bluuebunny/crossref_metadata_2025_split huggingface dataset:
Natural History of Nonoperatively Treated Symptomatic Rotator Cuff Tears in Patients 60 Years Old or Younger
Authors: Safran Ori , Schroeder Joshua , Bloom Ronald , Weil Yoram , Milgrom Charles 
Published: February 2011

Background: Rotator cuff tears are the most frequent tendon injury in the adult population. However, the natural history of nonoperatively treated full-thickness tears is poorly defined. Knowledge of the expected evolution in tear size is important when considering nonoperative versus surgical care, especially in relatively young, active patients. Purpose: To evaluate the size change of nonoperatively treated full-thickness rotator cuff tears over 2 to 3 years’ follow-up. Study Design: Case series; Level of evidence, 4. Methods: The authors prospectively followed patients 60 years old or younger who had a full-thickness rotator cuff tear equal to or larger than 5 mm, as diagnosed by bilateral shoulder ultrasound, and who were treated nonoperatively. At 2 to 3 years after the index ultrasound examination, a repeat ultrasound examination was performed by the same ultrasonographer. Results of the follow-up ultrasound examinations of both shoulders were compared with those of the index ultrasound examinations for change in rotator cuff tear size. The correlations were examined between these changes and age, sex, history of initial trauma, size of tear on the index ultrasound, and current shoulder symptoms. Results: Fifty-one patients with 61 rotator cuff tears were evaluated. At a follow-up of 25 to 39 months (mean, 29), 49% of the tears (30 tears) increased in size, 43% (26 tears) had not changed, and 8% (5 tears) decreased in size. For 25% (10 shoulders ) of initially intact shoulders (41 shoulders), a new full-thickness rotator cuff tear was diagnosed. No correlation was found between the change in tear size and age of the patient ( P = .85), sex ( P = .93), existence of a prior trauma ( P = .63), size of tear at index ultrasound ( P = .62), and bilateral tears ( P = 1.00). There was a correlation between the existence of considerable pain at the time of the follow-up ultrasound and a clinically significant increase in tear size ( P = .002). Conclusion: Full-thickness rotator cuff tears tend to increase in size in about half of patients aged 60 years or younger. Surgery should be initially considered in these patients to prevent a probable increase in size tear. Patients treated nonoperatively should be routinely monitored for tear size increase, especially if they remain symptomatic.
Regulation of S100A10 by the PML-RAR-α oncoprotein
Authors: O'Connell Paul A. , Madureira Patricia A. , Berman Jason N. , Liwski Robert S. , Waisman David M. 
Published: February 2011

AbstractAcute promyelocytic leukemia (APL) is a distinct subtype of acute myeloid leukemia that results from the expression of the promyelocytic leukemia–retinoic acid receptor α (PML-RAR-α) oncoprotein. It is characterized by severe hemorrhagic complications due in part to excessive fibrinolysis, resulting from the excessive generation of the fibrinolytic enzyme, plasmin, at the cell surface of the PML cells. The treatment of patients with all-trans retinoic acid (ATRA) effectively ameliorates the disease by promoting the destruction of the PML-RAR-α oncoprotein. In the present study we show for the first time that the plasminogen receptor, S100A10, is present on the extracellular surface of APL cells and is rapidly down-regulated in response to all-trans retinoic acid. The loss of S100A10 is concomitant with a loss in fibrinolytic activity. Furthermore, the induced expression of the PML-RAR-α oncoprotein increased the expression of cell surface S100A10 and also caused a dramatic increase in fibrinolytic activity. Depletion of S100A10 by RNA interference effectively blocked the enhanced fibrinolytic activity observed after induction of the PML-RAR-α oncoprotein. These experiments show that S100A10 plays a crucial role in the generation of plasmin leading to fibrinolysis, thus providing a link to the clinical hemorrhagic phenotype of APL.
Negative regulation of mTOR activation by diacylglycerol kinases
Authors: Gorentla Balachandra K. , Wan Chi-Keung , Zhong Xiao-Ping 
Published: February 2011

AbstractThe engagement of TCR induces T-cell activation, which initiates multiple characteristic changes such as increase in cell size, cell division, and the production of cytokines and other effector molecules. The mammalian target of rapamycin (mTOR) regulates protein synthesis, transcription, cell survival, and autophagy. Critical roles of mTOR in T-cell activation and effector/memory differentiation have been revealed using chemical inhibitors or by genetic ablation of mTOR in T cells. However, the connection between mTOR signaling and other signaling cascades downstream of TCR is unclear. We demonstrate that diacylglycerol (DAG) and TCR engagement activate signaling in both mTOR complexes 1 and 2 through the activation of the Ras–mitogen-activated protein kinase/extracellular signal–regulated kinase 1/2 (Mek1/2)–extracellular signal–regulated kinase 1/2 (Erk1/2)–activator protein 1 (AP-1), known collectively as the Ras-Mek1/2-Erk1/2-AP-1 pathway. Deficiency of RasGRP1 or inhibition of Mek1/2 activity drastically decreases TCR-induced mTOR activation, whereas constitutively active Ras or Mek1 promotes mTOR activation. Although constitutively active Akt promotes TCR-induced mTOR activation, such activation is attenuated by Mek1/2 inhibition. We demonstrated further that DAG kinases (DGKs) α and ζ, which terminate DAG-mediated signaling, synergistically inhibit TCR-induced mTOR activation by inhibiting the Ras-Mek1/2-Erk/12 pathway. These observations provide novel insights into the regulation of mTOR activation.
Propofolversuspropofol plus hydrocodone for flexible bronchoscopy: a randomised study
Authors: Schlatter L. , Pflimlin E. , Fehrke B. , Meyer A. , Tamm M. , Stolz D. 
Published: February 2011

Propofol and the combination of a benzodiazepine and an opiate have been established for sedation in flexible bronchoscopy. It is as yet unknown whether propofol in combination with an opiate is superior to propofol alone to suppress cough during the procedure.300 consecutive patients undergoing flexible bronchoscopy at a tertiary care university hospital were randomly allocated to receive either the combination propofol and hydrocodone or propofol alone in a double-blind fashion. The primary end-point was the cough score during the procedure as estimated by the physician using a visual analogue scale.Demographics were similar in both groups. Compared with propofol alone, median (interquartile range) cough scores assessed by physicians, nurses and patients were significantly lower in the group randomised to the combination propofol and hydrocodone (2.5 (1.5–4.0)versus2.0 (1.0–3.0), respectively, p=0.011). Additionally, patients receiving the combination required significantly lower doses of propofol than those receiving propofol alone (200 mg (140–280)versus260 mg (180–350), p<0.0001). Complex examinations, including bronchoalveolar lavage or transbronchial biopsy, benefited more from additional opiate. The duration of the procedure, time to discharge and complication rate were similar in both groups.The combination of propofol and hydrocodone is safe and superior to propofol alone for cough suppression in flexible bronchoscopy.
Airway inflammation is augmented by obesity and fatty acids in asthma
Authors: Scott H.A. , Gibson P.G. , Garg M.L. , Wood L.G. 
Published: February 2011

Obesity and asthma are associated, but the mechanism(s) of the association have yet to be elucidated. The aim of this study was to assess airway inflammation in relation to obesity and plasma fatty acids in males and females with and without asthma.Obese (n=68) and nonobese (n=47) adults with asthma, and obese (n=16) and nonobese (n=63) healthy controls had induced sputum and venous blood samples analysed for inflammatory markers.There was a positive interaction between obesity and asthma on sputum neutrophil percentage (p=0.012) and C-reactive protein level (p=0.003). Although sputum eosinophil percentage was elevated in asthma (p=0.001), there was no effect of obesity (p=0.16). Sputum neutrophil percentage was positively associated with body mass index in females with asthma (β=1.015, 95% CI 0.258–1.772; p=0.009) and neutrophilic asthma was present in a greater proportion of obese compared with non-obese females (42.9%versus16.2%; p=0.017). In males with asthma, sputum neutrophil percentage was positively associated with total plasma saturated fatty acids (β=0.108, 95% CI 0.036–0.180; p=0.004) and negatively with monounsaturated fatty acids (β= -0.068, 95% CI -0.131– -0.005; p=0.035).This was the first study to demonstrate an increase in neutrophilic airway inflammation in obese asthma. This relationship was significant only in females with asthma. In males, saturated and monounsaturated fatty acids were important predictors of neutrophilic airway inflammation in asthma.
Evaluation of moxifloxacin for the treatment of tuberculosis: 3 years of experience
Authors: Pranger A.D. , van Altena R. , Aarnoutse R.E. , van Soolingen D. , Uges D.R.A. , Kosterink J.G.W. , van der Werf T.S. , Alffenaar J.W.C. 
Published: February 2011

Moxifloxacin (MFX) is a powerful second-line anti-tuberculosis (TB) agent, but the optimal dose has not yet been established and long-term safety data are scarce.We retrospectively reviewed the medical charts of TB patients treated at the Tuberculosis Centre Beatrixoord, University Medical Centre Groningen (Haren, the Netherlands) receiving MFX 400 mg once daily as part of their TB treatment between January 1 2006 and January 1 2009. Safety data and drug–drug interactions were evaluated. Efficacy was predicted based on the area under the concentration–time curve up to 24 h post-dosage (AUC0–24h)/minimal inhibitory concentration (MIC) ratio.89 patients were treated with a median dose of 6.9 mg·kg−1MFX once daily for a median period of 74 days. Discontinuation of therapy occurred in only three patients due to gastrointestinal side-effects and hypersensitivity. Pharmacokinetic analysis showed an AUC0–24h/MIC ratio <100 in eight out of 16 patients. A large variation in protein binding affected the unbound AUC0–24hconsiderably.These data show that MFX treatment was well tolerated in 89 patients receiving a dose of 400 mg once daily for a prolonged period. Considering the variability in (un)bound AUC0–24h/MIC ratio, therapeutic drug monitoring is recommended in selected patients (i.e.rifampicin co-medication; MIC ≥0.25 mg·L−1) to assess optimal therapy.
The functional expression of extracellular calcium-sensing receptor in rat pulmonary artery smooth muscle cells
Authors: Li Guang-wei , Wang Qiu-shi , Hao Jing-hui , Xing Wen-jing , Guo Jin , Li Hong-zhu , Bai Shu-zhi , Li Hong-xia , Zhang Wei-hua , Yang Bao-feng , Yang Guang-dong , Wu Ling-yun , Wang Rui , Xu Chang-qing 
Published: February 2011

Abstract

Background
The extracellular calcium-sensing receptor (CaSR) belongs to family C of the G protein coupled receptors. Whether the CaSR is expressed in the pulmonary artery (PA) is unknown.

Methods
The expression and distribution of CaSR were detected by RT-PCR, Western blotting and immunofluorescence. PA tension was detected by the pulmonary arterial ring technique, and the intracellular calcium concentration ([Ca2+]i) was detected by a laser-scanning confocal microscope.

Results
The expressions of CaSR mRNA and protein were found in both rat pulmonary artery smooth muscle cells (PASMCs) and PAs. Increased levels of [Ca2+]o (extracellular calcium concentration) or Gd3+ (an agonist of CaSR) induced an increase of [Ca2+]i and PAs constriction in a concentration-dependent manner. In addition, the above-mentioned effects of Ca2+ and Gd3+ were inhibited by U73122 (specific inhibitor of PLC), 2-APB (specific antagonist of IP3 receptor), and thapsigargin (blocker of sarcoplasmic reticulum calcium ATPase).

Conclusions
CaSR is expressed in rat PASMCs, and is involved in regulation of PA tension by increasing [Ca2+]i through G-PLC-IP3 pathway.
Estimating developmental states of tumors and normal tissues using a linear time-ordered model
Authors: Zhang Bo , Chen Beibei , Wu Tao , Xuan Zhenyu , Zhu Xiaopeng , Chen Runsheng 
Published: February 2011

Abstract

Background
Tumor cells are considered to have an aberrant cell state, and some evidence indicates different development states appearing in the tumorigenesis. Embryonic development and stem cell differentiation are ordered processes in which the sequence of events over time is highly conserved. The "cancer attractor" concept integrates normal developmental processes and tumorigenesis into a high-dimensional "cell state space", and provides a reasonable explanation of the relationship between these two biological processes from theoretical viewpoint. However, it is hard to describe such relationship by using existed experimental data; moreover, the measurement of different development states is also difficult.

Results
Here, by applying a novel time-ordered linear model based on a co-bisector which represents the joint direction of a series of vectors, we described the trajectories of development process by a line and showed different developmental states of tumor cells from developmental timescale perspective in a cell state space. This model was used to transform time-course developmental expression profiles of human ESCs, normal mouse liver, ovary and lung tissue into "cell developmental state lines". Then these cell state lines were applied to observe the developmental states of different tumors and their corresponding normal samples. Mouse liver and ovarian tumors showed different similarity to early development stage. Similarly, human glioma cells and ovarian tumors became developmentally "younger".

Conclusions
The time-ordered linear model captured linear projected development trajectories in a cell state space. Meanwhile it also reflected the change tendency of gene expression over time from the developmental timescale perspective, and our finding indicated different development states during tumorigenesis processes in different tissues.
DNA moves sequentially towards the nuclear matrix during DNA replication in vivo
Authors: Rivera-Mulia Juan Carlos , Hernández-Muñoz Rolando , Martínez Federico , Aranda-Anzaldo Armando 
Published: February 2011

Abstract

Background
In the interphase nucleus of metazoan cells DNA is organized in supercoiled loops anchored to a nuclear matrix (NM). There is varied evidence indicating that DNA replication occurs in replication factories organized upon the NM and that DNA loops may correspond to the actual replicons in vivo. In normal rat liver the hepatocytes are arrested in G0 but they synchronously re-enter the cell cycle after partial-hepatectomy leading to liver regeneration in vivo. We have previously determined in quiescent rat hepatocytes that a 162 kbp genomic region containing members of the albumin gene family is organized into five structural DNA loops.

Results
In the present work we tracked down the movement relative to the NM of DNA sequences located at different points within such five structural DNA loops during the S phase and after the return to cellular quiescence during liver regeneration. Our results indicate that looped DNA moves sequentially towards the NM during replication and then returns to its original position in newly quiescent cells, once the liver regeneration has been achieved.

Conclusions
Looped DNA moves in a sequential fashion, as if reeled in, towards the NM during DNA replication in vivo thus supporting the notion that the DNA template is pulled progressively towards the replication factories on the NM so as to be replicated. These results provide further evidence that the structural DNA loops correspond to the actual replicons in vivo.
Identification of errors introduced during high throughput sequencing of the T cell receptor repertoire
Authors: Nguyen Phuong , Ma Jing , Pei Deqing , Obert Caroline , Cheng Cheng , Geiger Terrence L 
Published: February 2011

Abstract

Background
Recent advances in massively parallel sequencing have increased the depth at which T cell receptor (TCR) repertoires can be probed by >3log10, allowing for saturation sequencing of immune repertoires. The resolution of this sequencing is dependent on its accuracy, and direct assessments of the errors formed during high throughput repertoire analyses are limited.

Results
We analyzed 3 monoclonal TCR from TCR transgenic, Rag-/- mice using Illumina® sequencing. A total of 27 sequencing reactions were performed for each TCR using a trifurcating design in which samples were divided into 3 at significant processing junctures. More than 20 million complementarity determining region (CDR) 3 sequences were analyzed. Filtering for lower quality sequences diminished but did not eliminate sequence errors, which occurred within 1-6% of sequences. Erroneous sequences were pre-dominantly of correct length and contained single nucleotide substitutions. Rates of specific substitutions varied dramatically in a position-dependent manner. Four substitutions, all purine-pyrimidine transversions, predominated. Solid phase amplification and sequencing rather than liquid sample amplification and preparation appeared to be the primary sources of error. Analysis of polyclonal repertoires demonstrated the impact of error accumulation on data parameters.

Conclusions
Caution is needed in interpreting repertoire data due to potential contamination with mis-sequence reads. However, a high association of errors with phred score, high relatedness of erroneous sequences with the parental sequence, dominance of specific nt substitutions, and skewed ratio of forward to reverse reads among erroneous sequences indicate approaches to filter erroneous sequences from repertoire data sets.
Relapse according to antipsychotic treatment in schizophrenic patients: a propensity-adjusted analysis
Authors: Millier Aurelie , Sarlon Emmanuelle , Azorin Jean-Michel , Boyer Laurent , Aballea Samuel , Auquier Pascal , Toumi Mondher 
Published: February 2011

Abstract

Objective
To compare the rate of relapse as a function of antipsychotic treatment (monotherapy vs. polypharmacy) in schizophrenic patients over a 2-year period.

Methods
Using data from a multicenter cohort study conducted in France, we performed a propensity-adjusted analysis to examine the association between the rate of relapse over a 2-year period and antipsychotic treatment (monotherapy vs. polypharmacy).

Results
Our sample consisted in 183 patients; 50 patients (27.3%) had at least one period of relapse and 133 had no relapse (72.7%). Thirty-eight (37.7) percent of the patients received polypharmacy. The most severely ill patients were given polypharmacy: the age at onset of illness was lower in the polypharmacy group (p = 0.03). Patients that received polypharmacy also presented a higher general psychopathology PANSS subscore (p = 0.04) but no statistically significant difference was found in the PANSS total score or the PANSS positive or negative subscales. These patients were more likely to be given prescriptions for sedative drugs (p < 0.01) and antidepressant medications (p = 0.03). Relapse was found in 23.7% of patients given monotherapy and 33.3% given polypharmacy (p = 0.16). After stratification according to quintiles of the propensity score, which eliminated all significant differences for baseline characteristics, antipsychotic polypharmacy was not statistically associated with an increase of relapse: HR = 1.686 (0.812; 2.505).

Conclusion
After propensity score adjustment, antipsychotic polypharmacy is not statistically associated to an increase of relapse. Future randomised studies are needed to assess the impact of antipsychotic polypharmacy in schizophrenia.
Ambulatory oxygen: why do COPD patients not use their portable systems as prescribed? A qualitative study
Authors: Arnold Elizabeth , Bruton Anne , Donovan-Hall Maggie , Fenwick Angela , Dibb Bridget , Walker Elizabeth 
Published: February 2011

AbstractBackgroundPatients with COPD on long term oxygen therapy frequently do not adhere to their prescription, and they frequently do not use their ambulatory oxygen systems as intended. Reasons for this lack of adherence are not known. The aim of this study was to obtain in-depth information about perceptions and use of prescribed ambulatory oxygen systems from patients with COPD to inform ambulatory oxygen design, prescription and management.MethodsA qualitative design was used, involving semi-structured face-to-face interviews informed by a grounded theory approach. Twenty-seven UK community-dwelling COPD patients using NHS prescribed ambulatory systems were recruited. Ambulatory oxygen systems comprised cylinders weighing 3.4 kg, a shoulder bag and nasal cannulae.ResultsParticipants reported that they: received no instruction on how to use ambulatory oxygen; were uncertain of the benefits; were afraid the system would run out while they were using it (due to lack of confidence in the cylinder gauge); were embarrassed at being seen with the system in public; and were unable to carry the system because of the cylinder weight. The essential role of carers was also highlighted, as participants with no immediate carers did not use ambulatory oxygen outside the house.ConclusionsThese participants highlighted previously unreported problems that prevented them from using ambulatory oxygen as prescribed. Our novel findings point to: concerns with the lack of specific information provision; the perceived unreliability of the oxygen system; important carer issues surrounding managing and using ambulatory oxygen equipment. All of these issues, as well as previously reported problems with system weight and patient embarrassment, should be addressed to improve adherence to ambulatory oxygen prescription and enhance the physical and social benefits of maintaining mobility in this patient group. Increased user involvement in both system development and service provision planning, could have avoided many of the difficulties highlighted by this study.
Induction of strain-transcendent antibodies to placental-type isolates with VAR2CSA DBL3 or DBL5 recombinant proteins
Authors: Avril Marion , Cartwright Megan M , Hathaway Marianne J , Smith Joseph D 
Published: February 2011

Abstract

Background
Pregnancy associated malaria is a severe clinical syndrome associated with sequestration of Plasmodium falciparum-infected erythrocytes in the placenta. Placental binding is mediated by VAR2CSA, which adheres to chondroitin sulphate A (CSA). VAR2CSA is a large and polymorphic protein that has six Duffy binding-like (DBL) domains. There is still limited understanding as to how effective individual VAR2CSA domains are at generating inhibitory antibodies or the number of domain variants needed for universal vaccine coverage.

Methods
To investigate the immunogenic properties of single domain VAR2CSA recombinant proteins, rats or rabbits were immunized with five of the six VAR2CSA domains produced in Pichia pastoris. Immune plasma was analysed against a geographically diverse panel of CSA-binding lab lines to assess antibody breadth and inhibitory activity.

Results
Of the five domains, DBL3, and to a lesser extent DBL5, induced antibodies that cross-reacted on five diverse CSA-binding parasite lines by flow cytometry. By comparison, anti-DBL6 antibodies were highly strain-specific and anti-DBL1 and anti-DBL4 antibodies were poorly reactive by flow cytometry. From this series of recombinant proteins, adhesion-blocking activity was restricted to a single rat immunized against a DBL4 recombinant protein.

Conclusions
Single domain VAR2CSA recombinant proteins produced in P. pastoris had limited efficacy in eliciting adhesion blocking antibody responses, but VAR2CSA DBL3 and DBL5 domains contain strain-transcendent epitopes that can be targeted by vaccination and may have application for vaccine development.