.77). The uAnCR of patients with pre-renal AKI was lower compared to patients with AKI of other causes (median uAnCR 11.3 vs 80.2 ng/mg; P = 0.02).

Conclusions
Elevated urinary angiotensinogen is associated with adverse events in AKI patients in the ICU. It could be used to identify high risk patients who would benefit from timely intervention that could improve their outcomes.
Elevated cardiac markers are associated with higher mortality in patients after transjugular intrahepatic portosystemic shunt insertion
Authors: Vasatova Martina , Pudil Radek , Safka Vaclav , Fejfar Tomas , Buchler Tomas , Hulek Petr , Palicka Vladimir 
Published: April 2013

Background Transjugular intrahepatic portosystemic shunts (TIPSs) have become a widely accepted tool in the treatment of patients with symptomatic portal hypertension. The aim of our study was to assess the value of cardiac markers before and after TIPS insertion for the prediction of one-year mortality in cirrhotic patients. Methods The study population consisted of 55 patients (38 men and 17 women, aged 55.6 ± 8.9 y, range 37-74) with liver cirrhosis treated with transjugular portosystemic shunting. Biochemical markers were measured before and 24 h after TIPS. High-sensitivity cardiac troponin T (hs-cTnT) was tested by high-sensitivity immunoassay for Elecsys analyser (Roche Diagnostics). Concentrations of creatine kinase MB isoenzyme, myoglobin (MYO), glycogenphosphorylase BB isoenzyme (GPBB) and heart type of fatty acid binding protein (FABP) were measured by the Evidence Investigator protein biochip system (Randox Laboratories). Results In patients before TIPS insertion, hs-cTnT was increased above the cut-off (0.014 μg/L) in 39.2% of patients. Higher hs-cTnT and FABP concentrations were associated with poor survival in patients before TIPS (hs-cTnT: P = 0.018; FABP: P = 0.016). Twenty-four hours after the TIPS procedure, we found a significant elevation in serum GPBB in comparison with preprocedural values ( P < 0.001). There was an association between postprocedural concentrations of cardiac markers (MYO, hs-cTnT, FABP) and overall survival. Conclusions Measurement of cardiac markers, mainly hs-cTnT and FABP, may be useful for mortality prediction in cirrhotic patients after TIPS. Cardiac markers are better mortality predictors than other risk factors such as age, gender or Child-Pugh score.