bluuebunny/crossref_metadata_2025_split huggingface dataset:
Frequent Coinfection with Hepatitis among HIV-Positive Patients in Urumqi, China
Authors: Maimaiti Rena , Zhang Yuexin , Pan Kejun , Wubuli Maimaiti , Andersson Rune 
Published: October 2012

Objective: To analyze the epidemiology and outcome for patients with HIV coinfected with hepatitis in comparison with monoinfected patients. Methods: At the First Affiliated Hospital at Xinjiang Medical University in Urumqi, China, 395 patients were diagnosed with HIV between 2001 and 2010. The main routes of transmission were sexual (30%) and intravenous drug use (33%). The patient records were studied retrospectively. Results: A total of 135 patients had markers of viral hepatitis (34.2%). Abnormal liver function was seen among 48.9% of these patients. Hepatitis B surface antigen was positive in 24 patients (6.1%), with 15 (3.8%) being hepatitis B virus (HBV)-DNA positive, none on tenofovir treatment, because it is still not provided free in Xinjiang. Hepatitis C antibodies were found in 98 patients (24.8%), 46 (11.6%) were hepatitis C virus (HCV)-RNA positive. Only 1 patient had been treated with interferon and ribavirin. Both HBV and HCV were found in 13 (3.3%) of the patients. Conclusions: Nearly half of the HIV patients in Urumqi had markers of hepatitis. Only antiretroviral treatment is provided free, and most of the patients cannot afford the hepatitis treatment they need, which has to be addressed in the treatment programs.
Bacteria differentially induce degradation of Bcl-xL, a survival protein, by human platelets
Authors: Kraemer Bjoern F. , Campbell Robert A. , Schwertz Hansjörg , Franks Zechariah G. , Vieira de Abreu Adriana , Grundler Katharina , Kile Benjamin T. , Dhakal Bijaya K. , Rondina Matthew T. , Kahr Walter H. A. , Mulvey Matthew A. , Blaylock Robert C. , Zimmerman Guy A. , Weyrich Andrew S. 
Published: October 2012

AbstractBacteria can enter the bloodstream in response to infectious insults. Bacteremia elicits several immune and clinical complications, including thrombocytopenia. A primary cause of thrombocytopenia is shortened survival of platelets. We demonstrate that pathogenic bacteria induce apoptotic events in platelets that include calpain-mediated degradation of Bcl-xL, an essential regulator of platelet survival. Specifically, bloodstream bacterial isolates from patients with sepsis induce lateral condensation of actin, impair mitochondrial membrane potential, and degrade Bcl-xL protein in platelets. Bcl-xL protein degradation is enhanced when platelets are exposed to pathogenic Escherichia coli that produce the pore-forming toxin α-hemolysin, a response that is markedly attenuated when the gene is deleted from E coli. We also found that nonpathogenic E coli gain degrading activity when they are forced to express α-hemolysin. Like α-hemolysin, purified α-toxin readily degrades Bcl-xL protein in platelets, as do clinical Staphylococcus aureus isolates that produce α-toxin. Inhibition of calpain activity, but not the proteasome, rescues Bcl-xL protein degradation in platelets coincubated with pathogenic E coli including α-hemolysin producing strains. This is the first evidence that pathogenic bacteria can trigger activation of the platelet intrinsic apoptosis program and our results suggest a new mechanism by which bacterial pathogens might cause thrombocytopenia in patients with bloodstream infections.
The microRNA-30 family targets DLL4 to modulate endothelial cell behavior during angiogenesis
Authors: Bridge Gemma , Monteiro Rui , Henderson Stephen , Emuss Victoria , Lagos Dimitris , Georgopoulou Dimitra , Patient Roger , Boshoff Chris 
Published: October 2012

Abstract
Delta-like 4 (DLL4), a membrane-bound ligand belonging to the Notch signaling family, plays a fundamental role in vascular development and angiogenesis. We identified a conserved microRNA family, miR-30, which targets DLL4. Overexpression of miR-30b in endothelial cells led to increased vessel number and length in an in vitro model of sprouting angiogenesis. Microinjection of miR-30 mimics into zebrafish embryos resulted in suppression of dll4 and subsequent excessive sprouting of intersegmental vessels and reduction in dorsal aorta diameter. Use of a target protector against the miR-30 site within the dll4 3′UTR up-regulated dll4 and synergized with Vegfa signaling knockdown to inhibit angiogenesis. Furthermore, restoration of miR-30b or miR-30c expression during Kaposi sarcoma herpesvirus (KSHV) infection attenuated viral induction of DLL4. Together these results demonstrate that the highly conserved molecular targeting of DLL4 by the miR-30 family regulates angiogenesis.
Systemic delivery of a TLR7 agonist in combination with radiation primes durable antitumor immune responses in mouse models of lymphoma
Authors: Dovedi Simon J. , Melis Monique H. M. , Wilkinson Robert W. , Adlard Amy L. , Stratford Ian J. , Honeychurch Jamie , Illidge Timothy M. 
Published: October 2012

Abstract
Passive immunotherapy with monoclonal antibodies has improved outcome for patients with B-cell malignancies, although many still relapse and little progress has been made with T-cell malignancies. Novel treatment approaches are clearly required in this disease setting. There has been much recent interest in developing therapeutic approaches to enhance antitumor immune responses using novel immunomodulatory agents in combination with standard of care treatments. Here we report that intravenous administration of the Toll-like receptor 7 (TLR7) agonist, R848 in combination with radiation therapy (RT), leads to the longstanding clearance of tumor in T- and B-cell lymphoma bearing mice. In combination, TLR7/RT therapy leads to the expansion of tumor antigen-specific CD8+ T cells and improved survival. Furthermore, those mice that achieve long-term clearance of tumor after TLR7/RT therapy are protected from subsequent tumor rechallenge by the generation of a tumor-specific memory immune response. Our findings demonstrate the potential for enhancing the efficacy of conventional cytotoxic anticancer therapy through combination with a systemically administered TLR7 agonist to improve antitumor immune responses and provide durable remissions.
Classification of non-Hodgkin lymphoma in Central and South America: a review of 1028 cases
Authors: Laurini Javier A. , Perry Anamarija M. , Boilesen Eugene , Diebold Jacques , MacLennan Kenneth A. , Müller-Hermelink H. Konrad , Nathwani Bharat N. , Armitage James O. , Weisenburger Dennis D. 
Published: October 2012

AbstractThe distribution of non-Hodgkin lymphoma (NHL) subtypes differs around the world but a systematic study of Latin America has not been done. Therefore, we evaluated the relative frequencies of NHL subtypes in Central and South America (CSA). Five expert hematopathologists classified consecutive cases of NHL from 5 CSA countries using the WHO classification and compared them to 400 cases from North America (NA). Among the 1028 CSA cases, the proportions of B- and T-cell NHL and the sex distribution were similar to NA. However, the median age of B-cell NHL in CSA (59 years) was significantly lower than in NA (66 years; P < .0001). The distribution of high-grade (52.9%) and low-grade (47.1%) mature B-cell NHL in CSA was also significantly different from NA (37.5% and 62.5%; P < .0001). Diffuse large B-cell lymphoma was more common in CSA (40%) than in NA (29.2%; P < .0001), whereas the frequency of follicular lymphoma was similar in Argentina (34.1%) and NA (33.8%), and higher than the rest of CSA (17%; P < .001). Extranodal NK/T-cell NHL was also more common in CSA (P < .0001). Our study provides new objective evidence that the distribution of NHL subtypes varies significantly by geographic region and should prompt epidemiologic studies to explain these differences.
Platelet secretion is kinetically heterogeneous in an agonist-responsive manner
Authors: Jonnalagadda Deepa , Izu Leighton T. , Whiteheart Sidney W. 
Published: October 2012

Abstract
Platelets release numerous bioactive molecules stored in their granules enabling them to exert a wide range of effects on the vascular microenvironment. Are these granule cargo released thematically in a context-specific pattern or via a stochastic, kinetically controlled process? Here we sought to describe the platelet exocytosis using a systematic examination of platelet secretion kinetics. Platelets were stimulated for increasing times with different agonists (ie, thrombin, PAR1-agonist, PAR4-agonist, and convulxin) and micro-ELISA arrays were used to quantify the release of 28 distinct α-granule cargo molecules. Agonist potency directly correlated with the speed and extent of release. PAR4-agonist induced slower release of fewer molecules, whereas thrombin rapidly induced the greatest release. Cargo with opposing actions (eg, proangiogenic and antiangiogenic) had similar release profiles, suggesting limited thematic response to specific agonists. From the release time-course data, rate constants were calculated and used to probe for underlying patterns. Probability density function and operator variance analyses were consistent with 3 classes of release events, differing in their rates. The distribution of cargo into these 3 classes was heterogeneous, suggesting that platelet secretion is a stochastic process potentially controlled by several factors, such as cargo solubility, granule shape, and/or granule-plasma membrane fusion routes.
Matrix metalloproteases and PAR1 activation
Authors: Austin Karyn M. , Covic Lidija , Kuliopulos Athan 
Published: October 2012

AbstractCardiovascular diseases, including atherothrombosis, are the leading cause of morbidity and mortality in the United States, Europe, and the developed world. Matrix metalloproteases (MMPs) have recently emerged as important mediators of platelet and endothelial function, and atherothrombotic disease. Protease-activated receptor-1 (PAR1) is a G protein-coupled receptor that is classically activated through cleavage of the N-terminal exodomain by the serine protease thrombin. Most recently, 2 MMPs have been discovered to have agonist activity for PAR1. Unexpectedly, MMP-1 and MMP-13 cleave the N-terminal exodomain of PAR1 at noncanonical sites, which result in distinct tethered ligands that activate G-protein signaling pathways. PAR1 exhibits metalloprotease-specific signaling patterns, known as biased agonism, that produce distinct functional outputs by the cell. Here we contrast the mechanisms of canonical (thrombin) and noncanonical (MMP) PAR1 activation, the contribution of MMP-PAR1 signaling to diseases of the vasculature, and the therapeutic potential of inhibiting MMP-PAR1 signaling with MMP inhibitors, including atherothrombotic disease, in-stent restenosis, heart failure, and sepsis.
Detection of nitrogen deficiency QTL in juvenile wild barley introgression linesgrowing in a hydroponic system
Authors: Hoffmann Astrid , Maurer Andreas , Pillen Klaus 
Published: October 2012

Abstract

Background
In this report we studied the genetic regulation of juvenile development of wildbarley introgression lines (S42ILs) under two contrasting hydroponic nitrogen (N)supplies. Ten shoot and root related traits were examined among 42 S42ILs and therecurrent parent ‘Scarlett’. The traits included tiller number, leafnumber, plant height, leaf and root length, leaf to root length ratio, shoots androot dry weight, shoot to root weight ratio, and chlorophyll content. Our aimswere (1) to test the suitability of a hydroponic system for early detection offavourable S42ILs, (2) to locate quantitative trait loci (QTL) that control theexamined traits, (3) to identify favourable wild barley alleles that improve traitperformances in regard to N treatment and, finally, (4) to validate the identifiedQTL through comparison with previously reported QTL originating from the sameparental cross.

Results
The phenotypic data were analysed in a mixed model association study to detectQTL. The post-hoc Dunnett test identified 28 S42ILs that revealed significant(P < 0.01) effects for at least one trait. Forty-three, 41 and 42S42ILs revealed effects across both N treatments, under low N and under high Ntreatment, respectively. Due to overlapping or flanking wild barley introgressionsof the S42ILs, these associations were summarised to 58 QTL. In total, 12 QTL ofthe hydroponic N study corresponded to QTL that were also detected in field trialswith adult plants of a similar S42IL set or of the original S42 population. Forinstance, S42IL-135, -136 and -137, revealed increasing Hsp effects fortiller number, leaf number, leaf length, plant height and leaf to root ratio onthe long arm of chromosome 7H. These QTL correspond to QTL for ears per plant andplant height that were previously detected in field trials conducted with the sameS42ILs or with the S42 population.

Conclusion
Our results suggest that the QTL we identified under hydroponic N cultivationpartly correspond to QTL detected in field experiments. Due to this finding,screening of plants in early developmental stages grown in a hydroponic system maybe a fast and cost effective method for early QTL detection and marker-assistedallelic selection, potentially speeding up elite barley breeding programs.
Variation in endogenous oxidative stress in Escherichia coli natural isolates during growth in urine
Authors: Aubron Cecile , Glodt Jeremy , Matar Corine , Huet Olivier , Borderie Didier , Dobrindt Ulrich , Duranteau Jacques , Denamur Erick , Conti Marc , Bouvet Odile 
Published: October 2012

Abstract

Background
Uropathogenic strains of Escherichia coli cause symptomatic infections whereas asymptomatic bacteriuria (ABU) strains are well adapted for growth in the human urinary tract, where they establish long-term bacteriuria. Human urine is a very complex growth medium that could be perceived by certain bacteria as a stressful environment. To investigate a possible imbalance between endogenous oxidative response and antioxidant mechanisms, lipid oxidative damage estimated as thiobarbituric acid reactive substances (TBARS) content was evaluated in twenty-one E. coli belonging to various pathovars and phylogenetic groups. Antioxidant defense mechanisms were also analysed.

Results
During exponential growth in urine, TBARS level differs between strains, without correlation with the ability to grow in urine which was similarly limited for commensal, ABU and uropathogenic strains. In addition, no correlation between TBARS level and the phylogroup or pathogenic group is apparent. The growth of ABU strain 83972 was associated with a high level of TBARS and more active antioxidant defenses that reduce the imbalance.

Conclusions
Our results indicate that growth capacity in urine is not a property of ABU strains. However, E. coli isolates respond very differently to this stressful environment. In strain ABU 83972, on one hand, the increased level of endogenous reactive oxygen species may be responsible for adaptive mutations. On the other hand, a more active antioxidant defense system could increase the capacity to colonize the bladder.
Phase I trial of split-dose induction docetaxel, cisplatin, and 5-fluorouracil (TPF) chemotherapy followed by curative surgery combined with postoperative radiotherapy in patients with locally advanced oral and oropharyngeal squamous cell cancer (TISOC-1)
Authors: Oertel Katrin , Spiegel Karin , Schmalenberg Harald , Dietz Andreas , Maschmeyer Georg , Kuhnt Thomas , Sudhoff Holger , Wendt Thomas G , Guntinas-Lichius Orlando 
Published: October 2012

Abstract

Background
Induction chemotherapy (ICT) with docetaxel, cisplatin and fluorouracil (TPF) followed by radiotherapy is an effective treatment option for unresectable locally advanced head and neck cancer. This phase I study was designed to investigate the safety and tolerability of a split-dose TPF ICT regimen prior to surgery for locally advanced resectable oral and oropharyngeal cancer.

Methods
Patients received TPF split on two dosages on day 1 and 8 per cycle for one or three 3-week cycles prior to surgery and postoperative radiotherapy or radiochemotherapy. Docetaxel was escalated in two dose levels, 40 mg/m2 (DL 0) and 30 mg/m2 (DL −1), plus 40 mg/m2 cisplatin and 2000 mg/m2 fluorouracil per week using a 3 +3 dose escalation algorithm.

Results
Eighteen patients were enrolled and were eligible for toxicity and response. A maximum tolerated dose of 30 mg/m2 docetaxel per week was reached. The most common grade 3+ adverse event was neutropenia during ICT in 10 patients. Surgery reached R0 resection in all cases. Nine patients (50%) showed complete pathologic regression.

Conclusions
A split-dose regime of TPF prior to surgery is feasible, tolerated and merits additional investigation in a phase II study with a dose of 30 mg/m docetaxel per week.

Trial registration number
NCT01108042 (ClinicalTrials.gov Identifier)
L-DOPA decarboxylase mRNA expression is associated with tumor stage and size in head and neck squamous cell carcinoma: a retrospective cohort study
Authors: Geomela Panagiota-Aikaterini , Kontos Christos K , Yiotakis Ioannis , Fragoulis Emmanuel G , Scorilas Andreas 
Published: October 2012

Abstract

Background
Head and neck squamous cell carcinoma (HNSCC) represents one of the most commonly diagnosed malignancies worldwide. The DDC gene encodes L-DOPA decarboxylase, an enzyme catalyzing the decarboxylation of L-DOPA to dopamine. We have recently shown that DDC mRNA is a significant predictor of patients’ prognosis in colorectal adenocarcinoma and prostate cancer. The aim of the current study was to analyze the DDC mRNA expression in HNSCC patients.

Methods
53 malignant tumors were resected from the larynx, pharynx, tongue, buccal mucosa, parotid glands, and nasal cavity, as well as from 34 adjacent non-cancerous tissues of HNSCC patients, and were homogenized. Total RNA was isolated and converted into first-strand cDNA. An ultrasensitive real-time PCR method based on the SYBR Green chemistry was used for DDC mRNA quantification in head and neck tissue specimens. Relative quantification was performed using the comparative Ct (2-ddCt) method.

Results

DDC mRNA levels were lower in squamous cell carcinomas (SCCs) of the larynx and tongue than in adjacent non-cancerous tissue specimens. Furthermore, low DDC mRNA expression was noticed in laryngeal and tongue tumors of advanced TNM stage or bigger size, compared to early-stage or smaller tumors, respectively. No statistically significant differences were observed between SCCs resected from pharynx, buccal mucosa, or nasal cavity, and their normal counterparts.

Conclusion
This is the first study examining the DDC mRNA expression in HNSCC. According to our results, DDC mRNA expression may constitute a potential prognostic biomarker in tongue and/or larynx SCCs, which principally represent the overwhelming majority of HNSCC cases.
Chotosan ameliorates cognitive and emotional deficits in an animal model of type 2 diabetes: possible involvement of cholinergic and VEGF/PDGF mechanisms in the brain
Authors: Zhao Qi , Niu Yimin , Matsumoto Kinzo , Tsuneyama Koichi , Tanaka Ken , Miyata Takeshi , Yokozawa Takako 
Published: October 2012

Abstract

Background
Diabetes is one of the risk factors for cognitive deficits such as Alzheimer’s disease. To obtain a better understanding of the anti-dementia effect of chotosan (CTS), a Kampo formula, we investigated its effects on cognitive and emotional deficits of type 2 diabetic db/db mice and putative mechanism(s) underlying the effects.

Methods
Seven-week-old db/db mice received daily administration of CTS (375 – 750 mg/kg, p.o.) and the reference drug tacrine (THA: 2.5 mg/kg, i.p.) during an experimental period of 7 weeks. From the age of 9-week-old, the animals underwent the novel object recognition test, the modified Y-maze test, and the water maze test to elucidate cognitive performance and the elevated plus maze test to elucidate anxiety-related behavior. After completing behavioral studies, Western blotting and immunohistochemical studies were conducted.

Results
Compared with age-matched non-diabetic control strain (m/m) mice, db/db mice exhibited impaired cognitive performance and an increased level of anxiety. CTS ameliorated cognitive and emotional deficits of db/db mice, whereas THA improved only cognitive performance. The phosphorylated levels of Akt and PKCα in the hippocampus were significantly lower and higher, respectively, in db/db mice than in m/m mice. Expression levels of the hippocampal cholinergic marker proteins and the number of the septal cholinergic neurons were also reduced in db/db mice compared with those in m/m mice. Moreover, the db/db mice had significantly reduced levels of vasculogenesis/angiogenesis factors, vascular endothelial growth factor (VEGF), VEGF receptor type 2, platelet-derived growth factor-B, and PDGF receptor β, in the hippocampus. CTS and THA treatment reversed these neurochemical and histological alterations caused by diabetes.

Conclusion
These results suggest that CTS ameliorates diabetes-induced cognitive deficits by protecting central cholinergic and VEGF/PDGF systems via Akt signaling pathway and that CTS exhibits the anxiolytic effect via neuronal mechanism(s) independent of cholinergic or VEGF/PDGF systems in db/db mice.
Genetic diversity and recombination analysis of sweepoviruses from Brazil
Authors: Albuquerque Leonardo C , Inoue-Nagata Alice K , Pinheiro Bruna , Resende Renato O , Moriones Enrique , Navas-Castillo Jesús 
Published: October 2012

Abstract

Background
Monopartite begomoviruses (genus Begomovirus, family Geminiviridae) that infect sweet potato (Ipomoea batatas) around the world are known as sweepoviruses. Because sweet potato plants are vegetatively propagated, the accumulation of viruses can become a major constraint for root production. Mixed infections of sweepovirus species and strains can lead to recombination, which may contribute to the generation of new recombinant sweepoviruses.

Results
This study reports the full genome sequence of 34 sweepoviruses sampled from a sweet potato germplasm bank and commercial fields in Brazil. These sequences were compared with others from public nucleotide sequence databases to provide a comprehensive overview of the genetic diversity and patterns of genetic exchange in sweepoviruses isolated from Brazil, as well as to review the classification and nomenclature of sweepoviruses in accordance with the current guidelines proposed by the Geminiviridae Study Group of the International Committee on Taxonomy of Viruses (ICTV). Co-infections and extensive recombination events were identified in Brazilian sweepoviruses. Analysis of the recombination breakpoints detected within the sweepovirus dataset revealed that most recombination events occurred in the intergenic region (IR) and in the middle of the C1 open reading frame (ORF).

Conclusions
The genetic diversity of sweepoviruses was considerably greater than previously described in Brazil. Moreover, recombination analysis revealed that a genomic exchange is responsible for the emergence of sweepovirus species and strains and provided valuable new information for understanding the diversity and evolution of sweepoviruses.