bluuebunny/crossref_metadata_2025_split huggingface dataset:
Clinical Trial of the Potassium Channel Activator Diazoxide for Major Depressive Disorder Halted Due to Intolerability
Authors: Kadriu Bashkim , Yuan Shiwen , Farmer Cristan , Nugent Allison C. , Lener Marc S. , Niciu Mark J. , Park Minkyung , Yazdian Aaron , Ballard Elizabeth D. , Henn Fritz A. , Henter Ioline D. , Park Lawrence T. , Zarate Carlos A. 
Published: March 2018

Abstract

Background
Some glutamatergic modulators have demonstrated rapid and relatively sustained antidepressant properties in patients with major depressive disorder. Because the potassium channel activator diazoxide increases glutamate uptake via potassium channel activation, we hypothesized that it might exert antidepressant effects by increasing the removal of glutamate from the synaptic cleft, thereby reducing excessive glutamate transmission.

Methods
This randomized, double-blind, placebo-controlled, crossover, single-site inpatient clinical study was conducted at the National Institute of Mental Health to assess the efficacy and safety of a 3-week course of diazoxide (200–400 mg daily, twice a day) versus a 3-week course of placebo in 6 participants with treatment-refractory major depressive disorder. The primary clinical outcome measure was change in Montgomery-Asberg Depression Rating Scale score from baseline to posttreatment. Quantitative insulin sensitivity check index, as well as concomitant imaging measures (electroencephalography, proton magnetic resonance spectroscopy, magnetoencephalography), were used as potential surrogate markers of target (KATP channel) engagement.

Results
The study was halted due to severe adverse effects. Given the small sample size, statistical evaluation of the effect of diazoxide on Montgomery-Asberg Depression Rating Scale scores or the imaging measures was not pursued. Visual inspection of the quantitative insulin sensitivity check index test revealed no evidence of target engagement.

Conclusions
Although the results are negative, they are an important addition to the literature in this rapidly changing field.
Risk Factors for Anal Dysplasia in Transgender Women: A Retrospective Chart Review
Authors: Fein Lydia A. , Rosa Cunha Isabella , Slomovitz Brian , Potter JoNell 
Published: March 2018

Objective
The aim of the study was to assess risk factors for anal human papillomavirus (HPV) infection and anal dysplasia among a cohort of transgender women (TGW).

Methods
A retrospective chart review was conducted based on electronic medical records of TGW patients seen in the University of Miami Health System between 2010 and 2016. Outcome measures included risk factors of anal dysplasia, including HIV infection, receptive anal intercourse, and smoking history. Descriptive statistical analysis and χ2 testing were used.

Results
Sixty-nine TGW patients' charts were reviewed. Patients' ages ranged from 18 to 72 (mean = 38 [15]). Twenty-two (30%) were older than 50 years; 10 (15%) were black/African descent; 20 (29%) reported a smoking history; 6 (9%) were HIV positive, and 28 (72%) among those with known partner preference (n = 39) reported male partners. Male partner preference was significantly associated with being black/African descent (p = .009) and being single (p = .048). Older age was significantly associated with HIV-positive status (p = .023). The average number of risk factors per person was 2.10 (0.97). Sixty-one years or older had the highest average number of risk factors (2.90 [0.88]).

Conclusions
Because rates of HIV, dangerous sexual behaviors, and other risk factors for anal dysplasia continue to persist among TGW, this study reinforces the need to increase the focus on anal health in the care of TGW and the need for further research to guide patient care and anal dysplasia screening strategies among those individuals.
Esophageal pressure monitoring: why, when and how?
Authors: Yoshida Takeshi , Brochard Laurent 
Published: March 2018

Purpose of review
Esophageal manometry has shown its usefulness to estimate transpulmonary pressure, that is lung stress, and the intensity of spontaneous effort in patients with acute respiratory distress syndrome. However, clinical uptake of esophageal manometry in ICU is still low. Thus, the purpose of review is to describe technical tips to adequately measure esophageal pressure at the bedside, and then update the most important clinical applications of esophageal manometry in ICU.

Recent findings
Each esophageal balloon has its own nonstressed volume and it should be calibrated properly to measure pleural pressure accurately: transpulmonary pressure calculated on absolute esophageal pressure reflects values in the lung regions adjacent to the esophageal balloon (i.e. dependent to middle lung). Inspiratory transpulmonary pressure calculated from airway plateau pressure and the chest wall to respiratory system elastance ratio reasonably reflects lung stress in the nondependent ‘baby’ lung, at highest risk of hyperinflation. Also esophageal pressure can be used to detect and minimize patient self-inflicted lung injury.

Summary
Esophageal manometry is not a complicated technique. There is a large potential to improve clinical outcome in patients with acute respiratory distress syndrome, acting as an early detector of risk of lung injury from mechanical ventilation and vigorous spontaneous effort.
Chapter 1. The Historical Roots of Paediatric Gastroenterology, Hepatology, and Nutrition
Authors: Weaver Lawrence T. 
Published: March 2018

ABSTRACTThe last 50 years have seen the establishment of paediatric gastroenterology, hepatology, and nutrition (PGHAN) as a well‐recognised and thriving clinical specialty throughout most of Europe, and further afield. This has happened, in part, through the existence of the European Society for Paediatric Gastroenterology and Nutrition (ESPGHAN) as a forum for those interested in this branch of children's medicine. To illustrate the pan‐European roots of PGHAN, some key scientific and medical events, discoveries, and inventions relevant to 3 common clinical problems—diarrhoea, jaundice, and infant‐feeding—have been chosen to survey the historical development of the ways in which each was understood and treated within the changing thinking and practice of past times. Together they are used to trace the prehistory of ESPGHAN and provide a background against which to explain the genesis of the Society and how its spheres of clinical and scientific interest came to be defined.
Detection of Cytomegalovirus in Colonic Mucosa of Children With Inflammatory Bowel Disease
Authors: El‐Matary Wael , Stefanovici Camelia , Van Caeseele Paul , Deora Vini , McCurdy Jeff 
Published: March 2018

ABSTRACTObjectives:Although it has been recommended to perform sigmoidoscopy to screen for cytomegalovirus (CMV) reactivation in acute severe colitis, the frequency of CMV reactivation in children with inflammatory bowel disease (IBD) is unknown. The aim of this study was to determine the frequency and management of CMV detection in colonic mucosa of children with IBD.Methods:In a retrospective study, consecutive IBD patients, <17 years old, with moderate to severe colitis who had sigmoid biopsy specimens evaluated for CMV by hematoxylin and eosin (H&E) staining, immunohistochemistry (IHC), and polymerase chain reaction (PCR) were included.Results:A total of 90 sigmoid biopsies were collected from 67 patient encounters from 58 patients with colitis: 61 patient encounters (91%) with UC/IBD‐U including biopsy samples from colectomy specimens of eight patients who had colectomy during the study period. Medication exposure included corticosteroids for 40 (69%) patients, and immunosuppressive agents for 31 (53.4%) patients. Four of 61 patient encounters (6.6%) with UC/IBD‐U, two with corticosteroid refractory disease, had positive biopsies for CMV by PCR but negative H&E and IHC. They responded to escalated medical therapy, without needing anti‐viral therapy, and none required colectomy over a median duration of follow up of 1.1 year (IQR 1–1.6).Conclusions:CMV presence is uncommon in colonic mucosa of children with IBD. Studies examining the underlying sero‐prevalence of CMV and its role of reactivation of colitis are required to determine if the current recommendation for routine sigmoidoscopy to exclude CMV infection in corticosteroid‐refractory acute severe colitis is justified.
The Membrane‐bound O‐Acyltransferase7 rs641738 Variant in Pediatric Nonalcoholic Fatty Liver Disease
Authors: Di Sessa Anna , Umano Giuseppina Rosaria , Cirillo Grazia , Del Prete Angela , Iacomino Roberta , Marzuillo Pierluigi , del Giudice Emanuele Miraglia 
Published: March 2018

ABSTRACTBackground:The rs641738 polymorphism in the membrane‐bound O‐acyltransferase domain containing protein 7 (MBOAT7) gene has been associated with increased risk of nonalcoholic fatty liver disease (NAFLD).Objectives:To investigate the association between the MBOAT7 rs641738 polymorphism and both hepatic steatosis and biochemical markers of liver damage and to evaluate the potential additive effect of this variant and the I148M patatin‐like phospholipase domain‐containing 3 (PNPLA3) and the rs58542926 transmembrane 6 superfamily member 2 (TM6SF2) polymorphisms.Methods:One thousand and 2 obese children were genotyped for MBOAT7, PNPLA3, and TM6SF2 polymorphisms and underwent anthropometrical, ultrasonographic, and biochemical evaluation. Indirect measurement of liver fibrosis (Pediatric NAFLD Fibrosis Index [PNFI]) and a genetic risk score from these polymorphisms were calculated.Results:Carriers of the MBOAT7 T allele showed both higher alanine transaminase (ALT) (P = 0.004) and PNFI values (P = 0.04) than noncarriers. These findings were confirmed also for the carriers of the MBOAT7 T allele polymorphism with hepatic steatosis compared with noncarriers. A higher genetic risk score was associated with higher ALT (P = 0.011) and with an odds ratio (OR) to show elevated ALT of 3.4 (95% CI 1.3–5.5, P = 0.003). Patients belonging to genetic risk score 3 group had an OR to present steatosis of 2.6 (95% CI 1.43–4.83, P = 0.0018) compared with those belonging to lower genetic risk score group.Conclusions:We first demonstrated in childhood obesity the role of the MBOAT7 rs641738 variant on serum ALT and the combined effect of the MBOAT7, PNPLA3, and TM6SF2 variants on NAFLD risk. We also provided the first pediatric association of the MBOAT7 polymorphism with indirect markers of liver fibrosis.
Gavage Feed Volume Determines the Gastric Emptying Rate in Preterm Infants
Authors: Ferreira Cristina H.F. , Martinez Francisco E. , Crott Gerson C. , Belik Jaques 
Published: March 2018

ABSTRACTObjective:Feeding intolerance, manifesting as increased gastric residual, is a common finding in preterm neonates. Little is known about the regulation of gastric emptying early in life and the extent to which this plays a role in the preterm infants’ feeding tolerance. The goal of this study was to evaluate clinically stable 28‐ to 32‐week gestation neonates during the first 4 weeks of life and noninvasively determine their gastric emptying rate.Study design:Ultrasound measurements of gastric milk content volume were obtained from 25 neonates immediately after, 30 and/or 60 minutes following routine gavage feeds. The content emptying rate was calculated from the gastric volume data.Results:Gastric emptying rate was not postnatal age‐dependent, was significantly higher at 30 minutes, whenever compared with 60‐minute postfeed and directly proportional to the feed volume. At any postnatal age, the gastric emptying rate was at least 6‐fold greater, when comparing the lowest and highest average stomach content volumes.Conclusions:The gastric emptying rate of preterm infants is content volume‐dependent and unrelated to the postnatal age. Given the present findings, further investigation on the gastric residual of preterm infants receiving larger than currently administered feed volumes at the initiation of enteral nutrition, is warranted.
Thiopurine Optimization Through Combination With Allopurinol in Children With Inflammatory Bowel Diseases
Authors: Serpico Mark R. , Maltz Ross , Crandall Wallace , Bricker Josh , Dotson Jennifer L. , Kim Sandra C. , Boyle Brendan 
Published: March 2018

ABSTRACTObjectives:Thiopurines are commonly used in the maintenance of remission for children with inflammatory bowel diseases (IBDs). Variation in drug metabolism may affect hepatotoxicity or therapeutic effect. We aimed to describe our center's experience with thiopurine optimization through the use of reduced thiopurine dosing in combination with allopurinol upon hepatotoxicity, drug metabolite levels, and clinical outcomes in children with IBD.Methods:Patients aged 2 to 21 years with IBD treated with the combination of thiopurines/allopurinol between 2008 and 2015 were retrospectively reviewed. Patients previously treated with antitumor necrosis factor therapy were excluded. Demographic data, transaminase levels (aspartate transaminase, alanine transaminase), drug metabolites levels (6‐thioguanine [6‐TG], 6‐methylmercaptopurine), physician global assessment, and corticosteroid use were recorded at baseline, 6, and 12 months.Results:Fifty‐two patients (29 girls, 56%) met inclusion criteria. Thirty‐two of 52 (62%) remained on the combination for 12 months. In those remaining on the thiopurine/allopurinol combination, median alanine transaminase and aspartate transaminase levels were reduced (P < 0.001) and median 6‐TG levels were increased (P < 0.001) at both 6 and 12 months. Corticosteroid use was decreased at both 6 (P < 0.001) and 12 months (P < 0.001) compared to use at baseline. Remission rates also improved at both 6 (P = 0.013) and 12 months (P = 0.003). Twenty of the 52 patients (38%) had discontinued the thiopurine/allopurinol combination within 12 months of initiation with 17 of 52 (33%) initiating antitumor necrosis factor therapy.Conclusions:Low‐dose thiopurines in combination with allopurinol improved hepatotoxicity and increased 6‐TG levels in children with IBD. Corticosteroid use was reduced and remission rates improved in those patients remaining on this combination for 1 year. However, approximately 40% of patients required a change in therapy within 12 months.
Brief Report: Differential Timing of Cholesterol Increase During Successful HCV Therapy: Impact of Type of Drug Combination
Authors: Rivero-Juarez Antonio , Camacho Angela , Brieva Teresa , Frias Mario , Lopez-Lopez Pedro , Risalde María A. , Machuca Isabel , Caston Juan J. , Martínez-Peinado Antonio , Rivero Antonio 
Published: March 2018

Objective:
To evaluate factors associated with increased serum cholesterol levels during interferon-free hepatitis C virus (HCV) therapy.

Design:
Prospective longitudinal study.

Methods:
HIV-infected patients who started and successfully completed interferon-free therapy for chronic HCV infection were included. Patients were treated using 2 different regimens, based on the clinician's opinion: sofosbuvir and ledipasvir (SOF/LDV), or paritaprevir coadministered with ombitasvir and dasabuvir (PrOD). Both total cholesterol and low-density lipoprotein cholesterol were evaluated at baseline, weeks 1, 2, 4, 8, end of treatment (EOT), weeks SVR4, SVR12, and SVR24.

Results:
The study population therefore comprised 85 patients reaching sustained virological response, 42 (49.4%) of whom were treated with SOF/LDV, and 43 (50.6%) with PrOD. Patients using SOF/LDV was showed a higher increase on both total cholesterol and low-density lipoprotein cholesterol during treatment period than those receiving PrOD. Analyzing the overall increase from baseline to weeks 1, 2, 4, 8, and EOT, choice of HCV regimen was associated with differential increases in total cholesterol during therapy. After EOT, no differences were found between SOF/LDV and PrOD with respect to total cholesterol.

Conclusions:
Our study suggests that the differential timing of the restoration of cholesterol metabolism in HIV/HCV genotype 1 coinfected patients achieving sustained virological response is not mediated by HCV clearance but depends on the drug combination used.
Normative Data for the Low Anterior Resection Syndrome Score (LARS Score)
Authors: Juul Therese , Elfeki Hossam , Christensen Peter , Laurberg Søren , Emmertsen Katrine J. , Bager Palle 
Published: March 2018

Objective:
To provide normative data for the Low Anterior Resection Syndrome (LARS) score.

Background:
The LARS score is a validated and frequently used tool measuring bowel dysfunction after sphincter sparing surgery for rectal cancer. The interpretation of LARS score results has previously been limited by the lack of normative data.

Methods:
An age and sex-stratified random sample of 3440 citizens from the general population was drawn from the Danish civil registration system (age range 20–89 years, 50% females). A brief questionnaire including the LARS score and health-related items were distributed electronically or by post.

Results:
A total of 1875 (54.5%) responded, 54.0% were females. In the age group 50 to 79 years, relevant for most rectal cancer studies, the response rate was 70.5% (n = 807). In this specific age group, 18.8% of the females and 9.6% of the males had a LARS score ≥30, corresponding to the LARS score category “major LARS” (P = 0.001), and the median (interquartile range) LARS score was 16 (7–26) and 11 (4–22), respectively (P < 0.001). Responders with physical disease had a statistically significant higher risk of a LARS score ≥30, compared with responders without any physical disease (odds ratio 2.2, 95% confidence interval 1.6–2.9, P < 0.001).

Conclusions:
A LARS score ≥30 (major LARS) is common in the general population, especially in the age group 50 to 79 years. Normative data for the LARS score are now available and can be taken into account when interpreting LARS score results in scientific studies of bowel function after rectal cancer treatment.
Discovery of directional chromatin-associated regulatory motifs affecting human gene transcription
Authors: Osato Naoki 
Published: March 2018

AbstractBackgroundChromatin interactions are essential in enhancer-promoter interactions (EPIs) and transcriptional regulation. CTCF and cohesin proteins located at chromatin interaction anchors and other DNA-binding proteins such as YY1, ZNF143, and SMARCA4 are involved in chromatin interactions. However, there is still no good overall understanding of proteins associated with chromatin interactions and insulator functions.ResultsHere, I describe a systematic and comprehensive approach for discovering DNA-binding motifs of transcription factors (TFs) that affect EPIs and gene expression. This analysis identified 96 biased orientations [64 forward-reverse (FR) and 52 reverse-forward (RF)] of motifs that significantly affected the expression level of putative transcriptional target genes in monocytes, T cells, HMEC, and NPC and included CTCF, cohesin (RAD21 and SMC3), YY1, and ZNF143; some TFs have more than one motif in databases; thus, the total number is smaller than the sum of FRs and RFs. KLF4, ERG, RFX, RFX2, HIF1, SP1, STAT3, and AP1 were associated with chromatin interactions. Many other TFs were also known to have chromatin-associated functions. The predicted biased orientations of motifs were compared with chromatin interaction data. Correlations in expression level of nearby genes separated by the motif sites were then examined among 53 tissues.ConclusionOne hundred FR and RF orientations associated with chromatin interactions and functions were discovered. Most TFs showed weak directional biases at chromatin interaction anchors and were difficult to identify using enrichment analysis of motifs. These findings contribute to the understanding of chromatin-associated motifs involved in transcriptional regulation, chromatin interactions/regulation, and histone modifications.
Targeted Gene Bisulfite Sequencing Identifies Differential Methylation in p21
Authors: Kolli Ramya T. , Glenn Travis C. , Brown Bradley T. , Barnett Lillie M. , Lash Lawrence H. , Cummings Brian S. 
Published: March 2018

AbstractNext-generation sequencing (NGS) methods are widely available to assess methylation of whole-genomes, reduced representation of genomes, and target capture of many loci, but simple, flexible, and low-cost methods are needed to leverage NGS for sequencing single-locus amplicons from large numbers of samples. We developed a two-stage PCR approach, targeted gene bisulfite sequencing (TGBS) which uses the Illumina MiSeq and Bismark bisulfite mapper, to assess site specific changes in methylation of the cyclin-dependent kinase inhibitor p21 (CDKN1a) after exposure to a DNA methyltransferase inhibitor, 5-aza-2’-deoxycytidine (5-Aza) and determine the differences between human and rat p21 methylation. TGBS analysis of human embryonic kidney cells (HEK293) and human proximal tubular cells (hPT) demonstrated variation at a known methylation sensitive site (SIE-1), but not in rat kidney cells. Treatment of cells with 5-Aza altered the methylation of this site in correlation with increased p21 protein expression. We also found that human and rat p21 promoter sequences differ considerably in the amount of basal DNA methylation. These data showed the utility of TGBS for rapid analysis of DNA methylation of specific loci. We provide links to a ready-to-run Virtualbox that includes the program and commands for methylation analysis of bisulfite datasets, including step-by-step directions.
Does the use of honorific appellations in audit reports connote higher financial misstatement risk? Evidence from China
Authors: Chen Feng , Du Xingqiang , Lai Shaojuan , Ma Mary 
Published: March 2018

Purpose
From the sociolinguistic perspective, the purpose of this paper is to examine whether the honorific and actual-name appellations that Chinese auditors use to address clients in audit reports connote differential financial misstatement risk. Specifically, the authors hypothesize that auditors’ use of honorifics signals their inferior social status relative to their clients, thereby leading to compromised auditor independence, lower audit quality, and higher financial misstatement risk.

Design/methodology/approach
The authors use a sample of manually coded appellation data from audit reports of Chinese public firms between 2003 and 2012 to conduct the research.

Findings
The authors find significantly greater financial misstatements, both in terms of likelihoods and magnitudes, for companies addressed by honorifics than for those addressed by actual names. Moreover, compared to auditors’ consistent honorific usage, discretionary honorific usage has a stronger positive association with misstatements. The authors further show that the positive association between honorific usage and client misstatement risk weakens when the audit firm is a Top 10 accounting firms in China, is an industry specialist, is formed as a partnership, or resides in a more concentrated audit market.

Originality/value
This study contributes to the sociolinguistics literature in accounting and provides evidence supporting the reform proposed by the International Auditing and Assurance Standards Board to enhance the usefulness of audit reporting.