bluuebunny/crossref_metadata_2025_split huggingface dataset:
Leukocyte telomere length and serum polyunsaturated fatty acids, dietary habits, cardiovascular risk factors and features of myocardial infarction in elderly patients
Authors: Kalstad Are A. , Tveit Sjur , Myhre Peder L. , Laake Kristian , Opstad Trine B. , Tveit Arnljot , Schmidt Erik B. , Solheim Svein , Arnesen Harald , Seljeflot Ingebjørg 
Published: December 2019

AbstractBackgroundTelomeres are non-coding sequences at the end of eukaryote chromosomes, which in complex with associated proteins serve to protect subtelomeric DNA. Telomeres shorten with each cell division, are regarded as a biomarker for aging and have also been suggested to play a role in atherosclerosis and cardiovascular disease (CVD). The aim of the present study was to explore the associations between leukocyte telomere length and serum polyunsaturated fatty acids, diet, cardiovascular risk factors and features of myocardial infarction (MI) in elderly patients.MethodsThe material is based upon the first 299 included patients in the OMEMI trial, where patients aged 70–82 years of age are randomized to receive omega-3 supplements or corn oil (placebo) after MI. Patients were included 2–8 weeks after the index MI. DNA was extracted from whole blood, and leukocyte telomere length (LTL) was analyzed by qPCR and reported as a number relative to a reference gene. Serum long chain polyunsaturated fatty acid (LCPUFA) content was analyzed by gas chromatography. Diet was evaluated with the validated SmartDiet food frequency questionnaire. Medical records, patient interviews and clinical examination provided previous medical history and anthropometric data. Non-parametric statistical tests were used.ResultsMedian (25, 75 percentile) LTL was 0.55 (0.42, 0.72). Patients had a median age of 75 years, 70.2% were male and 45.2% used omega-3 supplements. There was a weak, but significant correlation between LTL and linoleic acid (r = 0.139,p = 0.017), but not with other LCPUFAs. There was a trend towards longer telomeres with a healthier diet, but this did not reach statistical significance (p = 0.073). No associations were found between LTL and CVD risk factors or features of MI.ConclusionsIn our population of elderly with a recent myocardial infarction LTL was associated with linoleic acid concentrations, but not with other LCPUFAs. Patients with a healthy diet tended to have longer telomeres. The limited associations may be due to age and the narrow age-span in our population. Further studies, designed to detect longitudinal changes should be performed to explore the role of telomeres in cardiovascular aging.Trial registrationClinical trials no.NCT01841944, registration date April 29, 2013.
Where have all the susceptible gonococci gone? A historical review of changes in MIC distribution over the past 75 years
Authors: Kenyon Chris , Laumen Jolein , Van Den Bossche Dorien , Van Dijck Christophe 
Published: December 2019

Abstract
Background
Does the emergence of antimicrobial resistance in Neisseria gonorrhoeae include the erasure of highly susceptible strains or does it merely involve a stretching of the MIC distribution? If it was the former this would be important to know as it would increase the probability that the loss of susceptibility is irreversible.

Methods
We conducted a historical analysis based on a literature review of changes of N. gonorrhoeae MIC distribution over the past 75 years for 3 antimicrobials (benzylpenicillin, ceftriaxone and azithromycin) in five countries (Denmark, Japan, South Africa, the United Kingdom and the United States).

Results
Changes in MIC distribution were most marked for benzylpenicillin and showed evidence of a right shifting of MIC distribution that was associated with a reduction/elimination of susceptible strains in all countries. In the case of ceftriaxone and azithromycin, where only more recent data was available, right shifting was also found in all countries but the extent of right shifting varied and the evidence for the elimination of susceptible strains was more mixed.

Conclusions
The finding of right shifting of MIC distribution combined with reduction/elimination of susceptible strains is of concern since it suggests that this shifting may not be reversible. Since excess antimicrobial consumption is likely to be responsible for this right shifting, this insight provides additional impetus to promote antimicrobial stewardship.
Urinary tract infections in renal transplant recipients at a quaternary care centre in Australia
Authors: OLENSKI Simon , SCUDERI Carla , CHOO Alex , BHAGAT SINGH Aneesha Kaur , WAY Mandy , JEYASEELAN Lakshmanan , JOHN George 
Published: December 2019

Abstract
Background
Urinary tract infections (UTI) are the most common of infections after renal transplantation. The consequences of UTIs in this population are serious, with increased morbidity and hospitalisation rates as well as acute allograft dysfunction. UTIs may impair overall graft and patient survival. We aimed to identify the prevalence and risk factors for post-transplant UTIs and assess UTIs’ effect on renal function during a UTI episode and if they result in declining allograft function at 2 years post-transplant. Additionally, the causative organism, the class of antibacterial drug employed for each UTI episode and utilisation rates of trimethoprim/sulfamethoxazole (TMP/SMX) prophylaxis were also quantified.

Methods
This was a retrospective study of 72 renal transplant patients over a 5-year period who were managed at the Royal Brisbane and Women’s Hospital. Patient charts, pathology records and dispensing histories were reviewed as part of this study and all UTIs from 2 years post transplantation were captured.

Results
Of these patients, 20 (27.8%) had at least one UTI. Older age (p = 0.015), female gender (p < 0.001), hyperglycaemia (p = 0.037) and acute rejection episodes (p = 0.046) were risk factors for developing a UTI on unadjusted analysis. Female gender (OR 4.93) and age (OR 1.03) were statistically significant risk factors for a UTI on adjusted analysis. On average, there was a 14.4% (SEM 5.20) increase in serum creatinine during a UTI episode, which was statistically significant (p = 0.027), and a 9.1% (SEM 6.23) reduction in serum creatinine after the UTI episode trending toward statistical significance.
(p = 0.076). Common organisms (Escherichia coli and Klebsiella pneumoniae) accounted for 82% of UTI episodes with 70% of UTI cases requiring only a single course of antibiotic treatment. Furthermore, the antibiotic class used was either a penicillin (49%) or cephalosporin (36%) in the majority of UTIs. The use of TMP/SMX prophylaxis for Pneumocystis carinii pneumonia prophylaxis did not influence the rate of UTI, with > 90% of the cohort using this treatment.

Conclusions
There was no significant change in serum creatinine and estimated glomerular filtrate rate from baseline to 2 years post-transplant between those with and without a UTI.
Action observation training for rehabilitation in brain injuries: a systematic review and meta-analysis
Authors: Buchignani Bianca , Beani Elena , Pomeroy Valerie , Iacono Oriana , Sicola Elisa , Perazza Silvia , Bieber Eleonora , Feys Hilde , Klingels Katrijn , Cioni Giovanni , Sgandurra Giuseppina 
Published: December 2019

AbstractBackgroundTo systematically review and analyse the effects of Action Observation Training on adults and children with brain damage.MethodsSeven electronic databases (Cochrane, EBSCO, Embase, Eric, PubMed, Scopus and Web of Science) were searched up to 16 September 2018 to select Randomized Controlled Trials focused on adults and children with brain damage that included AOT training on upper and/or lower limb carried out for at least 1 week. Identification of studies and data extraction was conducted with two reviewers working independently. Oxford Centre for Evidence-based Medicine (March2009) – Levels of Evidence and Physiotherapy Evidence Database scale were used to grade studies. The data collected from the articles were analysed using software R, version 3.4.3. Hedge’s g values were calculated and effect size estimates were pooled across studies. Separate meta-analyses were carried out for each ICF domain (i.e. body function and activity) for upper and lower limb.ResultsOut of the 210 records identified after removing duplicates, 22 were selected for systematic review and 19 were included in the meta-analysis. Thirteen studies included in the meta-analysis focused on upper limb rehabilitation (4 in children and 9 in adults) and 6 on lower limb rehabilitation (only studies in adults). A total of 626 patients were included in the meta-analysis. An overall statistically significant effect size was found for upper limb body function (0.44, 95% CI: [0.24, 0.64],p < 0.001) and upper limb activity domain (0.47, 95% CI: [0.30, 0.64],p < 0.001). For lower limb, only the activity domain was analysed, revealing a statistically significant overall effect size (0.56, 95% CI: [0.28, 0.84],p < 0.001).ConclusionsAction Observation Training (AOT) is an innovative rehabilitation tool for individuals with brain damage, which shows promising results in improving the activity domain for upper and lower limbs, and also the body function domain for the upper limb. However, the examined studies lack uniformity and further well-designed, larger controlled trials are necessary to determine the most suitable type of AOT particularly in children.Systematic review registrationCRD42019119600.
Microvascular decompression for the treatment of neurogenic hypertension with trigeminal neuralgia
Authors: Lu Wenchao , Wang Hui , Yan Zhongnan , Wang Yuangang , Che Hongmin 
Published: December 2019

Abstract
Background
To evaluate the efficacy of microvascular decompression (MVD) in reducing hypertension (HTN) in hypertensive patients with trigeminal neuralgia (TN).

Methods
The clinical data of 58 cases of neurogenic HTN with TN treated in our hospital were retrospectively reviewed. Preoperative MR revealed abnormal blood pressure in the left rostral ventrolateral medulla (RVLM) and the posterior cranial nerve root entry zone (REZ). The patients were divided into control group: only trigeminal nerve was treated with MVD; experimental group: trigeminal nerve, RVLM and REZ were treated with MVD at the same time. The patients were followed up for 6 months to 1 year to observe the changes of blood pressure.

Results
There was no significant difference in gender, age, course of TN, course of HTN, grade of HTN and preoperative blood pressure between the two groups. After operation, the effective rate of HTN improvement with MVD was 32.1% in the control group. There was no significant difference in the preoperative and post operative blood pressure. (P△SBP = 0.131; P△BDP = 0.078). In the experimental group, the effective rate was 83.3%. The postoperative blood pressure was significantly lower than preoperative values. (P△SBP < 0.001; P△DBP < 0.001).

Conclusions
MVD is an effective treatment for neurogenic HTN. However, the criteria for selecting hypertensive patients who need MVD to control their HTN still needs to be further determined. Possible indications may include: left trigeminal neuralgia, neurogenic HTN; abnormal blood pressure compression in the left RVLM and REZ areas on MR; and blood pressure in these patients can not be effectively controlled by drugs.
Normal fetal cardiac deformation values in pregnancy; a prospective cohort study protocol
Authors: van Oostrum Noortje H. M. , Oei S. Guid , van Laar Judith O. E. H. 
Published: December 2019

Abstract
Background
Myocardial deformation imaging offers the potential to measure myocardial function. Remodelling, the change in size, shape and function, appears as a result of pressure or volume changes and is thought to be the first sign of fetal adaptation to placental dysfunction. Deformation can be measured using speckle tracking echocardiography (STE). STE in the fetus might be useful for detection and follow up of the fetus endangered by placental dysfunction. Reference values for fetal myocardial deformation during gestation have not been comprehensively described and need further investigation before STE can be introduced in daily clinical practice. The aim of this study is to determine reference values for fetal myocardial deformation throughout gestation in uncomplicated pregnancies.

Methods
A longitudinal cohort will be performed. 150 Women, pregnant from a non-anomalous singleton, will be included from 19 to 21 + 6 weeks gestational age. Thereafter, fetal heart ultrasounds will be performed 4 weekly, until 41 weeks gestational age or delivery. Ultrasound data will be analysed using STE software to determine reference values for fetal cardiac deformation during gestation.

Discussion
Measuring cardiac deformation changes in pregnancy can be a promising tool to detect preclinical cardiac adaptation to placental dysfunction. However, previous studies used different ultrasound scans and STE software resulting in incomparable and contradictory results on deformation values. In this prospective study reference values during pregnancy, cardiac deformation values will be assessed with the same ultrasound and software package in 150 uncomplicated pregnancies.

Trial registration
National Trial Register number: NTR7132. Date of inclusion: 2018/04/06.
Mass incarceration and public health: the association between black jail incarceration and adverse birth outcomes among black women in Louisiana
Authors: Dyer Lauren , Hardeman Rachel , Vilda Dovile , Theall Katherine , Wallace Maeve 
Published: December 2019

Abstract
Background
A growing body of evidence is beginning to highlight how mass incarceration shapes inequalities in population health. Non-Hispanic blacks are disproportionately affected by incarceration and criminal law enforcement, an enduring legacy of a racially-biased criminal justice system with broad health implications for black families and communities. Louisiana has consistently maintained one of the highest rates of black incarceration in the nation. Concurrently, large racial disparities in population health persist.

Methods
We conducted a cross-sectional analysis of all births among non-Hispanic black women in Louisiana in 2014 to identify associations between parish-level (county equivalent) prevalence of jail incarceration within the black population and adverse birth outcomes (N = 23,954). We fit a log-Poisson model with generalized estimating equations to approximate the relative risk of preterm birth and low birth weight associated with an interquartile range increase in incarceration, controlling for confounders. In sensitivity analyses, we additionally adjusted for the parish-level index crime prevalence and analyzed regression models wherein white incarceration was used to predict the risk of adverse birth outcomes in order to quantify the degree to which mass incarceration may harm health above and beyond living in a high crime area.

Results
There was a significant 3% higher risk of preterm birth among black women associated with an interquartile range increase in the parish-level incarceration prevalence of black individuals, independent of other factors. Adjusting for the prevalence of index crimes did not substantively change the results of the models.

Conclusion
Due to the positive significant associations between the prevalence of black individuals incarcerated in Louisiana jails and estimated risk of preterm birth, mass incarceration may be an underlying cause of the persistent inequities in reproductive health outcomes experienced by black women in Louisiana. Not only are there economic and social impacts stemming from mass incarceration, but there may also be implications for population health and health inequities, including the persistence of racial disparities in preterm birth and low birth weight.
A phase 2 study of trametinib for patients with pediatric glioma or plexiform neurofibroma with refractory tumor and activation of the MAPK/ERK pathway: TRAM-01
Authors: Perreault Sébastien , Larouche Valérie , Tabori Uri , Hawkin Cynthia , Lippé Sarah , Ellezam Benjamin , Décarie Jean-Claude , Théoret Yves , Métras Marie-Élaine , Sultan Serge , Cantin Édith , Routhier Marie-Ève , Caru Maxime , Legault Geneviève , Bouffet Éric , Lafay-Cousin Lucie , Hukin Juliette , Erker Craig , Jabado Nada 
Published: December 2019

Abstract
Background
Pediatric low-grade gliomas (PLGG) are the most frequent brain tumors in children. Up to 50% will be refractory to conventional chemotherapy. It is now known that the majority of PLGG have activation of the MAPK/ERK pathway. The same pathway is also activated in plexiform neurofibromas (PNs) which are low-grade tumors involving peripheral nerves in patients with neurofibromatosis type 1 (NF1). These lesions are known to be refractory to chemotherapy. Specific MEK inhibitors such as trametinib are now available and have been approved for other cancers harboring mutations in the MAPK/ERK pathway such as melanoma. We have observed significant responses to trametinib in patients with refractory PLGG in our institutions and results from the phase I study are promising. The treatment appears not only efficacious but is also usually well tolerated. We hypothesize that we will observe responses in the majority of refractory PLGG and PN treated with trametinib in this phase 2 study.

Methods
The primary objective is to determine the objective response rate of trametinib as a single agent for treatment of progressing/refractory tumors with MAPK/ERK pathway activation. The TRAM-01 study is a phase II multicentric open-label basket trial including four groups. Group 1 includes NF1 patients with progressing/refractory glioma. Group 2 includes NF1 patients with plexiform neurofibroma. Group 3 includes patients with progressing/refractory glioma with KIAA1549-BRAF fusion. Group 4 includes other patients with progressing/refractory glioma with activation of the MAPK/ERK pathway. Eligible patients for a given study group will receive daily oral trametinib at full dose for a total of 18 cycles of 28 days. A total of 150 patients will be enrolled in seven Canadian centers. Secondary objectives include the assessment of progression-free survival, overall survival, safety and tolerability of trametinib, serum levels of trametinib and evaluation of quality of life during treatment.

Discussion
Trametinib will allow us to target directly and specifically the MAPK/ERK pathway. We expect to observe a significant response in most patients. Following our study, trametinib could be integrated into standard treatment of PLGG and PN.

Trial registration
ClinicalTrials.gov Identifier: NCT03363217 December 6, 2017.
In vitro activity of a G-quadruplex-stabilizing small molecule that synergizes with Navitoclax to induce cytotoxicity in acute myeloid leukemia cells
Authors: Montoya Justin J. , Turnidge Megan A. , Wai Daniel H. , Patel Apurvi R. , Lee David W. , Gokhale Vijay , Hurley Laurence H. , Arceci Robert J. , Wetmore Cynthia , Azorsa David O. 
Published: December 2019

Abstract
Background
Acute Myeloid Leukemia (AML) is a malignancy of myeloid precursor cells that arise from genomic alterations in the expression of key growth regulatory genes causing cells to assume an undifferentiated state and continue to proliferate. Recent efforts have focused on developing therapies that target specific protein products of aberrantly expressed genes. However, many of the identified proteins are difficult to target and thought to be “undrugable” because of structural challenges, protein overexpression, or mutations that confer resistance to therapy. A novel technology that circumvents some of these issues is the use of small molecules that stabilize secondary DNA structures present in the promoters of many potential oncogenes and modulate their transcription.

Methods
This study characterizes the in vitro activity of the G-quadruplex-stabilizing small molecule GQC-05 in AML cells. The effect of GQC-05 on three AML cell lines was analyzed using viability and apoptosis assays. GQC-05 has been shown to down-regulate MYC through G-quadruplex stabilization in Burkitt’s lymphoma cell lines. MYC expression was evaluated through qPCR and immunoblotting in the three AML cell lines following the treatment of GQC-05. In order to identify other therapeutic agents that potentiate the activity of GQC-05, combination drug screening was performed. The drug combinations were validated using in vitro cytotoxicity assays and compared to other commonly used chemotherapeutic agents.

Results
GQC-05 treatment of KG-1a, CMK and TF-1 cells decreased cell viability and resulted in increased DNA damage and apoptosis. Additionally, treatment of KG-1a, CMK and TF-1 with GQC-05 resulted in decreased expression of MYC mRNA and protein, with a more pronounced effect in KG-1a cells. Combination drug screening identified the Bcl-2/Bcl-XL inhibitor Navitoclax as a compound that potentiated GQC-05 activity. Co-treatment with GQC-05 and Navitoclax showed a synergistic decrease in cell viability of AML cells as determined by Chou-Talalay analysis, and induced more DNA damage, apoptosis, and rapid cytotoxicity. The cytotoxicity induced by GQC-05 and Navitoclax was more potent than that of Navitoclax combined with either cytarabine or doxorubicin.

Conclusion
These results suggest that the G-quadruplex stabilizing small molecule GQC-05 induces down regulated MYC expression and DNA damage in AML cells. Treatment with both GQC-05 with a Bcl-2/Bcl-XL inhibitor Navitoclax results in increased cytotoxic activity, which is more pronounced than Navitoclax or GQC-05 alone, and more significant than Navitoclax in combination with cytarabine and doxorubicin that are currently being used clinically.
Autism spectrum disorder is associated with gut microbiota disorder in children
Authors: Sun Hairong , You Zhong , Jia Libo , Wang Fang 
Published: December 2019

Abstract
Background
The aim of this study was to evaluate the occurrence and clinical characteristics of autism spectrum disorder (ASD) associated to the stable state of the gut microbiota.

Methods
A total of 9 children with ASD and 6 healthy children used as control were selected and feces samples were collected from all of them. The 16S gene ribosomal RNA sequencing was used to analyze the difference in gut microbiota between healthy control children and ASD patients.

Results
The results of 16S sequencing based on operational taxonomic units (OTUs) analysis showed that the ASD group and the healthy control (HC) group had a large difference in the abundance of microbiota at the level of family, genus and species. The abundance of Bacteroidales and Selenomonadales was significantly lower in the ASD group than in the HC group (p = 0.0110 and p = 0.0076, respectively). The abundance of Ruminococcaceae in the ASD group was higher than that in the HC group (p = 0.0285), while the amount of Prevotellaceae was significantly lower in the ASD group than in the HC group (p = 0.0111). The Tax4Fun analysis based on Kyoto Encyclopaedia of Genes and Genomes (KEGG) data indicated differentially expressed functional pathway between the ASD group and healthy control group associated to the nervous system, environmental information processing and cellular processing.

Conclusions
The abundance of gut microbiota in the ASD group is different from that in the healthy control children. These differences affect the biological function of the host. These results suggest that a disorder in the gut microbiota may be associated, at least in part, with ASD in children.