bluuebunny/crossref_metadata_2025_split huggingface dataset:
Recombinant BCG Expressing LTAK63 Adjuvant induces Superior Protection against Mycobacterium tuberculosis
Authors: Nascimento Ivan P. , Rodriguez Dunia , Santos Carina C. , Amaral Eduardo P. , Rofatto Henrique K. , Junqueira-Kipnis Ana P. , Gonçalves Eduardo D. C. , D’Império-Lima Maria R. , Hirata Mario H. , Silva Celio L. , Winter Nathalie , Gicquel Brigitte , Mills Kingston H. G. , Pizza Mariagrazia , Rappuoli Rino , Leite Luciana C. C. 
Published: May 2017

AbstractIn order to develop an improved BCG vaccine against tuberculosis we have taken advantage of the adjuvant properties of a non-toxic derivative of Escherichia coli heat labile enterotoxin (LT), LTAK63. We have constructed rBCG strains expressing LTAK63 at different expression levels. Mice immunized with BCG expressing low levels of LTAK63 (rBCG-LTAK63lo) showed higher Th1 cytokines and IL-17 in the lungs, and when challenged intratracheally with Mycobacterium tuberculosis displayed a 2.0–3.0 log reduction in CFU as compared to wild type BCG. Histopathological analysis of lung tissues from protected mice revealed a reduced inflammatory response. Immunization with rBCG-LTAK63lo also protected against a 100-fold higher challenge dose. Mice immunized with rBCG-LTAK63lo produced an increase in TGF-β as compared with BCG after challenge, with a corresponding reduction in Th1 and Th17 cytokines, as determined by Real Time RT-PCR. Furthermore, rBCG-LTAK63lo also displays protection against challenge with a highly virulent Beijing isolate. Our findings suggest that BCG with low-level expression of the LTAK63 adjuvant induces a stronger immune response in the lungs conferring higher levels of protection, and a novel mechanism subsequently triggers a regulatory immune response, which then limits the pathology. The rBCG-LTAK63lo strain can be the basis of an improved vaccine against tuberculosis.
Selection and characterization of a DNA aptamer inhibiting coagulation factor XIa
Authors: Donkor David A. , Bhakta Varsha , Eltringham-Smith Louise J. , Stafford Alan R. , Weitz Jeffrey I. , Sheffield William P. 
Published: May 2017

AbstractFactor XIa (FXIa) is a serine protease that catalyzes the activation of Factor IX (FIX) in the blood coagulation cascade. FXIa and its precursor FXI are emergent therapeutic targets for the development of safer anticoagulant agents. Here, we sought a novel DNA-based agent to inhibit FXIa. Towards this goal, an 80 base, single-stranded DNA aptamer library (containing a 40 base randomized core) was screened for FXIa-binding candidates, using ten rounds of positive and negative selection. After selection, 6 of 89 different sequences inhibited FXIa-mediated chromogenic substrate S2366 cleavage. The most active anti-FXIa aptamer had a hypervariable central sequence 5′-AACCTATCGGACTATTGTTAGTGATTTTTATAGTGT-3′ and was designated Factor ELeven Inhibitory APtamer (FELIAP). FELIAP, but not a scrambled aptamer control (SCRAPT), competitively inhibited FXIa-catalyzed S2366 cleavage, FIX activation, and complex formation with antithrombin. No effect of FELIAP on FXI activation was observed. FELIAP inhibited plasma clotting and thrombin generation assays to a significantly greater extent than SCRAPT. Immobilized FELIAP bound FXIa with strong affinity and an equilibrium binding constant (KD) in the low nanomolar range determined using surface plasmon resonance. FELIAP is the first FXIa-inhibitory aptamer to be described and constitutes a lead compound to develop related aptamers for in vivo use.
Fast diffusion of domesticated maize to temperate zones
Authors: Li Xiaolong , Jian Yinqiao , Xie Chuanxiao , Wu Jun , Xu Yunbi , Zou Cheng 
Published: May 2017

AbstractAdaptation to a temperate climate was a prerequisite for the spread of maize across a broad geographical range. To explicitly explore the demographic process underlying maize adaptation, we used a diffusion-based method to model the differentiation between temperate and tropical populations using the Non-Stiff Stalk group as a proxy for temperate maize. Based on multiple sequential Markovian coalescent approaches, we estimate that tropical and temperate maize diverged approximately 3‚000 to 5‚000 years ago and the population size shrank after the split. Using composite likelihood approaches, we identified a distinct tropical-temperate divergence event initiated 4‚958 years ago (95% confidence interval (CI): 4‚877–5‚039) from an ancestral population whose effective size was 24,162 (95% CI: 23,914–24,409). We found that continuous gene flow between tropical and temperate maize accompanied the differentiation of temperate maize. Long identical-by-descent tracts shared by tropical and temperate inbred lines have been identified, which might be the result of gene flow between tropical and temperate maize or artificial selection during domestication and crop improvement. Understanding the demographic history of maize diffusion not only provides evidence for population dynamics of maize, but will also assist the identification of regions under selection and the genetic basis of complex traits of agronomic importance.
Involvement of GATA1 and Sp3 in the activation of the murine STING gene promoter in NIH3T3 cells
Authors: Xu Yan-Yan , Jin Rui , Zhou Guo-Ping , Xu Hua-Guo 
Published: May 2017

AbstractStimulator of Interferon Gene (STING) is a key mediator of innate immune signaling. STING plays a pivotal role in the pathogenesis of many diseases including infectious diseases, auto-immune diseases and cancer. Many studies have been carried out recently in the field of STING-regulated pathway, however, rarely of transcriptional mechanisms. To characterize the murine STING (mSTING) promoter, we cloned a series of different nucleotide sequences of the 5′-flanking region of the mSTING gene. Transient transfection of promoter-reporter recombinant plasmids and luciferase assay illustrated the region (−77/+177) relative to the transcription start site (TSS) of the mSTING gene was sufficient for full promoter activity. This region contains GATA1, IK2, Sp1/Sp3 and STAT putative transcription factor binding sites. Mutation of GATA1 or Sp1/Sp3 sites led to obvious decrease of the mSTING promoter activity. Overexpression of GATA1 and Sp3 enhanced the mSTING promoter activity, whereas knockdown of GATA1 and Sp3 by a siRNA strategy significantly reduced the transcription activity. Chromatin immunoprecipitation assays demonstrated that GATA1 and Sp3 interact with the mSTING promoter in vivo. These results provided the first analysis of mSTING promoter and demonstrated that transcription factor GATA1 and Sp3 positively regulate the basal transcription of the mSTING gene.
TRAF3 enhances TCR signaling by regulating the inhibitors Csk and PTPN22
Authors: Wallis Alicia M. , Wallace Ellie C. , Hostager Bruce S. , Yi Zuoan , Houtman Jon C. D. , Bishop Gail A. 
Published: May 2017

AbstractThe adaptor protein TNF receptor associated factor (TRAF) 3 is required for effective TCR signaling and normal T cell effector functions, and associates with the CD3/CD28 complex upon activation. To determine how TRAF3 promotes proximal TCR signaling, we studied TRAF3-deficient mouse and human T cells, which showed a marked reduction in activating phosphorylation of the TCR-associated kinase Lck. The impact of TRAF3 on this very early signaling event led to the hypothesis that TRAF3 restrains one or both of two known inhibitors of Lck, C-terminal Src kinase (Csk) and protein tyrosine phosphatase N22 (PTPN22). TRAF3 associated with Csk, promoting the dissociation of Csk from the plasma membrane. TRAF3 also associated with and regulated the TCR/CD28 induced localization of PTPN22. Loss of TRAF3 resulted in increased amounts of both Csk and PTPN22 in T cell membrane fractions and decreased association of PTPN22 with Csk. These findings identify a new role for T cell TRAF3 in promoting T cell activation, by regulating localization and functions of early TCR signaling inhibitors.
Expression Profiling of mRNAs and Long Non-Coding RNAs in Aged Mouse Olfactory Bulb
Authors: Wang Ming , Liu Wei , Jiao Jian , Li Jingyun , Wang Chengshuo , Zhang Luo 
Published: May 2017

AbstractAge-related decline in olfactory function affects the quality of life in elderly people and also potentially represents an early clinical symptom of neurodegenerative disorder. Olfactory bulb (OB) plays a central role in olfactory information transmitting and signal processing. The mechanisms underlying this impairment remain unclear. In the current study, microarray was used to investigate differentially expressed protein coding genes (PCGs) and long non-coding RNAs (lncRNAs) in OBs from three groups of mice of different ages (2 months-old young adults, 6 months-old mature adults and 20 months-old aged adults), for their potential roles in olfactory impairment. Gene Ontology and pathway analysis results showed that the differentially expressed PCGs in the OBs from aged mice were mainly associated with signal transduction, regulation of gene expression and cellular microenvironment. Similarly, gene set enrichment analysis identified two differentially and inversely expressed lncRNAs (NONMMUT004524 and NONMMUT000384), both of which were significantly associated with neuroactive ligand-receptor interaction pathway in the OBs of aged mice. These findings suggest that a decline of olfactory function in aged mice may be linked to differential expression of specific lncRNAs and their potentially adverse effects on the neuroactive ligand-receptor interaction pathway in the OB.
DCE-MRI Background Parenchymal Enhancement Quantified from an Early versus Delayed Post-contrast Sequence: Association with Breast Cancer Presence
Authors: Wu Shandong , Zuley Margarita L. , Berg Wendie A. , Kurland Brenda F. , Jankowitz Rachel C. , Sumkin Jules H. , Gur David 
Published: May 2017

AbstractWe investigated automated quantitative measures of background parenchymal enhancement (BPE) derived from an early versus delayed post-contrast sequence in breast dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) for association with breast cancer presence in a case-control study. DCE-MRIs were retrospectively analyzed for 51 cancer cases and 51 controls with biopsy-proven benign lesions, matched by age and year-of-MRI. BPE was quantified using fully-automated validated computer algorithms, separately from three sequential DCE-MRI post-contrast-subtracted sequences (SUB1, SUB2, and SUB3). The association of BPE computed from the three SUBs and other known factors with breast cancer were assessed in terms of odds ratio (OR) and area under the receiver operating characteristic curve (AUC). The OR of breast cancer for the percentage BPE measure (BPE%) quantified from SUB1 was 3.5 (95% Confidence Interval: 1.3, 9.8; p = 0.015) for 20% increments. Slightly lower and statistically significant ORs were also obtained for BPE quantified from SUB2 and SUB3. There was no significant difference (p > 0.2) in AUC for BPE quantified from the three post-contrast sequences and their combination. Our study showed that quantitative measures of BPE are associated with breast cancer presence and the association was similar across three breast DCE-MRI post-contrast sequences.
Pseudomonas aeruginosa Exolysin promotes bacterial growth in lungs, alveolar damage and bacterial dissemination
Authors: Bouillot Stéphanie , Munro Patrick , Gallet Benoit , Reboud Emeline , Cretin François , Golovkine Guillaume , Schoehn Guy , Attrée Ina , Lemichez Emmanuel , Huber Philippe 
Published: May 2017

AbstractExolysin (ExlA) is a recently-identified pore-forming toxin secreted by a subset of Pseudomonas aeruginosa strains identified worldwide and devoid of Type III secretion system (T3SS), a major virulence factor. Here, we characterized at the ultrastructural level the lesions caused by an ExlA-secreting strain, CLJ1, in mouse infected lungs. CLJ1 induced necrotic lesions in pneumocytes and endothelial cells, resulting in alveolo-vascular barrier breakdown. Ectopic expression of ExlA in an exlA-negative strain induced similar tissue injuries. In addition, ExlA conferred on bacteria the capacity to proliferate in lungs and to disseminate in secondary organs, similar to bacteria possessing a functional T3SS. CLJ1 did not promote a strong neutrophil infiltration in the alveoli, owing to the weak pro-inflammatory cytokine reaction engendered by the strain. However, CLJ1 was rapidly eliminated from the blood in a bacteremia model, suggesting that it can be promptly phagocytosed by immune cells. Together, our study ascribes to ExlA-secreting bacteria the capacity to proliferate in the lung and to damage pulmonary tissues, thereby promoting metastatic infections, in absence of substantial immune response exacerbation.
Dynamical dispersion engineering in coupled vertical cavities employing a high-contrast grating
Authors: Taghizadeh Alireza , Chung Il-Sug 
Published: May 2017

AbstractPhoton’s effective mass is an important parameter of an optical cavity mode, which determines the strength of light-matter interaction. Here, we propose a novel method for controlling the photon’s effective mass by using coupled photonic cavities and designing the angular dependence of the coupling strength. This can be implemented by employing a high-contrast grating (HCG) as the coupling reflector in a system of two coupled vertical cavities, and engineering both the HCG reflection phase and amplitude response. Several examples of HCG-based coupled cavities with novel features are discussed, including a case capable of dynamically controlling the photon’s effective mass to a large extent while keeping the resonance frequency same. We believe that full-control and dynamical-tuning of the photon’s effective mass may enable new possibilities for cavity quantum electrodynamics studies or conventional/polariton laser applications. For instance, one can dynamically control the condensate formation in polariton lasers by modifying the polariton mass.
Lactobacillus johnsonii ameliorates intestinal, extra-intestinal and systemic pro-inflammatory immune responses following murine Campylobacter jejuni infection
Authors: Bereswill Stefan , Ekmekciu Ira , Escher Ulrike , Fiebiger Ulrike , Stingl Kerstin , Heimesaat Markus M. 
Published: May 2017

AbstractCampylobacter jejuni infections are progressively increasing worldwide. Probiotic treatment might open novel therapeutic or even prophylactic approaches to combat campylobacteriosis. In the present study secondary abiotic mice were generated by broad-spectrum antibiotic treatment and perorally reassociated with a commensal murine Lactobacillus johnsonii strain either 14 days before (i.e. prophylactic regimen) or 7 days after (i.e. therapeutic regimen) peroral C. jejuni strain 81–176 infection. Following peroral reassociation both C. jejuni and L. johnsonii were able to stably colonize the murine intestinal tract. Neither therapeutic nor prophylactic L. johnsonii application, however, could decrease intestinal C. jejuni burdens. Notably, C. jejuni induced colonic apoptosis could be ameliorated by prophylactic L. johnsonii treatment, whereas co-administration of L. johnsonii impacted adaptive (i.e. T and B lymphocytes, regulatory T cells), but not innate (i.e. macrophages and monocytes) immune cell responses in the intestinal tract. Strikingly, C. jejuni induced intestinal, extra-intestinal and systemic secretion of pro-inflammatory mediators (such as IL-6, MCP-1, TNF and nitric oxide) could be alleviated by peroral L. johnsonii challenge. In conclusion, immunomodulatory probiotic species might offer valuable strategies for prophylaxis and/or treatment of C. jejuni induced intestinal, extra-intestinal as well as systemic pro-inflammatory immune responses in vivo.
Combined Fractures of the Scaphoid and Distal Radius: Evaluation of Early Surgical Fixation (21 Patients with 22 Wrists)
Authors: Sügün Tahir , Kayalar Murat , Gürbüz Yusuf 
Published: May 2017

Introduction The purpose of this retrospective study, is to evaluate the clinical and functional results of early surgical fixation of the ipsilateral distal radius and scaphoid fractures in 22 of 21 patients.
Patients and Methods Overall, 22 combined ipsilateral scaphoid, and distal radius fracture treatments between 2002 and 2015 were evaluated. The mean age was 34.9 (range: 19–82) years. One patient had bilateral injuries. In 17 patients the injury was due to a fall from a height, and in 4 patients due to a motorcycle accident. According to the AO classification, there were 2 type B and 20 type C fractures of the distal radius. The volar locking plate fixation technique was applied in 14 wrists, screw fixation technique in 1, external fixation combined with Kirschner wires (K-wire) stabilization technique was used in 3 wrists, and only K-wire pinning technique was used in 4 wrists. All scaphoid fractures were type B (21 type B2, 1 type B1) according to the Herbert–Fischer classification. K-wire fixation was applied in 2 and cannulated screw fixation was performed in 20 fractures. Clinical evaluation was performed with measuring the pinch power, grip power, and range of motions. Functional evaluation was performed using patient-rated wrist evaluation score (PRWE).
Results The average follow-up period was 25 (range: 12–97) months. All radius and scaphoid fractures healed. The mean active wrist motions were found to be 45 degrees of flexion, 48.5 degrees of extension, 20 degrees of radial deviation, and 43 degrees ulnar deviation. Mean grip/pinch strengths were 31/8.5 kg. Mean PRWE score was 5.5 (range: 0–8.5). All patients returned to preoperative activity level and can do preinjury jobs.
Conclusion Combined ipsilateral fractures of distal radius and scaphoid are complex and rare injuries due to high energy traumas. Stable early primary fracture fixation in these injuries can be expected with good functional results.
Level of Evidence Level IV.
Outcome of Neonates with Meconium Aspiration Syndrome at the University Hospital of the West Indies, Jamaica: A Resource-Limited Setting
Authors: Panton L. , Trotman H. 
Published: May 2017

Aim To determine the outcome of neonates with meconium aspiration syndrome (MAS) at the University Hospital of the West Indies over a 5-year period.
Methods This was a retrospective, descriptive study looking at all inborn neonates with MAS. Data on maternal and neonatal demographics, clinical course, and outcome were recorded. Descriptive analyses were performed.
Results The incidence of MAS was 10 per 1,000 live births. Fetal distress was documented in 32 (30%) cases. Thirty-two (30%) neonates were postdates at the time of delivery and 32 (30%) neonates were delivered by emergency cesarean section. Seven (6%) neonates required mechanical ventilation and 16 (15%) required bubble continuous positive airway pressure. Seven (6%) neonates had hypoxic ischemic encephalopathy, 5(5%) had persistent pulmonary hypertension of the newborn, and 1 (4%) had a pneumothorax. There was a 1% mortality rate. Thick meconium beneath the cords, grunting, and hypoxia on admission were independent predictors of disease severity.
Conclusion The incidence of MAS was similar to that of other resource-limited settings; however, the disease spectrum was milder with lower morbidity and mortality.
Admission Systolic Blood Pressure and Outcomes in Preterm Infants of ≤ 26 Weeks' Gestation
Authors: Lyu Yanyu , Ye Xiang , Isayama Tetsuya , Alvaro Ruben , Nwaesei Chuks , Barrington Keith , Lee Shoo , Shah Prakesh ,   for the Canadian Neonatal Network Investigators
Published: May 2017

Objective To examine the relationship between admission systolic blood pressure (SBP) and adverse neonatal outcomes. Specifically, we aimed to identify the optimal SBP that is associated with the lowest rates of adverse outcomes in extremely preterm infants of ≤ 26 weeks' gestation.
Methods In this retrospective study, inborn neonates born at ≤ 26 weeks' gestational age and admitted to tertiary neonatal units participating in the Canadian Neonatal Network between 2003 and 2009 were included. The primary outcome was early mortality (≤ 7 days). Secondary outcomes included severe brain injury, late mortality, and a composite outcome defined as early mortality or severe brain injury. Nonlinear multivariable logistic regression models examined the relationship between admission SBP and outcomes.
Results Admission SBP demonstrated a U-shaped relationship with early mortality, severe brain injury, and composite outcome after adjustment for confounders (p < 0.01). The lowest risks of early mortality, severe brain injury, and composite outcome occurred at admission SBPs of 51, 55, and 54 mm Hg, respectively.
Conclusion In extremely preterm infants of ≤ 26 weeks' gestational age, the relationship between admission SBP, and early mortality and severe brain injury was “U-shaped.” The optimal admission SBP associated with lowest rates of adverse outcome was between 51 and 55 mm Hg.
Regionale Unterschiede bei demografischer Alterung
Authors: Alltag Sophie , Nowossadeck Sonja , Stein Janine , Hajek André , König Hans-Helmut , Riedel-Heller Steffi , Nowossadeck Enno 
Published: May 2017

Zusammenfassung
Ziel der Studie Darstellung regionaler Unterschiede in aktuellen und zukünftigen Pflegepotenzialen und Kontrastierung mit Pflegepräferenzen am Beispiel Sachsen als eines der Bundesländer mit der größten Überalterung.
Methodik Formelle (FIUK) und informelle (IIUK) intergenerationale Unterstützungskoeffizienten wurden für jeden Landkreis (2012 – 2035) gebildet. Pflegepräferenzen wurden im Rahmen eines repräsentativen Telefonsurveys (65+) erfragt.
Ergebnisse FIUK und IIUK entwickeln sich ähnlich und halbieren sich bis 2035. Die Mehrheit der Senioren bevorzugte die Versorgung im eigenen Zuhause.
Schlussfolgerung Zukünftige Pflegepotenziale sind wegen ihrer kritischen Entwicklung insbesondere im ländlichen Raum von großer Bedeutung für die Planung der Gesundheitsversorgung.
Self-Stigma of Depression Scale SSDS – Evaluation der deutschen Skalenversion
Authors: Makowski Anna , Mnich Eva , von dem Knesebeck Olaf 
Published: May 2017

Zusammenfassung
Ziel der Studie Erstmalig werden die Anwendbarkeit und psychometrische Charakteristika einer deutschen Version der Self-Stigma of Depression Scale (SSDS) getestet.
Methodik Basis ist eine bundesweite Befragung (N = 2013). Die 16 Items der SSDS wurden in einer Hauptkomponentenanalyse untersucht.
Ergebnisse Es ergaben sich 3 Subskalen („soziale Unzulänglichkeit“, „Hemmungen bei der Hilfesuche“, „eigene Schuldzuschreibung“). Die Gesamtskala und die ersten beiden Subskalen weisen akzeptable Reliabilitäten auf.
Schlussfolgerungen Selbststigma ist als ein mehrdimensionales Konstrukt aufzufassen. Eine Weiterentwicklung der Skala wird empfohlen.
Standardtherapie für Panikstörung mit/ohne Agoraphobie in der Hausarztpraxis
Authors: Sommer Michael , Hiller Thomas , Breitbart Jörg , Schneider Nico , Teismann Tobias , Freytag Antje , Gensichen Jochen ,   für die „Jena-PARADISE“ Study Group
Published: May 2017

Zusammenfassung
Ziel Beschreibung der hausärztlichen Standardtherapie (Therapy As Usual, TAU) bei Panikstörung mit/ohne Agoraphobie (PDA).
Methoden Schriftliche Befragung von 38 Hausärzten, die in einer Interventionsstudie 189 Patienten mit PDA behandelten.
Ergebnisse TAU beinhaltete eine Mischung aus psychosozialen (Besprechung psychosozialer Probleme, 83 %) und pharmakologischen (SSRI, 62 %) Interventionen.
Schlussfolgerung TAU erscheint weitgehend leitliniengerecht. Die Generalisierbarkeit der Ergebnisse ist studienbedingt eventuell eingeschränkt.