bluuebunny/crossref_metadata_2025_split huggingface dataset:
Treatment failure and associated factors among first line patients on highly active antiretroviral therapy in Ethiopia: a systematic review and meta-analysis
Authors: Assemie Moges Agazhe , Alene Muluneh , Ketema Daniel Bekele , Mulatu Selishi 
Published: October 2019

Abstract

Background
Antiretroviral therapy (ART) restores immune function and reduces human immunodeficiency virus (HIV) related adverse outcomes. The results of previous studies in Ethiopia were replete with inconsistent findings; nonexistence of national representative figures and determinant factors are found as significant gap. The aim of this systematic review and meta-analysis was to assess the existing evidence on ART treatment failure and associated factors in Ethiopia.

Methods
Relevant studies on ART treatment failure were retrieved from international databases: PubMed, Google Scholar, Scopus, and Science Direct systematically prior to March 14, 2019. All identified studies reporting the proportion of first line treatment failure among HIV patients in Ethiopia were included. Two authors independently extracted all necessary data using a standardized data extraction format. A random-effects model was used to calculate pooled estimates and associated factors in Stata/se Version-14. The Cochrane Q test statistics and I2 tests were used to assess the heterogeneity of the studies.

Results
From 18 articles reviewed; the pooled proportion of first line treatment failure among ART users in Ethiopia was 15.3% (95% CI: 12, 18.6) with (I2 = 97.9%, p < 0.001). The subgroup analysis by World Health Organization (WHO) treatment failure assessment criteria were carried out, accordingly the highest prevalence (11.5%) was noted on immunological and the lowest (5.8%) was observed virological treatment failure. We had found poor adherence (OR = 8.6, 95% CI: 5.6, 13.4), not disclosed (OR = 2.1, 95% CI: 1.5, 3.0), advanced WHO clinical stage III/IV (OR = 2.4, 95% CI: 1.5, 3.8), change in regimen (OR = 2.5, 95% CI: 1.6, 3.9) and being co-infected (OR = 2.56, 95% CI: 2.2, 3.0) were statistically significant factors for treatment failure.

Conclusion
In this study, treatment failure among ART users in Ethiopia was significant. Adherence, co-infection, advanced WHO clinical stage, regimen change, and disclosure are determinant factors for treatment failure. Therefore, improve drug adherence, prevent co-infection, close follow up, and prevent HIV-drug resistance are required in future remedial efforts.
Comprehensive evaluation model of wind power accommodation ability based on macroscopic and microscopic indicators
Authors: Li Gengyin , Li Guodong , Zhou Ming 
Published: October 2019

Abstract
This article explores and establishes comprehensive evaluation index system of wind power accommodation ability considering microscopic index and macroscopic index, and the index system includes conventional evaluation indexes such as forecast deviation, simultaneity factor and anti-peak rate, also newly introduced evaluation indexes such as installed capacity, power adequacy and accommodation space. Bayesian weight modified method is used for solving index weights of 8 wind power accommodation indexes. The paper puts forward a comprehensive evaluation model of wind power accommodation ability based on improved radar chart method, and this model changes traditional radar chart fan-shaped sector to quadrilateral evaluation region, and increasing angle bisector can solve the problem that evaluation results are not unique. It constructs new area and perimeter vectors of radar chart, which make the evaluation results give consideration to level of aggregation and balance degree of evaluation objectives, and case study results show that this model has a certain practical value.
Bone Mineral Density After Transitioning From Denosumab to Alendronate
Authors: Kendler David , Chines Arkadi , Clark Patricia , Ebeling Peter R , McClung Michael , Rhee Yumie , Huang Shuang , Stad Robert Kees 
Published: October 2019

Abstract

Context
There are few studies on patients transitioning from denosumab to bisphosphonates.

Objective
To investigate patient characteristics and changes in bone mineral density (BMD) after transitioning from denosumab to alendronate.

Design
Randomized, open-label, 2-year crossover Denosumab Adherence Preference Satisfaction (DAPS) study (NCT00518531).

Setting
25 study centers in the US and Canada.

Patients
Treatment-naïve postmenopausal women with BMD T-scores from −2.0 to −4.0.

Interventions
This post hoc analysis evaluated women randomized to subcutaneous denosumab 60 mg every 6 months in year 1 followed by once-weekly oral alendronate 70 mg in year 2.

Main Outcome Measure
A 3% BMD threshold identified participants who lost, maintained, or gained BMD in year 2 on alendronate.

Results
Of 126 participants randomized to denosumab, 115 (91%) transitioned to alendronate in year 2. BMD increased by 3% to 6% with denosumab in year 1 and by 0% to 1% with alendronate in year 2. After transitioning to alendronate, most participants maintained or increased BMD; 15.9%, 7.6%, and 21.7% lost BMD at the lumbar spine, total hip, and femoral neck, respectively. Few participants fell below their pretreatment baseline BMD value; this occurred most often in those who lost BMD in year 2. Women who lost BMD with alendronate in year 2 also showed a greater percent change in BMD with denosumab in year 1. The BMD change in year 2 was similar regardless of baseline characteristics or adherence to oral alendronate.

Conclusion
Alendronate can effectively maintain the BMD gains accrued after 1 year of denosumab in most patients, regardless of baseline characteristics.
Real-world Comparison of Afirma GEC and GSC for the Assessment of Cytologically Indeterminate Thyroid Nodules
Authors: San Martin Vicente T , Lawrence Lima , Bena James , Madhun Nabil Z , Berber Eren , Elsheikh Tarik M , Nasr Christian E 
Published: October 2019

Abstract

Context
Molecular tests have improved the accuracy of preoperative diagnosis of indeterminate thyroid nodules. The Afirma Gene Sequencing Classifier (GSC) was developed to improve the specificity of the Gene Expression Classifier (GEC). Independent studies are needed to assess the performance of GSC.

Objective
The aim was to compare the performance of GEC and GSC in the assessment of indeterminate nodules.

Design, Settings, and Participants
Retrospective analysis of Bethesda III and IV nodules tested with GEC or GSC in an academic center between December 2011 and September 2018. Benign call rates (BCRs) and surgical outcomes were compared. Histopathologic data were collected on nodules that were surgically resected to calculate measures of test performance.

Results
The BCR was 41% (73/178) for GEC and 67.8% (82/121) for GSC (P &lt; .001). Among specimens with dominant Hürthle cell cytology, the BCR was 22% (6/27) for GEC and 63.2% (12/19) for GSC (P = .005). The overall surgery rate decreased from 47.8% in the GEC group to 34.7% in the GSC group (P = .025). One GEC-benign and 3 GSC-benign nodules proved to be malignant on surgical excision. GSC had a statistically significant higher specificity (94% vs 60%, P &lt; .001) and positive predictive value (PPV) (85.3% vs 40%, P &lt; .001) than GEC. While sensitivity and negative predictive value (NPV) dropped with GSC (97.0% vs 90.6% and 98.6% vs 96.3%, respectively), these differences were not significant.

Conclusions
GSC reclassified more indeterminate nodules as benign and improved the specificity and PPV of the test. These enhancements appear to be resulting in fewer diagnostic surgeries.
Human Endometrial Transcriptome and Progesterone Receptor Cistrome Reveal Important Pathways and Epithelial Regulators
Authors: Chi Ru-pin Alicia , Wang Tianyuan , Adams Nyssa , Wu San-pin , Young Steven L , Spencer Thomas E , DeMayo Francesco 
Published: October 2019

Abstract

Context
Poor uterine receptivity is one major factor leading to pregnancy loss and infertility. Understanding the molecular events governing successful implantation is hence critical in combating infertility.

Objective
To define Progesterone Receptor (PGR)-regulated molecular mechanisms and epithelial roles in receptivity.

Design
RNA-sequencing and PGR-ChIP-seq were conducted in parallel to identify PGR-regulated pathways during the Window of implantation (WOI) in endometrium of fertile women.

Setting
Endometrial biopsies from the proliferative and mid-secretory phases were analyzed.

Patients or Other Participants
Participants were fertile, reproductive aged (18–37 years) women with normal cycle length, and without any history of dysmenorrhea, infertility, or irregular cycles. In total, 42 endometrial biopsies obtained from 42 women were analyzed in this study.

Interventions
There were no interventions during this study.

Main Outcome Measures
Here we measured the alterations in gene expression and PGR occupancy in the genome during the WOI, based on the hypothesis that PGR binds uterine chromatin cycle dependently to regulate genes involved in uterine cell differentiation and function.

Results
653 genes were identified with regulated PGR binding and differential expression during the WOI. These were involved in regulating inflammatory response, xenobiotic metabolism, epithelial mesenchymal transition, cell death, interleukin/Signal Transducer And Activator Of Transcription (STAT) signaling, estrogen response, and Mammalian target of rapamycin complex 1 (MTORC1) response. Transcriptome of the epithelium identified 3052 differentially expressed genes, of which 658 were uniquely regulated. Transcription factors Interferon Regulatory Factor 8 (IRF8) and Myocyte Enhancer Factor 2C (MEF2C) were found to be regulated in the epithelium during the WOI at the protein level, suggesting potentially important functions that are previously unrecognized.

Conclusion
PGR binds the genomic regions of genes regulating critical processes in uterine receptivity and function.
Increases in Bioactive IGF do not Parallel Increases in Total IGF-I During Growth Hormone Treatment of Children Born SGA
Authors: Wegmann Mathilde Gersel , Jensen Rikke Beck , Thankamony Ajay , Frystyk Jan , Roche Edna , Hoey Hilary , Kirk Jeremy , Shaikh Guftar , Ivarsson Sten-A , Söder Olle , Dunger David B , Juul Anders 
Published: October 2019

Abstract

Background
Some children born small for gestational age (SGA) experience supra-physiological insulin-like growth factor-I (IGF-I) concentrations during GH treatment. However, measurements of total IGF-I concentrations may not reflect the bioactive fraction of IGF-I which reaches the IGF-I receptor at target organs. We examined endogenous IGF-bioactivity using an IGF-I kinase receptor activation (KIRA) assay that measures the ability of IGF-I to activate the IGF-IR in vitro.

Aim
To compare responses of bioactive IGF and total IGF-I concentrations in short GH treated SGA children in the North European Small for Gestational Age Study (NESGAS).

Material and method
In NESGAS, short SGA children (n = 101, 61 males) received GH at 67 µg/kg/day for 1 year. IGF-I concentrations were measured by Immulite immunoassay and bioactive IGF by in-house KIRA assay.

Results
Bioactive IGF increased with age in healthy pre-pubertal children (n = 94). SGA children had low-normal bioactive IGF levels at baseline (-0.12 (1.8 SD), increasing significantly after one year of high-dose GH treatment to 1.1 (1.4) SD, P &lt; 0.01. Following high-dose GH, 68% (n = 65) of SGA children had a total IGF-I concentration &gt;2SD (mean IGF-I 2.8 SDS), whereas only 15% (n = 15) had levels of bioactive IGF slightly above normal reference values. At baseline, bioactive IGF (SDS) was significantly correlated to height (SDS) (r = 0.29, P = 0.005), in contrast to IGF-I (SDS) (r = 0.17, P = 0.10). IGF-I (SDS) was inversely correlated to delta height (SDS) after one year of high-dose GH treatment (r = -0.22, P = 0.02).

Conclusion
In contrast to total IGF-I concentrations, bioactive IGF stayed within the normal reference ranges for most SGA children during the first year of GH treatment.
Time to Diagnosis in Cushing’s Syndrome: A Meta-Analysis Based on 5367 Patients
Authors: Rubinstein German , Osswald Andrea , Hoster Eva , Losa Marco , Elenkova Atanaska , Zacharieva Sabina , Machado Márcio Carlos , Hanzu Felicia Alexandra , Zopp Stephanie , Ritzel Katrin , Riester Anna , Braun Leah Theresa , Kreitschmann-Andermahr Ilonka , Storr Helen L , Bansal Prachi , Barahona María-José , Cosaro Elisa , Dogansen Sema Ciftci , Johnston Philip C , Santos de Oliveira Ricardo , Raftopoulos Christian , Scaroni Carla , Valassi Elena , van der Werff Steven J A , Schopohl Jochen , Beuschlein Felix , Reincke Martin 
Published: October 2019

Abstract

Context
Signs and symptoms of Cushing’s syndrome (CS) overlap with common diseases, such as the metabolic syndrome, obesity, osteoporosis, and depression. Therefore, it can take years to finally diagnose CS, although early diagnosis is important for prevention of complications.

Objective
The aim of this study was to assess the time span between first symptoms and diagnosis of CS in different populations to identify factors associated with an early diagnosis.

Data Sources
A systematic literature search via PubMed was performed to identify studies reporting on time to diagnosis in CS. In addition, unpublished data from patients of our tertiary care center and 4 other centers were included.

Study Selection
Clinical studies reporting on the time to diagnosis of CS were eligible. Corresponding authors were contacted to obtain additional information relevant to the research question.

Data Extraction
Data were extracted from the text of the retrieved articles and from additional information provided by authors contacted successfully. From initially 3326 screened studies 44 were included.

Data Synthesis
Mean time to diagnosis for patients with CS was 34 months (ectopic CS: 14 months; adrenal CS: 30 months; and pituitary CS: 38 months; P &lt; .001). No difference was found for gender, age (&lt;18 and ≥18 years), and year of diagnosis (before and after 2000). Patients with pituitary CS had a longer time to diagnosis in Germany than elsewhere.

Conclusions
Time to diagnosis differs for subtypes of CS but not for gender and age. Time to diagnosis remains to be long and requires to be improved.
GLP-1 Analog Modulates Appetite, Taste Preference, Gut Hormones, and Regional Body Fat Stores in Adults with Obesity
Authors: Kadouh Hoda , Chedid Victor , Halawi Houssam , Burton Duane D , Clark Matthew M , Khemani Disha , Vella Adrian , Acosta Andres , Camilleri Michael 
Published: October 2019

Abstract

Purpose
Obesity is associated with alterations in appetite, gastrointestinal hormone levels and excessive fat mass. We previously published a double-blind, placebo-controlled, randomized, 16-week trial on effects of once-daily glucagon-like peptide-1 (GLP-1) analog, liraglutide on weight, satiation, and gastric functions in obese volunteers. The aim of this substudy is to compare to placebo the effects of liraglutide on appetite, taste preference, regional body fat stores, and anthropometric measurements.

Methods
Forty obese adults received standard instruction for weight management, monthly behavioral intervention utilizing motivational interviews, and 16-week treatment of once-daily liraglutide (escalated to 3 mg SQ daily). At baseline and 16 weeks, the following were measured: appetite and taste preferences rated every 30 min for 5 h after ingesting 300 mL Ensure®; maximal tolerated volume (MTV) with a nutrient drink test; fasting and postprandial bioactive GLP-1 (7–36) and peptide YY (PYY) levels; total and regional body fat with dual-energy X-ray absorptiometry, and waist and hip circumference.

Results
Thirty-five participants (17 liraglutide; 18 placebo) completed the trial. Compared to placebo group, liraglutide group had significant reductions in MTV; prospective food consumption score; desire to eat something sweet, salty, savory or fatty; and an increase in perceived fullness. Postprandial plasma levels of GLP-1 decreased and PYY levels increased with liraglutide relative to baseline. Significant reductions in total body, trunk, and upper and lower body fat without reduction in lean body mass were observed.

Conclusion
Liraglutide 3 mg SQ modulates appetite, taste preference, gut hormones, and regional body fat stores in adults with obesity without reduction in lean body mass.
Urine Steroid Metabolomics as a Novel Tool for Detection of Recurrent Adrenocortical Carcinoma
Authors: Chortis Vasileios , Bancos Irina , Nijman Thomas , Gilligan Lorna C , Taylor Angela E , Ronchi Cristina L , O’Reilly Michael W , Schreiner Jochen , Asia Miriam , Riester Anna , Perotti Paola , Libé Rosella , Quinkler Marcus , Canu Letizia , Paiva Isabel , Bugalho Maria J , Kastelan Darko , Dennedy M Conall , Sherlock Mark , Ambroziak Urszula , Vassiliadi Dimitra , Bertherat Jerome , Beuschlein Felix , Fassnacht Martin , Deeks Jonathan J , Biehl Michael , Arlt Wiebke 
Published: October 2019

Abstract

Context
Urine steroid metabolomics, combining mass spectrometry-based steroid profiling and machine learning, has been described as a novel diagnostic tool for detection of adrenocortical carcinoma (ACC).

Objective, Design, Setting
This proof-of-concept study evaluated the performance of urine steroid metabolomics as a tool for postoperative recurrence detection after microscopically complete (R0) resection of ACC.

Patients and Methods
135 patients from 14 clinical centers provided postoperative urine samples, which were analyzed by gas chromatography–mass spectrometry. We assessed the utility of these urine steroid profiles in detecting ACC recurrence, either when interpreted by expert clinicians or when analyzed by random forest, a machine learning-based classifier. Radiological recurrence detection served as the reference standard.

Results
Imaging detected recurrent disease in 42 of 135 patients; 32 had provided pre- and post-recurrence urine samples. 39 patients remained disease-free for ≥3 years. The urine “steroid fingerprint” at recurrence resembled that observed before R0 resection in the majority of cases. Review of longitudinally collected urine steroid profiles by 3 blinded experts detected recurrence by the time of radiological diagnosis in 50% to 72% of cases, improving to 69% to 92%, if a preoperative urine steroid result was available. Recurrence detection by steroid profiling preceded detection by imaging by more than 2 months in 22% to 39% of patients. Specificities varied considerably, ranging from 61% to 97%. The computational classifier detected ACC recurrence with superior accuracy (sensitivity = specificity = 81%).

Conclusion
Urine steroid metabolomics is a promising tool for postoperative recurrence detection in ACC; availability of a preoperative urine considerably improves the ability to detect ACC recurrence.
Surgery as a Viable Alternative First-Line Treatment for Prolactinoma Patients. A Systematic Review and Meta-Analysis
Authors: Zamanipoor Najafabadi Amir H , Zandbergen Ingrid M , de Vries Friso , Broersen Leonie H A , van den Akker-van Marle M Elske , Pereira Alberto M , Peul Wilco C , Dekkers Olaf M , van Furth Wouter R , Biermasz Nienke R 
Published: October 2019

Abstract

Context
The improved remission and complication rates of current transsphenoidal surgery warrant reappraisal of the position of surgery as a viable alternative to dopamine agonists in the treatment algorithm of prolactinomas.

Objective
To compare clinical outcomes after dopamine agonist withdrawal and transsphenoidal surgery in prolactinoma patients.

Methods
Eight databases were searched up to July 13, 2018. Primary outcome was disease remission after drug withdrawal or surgery. Secondary outcomes were biochemical control and side effects during dopamine agonist treatment and postoperative complications. Fixed- or random-effects meta-analysis was performed to estimate pooled proportions. Robustness of results was assessed by sensitivity analyses.

Results
A total of 1469 articles were screened: 55 (10 low risk of bias) on medical treatment (n = 3564 patients) and 25 (12 low risk of bias) on transsphenoidal surgery (n = 1836 patients). Long-term disease remission after dopamine agonist withdrawal was 34% (95% confidence interval [CI], 26-46) and 67% (95% CI, 60-74) after surgery. Subgroup analysis of microprolactinomas showed 36% (95% CI, 21-52) disease remission after dopamine agonist withdrawal, and 83% (95% CI, 76-90) after surgery. Biochemical control was achieved in 81% (95% CI, 75-87) of patients during dopamine agonists with side effects in 26% (95% CI, 13-41). Transsphenoidal surgery resulted in 0% mortality, 2% (95% CI, 0-5) permanent diabetes insipidus, and 3% (95% CI, 2-5) cerebrospinal fluid leakage. Multiple sensitivity analyses yielded similar results.

Conclusions
In the majority of prolactinoma patients, disease remission can be achieved through surgery, with low risks of long-term surgical complications, and disease remission is less often achieved with dopamine agonists.
Endometrial Liquid Biopsy Provides a miRNA Roadmap of the Secretory Phase of the Human Endometrium
Authors: Grasso Alessia , Navarro Roser , Balaguer Nuria , Moreno Inmaculada , Alama Pilar , Jimenez Jorge , Simón C , Vilella F 
Published: October 2019

Abstract

Context
Endometrial liquid biopsy (ELB) is a minimally invasive alternative for research and diagnosis in endometrial biology.

Objective
We sought to establish an endometrial micro ribonucleic acid (miRNA) roadmap based on ELB during the secretory phase of the menstrual cycle in both natural and hormonal replacement therapy (HRT) cycles.

Design
Human ELB samples (n = 58) were obtained from healthy ovum donors undergoing a natural and an HRT cycle consecutively. miRNA profiles were identified using next-generation sequencing (NGS). For functional analysis, messenger ribonucleic acid targets were chosen among those reported in the endometrial receptivity analysis.

Results
The human endometrial secretory phase is characterized by a dynamic miRNA secretion pattern that varies from the prereceptive to the receptive stages. No differences in miRNA profiles were found among natural versus HRT cycles in the same women, reinforcing the similarities in functional and clinical outcomes in natural versus medicated cycles. Bioinformatic analysis revealed 62 validated interactions and 81 predicted interactions of miRNAs differentially expressed in the HRT cycle. Annotation of these genes linked them to 51 different pathways involved in endometrial receptivity.

Conclusion
This NGS-based study describes the miRNA signature in human ELB during the secretory phase of natural and HRT cycles. A consistent endometrial miRNA signature was observed in the acquisition of endometrial receptivity. Interestingly, no significant differences in miRNA expression were found in natural versus HRT cycles reinforcing the functional clinical similarities between both approaches.
Non-Electronic Aromatic Ring Activation by Simple Steric Repulsion between Substituents in 1-Methylquinolinium Salt Systems
Authors: Iwai Kento , Yokoyama Soichi , Asahara Haruyasu , Nishiwaki Nagatoshi 
Published: October 2019

Abstract
A systematic study of non-electronic activation of an aromatic ring was performed using a series of 8-substituted 1-methylquinolinium salts. As the 8-substituent became bulkier, the quinoline framework was distorted by steric repulsion between substituents at the 1- and 8-positions. This was accompanied by lack of coplanarity, which brought about dearomatization. Consequently, quinolinium ions possessing a bulky 8-substituent exhibited high reactivity undergoing nucleophilic addition at the 2-position efficiently. We demonstrate that the activation was achieved sterically and not electronically.