bluuebunny/crossref_metadata_2025_split huggingface dataset:
Review of aerobic glycolysis and its key enzymes – new targets for lung cancer therapy
Authors: Li Xue‐bing , Gu Jun‐dong , Zhou Qing‐hua 
Published: June 2014

AbstractMost tumor cells show different metabolic pathways than normal cells. Even under the conditions of sufficient oxygen, they produce energy by a high rate of glycolysis followed by lactic acid fermentation in the cytosol, which is known as aerobic glycolysis or the Warburg effect. Lung cancer is a malignant tumor with one of the highest incidence and mortality rates in the world at present. However, the exact mechanisms underlying lung cancer development remain unclear. The three key enzymes of glycolysis are hexokinase, phosphofructokinase, and pyruvate kinase. Lactate dehydrogenase catalyzes the transfer of pyruvate to lactate. All four enzymes have been reported to be overexpressed in tumors, including lung cancer, and can be regulated by many oncoproteins to promote tumor proliferation, migration, and metastasis with dependence or independence of glycolysis. The discovery of aerobic glycolysis in the 1920s has provided new means and potential therapeutic targets for lung cancer.
An automated approach towards measuring time‐activity budgets in colonial seabirds
Authors: Rishworth Gavin M. , Tremblay Yann , Green David B. , Pistorius Pierre A. 
Published: June 2014

Summary

Seabird proxies have the potential to act as useful and cost‐effective indicators of the state of the marine environment. Seabird time‐activity budgets, in particular, reflect short‐term changes in prey conditions.

We tested an automated technique for long‐term continuous recording of Cape gannet, Morus capensis, time‐activity budgets using coded very high frequency (VHF) transmitters allowing for simultaneous monitoring of a large sample of study birds.

Radiotransmitters attached to leg‐rings had no impact on adult foraging trip and nest attendance durations, breeding success or chick growth. Furthermore, frequencies of nest attendance and foraging trip durations estimated by the VHF logging system were no different to those estimated from hourly direct observations.

Using time‐depth recorders, the relationship between the time that birds rested on the sea surface in relation to foraging trip duration was assessed. Trip duration during chick rearing was clearly an accurate proxy for foraging effort.

The VHF monitoring system provides a simple method of accurately assessing the time‐activity budgets of colonial seabirds, which can be expanded to a range of other colonially breeding taxa. In the case of seabirds, this approach can potentially provide sensitive, real‐time indicators of prey abundance for fisheries management.
Mirrored: Crisis in the Congo
Authors: Abram Dorothy 
Published: June 2014

SummarySet on a hillside in the Congo, a woman hoes her cassava garden. She is interrupted by the arrival of western UN and other NGO officials (represented by the audience) who have come to assess conditions in the land. Tumaini (her name means “hope”) tells her story of rape, pregnancy, stigma, and social shunning that she has endured. In the process of caring for the child that resulted from the rape by Interhamure militia, Tumaini discovers that her only hope rests in renouncing the stigma that the village has put on her and her child. By seeing herself in her child, as a freshly‐harvested cassava root, she regains the love she needs to nurture her child—and herself—and names her Tumaini.
One‐year outcome of two different initial dosing regimens of intravitreal ranibizumab for myopic choroidal neovascularization
Authors: Kung Ya‐Hsin , Wu Tsung‐Tien , Huang Ya‐Hui 
Published: June 2014

AbstractPurposeTo evaluate and compare the 12‐month outcomes of two different initial dosing regimens of intravitreal ranibizumab for myopic choroidal neovascularization (CNV).MethodsWe retrospectively reviewed the medical records of 46 consecutive, treatment‐naive eyes which received intravitreal ranibizumab for subfoveal and juxtafoveal CNV secondary to pathologic myopia with a follow‐up of 12 months. Two groups were created according to different initial dosing regimens: group 1 included 25 eyes treated by a single intravitreal injection; group 2 included 21 eyes treated by three consecutive monthly injections. Additional injections were performed if needed. Patients' demographic data, best‐corrected visual acuity (BCVA), recurrence of CNV and total number of treatments were recorded and evaluated.ResultsThere was no significant difference between two groups among baseline demographic data. At 12 months, the mean logMAR BCVA improved from 0.58 to 0.23 in group 1 and from 0.55 to 0.22 in group 2 (both p < 0.001; Wilcoxon signed‐rank test). The mean logMAR BCVA at 12 months did not differ significantly. The average number of injections was 2.32 (SD 1.22) in group 1 and 3.57 (SD 1.12) in group 2 (p = 0.001; two‐tailed t‐test). During the follow‐up, 17 of 25 eyes in group 1 and 5 of 21 eyes in group 2 received additional injections (p = 0.004).ConclusionsSimilar visual improvement was achieved in both groups. Although the eyes with a loading dose of 3 monthly injections required a higher number of total injections over 1 year, there was a much lower rate of retreatment needed.
The spectrum of somatic mutations in high‐risk acute myeloid leukaemia with ‐7/del(7q)
Authors: McNerney Megan E. , Brown Christopher D. , Peterson April L. , Banerjee Mekhala , Larson Richard A. , Anastasi John , Le Beau Michelle M. , White Kevin P. 
Published: June 2014

Summary‐7/del(7q) occurs in half of myeloid malignancies with adverse‐risk cytogenetic features and is associated with poor survival. We identified the spectrum of mutations that co‐occur with ‐7/del(7q) in 40 patients with de novo or therapy‐related myeloid neoplasms. ‐7/del(7q) leukaemias have a distinct mutational profile characterized by low frequencies of alterations in genes encoding transcription factors, cohesin and DNA‐methylation‐related proteins. In contrast, RAS pathway activating mutations occurred in 50% of cases, a significantly higher frequency than other acute myeloid leukaemias and higher than previously reported. Our data provide guidance for which pathways may be most relevant in the treatment of adverse‐risk myeloid leukaemia.
Evaluation of peripheral versus central effects of GABAB receptor activation using a novel, positive allosteric modulator of the GABAB receptor ADX71943, a pharmacological tool compound with a fully peripheral activity profile
Authors: Kalinichev M , Donovan‐Rodriguez T , Girard F , Riguet E , Rouillier M , Bournique B , Haddouk H , Mutel V , Poli S 
Published: June 2014

Background and PurposeThe GABAB receptor agonist, baclofen, has shown promising effects in patients suffering from pain, post‐traumatic stress disorder, alcoholism, overactive bladder and gastroesophageal reflux disease. However, baclofen's short duration of action and side effects limit its wider use. Here we characterized a novel, GABAB receptor positive allosteric modulator (PAM) ADX71943.Experimental ApproachIn vitro, ADX71943 was assessed for pharmacological activity and selectivity using recombinant and native GABAB receptors. In vivo ADX71943 was assessed in the acetic acid‐induced writhing (AAW) test in mice and formalin tests (FTs) in mice and rats. Marble burying (MB) and elevated plus maze (EPM) tests, rotarod, spontaneous locomotor activity (sLMA) and body temperature (BT) tests in mice and rats were used to investigate centrally‐mediated effects.Key ResultsIn vitro, in the presence of GABA, ADX71943 increased the potency and efficacy of agonists and showed selectivity at the GABAB receptor. ADX71943 reduced pain‐associated behaviours in AAW; an effect blocked by GABAB receptor antagonist CGP63360. ADX71943 reduced pain in the FT in mice and rats, but was inactive in the MB and EPM despite reaching high concentrations in plasma. ADX71943 had no effect on BT, rotarod and sLMA.Conclusions and ImplicationsADX71943 showed consistent and target‐related efficacy in tests of disorders that have a significant peripheral component (acute and chronic pain), while having no effect in those associated with centrally‐mediated anxiety‐like reactivity and side effects. Thus, ADX71943 is a useful pharmacological tool for delineation of peripherally‐ versus centrally‐mediated effects of GABAB receptor activation.
Synthetic gestagens exert differential effects on arterial thrombosis and aortic gene expression in ovariectomized apolipoprotein E‐deficient mice
Authors: Freudenberger T , Deenen R , Kretschmer I , Zimmermann A , Seiler L F , Mayer P , Heim H‐K , Köhrer K , Fischer J W 
Published: June 2014

Background and PurposeCombined hormone replacement therapy with oestrogens plus the synthetic progestin medroxyprogesterone acetate (MPA) is associated with an increased risk of thrombosis. However, the mechanisms of this pro‐thrombotic effect are largely unknown. The purpose of this study was to: (i) compare the pro‐thrombotic effect of MPA with another synthetic progestin, norethisterone acetate (NET‐A), (ii) determine if MPA's pro‐thrombotic effect can be antagonized by the progesterone and glucocorticoid receptor antagonist mifepristone and (iii) elucidate underlying mechanisms by comparing aortic gene expression after chronic MPA with that after NET‐A treatment.Experimental ApproachFemale apolipoprotein E‐deficient mice were ovariectomized and treated with placebo, MPA, a combination of MPA + mifepristone or NET‐A for 90 days on a Western‐type diet. Arterial thrombosis was measured in vivo in a photothrombosis model. Aortic gene expression was analysed using microarrays; GeneOntology and KEGG pathway analyses were conducted.Key ResultsMPA's pro‐thrombotic effects were prevented by mifepristone, while NET‐A did not affect arterial thrombosis. Aortic gene expression analysis showed, for the first time, that gestagens induce similar effects on a set of genes potentially promoting thrombosis. However, in NET‐A‐treated mice other genes with potentially anti‐thrombotic effects were also affected, which might counterbalance the effects of the pro‐thrombotic genes.Conclusions and ImplicationsThe pro‐thrombotic effects of synthetic progestins appear to be compound‐specific, rather than representing a class effect of gestagens. Furthermore, the different thrombotic responses elicited by MPA and NET‐A might be attributed to a more balanced, ‘homeostatic’ gene expression induced in NET‐A‐ as compared with MPA‐treated mice.
Synthesis and Evaluation of a New Series of 3,5‐bis((5‐bromo‐6‐methyl‐2‐t‐aminopyrimidin‐4‐yl)thio)‐4H‐1,2,4‐triazol‐4‐amines and their Cyclized Products ‘Pyrimidinylthio Pyrimidotriazolothiadiazines’ as 15‐ Lipo‐Oxygenase Inhibitors
Authors: Asghari Tayebe , Bakavoli Mehdi , Rahimizadeh Mohammad , Eshghi Hossein , Saberi Sattar , Karimian Azam , Hadizadeh Farzin , Ghandadi Moreteza 
Published: June 2014

A series of new 3,5‐bis((5‐bromo‐6‐methyl‐2‐t‐aminopyrimidin‐4‐yl)thio)‐4H‐1,2,4‐triazol‐4‐amines and their cyclized products ‘pyrimidinylthio pyrimidotriazolothiadiazines’ were designed, synthesized, and evaluated as potential inhibitors of 15‐lipo‐oxygenase (15‐LO). Their syntheses started by initial condensation of 2:1 equivalents of pyrimidine with triazole and subsequent nucleophilic displacement of the chlorine atoms with secondary amines and finally cyclocondensation in the presence of NaNH2. The compounds 4d and 4f showed the best IC50 of 15‐LO inhibition (IC50 = 9 and 12 μm, respectively). Compounds 4a–g were docked into 15‐LO. We suggest that the hydrogen bonds in quaternary nitrogen of piperazine ring of compounds 4d and 4f appear to play major role in lipo‐oxygenase inhibition by this set of synthesized analogs and hydrophobic nature of this protein's binding site should be considered in ongoing investigations.
Expression and regulation of triggering receptor expressed on myeloid cells 1 in periodontal diseases
Authors: Willi M , Belibasakis G N , Bostanci N 
Published: June 2014

Summary
Periodontitis is an inflammatory infectious disease that destroys the tooth-supporting tissues. It is caused by multi-species subgingival biofilms that colonize the tooth surface. Porphyromonas gingivalis, Treponema denticola and Tannerella forsythia (i.e. ‘red complex’ bacteria) are characteristic subgingival biofilm species. The triggering receptor expressed on myeloid cells 1 (TREM-1) is a cell surface receptor of the immunoglobulin superfamily, with a role in the amplification of proinflammatory cytokine production during infection. This study aimed to investigate TREM-1 mRNA expression in gingival tissues from patients with chronic periodontitis, generalized aggressive periodontitis and healthy subjects and its correlation with the levels of periodontal pathogens in the tissue. A further aim was to investigate the regulation of TREM-1 in human monocytic cells (MM6) challenged with an in-vitro subgingival biofilm model. Gingival tissue TREM-1 expression was increased in both chronic and aggressive periodontitis, compared to health, and correlated with the levels of the ‘red complex’ species in the tissue. No significant differences were detected between the two forms of periodontitis. Biofilm-challenged MM6 cells exhibited higher TREM-1 expression and secretion compared to controls, with partial involvement of the ‘red complex’. Engagement or inhibition of TREM-1 affected the capacity of the biofilms to stimulate interleukin (IL)-1β, but not IL-8, secretion by the cells. In conclusion, this study reveals that TREM-1 tissue expression is enhanced in periodontal disease, and correlates with the level of periodontal pathogens. It also provides a mechanistic insight into the regulation of TREM-1 expression and the associated IL-1β production in biofilm-challenged monocytes.
The effects of good glycaemic control on left ventricular and coronary endothelial functions in patients with poorly controlled Type 2 diabetes mellitus
Authors: Erdogan Dogan , Akcay Salaheddin , Yucel Habil , Ersoy I. Hakkı , Icli Atilla , Kutlucan Ali , Arslan Akif , Yener Mahmut , Ozaydin Mehmet , Tamer M. Numan 
Published: June 2014

SummaryObjectiveDiabetics are at risk for developing overt heart failure and subclinical left ventricular (LV) dysfunction. Also, impaired coronary flow reserve (CFR) reflecting coronary microvascular dysfunction is common in diabetics. However, no substantial data regarding the effects of good glycaemic control on subclinical LV dysfunction and CFR are available.ContextTo investigate whether good glycaemic control had favourable effects on subclinical LV dysfunction and CFR.DesignProspective, open‐label, follow‐up study.PatientsDiabetics (n = 202) were classified based on baseline HbA1C levels: patients with good (group 1) (<7·0%) and poor glycaemic control (≥7·0%).MeasurementsAll patients underwent echocardiographic examination at baseline evaluation, and it was repeated at months 6 and 12. Based on HbA1C levels obtained at month 6, the patients with poor glycaemic control were divided into two groups: achieved (group 2) and not achieved good glycaemic control (group 3).ResultsThe groups were comparable with respect to diastolic function parameters including left atrium diameter, mitral E/A, Sm, Em/Am, E/E′ and Tei index, and these parameters did not significantly change at follow‐up in the groups. At baseline, CFR was slightly higher in group 1 than in group 2 and group 3, but it did not reach statistically significant level. At follow‐up, CFR remained unchanged in group 1 (P = 0·58) and group 3 (P = 0·86), but increased in group 2 (P = 0·02: month 6 vs baseline and P = 0·004: month 12 vs baseline).ConclusionsDiabetics with poor and good glycaemic control were comparable with respect to echocardiographic parameters reflecting subclinical LV dysfunction, and good glycaemic control did not affect these parameters. However, good glycaemic control improved CFR.
Thyroid imaging reporting and data system score combined with Bethesda system for malignancy risk stratification in thyroid nodules with indeterminate results on cytology
Authors: Maia Frederico F. R. , Matos Patrícia S. , Pavin Elizabeth J. , Zantut‐Wittmann Denise E. 
Published: June 2014

SummaryContextThe thyroid imaging reporting and data system (TI‐RADS) was designed to better select patients who had undergone fine‐needle aspiration biopsies (FNABs) with high sensitivity and accuracy. However, the combination of TI‐RADS scores and Bethesda system categories in indeterminate thyroid nodules has not been examined extensively.ObjectiveThis study aimed to stratify indeterminate thyroid nodules (Bethesda categories III, IV and V) according to risk of malignancy as determined by combining TI‐RADS score with Bethesda system classification.DesignRetrospective study. Histopathological, cytological and ultrasound (US) data were available for 242 cases after surgery, including 136 indeterminate nodules.MethodsAll thyroid cytopathological slides and US reports were reviewed and classified according to Bethesda system and TI‐RADS categories. The malignancy rate was determined for each Bethesda category, TI‐RADS score and both methods combined of indeterminate nodules.ResultsThe malignancy rates were 8·7%, 51·3% and 67·5% for Bethesda categories III, IV and V, respectively. Based on histopathological comparison, the accuracy was 66·7% for TI‐RADS greyscale. TI‐RADS 3 and 4A scores were observed in 80% of Bethesda III cases, which led to 80% sensitivity and 90% of negative predictive value (NPV). In contrast, for nodules scored as TI‐RADS 4B and 5, the combined cytological results of Bethesda IV and V resulted in a higher risk of malignancy (75% and 76·9%, respectively, P < 0·001).ConclusionsIn view of the high NPV of TI‐RADS 3/4A only in Bethesda III category, a surgical approach could be considered for lesions defined as Bethesda III, IV and V when TI‐RADS 4B and 5 were concomitant.
BMP4 promotes SSEA‐1+hUC‐MSC differentiation into male germ‐like cells in vitro
Authors: Li N. , Pan S. , Zhu H. , Mu H. , Liu W. , Hua J. 
Published: June 2014

AbstractObjectivesRecent studies have demonstrated that primordial germ cells (PGC) can be differentiated from human umbilical cord mesenchymal stem cells (hUC‐MSCs), and embryonic stem cells (ESCs) in vitro. Nevertheless, efficiencies were low and unstable. Here, whether hUC‐MSCs can be induced to differentiate into germ‐like cells with the aid of bone morphogenetic protein (BMP4) was investigated.Materials and methodsHuman umbilical cord mesenchymal stem cells were freshly isolated and cultured with BMP4. SSEA‐1+/− cells were purified using magnetic‐activated cell sorting (MACS) from the hUC‐MSCs, and further induced with BMP4. Quantitative real‐time PCR (qRT‐PCR) and immunofluorescence analysis were used to determine PGC and germ‐like cell‐specific markers.ResultsHuman umbilical cord mesenchymal stem cells differentiated into SSEA‐1+ spherical PGC‐like cells efficiently with 12.5 ng/ml BMP4. qRT‐PCR and immunofluorescence analysis demonstrated that SSEA‐1+ cells expressed higher levels of PGC‐specific markers than SSEA‐1− cells. Furthermore, SSEA‐1+ cells were induced with BMP4 to differentiate into STRA8, SCP3, DMRT1 and PLZF‐positive male germ‐like cells, and some sperm‐like cells were obtained by 7–14 days after induction.ConclusionThese results suggest that SSEA‐1+ hUC‐MSCs can differentiate into male germ‐like cells in the presence of BMP4. This study provides an efficient protocol to study germ‐cell development using hUC‐MSCs.
Infection and rejection risk after cardiac transplantation with induction vs. no induction: a multi‐institutional study
Authors: Mazimba Sula , Tallaj Jose A. , George James F. , Kirklin James K. , Brown Robert N. , Pamboukian Salpy V. 
Published: June 2014

AbstractData from Cardiac Transplant Research Database (CTRD) were analyzed from 1999 to 2006 to examine the effects of different induction strategies at the time of cardiac transplantation. A total of 2090 primary heart transplants were categorized by induction with interleukin‐2 receptor blocker (IL‐2RB), antithymocyte globulin (ATG), or no induction (NI). Probabilities for rejection and infection were estimated with parametric time‐related models. Using these models, hazard was calculated for two theoretical patient profiles, one at lower risk for rejection and higher risk of infection (Profile 1) and higher risk for rejection and lower risk of infection (Profile 2). Of the 2090 transplants, 49.8% (1095) did not receive induction, 27.3% (599) received IL‐2RB, and 18.0% (396) received ATG. Profile 1 patients had lower hazard for rejection with IL‐2RB compared to ATG and NI (p < 0.01), but at the cost of increased risk of infection (5.0 vs. 1.8 vs. 1.6, respectively, at four wk, p < 0.01). Profile 2 patients experienced a fivefold decreased hazard for rejection when treated with IL‐2RB compared with ATG and NI (p < 0.01). In patients at high risk of infection, IL‐2RB reduced risk of rejection but at the expense of increased hazard for infection.
Assessment of endothelial dysfunction in Asian Indian patients with chronic kidney disease and changes following renal transplantation
Authors: Sharma Jugal , Kapoor Aditya , Muthu Ranjanee , Prasad Narayan , Sinha Archana , Khanna Roopali , Kumar Sudeep , Garg Naveen , Tewari Satyendra , Sharma Raj K. , Goel Pravin 
Published: June 2014

AbstractBackgroundEndothelial dysfunction may explain increased cardiovascular risk in patients with chronic kidney disease (CKD).MethodsBrachial artery was imaged during reactive hyperemia (endothelium‐dependent, flow‐mediated dilatation, FMD) and during glyceryl trinitrate‐mediated dilatation (nitroglycerine‐mediated dilatation, NMD, endothelium‐independent) in 108 patients with CKD and three months following renal transplantation (RT) in 60 of them.ResultsPatients with CKD had significantly lower FMD vs. controls (9.1% vs. 18.3%, p < 0.001) while NMD was comparable (19.8% vs. 21.8%, p = ns). Impaired FMD (<4.5%) was observed in 26.8% patients with CKD and was more common in those on hemodialysis (HD; 28.4% vs. 15.4%) vs. those not on dialysis. FMD for patients with glomerular filtration rate (GFR) 15–60 vs. <15 mL/min/1.73 m2 was 12.9% and 8.8% (p = 0.05; respectively −29% and −52% lower vs. controls), indicating reduced FMD with increasing CKD severity. There was +72% increase in FMD following RT (9.1 to 15.7%, p < 0.001) while mean NMD was unchanged. Following RT, only 3.3% had impaired FMD.ConclusionsPatients with CKD have endothelial dysfunction as evidenced by reduced FMD. Decreased FMD indicating worsening endothelial function was noted with increasing severity of CKD. Within three months of RT, there was significant improvement in FMD, while NMD values did not change.