bluuebunny/crossref_metadata_2025_split huggingface dataset:
Ertugliflozin Compared with Glimepiride in Patients with Type 2 Diabetes Mellitus Inadequately Controlled on Metformin: The VERTIS SU Randomized Study
Authors: Hollander Priscilla , Liu Jie , Hill Julie , Johnson Jeremy , Jiang Zhi Wei , Golm Gregory , Huyck Susan , Terra Steven G. , Mancuso James P. , Engel Samuel S. , Lauring Brett 
Published: December 2017

Abstract
Introduction
This study assessed the safety and efficacy of ertugliflozin (an oral sodium-glucose cotransporter 2 inhibitor) vs. glimepiride in patients with type 2 diabetes mellitus (T2DM) inadequately controlled on metformin.

Methods
This phase III, double-blind, non-inferiority study (NCT01999218) randomized patients with HbA1c ≥ 7.0% and ≤ 9.0% on stable metformin ≥ 1500 mg/day 1:1:1 to ertugliflozin 15 or 5 mg once-daily (QD), or glimepiride (titrated from 1 mg QD). The primary hypothesis was that ertugliflozin 15 mg was non-inferior to glimepiride on HbA1c (non-inferiority criterion: upper bound of the 95% confidence interval [CI] about the treatment difference < 0.3%).

Results
Mean baseline HbA1c of randomized patients (N = 1326) was 7.8%. Mean and median doses of glimepiride were 3.0 mg/day throughout the study. At week 52, the least squares mean change (95% CI) from baseline in HbA1c was − 0.6% (− 0.7, − 0.5), − 0.6% (− 0.6, − 0.5), and − 0.7% (− 0.8, − 0.7) in the ertugliflozin 15 mg, ertugliflozin 5 mg, and glimepiride groups, respectively. The between-group difference for ertugliflozin 15 mg and glimepiride of 0.1% (− 0.0, 0.2) met the pre-specified non-inferiority criterion. Relative to glimepiride, greater body weight and systolic blood pressure (SBP) reductions were observed with ertugliflozin. The overall incidence of adverse events (AEs) was similar across groups. The incidence of symptomatic hypoglycemia and genital mycotic infection (GMI) were, respectively, lower and higher with ertugliflozin relative to glimepiride. The incidences of urinary tract infection and hypovolemia AEs were not meaningfully different among the groups.

Conclusions
Ertugliflozin 15 mg was non-inferior to glimepiride in reducing HbA1c when added to metformin in patients with T2DM. Ertugliflozin had an acceptable safety profile and resulted in less hypoglycemia and more GMIs than glimepiride.

Clinical Trial Registration
Clinicaltrials.gov NCT01999218.
Violence in Brazilian schools: Analysis of the effect of the #Tamojunto prevention program for bullying and physical violence
Authors: Gusmões Júlia D.S.P. , Sañudo Adriana , Valente Juliana Y. , Sanchez Zila M. 
Published: December 2017

ABSTRACTA randomized controlled trial was conducted with 6637 7th‐ and 8th‐grade students in 72 public schools in 6 Brazilian cities to evaluate the effects of the European drug prevention program Unplugged, called #Tamojunto in Brazil. This article evaluates the effects of #Tamojunto on the prevention of bullying and physical violence. Baseline data were collected from both intervention and control groups prior to program implementation. Follow‐up data collection was performed 9 and 21 months later. Generalized estimating equations were used to evaluate changes in the reporting of receiving or practicing bullying and physical violence over time. The program was found to reduce the likelihood of receiving bullying, particularly in the stratum of girls aged 13–15 years at the 9‐month follow‐up time point. The effect was not sustained at 21 months. There was no significant effect for practicing bullying and for receiving or practicing physical violence.
Perianal hidradenoma papilliferum
Authors: Rosetti Filho Eduardo , Formiga Fernanda Bellotti , Miotto Sabrina , Formiga Galdino José Sitonio 
Published: December 2017

AbstractHidradenoma papilliferum is a benign cystic tumor originated in apocrine sweat glands of the anogenital region. It is common in vulvar topography and rare in the perianal region. A well-documented case of a patient with slow-growing perianal nodulation without pain or other symptoms is reported. The histological study shows a hidradenoma papilliferum. The article reviews the topic and discusses the importance of the differential diagnosis of proctological conditions. A biopsy is mandatory in anal lesions of unusual presentation.
Three-dimensional virtual reconstruction as a tool for preoperative planning in the management of complex anorectal fistulas
Authors: Sousa Júnior Edilson Carvalho , Nogueira Alexandre Tolstenko , Rocha Bruno Aragão , Eulálio Filho Walberto Monteiro Neiva , Meneses Aurus Dourado 
Published: December 2017

AbstractThe making of three-dimensional virtual models is a promising technology in preoperative planning, but that is not used in the treatment of anorectal fistulas. The objective of this work is to describe the development and initial experience of the construction of a virtual three-dimensional model of the pelvic anatomy of a patient, allowing the exact identification of the relationships between the fistulous tracts of complex anorectal fistulas and the other pelvic structures. An MRI was performed on this patient, and the images were exported to the Vitrea fX Workstation® software. A radiologist did the analysis and segmentation of the images that were then sent to a three-dimensional image processor (Meshlab v. 1.3.3 – ISTI – CNR Research Center, Pisa University, Italy). The final 3D color image was analyzed by the surgeon and used to guide the catheterization of the fistulous pathways, the internal orifice and to assist in the identification of adjacent structures. The final three-dimensional model presented a high correlation with the intraoperative findings and facilitated the surgical planning.
Childhood Abuse Experiences and the COMT and MTHFR Genetic Variants Associated With Male Sexual Orientation in the Han Chinese Populations: A Case-Control Study
Authors: Qin Jia-Bi , Zhao Guang-Lu , Wang Feng , Cai Yu-Mao , Lan Li-Na , Yang Lin , Feng Tie-Jian 
Published: December 2017

Abstract

Background
Although it is widely acknowledged that genetic and environmental factors are involved in the development of male homosexuality, the causes are not fully understood.

Aim
To explore the association and interaction of childhood abuse experiences and genetic variants of the catechol-O-methyltransferase (COMT) and methylenetetrahydrofolate reductase (MTHFR) genes with the development of male homosexuality.

Methods
A case-control study of 537 exclusively homosexual men and 583 exclusively heterosexual men was conducted, with data collected from March 2013 to August 2015. Data were analyzed using χ2 tests and logistic regression models.

Outcomes
Sociodemographic characteristics, childhood abuse experiences, and polymorphisms of COMT at rs4680, rs4818, and rs6267 and MTHFR at rs1801133.

Results
More frequent occurrence of physical (adjusted odds ratio [aOR] = 1.78), emotional (aOR = 2.07), and sexual (aOR = 2.53) abuse during childhood was significantly associated with the development of male homosexuality. The polymorphisms of MTHFR at rs1801133 and COMT at rs4818 also were significantly associated with the development of male homosexuality in the homozygote comparisons (T/T vs C/C at rs1801133, aOR = 1.68; G/G vs C/C at rs4818, aOR = 1.75). In addition, significant interaction effects between childhood abuse experiences and the COMT and MTHFR genetic variants on the development of male homosexuality were found.

Clinical Translation
This is the first time that an association of childhood abuse, COMT and MTHFR genetic variants, and their interactions with development of male homosexuality was exhaustively explored, which could help provide new insight into the etiology of male homosexuality.

Strengths and Limitations
Because homosexual men are a relatively obscure population, it was impossible to select the study participants by random sampling, which could lead to selection bias. In addition, because this was a case-control study, recall bias was inevitable, and we could not verify causality.

Conclusions
Childhood abuse and the COMT and MTHFR genetic variants could be positively associated with the development of homosexuality. However, it remains unknown how these factors jointly play a role in the development of homosexuality, and more studies in different ethnic populations and with a larger sample and a prospective design are required to confirm our findings.
One Session of Autogenic Training Increases Acute Subjective Sexual Arousal in Premenopausal Women Reporting Sexual Arousal Problems
Authors: Stanton Amelia M. , Hixon J. Gregory , Nichols Lindsey M. , Meston Cindy M. 
Published: December 2017

Abstract

Background
Below average heart rate variability (HRV) has been associated with sexual arousal dysfunction and overall sexual dysfunction in women. Autogenic training, a psychophysiologic relaxation technique, has been shown to increase HRV. In a recent study, sexually healthy women experienced acute increases in physiologic (ie, genital) and subjective sexual arousal after 1 brief session of autogenic training.

Aim
To build on these findings by testing the effects of a single session of autogenic training on sexual arousal in a sample of women who reported decreased or absent sexual arousal for at least 6 months.

Methods
Genital sexual arousal, subjective sexual arousal, and perceived genital sensations were assessed in 25 women 20 to 44 years old before and after listening to a 22-minute autogenic training recording. HRV was assessed with electrocardiography.

Outcomes
Change in genital sexual arousal, subjective sexual arousal, and perceived genital sensations from the pre-manipulation erotic film to the post-manipulation erotic film.

Results
Marginally significant increases in discrete subjective sexual arousal (P = .051) and significant increases in perceived genital sensations (P = .018) were observed. In addition, degree of change in HRV significantly moderated increases in subjective arousal measured continuously over time (P &lt; .0001). There were no significant increases in genital arousal after the manipulation.

Clinical Implications
The results of this study suggest that autogenic training, and other interventions that aim to increase HRV, could be a useful addition to treatment protocols for women who are reporting a lack of subjective arousal or decreased genital sensations.

Strengths and Limitations
There are few treatment options for women with arousal problems. We report on a new psychosocial intervention that could improve arousal. Limitations include a relatively small sample and the lack of a control group.

Conclusion
Our findings indicate that autogenic training significantly improves acute subjective arousal and increases perceived genital sensations in premenopausal women with self-reported arousal concerns.
The British Rhinological Society multidisciplinary consensus recommendations on the hospital management of epistaxis
Authors:   INTEGRATE (The National ENT Trainee Research Network)
Published: December 2017

AbstractObjective:Epistaxis is a common ENT emergency in the UK; however, despite the high incidence, there are currently no nationally accepted guidelines for its management. This paper seeks to recommend evidence-based best practice for the hospital management of epistaxis in adults.Methods:Recommendations were developed using an Appraisal of Guidelines for Research and Evaluation (‘AGREE II’) framework. A multifaceted systematic review of the relevant literature was performed and a multidisciplinary consensus event held. Management recommendations were generated that linked the level of supporting evidence and a Grading of Recommendations Assessment, Development and Evaluation (‘GRADE’) score explaining the strength of recommendation.Recommendations:Despite a paucity of high-level evidence, management recommendations were formed across five management domains (initial assessment, cautery, intranasal agents, haematological factors, and surgery and radiological intervention).Conclusion:These consensus recommendations combine a wide-ranging review of the relevant literature with established and rigorous methods of guideline generation. Given the lack of high-level evidence supporting the recommendations, an element of caution should be used when implementing these findings.
Intranasal cautery for the management of adult epistaxis: systematic review
Authors: Mcleod R W J , Price A , Williams R J , Smith M E , Smith M , Owens D 
Published: December 2017

AbstractBackground:Cauterisation techniques are commonly used and widely accepted for the management of epistaxis. This review assesses which methods of intranasal cautery should be endorsed as optimum treatment on the basis of benefits, risks, patient tolerance and economic assessment.Method:A systematic review of the literature was performed using a standardised methodology and search strategy.Results:Eight studies were identified: seven prospective controlled trials and one randomised controlled trial. Pooling of data was possible from 3 studies, yielding a total of 830 patients. Significantly lower re-bleed rates were identified (p< 0.01) using electrocautery (14.5 per cent) when compared to chemical cautery (35.1 per cent). No evidence suggested that electrocautery was associated with more adverse events or discomfort. Limited evidence supported the use of a vasoconstrictor agent and operating microscope during the procedure. The included studies had considerable heterogeneity in terms of design and outcome measures.Conclusion:Consistent evidence suggests that electrocautery has higher success rates than chemical cautery, and is not associated with increased complications or patient discomfort. Lower quality evidence suggests that electrocautery reduces costs and duration of hospital stay.
Intranasal packs and haemostatic agents for the management of adult epistaxis: systematic review
Authors: Iqbal I Z , Jones G H , Dawe N , Mamais C , Smith M E , Williams R J , Kuhn I , Carrie S 
Published: December 2017

AbstractBackground:The mainstay of management of epistaxis refractory to first aid and cautery is intranasal packing. This review aimed to identify evidence surrounding nasal pack use.Method:A systematic review of the literature was performed using standardised methodology.Results:Twenty-seven eligible articles were identified relating to non-dissolvable packs and nine to dissolvable packs. Nasal packing appears to be more effective when applied by trained professionals. For non-dissolvable packs, the re-bleed rates for Rapid Rhino and Merocel were similar, but were higher with bismuth iodoform paraffin paste packing. Rapid Rhino packs were the most tolerated non-dissolvable packs. Evidence indicates that 96 per cent of re-bleeding occurs within the first 4 hours after nasal pack removal. Limited evidence suggests that dissolvable packs are effective and well tolerated by patients. There was a lack of evidence relating to: the duration of pack use, the economic effects of pack choice and the appropriate care setting for non-dissolvable packs.Conclusion:Rapid Rhino packs are the best tolerated, with efficacy equivalent to nasal tampons. FloSeal is easy to use, causes less discomfort and may be superior to Merocel in anterior epistaxis cases. There is no strong evidence to support prophylactic antibiotic use.
Haematological factors in the management of adult epistaxis: systematic review
Authors: Williams A , Biffen A , Pilkington N , Arrick L , Williams R J , Smith M E , Smith M , Birchall J 
Published: December 2017

AbstractBackground:The management of epistaxis requires an understanding of haematological factors that may complicate its treatment. This systematic review includes six distinct reviews examining the evidence supporting epistaxis-specific management strategies relating to warfarin, direct oral anticoagulants, heparin, antiplatelet agents, tranexamic acid and transfusion.Method:A systematic review of the literature was performed using a standardised methodology and search strategy.Results:Limited numbers of articles were identified in each systematic review, with level 1 evidence only regarding the use of tranexamic acid. No studies met the inclusion criteria within the heparin, direct oral anticoagulants or transfusion systematic reviews. Many studies were limited by small sample sizes and significant risk of bias.Conclusion:The management of major bleeding and transfusion practice is well documented in national guidance from multiple sources. The guidelines include advice on anticoagulants, antiplatelet agents and tranexamic acid. In the absence of more specific evidence, these guidelines should be applied in the management of epistaxis.
Human Rights in the Paris Agreement: Too Little, Too Late?
Authors: Adelman Sam 
Published: December 2017

AbstractThis article examines the impact of the Paris Agreement on the human rights of communities who are particularly vulnerable to the impacts of anthropogenic warming because of their geographical location, their spiritual and cultural connections with land and the wider environment, and their histories of colonialism, dispossession and other forms of exploitation. It focuses on two groups: forest dwellers, and inhabitants of small island developing states who are in danger of inundation as a result of rising sea levels. The Paris Agreement on climate change includes stand-alone articles on reducing emissions from deforestation and forest degradation (REDD+), and loss and damage. The main argument in this article is that the inclusion of human rights in the Preamble to the Paris Agreement is a step forward, but is incommensurate with the scale and urgency of climate change.
Risk factors for arterial versus venous thrombosis in polycythemia vera: a single center experience in 587 patients
Authors: Cerquozzi S. , Barraco D. , Lasho T. , Finke C. , Hanson C. A. , Ketterling R. P. , Pardanani A. , Gangat N. , Tefferi A. 
Published: December 2017

AbstractIn a recent International Working Group on Myeloproliferative Neoplasms Research and Treatment (IWG-MRT) study, prior arterial events and hypertension were predictors of subsequent arterial thrombosis whereas prior venous events and age ≥65 years predicted venous thrombosis in polycythemia vera (PV). In the current study, we sought to validate the above findings and identify additional predictors of arterial versus venous thrombosis. At a median follow up of 109 months, thrombosis after diagnosis occurred in 128 (22%) patients; 82 (14%) arterial and 57 (10%) venous events. On multivariate analysis, prior arterial events (<0.0001), hyperlipidemia (p = 0.03), and hypertension (p = 0.02) predicted subsequent arterial events. In comparison, prior venous events (p = 0.05), leukocytosis ≥11 × 109/L (p = 0.002), and major hemorrhage (p = 0.02) were predictors of subsequent venous events. Salient associations with arterial thrombosis included age ≥ 60 years, hypertension, diabetes, hyperlipidemia and normal karyotype whereas age ≤ 60 years, females, palpable splenomegaly and history of major hemorrhage were associated with venous thrombosis. TET2 or ASXL1 mutations did not impact arterial nor venous thrombosis. In conclusion, we identify distinct associations for arterial versus venous thrombosis in PV and confirm that a prior arterial or venous thrombotic event is the most reliable predictor of subsequent events.
Obligatory and facilitative allelic variation in the DNA methylome within common disease-associated loci
Authors: Bell Christopher G. , Gao Fei , Yuan Wei , Roos Leonie , Acton Richard J. , Xia Yudong , Bell Jordana , Ward Kirsten , Mangino Massimo , Hysi Pirro G. , Wang Jun , Spector Timothy D. 
Published: December 2017

AbstractIntegrating epigenetic data with genome-wide association study (GWAS) results can reveal disease mechanisms. The genome sequence itself also shapes the epigenome, with CpG density and transcription factor binding sites (TFBSs) strongly encoding the DNA methylome. Therefore, genetic polymorphism impacts on the observed epigenome. Furthermore, large genetic variants alter epigenetic signal dosage. Here, we identify DNA methylation variability between GWAS-SNP risk and non-risk haplotypes. In three subsets comprising 3128 MeDIP-seq peripheral-blood DNA methylomes, we find 7173 consistent and functionally enriched Differentially Methylated Regions. 36.8% can be attributed to common non-SNP genetic variants. CpG-SNPs, as well as facilitative TFBS-motifs, are also enriched. Highlighting their functional potential, CpG-SNPs strongly associate with allele-specific DNase-I hypersensitivity sites. Our results demonstrate strong DNA methylation allelic differences driven by obligatory or facilitative genetic effects, with potential direct or regional disease-related repercussions. These allelic variations require disentangling from pure tissue-specific modifications, may influence array studies, and imply underestimated population variability in current reference epigenomes.
Granulocyte-colony stimulating factor controls neural and behavioral plasticity in response to cocaine
Authors: Calipari Erin S. , Godino Arthur , Peck Emily G. , Salery Marine , Mervosh Nicholas L. , Landry Joseph A. , Russo Scott J. , Hurd Yasmin L. , Nestler Eric J. , Kiraly Drew D. 
Published: December 2017

AbstractCocaine addiction is characterized by dysfunction in reward-related brain circuits, leading to maladaptive motivation to seek and take the drug. There are currently no clinically available pharmacotherapies to treat cocaine addiction. Through a broad screen of innate immune mediators, we identify granulocyte-colony stimulating factor (G-CSF) as a potent mediator of cocaine-induced adaptations. Here we report that G-CSF potentiates cocaine-induced increases in neural activity in the nucleus accumbens (NAc) and prefrontal cortex. In addition, G-CSF injections potentiate cocaine place preference and enhance motivation to self-administer cocaine, while not affecting responses to natural rewards. Infusion of G-CSF neutralizing antibody into NAc blocks the ability of G-CSF to modulate cocaine’s behavioral effects, providing a direct link between central G-CSF action in NAc and cocaine reward. These results demonstrate that manipulating G-CSF is sufficient to alter the motivation for cocaine, but not natural rewards, providing a pharmacotherapeutic avenue to manipulate addictive behaviors without abuse potential.
Fasoracetam in adolescents with ADHD and glutamatergic gene network variants disrupting mGluR neurotransmitter signaling
Authors: Elia Josephine , Ungal Grace , Kao Charlly , Ambrosini Alexander , De Jesus-Rosario Nilsa , Larsen Lene , Chiavacci Rosetta , Wang Tiancheng , Kurian Christine , Titchen Kanani , Sykes Brian , Hwang Sharon , Kumar Bhumi , Potts Jacqueline , Davis Joshua , Malatack Jeffrey , Slattery Emma , Moorthy Ganesh , Zuppa Athena , Weller Andrew , Byrne Enda , Li Yun R. , Kraft Walter K. , Hakonarson Hakon 
Published: December 2017

AbstractThe glutamatergic neurotransmitter system may play an important role in attention-deficit hyperactivity disorder (ADHD). This 5-week, open-label, single-blind, placebo-controlled study reports the safety, pharmacokinetics and responsiveness of the metabotropic glutamate receptor (mGluR) activator fasoracetam (NFC-1), in 30 adolescents, age 12–17 years with ADHD, harboring mutations in mGluR network genes. Mutation status was double-blinded. A single-dose pharmacokinetic profiling from 50–800 mg was followed by a single-blind placebo at week 1 and subsequent symptom-driven dose advancement up to 400 mg BID for 4 weeks. NFC-1 treatment resulted in significant improvement. Mean Clinical Global Impressions-Improvement (CGI-I) and Severity (CGI-S) scores were, respectively, 3.79 at baseline vs. 2.33 at week 5 (P < 0.001) and 4.83 at baseline vs. 3.86 at week 5 (P < 0.001). Parental Vanderbilt scores showed significant improvement for subjects with mGluR Tier 1 variants (P < 0.035). There were no differences in the incidence of adverse events between placebo week and weeks on active drug. The trial is registered at https://clinicaltrials.gov/ct2/show/study/NCT02286817.