bluuebunny/crossref_metadata_2025_split huggingface dataset:
Poly (ADP-ribose) polymerase plays an important role in intermittent hypoxia-induced cell death in rat cerebellar granule cells
Authors: Chiu Sheng-Chun , Huang Sung-Ying , Tsai Yu-Chieh , Chen Shee-Ping , Pang Cheng-Yoong , Lien Chih-Feng , Lin Yu-Jou , Yang Kun-Ta 
Published: March 2012

Abstract

Background
Episodic cessation of airflow during sleep in patients with sleep apnea syndrome results in intermittent hypoxia (IH). Our aim was to investigate the effects of IH on cerebellar granule cells and to identify the mechanism of IH-induced cell death.

Methods
Cerebellar granule cells were freshly prepared from neonatal Sprague-Dawley rats. IH was created by culturing the cerebellar granule cells in the incubators with oscillating O2 concentration at 20% and 5% every 30 min for 1-4 days. The results of this study are based on image analysis using a confocal microscope and associated software. Cellular oxidative stress increased with increase in IH. In addition, the occurrence of cell death (apoptosis and necrosis) increased as the duration of IH increased, but decreased in the presence of an iron chelator (phenanthroline) or poly (ADP-ribose) polymerase (PARP) inhibitors [3-aminobenzamide (3-AB) and DPQ]. The fluorescence of caspase-3 remained the same regardless of the duration of IH, and Western blots did not detect activation of caspase-3. However, IH increased the ratio of apoptosis-inducing factor (AIF) translocation to the nucleus, while PARP inhibitors (3-AB) reduced this ratio.

Results
According to our findings, IH increased oxidative stress and subsequently leading to cell death. This effect was at least partially mediated by PARP activation, resulting in ATP depletion, calpain activation leading to AIF translocation to the nucleus.

Conclusions
We suggest that IH induces cell death in rat primary cerebellar granule cells by stimulating oxidative stress PARP-mediated calpain and AIF activation.
Comparative effectiveness research on patients with acute ischemic stroke using Markov decision processes
Authors: Wu Darong , Cai Yefeng , Cai Jianxiong , Liu Qiuli , Zhao Yuanqi , Cai Jingheng , Zhao Min , Huang Yonghui , Ye Liuer , Lu Yubo , Guo Xianping 
Published: March 2012

Abstract

Background
Several methodological issues with non-randomized comparative clinical studies have been raised, one of which is whether the methods used can adequately identify uncertainties that evolve dynamically with time in real-world systems. The objective of this study is to compare the effectiveness of different combinations of Traditional Chinese Medicine (TCM) treatments and combinations of TCM and Western medicine interventions in patients with acute ischemic stroke (AIS) by using Markov decision process (MDP) theory. MDP theory appears to be a promising new method for use in comparative effectiveness research.

Methods
The electronic health records (EHR) of patients with AIS hospitalized at the 2nd Affiliated Hospital of Guangzhou University of Chinese Medicine between May 2005 and July 2008 were collected. Each record was portioned into two "state-action-reward" stages divided by three time points: the first, third, and last day of hospital stay. We used the well-developed optimality technique in MDP theory with the finite horizon criterion to make the dynamic comparison of different treatment combinations.

Results
A total of 1504 records with a primary diagnosis of AIS were identified. Only states with more than 10 (including 10) patients' information were included, which gave 960 records to be enrolled in the MDP model. Optimal combinations were obtained for 30 types of patient condition.

Conclusion
MDP theory makes it possible to dynamically compare the effectiveness of different combinations of treatments. However, the optimal interventions obtained by the MDP theory here require further validation in clinical practice. Further exploratory studies with MDP theory in other areas in which complex interventions are common would be worthwhile.
Keeping participants on board: increasing uptake by automated respondent reminders in an Internet-based Chlamydia Screening in the Netherlands
Authors: Dokkum Nynke FB , Koekenbier Rik H , van den Broek Ingrid VF , van Bergen Jan EAM , Brouwers Elfi EHG , Fennema Johannes SA , Götz Hannelore M , Hoebe Christian JPA , Pars Lydia L , van Ravesteijn Sander M , Op de Coul Eline LM 
Published: March 2012

Abstract

Background
Effectiveness of Chlamydia screening programs is determined by an adequate level of participation and the capturing of high-risk groups. This study aimed to evaluate the contribution of automated reminders by letter, email and short message service (SMS) on package request and sample return in an Internet-based Chlamydia screening among people aged 16 to 29 years in the Netherlands.

Methods
Individuals not responding to the invitation letter received a reminder letter after 1 month. Email- and SMS-reminders were sent to persons who did not return their sample. It was examined to what extent reminders enhanced the response rate (% of package requests) and participation rate (% of sample return). Sociodemographic and behavioural correlates of providing a cell phone number and participation after the reminder(s) were studied by logistic regression models.

Results
Of all respondents (screening round 1: 52,628, round 2: 41,729), 99% provided an email address and 72% a cell phone number. Forty-two percent of all package requests were made after the reminder letter. The proportion of invitees returning a sample increased significantly from 10% to 14% after email/SMS reminders (round 2: from 7% to 10%). Determinants of providing a cell-phone number were younger age (OR in 25-29 year olds versus 16-19 year olds = 0.8, 95%CI 0.8-0.9), non-Dutch (OR in Surinam/Antillean versus Dutch = 1.3, 95%CI 1.2-1.4, Turkish/Moroccan: 1.1, 95%CI 1.0-1.2, Sub Sahara African: 1.5, 95%CI 1.3-1.8, non-Western other 1.1, 95%CI 1.1-1.2), lower educational level (OR in high educational level versus low level = 0.8, 95%CI 0.7-0.9), no condom use during the last contact with a casual partner (OR no condom use versus condom use 1.2, 95%CI 1.1-1.3), younger age at first sexual contact (OR 19 years or older versus younger than 16: 0.7, 95%CI 0.6-0.8). Determinants for requesting a test-package after the reminder letter were male gender (OR female versus male 0.9 95%CI 0.8-0.9), non-Dutch (OR in Surinam/Antillean versus Dutch 1.3, 95%CI 1.2-1.4, Turkish/Moroccan: 1.4, 95%CI 1.3-1.5, Sub Sahara African: 1.4, 95%CI 1.2-1.5, non-Western other: 1.2, 95%CI 1.1-1.2), having a long-term steady partnership (long-term versus short-term.1.2 95%CI 1.1-1.3). Email/SMS reminders seem to have resulted in more men and people aged 25-29 years returning a sample.

Conclusions
Nearly all respondents (99.5%) were reachable by modern communication media. Response and participation rates increased significantly after the reminders. The reminder letters also seemed to result in reaching more people at risk. Incorporation of automated reminders in Internet-based (Chlamydia) screening programs is strongly recommended.
B-cell activity in children with malaria
Authors: Korir Jackson C , Magambo Japhet K , Mwatha Joseph K , Waitumbi John N 
Published: March 2012

AbstractBackgroundRecent studies implicate deficiency of red blood cell (RBC) complement regulatory proteins (CR1 and CD55) in the pathogenesis of malarial anaemia. This study explored the involvement of B cell CD21, which has an analogous role to RBC CR1.MethodsIn a case control study conducted in Kisumu District hospital, western Kenya, children with severe malaria anaemia (SMA) and those with uncomplicated malaria (UM) were assessed by flow cytometry for B cells (CD20+) numbers, expression levels of CD21 and deposition of C3dg and by ELISA for soluble CD21 (sCD21). Paired t tests were used to determine statistical significance at a = 0.05.ResultsChildren with SMA had significantly higher lymphocyte count (9,627.7 ± 8786.1 SD vs. 5,507 ± 2436 SD,P= 0.04 in the UM group) and the computed geometric mean of mature B-cell numbers based on the absolute lymphocyte count was significantly higher for SMA group: 1,823 (1,126 to 2,982, 95% CI) and 826.6 (564 to 1,220, 95% CI)] for UM group (P= 0.003). SMA group also had a higher percentage of CD20+ B cells (26.8 ± 9.7SD vs 20.9 ± 9.01 SD in the UM) (P =0.03), indicating considerable polyclonal B-cell activation. The CD21 median flourescence intensity was lower in the SMA (246.4 ± 87.4 SD vs 369 ± 137.7 SD) (P <0.0001), probably due to complement mediated shaving of CD21 by fixed tissue macrophages. The CD20+ B cells of SMAs had higher levels of the complement split product C3dg (18.35 ± 10 SD vs 11.5 ± 6.8 S.D), (P= 0.0002), confirming possible role of complement in CD21 removal. Unexpectedly, the SMAs had lower levels of sCD21 (226.5 ± 131.5 SD vs 341.4 ± 137.3 SD in the UM) (P< 0.0001), indicating that the shaved CD21 is not released to peripheral circulation.ConclusionsThese results implicate B-cell in pathophysiology of severe malaria that involves increased B-cell proliferation, increased complement deposition and subsequent loss of membrane-bound CD21. The loss of CD21 is not by the classical enzmatic cleavage.
Biological activities of nitidine, a potential anti-malarial lead compound
Authors: Bouquet Jérome , Rivaud Marion , Chevalley Séverine , Deharo Eric , Jullian Valérie , Valentin Alexis 
Published: March 2012

Abstract

Background
Nitidine is thought to be the main active ingredient in several traditional anti-malarial remedies used in different parts of the world. The widespread use of these therapies stresses the importance of studying this molecule in the context of malaria control. However, little is known about its potential as an anti-plasmodial drug, as well as its mechanism of action.

Methods
In this study, the anti-malarial potential of nitidine was evaluated in vitro on CQ-sensitive and -resistant strains. The nitidine's selectivity index compared with cancerous and non-cancerous cell lines was then determined. In vivo assays were then performed, using the four-day Peter's test methodology. To gain information about nitidine's possible mode of action, its moment of action on the parasite cell cycle was studied, and its localization inside the parasite was determined using confocal microscopy. The in vitro abilities of nitidine to bind haem and to inhibit β-haematin formation were also demonstrated.

Results
Nitidine showed similar in vitro activity in CQ-sensitive and resistant strains, and also a satisfying selectivity index (> 10) when compared with a non-cancerous cells line. Its in vivo activity was moderate; however, no sign of acute toxicity was observed during treatment. Nitidine's moment of action on the parasite cycle showed that it could not interfere with DNA replication; this was consistent with the observation that nitidine did not localize in the nucleus, but rather in the cytoplasm of the parasite. Nitidine was able to form a 1-1 complex with haem in vitro and also inhibited β-haematin formation with the same potency as chloroquine.

Conclusion
Nitidine can be considered a potential anti-malarial lead compound. Its ability to complex haem and inhibit β-haematin formation suggests a mechanism of action similar to that of chloroquine. The anti-malarial activity of nitidine could therefore be improved by structural modification of this molecule to increase its penetration of the digestive vacuole in the parasite, where haemoglobin metabolization takes place.
Effect of cancer-associated mutations in the PlexinB1 gene
Authors: Zhou Chun , Wong Oscar Gee-Wan , Masters John R , Williamson Magali 
Published: March 2012

Abstract

Background
Semaphorins act as chemotactic cues for cell movement via their transmembrane receptors, plexins. Somatic missense mutations in the plexinB1 gene coupled with overexpression of the protein frequently occur in prostate tumours, indicating a role for plexinB1 in the pathogenesis of prostate cancer.

Results
Two specific mutations found in prostate cancer enhance RhoD binding and one other mutation results in loss of inhibition of Rac-dependent Pak1 phosphorylation and lamellipodia formation and in impairment of trafficking of plexinB1 to the membrane. None of the three characterised mutations affect PDZRhoGEF binding, RhoA activity, the interaction of plexinB1with the oncogenes ErbB2 or c-Met or ErbB2 phosphorylation. The mutations have the net effect of increasing cell motility by blocking plexinB1-mediated inhibition of Rac while enhancing the interaction with RhoD, an anti-migratory factor.

Conclusions
PlexinB1 mutations block plexinB1-mediated signalling pathways that inhibit cell motility.
Anti-inflammation effects of hydrogen saline in LPS activated macrophages and carrageenan induced paw oedema
Authors: Xu Zheng , Zhou Jiangrui , Cai Jianmei , Zhu Zhen , Sun Xuejun , Jiang Chunlei 
Published: March 2012

Abstract

Background
Oxidative stress is thought to play an important role in the pathogenesis of inflammation. Recent studies have found that hydrogen gas has the effect of eliminating free radicals. Whether hydrogen saline (more convenient to be used than hydrogen gas) has the anti-inflammation effect or not is still unknown.

Methods
Carrageenan-induced paw oedema and LPS-activated macrophages are studied in this article. Injection of carrageenan into the foot of a mouse elicited an acute inflammatory response characterized by increase of foot volume and infiltration of neutrophils. While tumor necrosis factorα(TNF-α) secreted by activated macrophages was determined by ELISA and real-time PCR.

Results
All parameters of inflammation (foot volume, infiltration of neutrophils, amount of TNF-α and the level of TNF-α's mRNA) were attenuated by the hydrogen saline treatment.

Conclusion
As a more convenient way than inhaling H2, hydrogen saline exhibits a protective effect against inflammation and it might provide a novel therapeutic approach for inflammatory diseases.
Differential p38-dependent signalling in response to cellular stress and mitogenic stimulation in fibroblasts
Authors: Faust Dagmar , Schmitt Christina , Oesch Franz , Oesch-Bartlomowicz Barbara , Schreck Ilona , Weiss Carsten , Dietrich Cornelia 
Published: March 2012

Abstractp38 MAP kinase is known to be activated by cellular stress finally leading to cell cycle arrest or apoptosis. Furthermore, a tumour suppressor role of p38 MAPK has been proposed. In contrast, a requirement of p38 for proliferation has also been described. To clarify this paradox, we investigatedstress- andmitogen-induced p38 signalling in the same cell type using fibroblasts. We demonstrate that - in the same cell line - p38 is activated by mitogens or cellular stress, but p38-dependent signalling is different. Exposure to cellular stress, such as anisomycin, leads to a strong and persistent p38 activation independent of GTPases. As a result, MK2 and downstream the transcription factor CREB are phosphorylated. In contrast, mitogenic stimulation results in a weaker and transient p38 activation, which upstream involves small GTPases and is required for cyclin D1 induction. Consequently, the retinoblastoma protein is phosphorylated and allows G1/S transition. Our data suggest a dual role of p38 and indicate that the level and/or duration of p38 activation determines the cellular response, i.e either proliferation or cell cycle arrest.
Design of broadband beamformers with low complexity
Authors: Feng Zhiguo , Yiu Cedric Ka Fai , Teo Kok-Lay , Nordholm Sven 
Published: March 2012

Abstract
In this article, we consider the design of broadband beamformers with low complexity. In fact, the design problem is multi-objective in nature, trading off between speech distortion and noise suppression. Finding a balance between these two objectives is important in order to achieve a desired sound quality. These measures are introduced as the objectives here. The design can then be obtained via a bi-objective integer programming problem, where the coefficients of the filters are expressed as sums of signed powers-of-two terms. We study two different integer spaces and penalty functions for solving the problem. Then, an algorithm based on a discrete filled function is developed for finding the optimal design. In order to illustrate the effectiveness of the algorithm, real data is used and two broadband beamformers are demonstrated.
Advances in using PARP inhibitors to treat cancer
Authors: Kummar Shivaani , Chen Alice , Parchment Ralph E , Kinders Robert J , Ji Jay , Tomaszewski Joseph E , Doroshow James H 
Published: March 2012

Abstract
The poly (ADP-ribose) polymerase (PARP) family of enzymes plays a critical role in the maintenance of DNA integrity as part of the base excision pathway of DNA repair. PARP1 is overexpressed in a variety of cancers, and its expression has been associated with overall prognosis in cancer, especially breast cancer. A series of new therapeutic agents that are potent inhibitors of the PARP1 and PARP2 isoforms have demonstrated important clinical activity in patients with breast or ovarian cancers that are caused by mutations in either the BRCA1 or 2 genes. Results from such studies may define a new therapeutic paradigm, wherein simultaneous loss of the capacity to repair DNA damage may have antitumor activity in itself, as well as enhance the antineoplastic potential of cytotoxic chemotherapeutic agents.
Mouse-adapted scrapie strains 139A and ME7 overcome species barrier to induce experimental scrapie in hamsters and changed their pathogenic features
Authors: Shi Qi , Zhang Bao-Yun , Gao Chen , Zhang Jin , Jiang Hui-Ying , Chen Cao , Han Jun , Dong Xiao-Ping 
Published: March 2012

Abstract

Background
Transmissible spongiform encephalopathy (TSE) diseases are known to be zoonotic diseases that can infect different kinds of animals. The transmissibility of TSE, like that of other infectious diseases, shows marked species barrier, either being unable to infect heterologous species or difficult to form transmission experimentally. The similarity of the amino acid sequences of PrP among species is believed to be one of the elements in controlling the transmission TSE interspecies. Other factors, such as prion strains and host's microenvironment, may also participate in the process.

Methods
Two mouse-adapted strains 139A and ME7 were cerebrally inoculated to Golden hamsters. Presences of scrapie associate fibril (SAF) and PrPSc in brains of the infected animals were tested by TEM assays and Western blots dynamically during the incubation periods. The pathogenic features of the novel prions in hamsters, including electrophoretic patterns, glycosylating profiles, immunoreactivities, proteinase K-resistances and conformational stabilities were comparatively evaluated. TSE-related neuropathological changes were assayed by histological examinations.

Results
After long incubation times, mouse-adapted agents 139A and ME7 induced experimental scrapie in hamsters, respectively, showing obvious spongiform degeneration and PrPSc deposits in brains, especially in cortex regions. SAF and PrPSc in brains were observed much earlier than the onset of clinical symptoms. The molecular characteristics of the newly-formed PrPSc in hamsters, 139A-ha and ME7-ha, were obviously distinct from the original mouse agents, however, greatly similar as that of a hamster-adapted scrapie strain 263 K. Although the incubation times and main disease signs of the hamsters of 139A-ha and ME7-ha were different, the pathogenic characteristics and neuropathological changes were highly similar.

Conclusions
This finding concludes that mouse-adapted agents 139A and ME7 change their pathogenic characteristics during the transmission to hamsters. The novel prions in hamsters' brains obtain new molecular properties with hamster-specificity.
Indicators of the need for ICU admission following suicide bombing attacks
Authors: Bala Miklosh , Willner Dafna , Keidar Asaf , Rivkind Avraham I , Bdolah-Abram Tali , Almogy Gidon 
Published: March 2012

Abstract

Introduction
Critical hospital resources, especially the demand for ICU beds, are usually limited following mass casualty incidents such as suicide bombing attacks (SBA). Our primary objective was to identify easily diagnosed external signs of injury that will serve as indicators of the need for ICU admission. Our secondary objective was to analyze under- and over-triage following suicidal bombing attacks.

Methods
A database was collected prospectively from patients who were admitted to Hadassah University Hospital Level I Trauma Centre, Jerusalem, Israel from August 2001-August 2005 following a SBA. One hundred and sixty four victims of 17 suicide bombing attacks were divided into two groups according to ICU and non-ICU admission.

Results
There were 86 patients in the ICU group (52.4%) and 78 patients in the non-ICU group (47.6%). Patients in the ICU group required significantly more operating room time compared with patients in the non-ICU group (59.3% vs. 25.6%, respectively, p = 0.0003). For the ICU group, median ICU stay was 4 days (IQR 2 to 8.25 days). On multivariable analysis only the presence of facial fractures (p = 0.014), peripheral vascular injury (p = 0.015), injury ≥ 4 body areas (p = 0.002) and skull fractures (p = 0.017) were found to be independent predictors of the need for ICU admission. Sixteen survivors (19.5%) in the ICU group were admitted to the ICU for one day only (ICU-LOS = 1) and were defined as over-triaged. Median ISS for this group was significantly lower compared with patients who were admitted to the ICU for > 1 day (ICU-LOS > 1). This group of over-triaged patients could not be distinguished from the other ICU patients based on external signs of trauma. None of the patients in the non-ICU group were subsequently transferred to the ICU.

Conclusions
Our results show that following SBA, injury to ≥ 4 areas, and certain types of injuries such as facial and skull fractures, and peripheral vascular injury, can serve as surrogates of severe trauma and the need for ICU admission. Over-triage rates following SBA can be limited by a concerted, focused plan implemented by dedicated personnel and by the liberal utilization of imaging studies.
Current and emerging therapeutic strategies for Fanconi anemia
Authors: Shukla Pallavi , Ghosh Kanjaksha , Vundinti Babu R 
Published: March 2012

Abstract
Fanconi Anemia (FA) is a rare disorder with incidence of 1in 350,000 births. It is characterized by progressive bone marrow failure leading to death of many patients in their childhood while development of cancer at later stages of life in some. The treatment of FA is still a medical challenge. Current treatments of FA include androgen administration, hematopoietic growth factors administration and hematopoietic stem cell transplantation (HSCT). Clinical gene therapy trials are still ongoing. The partial success of current therapies has renewed interest in the search for new treatments. Generation of patient-specific induced pluripotent stem (iPS) has shown promising results for cell and gene based therapy. Small molecule interventions have been observed to delay tumor onset in FA. Tumors deficient in FA pathway can be treated by profiling of DNA repair pathway through synthetic lethality mechanism. Targeting toll-like receptor 8 (TLR8) dependent TNFα overexpression is yet another upcoming therapeutic approach to treat FA patients. In conclusion, in the present scenario of treatments available for FA, a proper algorithm of treatment decisions must be followed for better management of FA patients and to ensure their increased survival. Innovative therapeutic approaches that can prevent both anemia and cancer should be developed for more effective treatment of FA.