bluuebunny/crossref_metadata_2025_split huggingface dataset:
Activation of HER Family Signaling as a Mechanism of Acquired Resistance to ALK Inhibitors in EML4-ALK–Positive Non–Small Cell Lung Cancer
Authors: Tanizaki Junko , Okamoto Isamu , Okabe Takafumi , Sakai Kazuko , Tanaka Kaoru , Hayashi Hidetoshi , Kaneda Hiroyasu , Takezawa Ken , Kuwata Kiyoko , Yamaguchi Haruka , Hatashita Erina , Nishio Kazuto , Nakagawa Kazuhiko 
Published: July 2012

Abstract
Purpose: Anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitors (TKI) such as crizotinib show marked efficacy in patients with non–small cell lung cancer positive for the echinoderm microtubule-associated protein–like 4 (EML4)–ALK fusion protein. However, acquired resistance to these agents has already been described in treated patients, and the mechanisms of such resistance remain largely unknown.
Experimental Design: We established lines of EML4-ALK–positive H3122 lung cancer cells that are resistant to the ALK inhibitor TAE684 (H3122/TR cells) and investigated their resistance mechanism with the use of immunoblot analysis, ELISA, reverse transcription and real-time PCR analysis, and an annexin V binding assay. We isolated EML4-ALK–positive lung cancer cells (K-3) from a patient who developed resistance to crizotinib and investigated their characteristics.
Results: The expression of EML4-ALK was reduced at the transcriptional level, whereas phosphorylation of epidermal growth factor receptor (EGFR), HER2, and HER3 was upregulated, in H3122/TR cells compared with those in H3122 cells. This activation of HER family proteins was accompanied by increased secretion of EGF. Treatment with an EGFR-TKI induced apoptosis in H3122/TR cells, but not in H3122 cells. The TAE684-induced inhibition of extracellular signal–regulated kinase (ERK) and STAT3 phosphorylation observed in parental cells was prevented by exposure of these cells to exogenous EGF, resulting in a reduced sensitivity of cell growth to TAE684. K-3 cells also manifested HER family activation accompanied by increased EGF secretion.
Conclusions: EGF-mediated activation of HER family signaling is associated with ALK-TKI resistance in lung cancer positive for EML4-ALK. Clin Cancer Res; 18(22); 6219–26. ©2012 AACR.
Improving balance control and self-reported lower extremity function in community-dwelling older adults: a randomized control trial
Authors: Melzer Itshak , Oddsson Lars IE 
Published: July 2012

Objectives: To evaluate the effect of a group-based functional and specific balance training programme that included dual-task exercises on balance function in healthy older adults. Design: A single-blind randomized controlled trial. Setting: General community. Participants: Sixty-six community-dwelling older adults (age 77.0 ± 6.5 years), without functional balance impairment were recruited and allocated at random to an intervention group ( n = 33) or a reference group ( n = 33). Intervention: The intervention group received 24 training sessions over three months that included perturbation as well as dual-task exercises. The reference group received no intervention. Outcome measures: The voluntary step execution times during single- and dual-task conditions, stabilogram-diffusion analysis in upright standing, and self-reported physical function; all were measured assessed at baseline and at the end of intervention. The intervention group was retested after six months. Results: Compared with the reference group, participation in group-based functional and specific balance training led to faster voluntary step execution times under single-task ( P = 0.02; effect size (ES) = 0.34) and dual-task ( P = 0.036; ES = 0.55) conditions; lower transition displacement and shorter transition time of the stabilogram-diffusion analysis under eyes-closed conditions ( P = 0.007, ES = 0.30 and P = 0.08, ES = 0.44, respectively); and improved self-reported lower extremity function ( P = 0.006, ES = 0.37). Effects were lost at six-month follow-up. Conclusions: Functional and specific balance training can improve voluntary stepping and balance control in healthy older non-fallers, parameters previously found to be related to increased risk of falls and injury in older adults.
Influences motivating smokers in a radon-affected area to quit smoking
Authors: Groves-Kirkby Christopher J , Timson Karen , Shield George , Denman Antony R , Rogers Stephen , Campbell Jackie , Phillips Paul S , Ekberg Merryn 
Published: July 2012

Aims: Domestic radon gas concentrations in parts of the UK are sufficiently high to increase lung cancer risk among residents, and recent studies have confirmed that the risk of smokers developing lung cancer is significantly enhanced by the presence of radon. Despite campaigns encouraging residents of radon-affected areas (RAEs) to test and remediate their homes, public response to the risks posed by radon remains relatively modest, particularly among smokers and young families, limiting the health benefits and cost-effectiveness achievable by remediation. The observation that smokers, who are most at risk from radon, are not explicitly targeted by current radon remediation campaigns prompted an assessment of the value of smoking-cessation initiatives in reducing radon-induced lung cancers by reaching at-risk subgroups of the population hitherto uninfluenced by radon-awareness programmes. This study addresses the motivation of current quitters in a designated RAE using a postal questionnaire administered around one year after the cessation attempt. Methods: Residents of the Northamptonshire RAE who had joined the smoking-cessation programme between July and September 2006 and who remained verifiably tobacco free at four weeks, were subsequently invited to participate in a questionnaire-based investigation into factors affecting their decision to cease smoking. From an initial population of 445 eligible individuals, 205 of those contacted by telephone after 12 months agreed to complete postal questionnaires, and unsolicited questionnaires were sent to a further 112 participants for whom telephone contact had proved impossible. One hundred and three completed questionnaires were returned and analysed, the principal tools being χ2, Mann-Whitney and Kruskal-Wallis tests. Results: Individuals decide to quit smoking from self-interest, principally on health grounds, and regard the effects of their smoke on others, particularly children and unborn babies, as less significant. The risk of developing respiratory, coronary/cardiac or cancerous conditions provides the greatest motivation to the decision to quit, with knowledge of radon among the lowest-ranked influences. Conclusions: This study confirms that quitters place risks to their personal health as the highest factors influencing their decision to quit, and health professionals should be aware of this when designing smoking-cessation initiatives. As radon risk is ranked very low by quitters, there would appear to be the potential to raise radon awareness through smoking-cessation programmes, with the objective of increasing the uptake and success rate of such programmes and encouraging participation in radon-remediation programmes.
WNT7B in fibroblastic foci of idiopathic pulmonary fibrosis
Authors: Meuten Travis , Hickey Ariel , Franklin Katherine , Grossi Brian , Tobias Jeremy , Newman Donna R , Jennings Samuel H , Correa Maria , Sannes Philip L 
Published: July 2012

Abstract

Background
Idiopathic pulmonary fibrosis (IPF) is a devastating interstitial pneumonia causing a loss of respiratory surface area due to a proliferative fibrotic response involving hyperplastic, hypertrophic, and metaplastic epithelium, cystic honeycomb change, septal expansion, and variable inflammation. Wnt (wingless) signaling glycoproteins are known to be involved in lung development and tissue repair, and are up-regulated in patients with IPF. Based on previous qRT-PCR data showing increased Wnt7B in lungs of IPF patients, a systematic, quantitative examination of its tissue site distribution was undertaken.

Methods
Tissue samples from the Lung Tissue Research Consortium (LTRC) of 39 patients diagnosed with mild to severe IPF/usual interstitial pneumonia (UIP) and 19 normal patients were examined for the immunolocalization of Wnt7B.

Results
In normal lung, moderate Wnt7B reactivity was confined to airway epithelium, smooth muscle of airways and vasculature, and macrophages. IPF lung showed strong Wnt7B reactivity in fibroblastic foci, dysplastic airway and alveolar epithelium, and in highly discrete subepithelial, basement membrane-associated regions. All reactive sites were sized and counted relative to specific microscopic regions. Those in the subepithelial sites were found in significantly greater numbers and larger relative area compared with the others. No reactive sites were present in normal patient controls.

Conclusions
The results demonstrate Wnt7B to be expressed at high concentrations in regions of active hyperplasia, metaplasia, and fibrotic change in IPF patients. In this context and its previously established biologic activities, Wnt7B would be expected to be of potential importance in the pathogenesis of IPF.
Erratum to: A linear classifier based on entity recognition tools and a statistical approach to method extraction in the protein-protein interaction literature
Authors: Lourenço Anália , Conover Michael , Wong Andrew , Nematzadeh Azadeh , Pan Fengxia , Shatkay Hagit , Rocha Luis M 
Published: July 2012

Abstract
Correction to A. Lourenço, M. Conover, A. Wong, A. Nematzadeh, F. Pan, H. Shatkay, and L.M. Rocha."A Linear Classifier Based on Entity Recognition Tools and a Statistical Approach to Method Extraction in the Protein-Protein Interaction Literature". BMC Bioinformatics 2011, 12(Suppl 8):S12. doi:http://10.1186/1471-2105-12-S8-S12.
Microbial transformation from normal oral microbiota to acute endodontic infections
Authors: Hsiao William W L , Li Kevin L , Liu Zhenqiu , Jones Cheron , Fraser-Liggett Claire M , Fouad Ashraf F 
Published: July 2012

Abstract

Background
Endodontic infections are a leading cause of oro-facial pain and tooth loss in western countries, and may lead to severe life-threatening infections. These infections are polymicrobial with high bacterial diversity. Understanding the spatial transition of microbiota from normal oral cavities through the infected root canal to the acute periapical abscess can improve our knowledge of the pathogenesis of endodontic infections and lead to more effective treatment. We obtained samples from the oral cavity, infected root canal and periapical abscess of 8 patients (5 with localized and 3 with systemic infections). Microbial populations in these samples were analyzed using next-generation sequencing of 16S rRNA amplicons. Bioinformatics tools and statistical tests with rigorous criteria were used to elucidate the spatial transition of the microbiota from normal to diseased sites.

Results
On average, 10,000 partial 16S rRNA gene sequences were obtained from each sample. All sequences fell into 11 different bacterial phyla. The microbial diversity in root canal and abscess samples was significantly lower than in the oral samples. Streptococcus was the most abundant genus in oral cavities while Prevotella and Fusobacterium were most abundant in diseased samples. The microbiota community structures of root canal and abscess samples were, however, more similar to each other than to the oral cavity microbiota. Using rigorous criteria and novel bioinformatics tools, we found that Granulicatella adiacens, Eubacterium yurii, Prevotella melaninogenica, Prevotella salivae, Streptococcus mitis, and Atopobium rimae were over-represented in diseased samples.

Conclusions
We used a novel approach and high-throughput methodologies to characterize the microbiota associated normal and diseased oral sites in the same individuals.
A national survey into perioperative anesthetic management of patients with a fractured neck of femur
Authors: Soinikoski Mirka , Kuusniemi Kristiina , Jalonen Jouko , Kuitunen Sari , Tuppurainen Tapani , Leino Kari 
Published: July 2012

Abstract

Background
We made a survey among Finnish anesthesiologists concerning the current perioperative anesthetic practice of hip fracture patients for further development in patient care.

Methods
All members of the Finnish Society of Anesthesiologists with a known e-mail address (786) were invited to participate in an internet-based survey.

Results
The overall response rate was 55% (423 responses); 298 respondents participated in the care of hip fracture patients. Preoperative analgesia was mostly managed with oxycodone and paracetamol; every fifth respondent applied an epidural infusion. Most respondents (98%) employed a spinal block with or without an epidural catheter for intraoperative anesthesia. Midazolam, propofol and/or fentanyl were used for additional sedation. General anesthesia was used rarely. Postoperatively, paracetamol and non-steroidal anti-inflammatory drugs and occasionally peroral oxycodone, were prescribed in addition to epidural analgesia.

Conclusions
The survey suggests that the impact of more individualised analgesia regimens, both preoperatively and postoperatively, should be investigated in further studies.
Worsening angle closure glaucoma and choroidal detachments subsequent to closure of a carotid cavernous fistula
Authors: Thinda Sumeer , Melson Mark R , Kuchtey Rachel W 
Published: July 2012

Abstract

Background
Carotid cavernous fistulas are abnormal communications between the cavernous sinus and the external or internal carotid arteries. Although rare, closure of carotid cavernous fistulas can lead to immediate ocular complications. To our knowledge, our case represents the first report of worsening angle closure glaucoma and choroidal detachments over an extended period of two months subsequent to closure of a carotid cavernous fistula.

Case presentation
A 70-year-old female with a history of primary angle closure glaucoma presented with 4 mm of proptosis, resistance to retropulsion, tortuous corkscrew blood vessels and an orbital bruit of the right eye. Diagnostic cerebral angiogram showed a small indirect Barrow type D right carotid cavernous fistula. Transarterial embolization was planned but repeat cerebral angiography prior to the procedure demonstrated spontaneous partial closure of the carotid cavernous fistula and the procedure was aborted. One month later, our patient was noted to have worsening vision and choroidal detachments of the right eye. She declined further testing and was thus started on self-administered manual carotid jugular compressions. One month later, she developed progressive worsening of her choroidal detachments and angle closure. She eventually opted for surgical intervention but repeat cerebral angiography showed significant thrombosis of the carotid cavernous fistula and no intervention was warranted. Examination two months later showed complete resolution of the choroidal detachments and open angles of both eyes.

Conclusions
Our patient demonstrated worsening angle closure glaucoma and choroidal detachments after spontaneous closure of her carotid cavernous fistula had been noted. Ocular complications, including acute angle closure, have been reported to occur immediately after closure of carotid cavernous fistulas, but not over months as in our patient. It is imperative that individuals who have undergone apparent closure of a carotid cavernous fistula be carefully monitored for worsening ocular complications.
Physical activity and fat mass gain in Mexican school-age children: a cohort study
Authors: Jáuregui Alejandra , Villalpando Salvador , Rangel-Baltazar Eduardo , Lara-Zamudio Yaveth A , Castillo-García Marcia M 
Published: July 2012

Abstract

Background
In México, the prevalence of unhealthy weight increased from 24% at 6 y to 33% at 12 y of age, opening a window of opportunity to better understand the pathogenesis of obesity. The objective of this study was to explore the association between time spent on medium, vigorous physical activity (MVPA) and concurrent gains in BMI, fat mass (FM) and fat-free mass (FFM), alternately, in a cohort of Mexican children followed from kindergarten (baseline) to 2nd grade elementary school (endline).

Methods
The MVPA (5-d accelerometry), BMI, FM and FFM (air displacement plethysmography) were measured at baseline and endline. Associations between gains in BMI, FM and FFM and changes in MVPA were examined using lagged and dynamic regression models, controlling for energy intake and demographic variables.

Results
A total of 205 children were analyzed. Gender affected the effect of MVPA on FM gain. In girls, a high baseline MVPA predicted a lower FM gain (-0.96 kg, p=0.025) compared to low/medium MVPA. Increasing, decreasing or having a persistently high MVPA predicted a lower FM gain (range -1.6 to -1.03 kg, p<0.05) compared to persistently low MVPA. In boys, increases in MVPA were associated with higher gains in BMI (+0.76 kg/m2, p=0.04) and FFM (+1.1 kg, p=0.01) compared to persistently low MVPA.

Conclusion
These results support a protective role of MVPA on FM gain in girls, suggesting that it may play a crucial role in the development of obesity. Further research on the gender effect of MVPA is warranted to better understand its role in the prevention and control of overweight and obesity.
Psychosocial factors associated with becoming a young father in Finland: a nationwide longitudinal study
Authors: Lehti Venla , Sourander Andre , Sillanmäki Lauri , Helenius Hans , Tamminen Tuula , Kumpulainen Kirsti , Almqvist Fredrik 
Published: July 2012

Abstract

Background
Little is known about the characteristics of boys who become fathers at young age. Some studies have suggested that antisocial adolescents are more likely to be young fathers. The aim of this study was to examine the associations of psychosocial factors in childhood with becoming a young father, and to assess if they are independent of criminal behavior in adolescence.

Methods
The baseline assessment in 1989 included 2,946 boys born in 1981. Information about psychiatric symptoms at age eight was collected with Rutter questionnaires from parents and teachers and with the Child Depression Inventory from the children themselves. Data on criminal offenses at age 16–20 was collected from a police register. Register-based follow-up data on becoming a father under the age of 22 was available for 2,721 boys.

Results
The factors measured at age eight, which were associated with becoming a young father independently of adolescent criminality, were conduct problems, being born to a young father and having a mother with a low educational level. Having repeatedly committed criminal offences in adolescence was associated with becoming a young father independently of psychosocial factors in childhood.

Conclusions
Antisocial tendencies both in childhood and adolescence are associated with becoming a young father. They should be taken into consideration when designing preventive or supportive interventions.
Increased expression of the yeast multidrug resistance ABC transporter Pdr18 leads to increased ethanol tolerance and ethanol production in high gravity alcoholic fermentation
Authors: Teixeira Miguel C , Godinho Cláudia P , Cabrito Tânia R , Mira Nuno P , Sá-Correia Isabel 
Published: July 2012

Abstract

Background
The understanding of the molecular basis of yeast tolerance to ethanol may guide the design of rational strategies to increase process performance in industrial alcoholic fermentations. A set of 21 genes encoding multidrug transporters from the ATP-Binding Cassette (ABC) Superfamily and Major Facilitator Superfamily (MFS) in S. cerevisiae were scrutinized for a role in ethanol stress resistance.

Results
A yeast multidrug resistance ABC transporter encoded by the PDR18 gene, proposed to play a role in the incorporation of ergosterol in the yeast plasma membrane, was found to confer resistance to growth inhibitory concentrations of ethanol. PDR18 expression was seen to contribute to decreased 3 H-ethanol intracellular concentrations and decreased plasma membrane permeabilization of yeast cells challenged with inhibitory ethanol concentrations. Given the increased tolerance to ethanol of cells expressing PDR18, the final concentration of ethanol produced during high gravity alcoholic fermentation by yeast cells devoid of PDR18 was lower than the final ethanol concentration produced by the corresponding parental strain. Moreover, an engineered yeast strain in which the PDR18 promoter was replaced in the genome by the stronger PDR5 promoter, leading to increased PDR18 mRNA levels during alcoholic fermentation, was able to attain a 6 % higher ethanol concentration and a 17 % higher ethanol production yield than the parental strain. The improved fermentative performance of yeast cells over-expressing PDR18 was found to correlate with their increased ethanol tolerance and ability to restrain plasma membrane permeabilization induced throughout high gravity fermentation.

Conclusions

PDR18 gene over-expression increases yeast ethanol tolerance and fermentation performance leading to the production of highly inhibitory concentrations of ethanol. PDR18 overexpression in industrial yeast strains appears to be a promising approach to improve alcoholic fermentation performance for sustainable bio-ethanol production.
Hydroxy decenoic acid down regulates gtfB and gtfC expression and prevents Streptococcus mutans adherence to the cell surfaces
Authors: Yousefi Behnam , Ghaderi Shahrooz , Rezapoor-Lactooyi Alireza , Amiri Niusha , Verdi Javad , Shoae-Hassani Alireza 
Published: July 2012

Abstract

Background
10- Hydroxy-2-decenoic acid, an unsaturated fatty acid is the most active and unique component to the royal jelly that has antimicrobial properties. Streptococcus mutans is associated with pathogenesis of oral cavity, gingivoperiodontal diseases and bacteremia following dental manipulations. In the oral cavity, S. mutans colonize the soft tissues including tongue, palate, and buccal mucosa. When considering the role of supragingival dental plaque in caries, the proportion of acid producing bacteria (particularly S. mutans), has direct relevance to the pathogenicity of the plaque. The genes that encode glucosyltransferases (gtf s) especially gtfB and gtfC are important in S. mutans colonization and pathogenesis. This study investigated the hydroxy-decenoic acid (HDA) effects on gtfB and gtfC expression and S. mutans adherence to cells surfaces.

Methods

Streptococcus mutans was treated by different concentrations of HPLC purified HDA supplied by Iran Beekeeping and Veterinary Association. Real time RT-PCR and western blot assays were conducted to evaluate gtfB and gtfC genes transcription and translation before and after HDA treatment. The bacterial attachment to the cell surfaces was evaluated microscopically.

Results
500 μg ml-1 of HDA inhibited gtfB and gtfC mRNA transcription and its expression. The same concentration of HDA decreased 60% the adherence of S. mutans to the surface of P19 cells.

Conclusion
Hydroxy-decenoic acid prevents gtfB and gtfC expression efficiently in the bactericide sub-concentrations and it could effectively reduce S. mutans adherence to the cell surfaces. In the future, therapeutic approaches to affecting S. mutans could be selective and it’s not necessary to put down the oral flora completely.