bluuebunny/crossref_metadata_2025_split huggingface dataset:
Transcriptional Responses toward Diffusible Signals from Symbiotic Microbes Reveal MtNFP- and MtDMI3-Dependent Reprogramming of Host Gene Expression by Arbuscular Mycorrhizal Fungal Lipochitooligosaccharides
Authors: Czaja Lisa F. , Hogekamp Claudia , Lamm Patrick , Maillet Fabienne , Martinez Eduardo Andres , Samain Eric , Dénarié Jean , Küster Helge , Hohnjec Natalija 
Published: June 2012

Abstract
The formation of root nodules and arbuscular mycorrhizal (AM) roots is controlled by a common signaling pathway including the calcium/calmodulin-dependent kinase Doesn’t Make Infection3 (DMI3). While nodule initiation by lipochitooligosaccharide (LCO) Nod factors is well characterized, diffusible AM fungal signals were only recently identified as sulfated and nonsulfated LCOs. Irrespective of different outcomes, the perception of symbiotic LCOs in Medicago truncatula is mediated by the LysM receptor kinase M. truncatula Nod factor perception (MtNFP). To shed light on transcriptional responses toward symbiotic LCOs and their dependence on MtNFP and Ca2+ signaling, we performed genome-wide expression studies of wild-type, Nod-factor-perception mutant1, and dmi3 mutant roots challenged with Myc- and Nod-LCOs. We show that Myc-LCOs lead to transient, quick responses in the wild type, whereas Nod-LCOs require prolonged incubation for maximal expression activation. While Nod-LCOs are most efficient for an induction of persistent transcriptional changes, sulfated Myc-LCOs are less active, and nonsulfated Myc-LCOs display the lowest capacity to activate and sustain expression. Although all symbiotic LCOs up-regulated a common set of genes, discrete subsets were induced by individual LCOs, suggesting common and specific functions for these in presymbiotic signaling. Surprisingly, even sulfated fungal Myc-LCOs and Sinorhizobium meliloti Nod-LCOs, having very similar structures, each elicited discrete subsets of genes, while a mixture of both Myc-LCOs activated responses deviating from those induced by single treatments. Focusing on the precontact phase, we identified signaling-related and transcription factor genes specifically up-regulated by Myc-LCOs. Comparative gene expression studies in symbiotic mutants demonstrated that transcriptional reprogramming by AM fungal LCOs strictly depends on MtNFP and largely requires MtDMI3.
Comparison between famciclovir and valacyclovir for acute pain in adult Japanese immunocompetent patients with herpes zoster
Authors: ONO Fumitake , YASUMOTO Shinichiro , FURUMURA Minao , HAMADA Takahiro , ISHII Norito , GYOTOKU Takashi , HIGUCHI Mitsunari , INOKUCHI Kenichiro , JYO Kazuo , KOGA Hideaki , KOMAI Ayako , MARUTA Koji , MASHIKO Tami , MIHARA Tsukasa , MIYAHARA Hiroko , MIYASATO Minoru , MUTO Koichiro , NAGASE Koichi , NAGATA Masakazu , SAKIHAMA Hideki , TANAHASHI Tomoko , UEDA Atsuto , YAMAKAWA Kyoko , OHATA Chika , DAINICHI Teruki , TSURUTA Daisuke , HASHIMOTO Takashi 
Published: June 2012

AbstractFamciclovir is a guanine analog antiviral drug used commonly for herpes zoster. Efficacy of famciclovir treatment has been reported to be comparable to valacyclovir treatment. Both of these medications reduce the time to complete cessation of zoster‐associated pain including post‐herpetic neuralgia, as compared to acyclovir. We conducted a multicenter, randomized, open clinical trial in order to evaluate the extent of pain relief afforded by these two antiviral drugs during the acute disease phase of herpes zoster. The study group comprised 86 immunocompetent adult patients suffering from herpes zoster, who were treated with either famciclovir or valacyclovir for 7 days. Of these, 55 patients enrolled in this study within 72 h of the onset of the rash and 31 patients after 72 h of the onset. There was a significant reduction in acute herpes zoster pain with famciclovir on day 7 and at 2–3 weeks in both of these patient groups, while with valacyclovir, there was not significant reduction in pain on day 7. Of patients aged 50 years or older, there was a significantly earlier reduction in pain with famciclovir than with valacyclovir. In addition, a significant reduction in the number of patients with pain was observed as early as days 3–4 with famciclovir treatment as compared with valacyclovir treatment. We conclude that famciclovir was superior to valacyclovir in the relief of acute pain of herpes zoster. Accordingly, famciclovir is recommended for herpes zoster patients with moderate symptoms and a visual analog scale score of under 50 mm.
A new technique for percutaneous dilatational tracheostomy (G‐Trach): preliminary experience in pigs
Authors: Guerra R. , De Monte A. , Girardis M. 
Published: June 2012

SummaryTracheostomies are currently used for airway management in patients requiring long‐term respiratory assistance. The dilatational percutaneous technique of forming tracheostomies is a valuable alternative to traditional surgical ‘open’ techniques. In this study, we tested a new dilatational percutaneous tracheostomy device using a balloon dilator with a particular innovative shape (G‐Trach). At the Autonomous University of Barcelona Veterinary Institute, eight pigs (weighing 20–40 kg) were anaesthetised and underwent tracheostomy using the novel G‐Trach technique. The mean (SD) procedure time was 2.63 (0.64) min from tracheal puncture to ventilation through the tracheostomy tube, and the mean (SD) time from positioning the dilator balloon to introducing the cannula was 0.71 (0.38) min. Vital functions and oxygen saturation remained constant throughout the procedures. Postmortem examinations did not reveal any tracheal injury. The G‐Trach seems to be a safe and easy new dilatational percutaneous technique for forming tracheostomies. The minimal subcutaneous tissue dissection could potentially decrease complications when compared with standard dilatational percutaneous tracheostomy methods. To confirm this hypothesis a human trial is ongoing.
A randomised comparison of the self‐pressurised air‐QTM intubating laryngeal airway with the LMA UniqueTM in children*
Authors: Jagannathan N. , Sohn L. E. , Sawardekar A. , Shah R. , Ryan K. , Jagannathan R. , Anderson K. 
Published: June 2012

SummaryWe conducted a randomised trial comparing the self‐pressurised air‐QTM intubating laryngeal airway (air‐Q SP) with the LMA‐Unique in 60 children undergoing surgery. Outcomes measured were airway leak pressure, ease and time for insertion, fibreoptic examination, incidence of gastric insufflation and complications. Median (IQR [range]) time to successful device placement was faster with the air‐Q SP (12 (10–15 [5–18])) s than with the LMA‐Unique (14 (12–17 [6–22]) s; p = 0.05). There were no statistically significant differences between the air‐Q SP and LMA‐Unique in initial airway leak pressures (16 (14–18 [10–29]) compared with 18 (15–20 [10–30]) cmH2O, p = 0.12), an airway leak pressures at 10 min (19 (16–22 [12–30]) compared with 20 (16–22 [10–30]) cmH2O, p = 0.81); fibreoptic position, incidence of gastric insufflation, or complications. Both devices provided effective ventilation without the need for airway manipulation. The air‐Q SP is an alternative to the LMA‐Unique should the clinician prefer a device not requiring cuff monitoring during anaesthesia.
Assessment of potential drug interactions by characterization of human drug metabolism pathways using non‐invasive bile sampling
Authors: Bloomer Jackie C. , Nash Mike , Webb Alison , Miller Bruce E. , Lazaar Aili L. , Beaumont Claire , Guiney William J. 
Published: June 2012

AimCharacterization of the biliary disposition of GSK1325756, using a non‐invasive bile sampling technique and spectrometric analyses, to inform the major routes of metabolic elimination and to enable an assessment of victim drug interaction risk.MethodSixteen healthy, elderly subjects underwent non‐invasive bile capture using a peroral string device (Entero‐Test®) prior to and following a single oral dose of GSK1325756 (100 mg). The device was swallowed by each subject and once the weighted string was judged to have reached the duodenum, gallbladder contraction was stimulated in order to release bile. The string was then retrieved via the mouth and bile samples were analyzed for drug‐related material using spectrometric and spectroscopic techniques following solvent extraction.ResultsNuclear magnetic resonance spectroscopy (NMR) indicated that the O‐glucuronide metabolite was the major metabolite of GSK1325756, representing approximately 80% of drug‐related material in bile. As bile is the major clearance route for GSK1325756 (only 4% of the administered dose was excreted in human urine), this result indicates that uridine 5'‐diphospho‐glucuronosyltransferases (UGTs) are the major drug metabolizing enzymes responsible for drug clearance. The relatively minor contribution made by oxidative routes reduces the concern of CYP‐mediated victim drug interactions.ConclusionThe results from this study demonstrate the utility of deploying the Entero‐Test® in early human studies to provide information on the biliary disposition of drugs and their metabolites. This technique can be readily applied in early clinical development studies to provide information on the risk of interactions for drugs that are metabolized and eliminated in bile.
Treatment of Philadelphia chromosome‐positive acute lymphoblastic leukaemia with imatinib combined with a paediatric‐based protocol
Authors: Thyagu Santhosh , Minden Mark D. , Gupta Vikas , Yee Karen W.L. , Schimmer Aaron D. , Schuh Andre C. , Lipton Jeffrey H. , Messner Hans A. , Xu Wei , Brandwein Joseph M. 
Published: June 2012

SummaryAlthough the combination of tyrosine kinase inhibitors with chemotherapy is widely used for young adults with Philadelphia chromosome positive‐acute lymphoblastic leukaemia (Ph+ ALL), the outcome and safety of this combination using intensive paediatric‐based protocols has not been well described. The clinical course of 32 adults age 18–60 years with Ph+ ALL treated with a paediatric‐based protocol plus imatinib was evaluated. The complete response rate was 94%. Grade 3–4 infections, neuropathy, myopathy and liver function abnormalities were common, resulting in major treatment delays and dose reductions, and declines in performance status (physical deconditioning), particularly in patients aged 41–60 years. Median and 3‐year overall survival (OS) was 40·7 months and 53%, respectively, and median and 3‐year even‐free survival (EFS) was 30·1 months and 50%, respectively. OS and EFS were inferior in deconditioned patients. Of 16 patients who underwent haematopoietic stem cell transplantation (HSCT) in first complete remission, six died of non‐relapse complications. There was no significant difference in OS and EFS between transplanted and non‐transplanted patients, based on an intention‐to‐treat and time‐to‐donor identification analysis. The combination of imatinib with a paediatric‐based regimen in adults produced high response rates, but was associated with considerable toxicity and high non‐relapse mortality post‐HSCT.
Equisetum arvense hydromethanolic extracts in bone tissue regeneration: in vitro osteoblastic modulation and antibacterial activity
Authors: Bessa Pereira C. , Gomes P. S. , Costa‐Rodrigues J. , Almeida Palmas R. , Vieira L. , Ferraz M. P. , Lopes M. A. , Fernandes M. H. 
Published: June 2012

AbstractObjectives
E
quisetum arvense preparations have long been used to promote bone healing. The aim of this work was to evaluate osteogenic and antibacterial effects of E
. arvense hydromethanolic extracts.Materials and methodsDried aerial components of E
. arvense were extracted using a mixture of methanol:water (1:1), for 26 days, yielding three extracts that were tested (10–1000 μg/ml) in human osteoblastic cells: E1, E2 and EM (a mixture of E1 and E2, 1:1). Cell cultures, performed on cell culture plates or over hydroxyapatite (HA) substrates, were assessed for osteoblastic markers. In addition, effects of the extracts on S
taphylococcus aureus were addressed.ResultsSolution E1 caused increased viability/proliferation and ALP activity at 50–500 μg/ml, and deleterious effects at levels ≥1000 μg/ml. E2 inhibited cell proliferation at levels ≥500 μg/ml. EM presented a profile between those observed with E1 and E2. In addition, E1, E2 and EM, 10–1000 μg/ml, inhibited expansion of S
. aureus. Furthermore, E1, tested in HA substrates colonized with osteoblastic cells, causing increase in cell population growth (10–100 μg/ml). E1 also exhibited antibacterial activity against S
. aureus cultured over HA.ConclusionsResults showed that E
. arvense extracts elicited inductive effects on human osteoblasts while inhibiting activity of S
. aureus, suggesting a potentially interesting profile regarding bone regeneration strategies.
Cord blood Th2‐related chemokine CCL22 levels associate with elevated total‐IgE during preschool age
Authors: Følsgaard N. V. , Chawes B. L. K. , Bønnelykke K. , Jenmalm M. C. , Bisgaard H. 
Published: June 2012

SummaryBackgroundEarly‐life immune deviation is suspected in the inception of atopic disease.ObjectiveTo investigate the association between cord blood chemokines and the subsequent development of atopic biomarkers and clinical end‐points during the first 6 years of life.MethodsThe Th1‐associated chemokines CXCL10 and CXCL11 and the Th2‐associated chemokines CCL17 and CCL22 were assessed in cord blood of asymptomatic at‐risk newborn children from the Copenhagen Prospective Study on Asthma in Childhood (COPSAC2000) birth cohort and associated with the longitudinal development of biomarkers and clinical end‐points of asthma, eczema, and allergic rhinitis during the first 6 years of life.ResultsCord blood CCL22 levels were significantly associated to total‐IgE levels measured at four time‐points during the first 6 years of life; overall odds ratio, 1.54 [CI, 1.25–1.89; P < 0.0001]. CXCL10 and CXCL11 were not associated with development of any atopic disorders or biomarkers.Conclusion and Clinical RelevanceHigh cord blood levels of the Th2 related chemokine CCL22 were significantly associated with high total‐ IgE levels during the first 6 years of life, but not with specific sensitization, asthma, eczema or allergic rhinitis. This suggests an inborn skewing of the immune system in healthy newborns developing elevated total‐ IgE later in life.
Persistent molecular microchimerism induces long‐term tolerance towards a clinically relevant respiratory allergen
Authors: Baranyi U. , Pilat N. , Gattringer M. , Linhart B. , Klaus C. , Schwaiger E. , Iacomini J. , Valenta R. , Wekerle T. 
Published: June 2012

SummaryBackgroundDevelopment of antigen‐specific preventive strategies is a challenging goal in IgE‐mediated allergy. We have recently shown in proof‐of‐concept experiments that allergy can be successfully prevented by induction of durable tolerance via molecular chimerism. Transplantation of syngeneic hematopoietic stem cells genetically modified to express the clinically relevant grass pollen allergen Phl p 5 into myeloablated recipients led to high levels of chimerism (i.e. macrochimerism) and completely abrogated Phl p 5‐specific immunity despite repeated immunizations with Phl p 5.ObjectiveIt was unclear, however, whether microchimerism (drastically lower levels of chimerism) would be sufficient as well which would allow development of minimally toxic tolerance protocols.MethodsBone marrow cells were transduced with recombinant viruses integrating Phl p 5 to be expressed in a membrane‐anchored fashion. The syngeneic modified cells were transplanted into non‐myeloablated recipients that were subsequently immunized repeatedly with Phl p 5 and Bet v 1 (control). Molecular chimerism was monitored using flow cytometry and PCR. T cell, B‐cell and effector‐cell tolerance were assessed by allergen‐specific proliferation assays, isotype levels in sera and RBL assays.ResultsHere we demonstrate that transplantation of Phl p 5‐expressing bone marrow cells into recipients having received non‐myeloablative irradiation resulted in chimerism persisting for the length of follow‐up. Chimerism levels, however, declined from transient macrochimerism levels to persistent levels of microchimerism (followed for 11 months). Notably, these chimerism levels were sufficient to induce B‐cell tolerance as no Phl p 5‐specific IgE and other high affinity isotypes were detectable in sera of chimeric mice. Furthermore, T‐cell and effector‐cell tolerance were achieved.Conclusions and Clinical RelevanceLow levels of persistent molecular chimerism are sufficient to induce long‐term tolerance in IgE‐mediated allergy. These results suggest that it will be possible to develop minimally toxic conditioning regimens sufficient for low level engraftment of genetically modified bone marrow.
The combination of FRAX and Ageing Male Symptoms scale better identifies treated HIV males at risk for major fracture
Authors: Pepe Jessica , Isidori Andrea M. , Falciano Mario , Iaiani Giancarlo , Salotti Alessandra , Diacinti Daniele , Del Fiacco Romano , Sbardella Emilia , Cipriani Cristiana , Piemonte Sara , Romagnoli Elisabetta , Lenzi Andrea , Minisola Salvatore 
Published: May 2012

AbstractObjectiveOsteoporosis and hypogonadism are common in men with HIV infection. Ageing Male Symptoms (AMS) scale measures symptoms related to hypogonadism. FRAX provides 10‐year probability of major fractures. We investigated the role of AMS scale combined with FRAX without bone mineral density (BMD), in identifying HIV men with bone fragility.DesignCross‐sectional observational study.MethodsFifty HIV‐positive men treated with highly active antiretroviral therapy and 27 controls underwent hormonal evaluation, BMD scan and spine X‐ray. The AMS questionnaire was administered.ResultsOsteoporosis was found in 24·0% of HIV patients and in 3·7% of controls (P = 0·05). In HIV patients, 9 radiological vertebral fractures were found (none in controls, P = 0·04). Calculated free testosterone suggested hypogonadism in 26% of HIV patients vs 4% of controls (P = 0·04); an abnormal AMS score (≥27) was found in 62% HIV patients compared with 41% controls (P = 0·04). ROC curves showed that FRAX for major fracture had a 23% sensitivity and a 100% specificity in identifying HIV patients with bone fragility (P = 0·002, with the threshold of 7% at which bisphosphonate therapy is cost‐effective). Considering a value of AMS ≥27, we obtained an 82·6% sensitivity and a 42·9% specificity (P = 0·04). The combination of AMS and FRAX score achieved a 77·3% sensitivity and a 69% specificity (P = 0·02, cut‐off 34).ConclusionCombination of FRAX (without BMD) and AMS improved sensitivity of FRAX alone in identifying HIV patients at fracture risk, at the expense of reduced specificity.
Immune regulatory gene polymorphisms as predisposing risk factors for the development of factor VIII inhibitors in Indian severe haemophilia A patients
Authors: Pinto P. , Ghosh K. , Shetty S. 
Published: May 2012

SummaryDevelopment of inhibitors to factor VIII, a serious complication of replacement therapy in haemophilia A patients, leads to increased bleeding, morbidity and mortality. There is no data on the risk factors for inhibitor development in Indian patients with severe haemophilia A. Our aim was to study the role of immune regulatory gene polymorphisms in the development of inhibitors. Fourteen immune regulatory gene polymorphisms (IL1β, IL4, IL10, TNFA and CTLA4) were analysed in 120 patients with severe haemophilia A, i.e. 50 inhibitor positive patients, and 70 inhibitor negative control patients, by PCR‐RFLP, DNA sequencing and allele‐specific PCRs. The IL10 promoter ‘GCC’ haplotypes overall (P: 0.002, OR: 3.452, 95% CI: 1.607–7.416), and ‘GCC/ATA’ (P: 0.011, OR: 3.492, 95% CI: 1.402–8.696) haplotype, associated with high and intermediate IL10 production, respectively, were significantly higher in inhibitor positive patients, whereas the ‘non‐GCC’ haplotypes overall (P: 0.002,OR: 0.290, 95% CI 0.135–0.622) and ‘ATA/ATA’ haplotype (P: 0.025, OR: 0.278, 95% CI: 0.096–0.802), associated with low IL10 synthesis, were significantly higher among inhibitor negative patients. The TNFA rs1799724 C/T heterozygote prevalence was significantly higher in the inhibitor positive group (P: 0.021, OR: 3.190, 95% CI: 1.273–7.990), whereas the other polymorphisms showed no statistically significant association with the presence of inhibitors. Different immune regulatory gene polymorphisms play a significant role as possible risk factors for the development of inhibitors in severe haemophilia A patients.
Strategy of lipid recognition by invariant natural killer T cells: ‘one for all and all for one’
Authors: Mallevaey Thierry , Selvanantham Thirumahal 
Published: June 2012

SummaryInvariant natural killer T (iNKT) cells are evolutionarily conserved lipid‐reactive T cells that bridge innate and adaptive immune responses. Despite a relatively restricted T‐cell receptor (TCR) diversity, these cells respond to a variety of structurally distinct foreign (i.e. microbial or synthetic) as well as host‐derived (self‐) lipid antigens presented by the CD1d molecule. These multi‐tasking lymphocytes are among the first responders in immunity, and produce an impressive array of cytokines and chemokines that can tailor the ensuing immune response. Accordingly, iNKT cells play important functions in autoimmune diseases, cancer, infection and inflammation. These properties make iNKT cells appealing targets in immune‐based therapies. Yet, much has to be learned on the mechanisms that allow iNKT cells to produce polarized responses. Responses of iNKT cells are influenced by the direct signals perceived by the cells through their TCRs, as well as by indirect co‐stimulatory (and potentially co‐inhibitory) cues that they receive from antigen‐presenting cells or the local milieu. A decade ago, biochemists and immunologists have started to describe synthetic lipid agonists with cytokine skewing potential, paving a new research avenue in the iNKT cell field. Yet how iNKT cells translate various antigenic signals into distinct functional responses has remained obscure. Recent findings have revealed a unique and innate mode of lipid recognition by iNKT cells, and suggest that both the lipid antigen presented and the diversity of the TCR modulate the strength of CD1d‐iNKT TCR interactions. In this review, we focus on novel discoveries on lipid recognition by iNKT cells, and how these findings may help us to design effective strategies to steer iNKT cell responses for immune intervention.
Personal information privacy and emerging technologies
Authors: Conger Sue , Pratt Joanne H. , Loch Karen D. 
Published: June 2012

AbstractThis research presents a model of personal information privacy (PIP) that includes not only transactional data gathering, but also interorganisational data sharing. Emerging technologies are used as a lens through which the discussion of PIP management is extended. Research directions are developed for aspects of privacy, privacy‐preserving technologies, interorganisational data sharing and policy development.