bluuebunny/crossref_metadata_2025_split huggingface dataset:
Proceedings from the 2018 Association for Chemoreception Annual Meeting Symposium: Bariatric Surgery and Its Effects on Taste and Food Selection
Authors: Spector Alan C , Kapoor Natasha , Price Ruth K , Pepino M Yanina , Livingstone M Barbara E , Le Roux Carel W 
Published: November 2018

Abstract
This article provides a summary of the topics discussed at the symposium titled “Bariatric Surgery and Its Effects on Taste and Food Selection,” which was held at the Fortieth Annual Meeting of the Association for Chemoreception Sciences. Bariatric surgery such as Roux-en-Y gastric bypass (RYGB) is currently one of the most effective treatments available for weight loss and Type 2 diabetes. For this reason, it is of great interest to clinicians as well as to basic scientists studying the controls of feeding and energy balance. Despite the commonly held view by clinicians that RYGB patients change their food preferences away from fats and sugars in favor of less energy dense alternatives such as vegetables, the empirical support for this claim is equivocal. It is currently thought that the taste and palatability of fats and sugars are affected by the surgery. Some key preclinical and clinical findings addressing these issues were evaluated in this symposium.
Can the financial burden of being a community health volunteer in western Kenya exacerbate poverty?
Authors: Kelly Alyssa , Mitra Sanjana , Elung’at Justus , Songok Julia , Jackson Suzanne , Christoffersen-Deb Astrid 
Published: November 2018

Summary
Community health volunteers (CHVs) act as vital links between communities and health facilities, bridging the health service delivery gap common in low- and middle-income countries. In 2013, changes in funding in western Kenya left most CHVs without their individual monthly stipend. In this article, we explore how the implementation of a pooled incentive model had an impact on the lives of CHVs from two counties in western Kenya. Participation in this form of table banking was meant to allow CHVs to pool their resources together and invest in income-generating activities to offset the costs of unpaid health work. A pre-post qualitative study, consisting of focus group discussions and in-depth interviews explored CHV compensation, motivations and challenges experienced in 2013 and 2015, prior to and after the implementation of this pooled incentive model. Following withdrawal of the monthly stipend, we found that CHVs continued to take on roles and responsibilities of paid health workers, motivated by shared social identities and connections to their communities. However, replacing the stipend with a pooled-group incentive model seemingly exacerbated the financial burden already experienced by this vulnerable population. This study brings into question the sustainability and viability of a volunteer community health worker programme and highlights the need to address the financial burden associated with the CHV role in western Kenya.
Acute Pharmacokinetic Profile of Smoked and Vaporized Cannabis in Human Blood and Oral Fluid
Authors: Spindle Tory R , Cone Edward J , Schlienz Nicolas J , Mitchell John M , Bigelow George E , Flegel Ronald , Hayes Eugene , Vandrey Ryan 
Published: November 2018

Abstract
Currently, an unprecedented number of individuals can legally access cannabis. Vaporization is increasingly popular as a method to self-administer cannabis, partly due to perception of reduced harm compared with smoking. Few controlled laboratory studies of cannabis have used vaporization as a delivery method or evaluated the acute effects of cannabis among infrequent cannabis users. This study compared the concentrations of cannabinoids in whole blood and oral fluid after administration of smoked and vaporized cannabis in healthy adults who were infrequent users of cannabis. Seventeen healthy adults, with no past-month cannabis use, self-administered smoked or vaporized cannabis containing Δ9-tetrahydrocannabinol (THC) doses of 0, 10 and 25 mg in six double-blind outpatient sessions. Whole blood and oral fluid specimens were obtained at baseline and for 8 h after cannabis administration. Cannabinoid concentrations were assessed with enzyme-linked immunosorbent assay (ELISA) and liquid chromatography–tandem mass spectrometry (LC–MS-MS) methods. Sensitivity, specificity and agreement between ELISA and LC–MS-MS results were assessed. Subjective, cognitive performance and cardiovascular effects were assessed. The highest concentrations of cannabinoids in both whole blood and oral fluid were typically observed at the first time point (+10 min) after drug administration. In blood, THC, 11-OH-THC, THCCOOH and THCCOOH-glucuronide concentrations were dose-dependent for both methods of administration, but higher following vaporization compared with smoking. THC was detected longer in oral fluid compared to blood and THCCOOH detection in oral fluid was rare and highly erratic. For whole blood, greater detection sensitivity for ELISA testing was observed in vaporized conditions. Conversely, for oral fluid, greater sensitivity was observed in smoked sessions. Blood and/or oral fluid cannabinoid concentrations were weakly to moderately correlated with pharmacodynamic outcomes. Cannabis pharmacokinetics vary by method of inhalation and biological matrix being tested. Vaporization appears to be a more efficient method of delivery compared with smoking.
The role of surfactant protein-A in sinusitis
Authors: Chang Eugene H. 
Published: November 2018

Purpose of review
Surfactant protein-A (SP-A) is a collectin protein expressed in airway epithelia that is critical in the modulation of both innate and adaptive immunity against inhaled pathogens. In this review, we highlight associations of altered SP-A function in asthma and chronic rhinosinusitis, and its potential role as a targeted therapy for sinusitis.

Recent findings
SP-A has been shown to bind and opsonize inhaled pathogens, thereby clearing bacteria through phagocytosis. We have recently identified that SP-A levels are increased in response to Pseudomonas aeruginosa, a common bacterial pathogen in chronic rhinosinusitis. Moreover, SP-A has also been shown to modulate epithelial inflammatory mediators and play a role in eosinophil-mediated airway disease. The development of a transgenic murine model expressing human genetic variants of SP-A2 have suggested that the human surfactant protein-A2 223K variant significantly increases eosinophil degranulation, suggesting a genotype-phenotype correlation in human airway disease.

Summary
SP-A is important in both the innate and adaptive host defense mechanisms in the upper and lower airways. Although research in this field in sinusitis is nascent, initial work suggests that aberrant SP-A regulation may be one etiologic factor in the development of bacterial and eosinophilic-associated sinusitis.
Preventing the development of asthma: stopping the allergic march
Authors: Maciag Michelle C. , Phipatanakul Wanda 
Published: November 2018

Purpose of review
To describe important precipitants of asthma and allergic disease, to highlight the links between these triggers and modifications within the immune system, and to examine innovative research regarding asthma prevention with focus on attenuating the atopic march.

Recent findings
Allergen avoidance, allergen immunotherapy, IgE antagonists, prevention and treatment of respiratory infections, as well as management of gastrointestinal and respiratory dysbiosis have been considered as strategies in asthma prevention. Antenatal vitamin D supplementation in expectant mothers and aggressive control of atopic dermatitis to prevent the development of other allergic conditions were carefully studied as well.

Summary
Asthma is a major cause of morbidity and lost productivity. Despite the tremendous burden of this disease, the scientific community is still struggling to find an effective means of prevention. The contribution of genetics to the development of atopy cannot be altered, but environmental changes as well as pharmacotherapy have been studied as modifiable risk factors. Many trials to date have been effective only for subjects with certain characteristics. This is likely because asthma is a heterogenous condition, with a variety of triggers and clinical phenotypes. Thus far, a universally effective prevention strategy has eluded us. However, if an intervention can be found to prevent asthma and the allergic march, it will greatly improve quality of life for millions of sufferers and decrease healthcare expenditures.
Obesity and adiposity indicators in asthma and allergic rhinitis in children
Authors: Tajima Hanako , Pawankar Ruby 
Published: November 2018

Purpose of review
The prevalence of obesity and allergic diseases, such as asthma and allergic rhinitis, is increasing worldwide not only in adults, but also in children. Experimental and clinical studies have demonstrated the effect of obesity not only on asthma, but also on other allergic diseases.

Recent findings
Allergic diseases, such as asthma and allergic rhinitis, are common chronic inflammatory diseases of the airways. Obesity is an increasingly common pediatric disease and is a risk factor for the development of asthma in that obese patients with asthma tend to have more severe asthma that does not respond well to standard asthma therapy. On the contrary, children with asthma maybe at a high risk of obesity, suggesting that the relationship of asthma and obesity seems to be interrelated. The role of obesity on the development of allergic rhinitis is not well defined, whereas allergic rhinitis may have an impact on obesity.

Summary
Childhood obesity is often considered to be less serious than obesity in adults because of the greater risk of complications in obese adults. In this review, we discuss the allergic confounders of obesity and the impact of allergic diseases on obesity. Proper control of the BMI within the normal range in children with allergic diseases is important.
Quantification of Thiopurine Nucleotides in Erythrocytes and Clinical Application to Pediatric Acute Lymphoblastic Leukemia
Authors: Moon Soo Young , Lim Ji-Hyun , Kim Eun-Hee , Nam Youngwon , Yu Kyung-Sang , Hong Kyung Taek , Choi Jung Yoon , Hong Che Ry , Kim Hyery , Kang Hyoung Jin , Shin Hee Young , Lee Kyunghoon , Song Junghan , Lee Soo-Youn , Song Sang Hoon 
Published: November 2018

Background:
Concentrations of 6-thioguanine (6TG) nucleotides and 6-methylmercaptopurine (6MMP) nucleotides in RBCs were measured using liquid chromatography-tandem mass spectrometry (LC-MS/MS). This assay was validated for clinical use and was applied to blood samples from patients taking mercaptopurine (6MP).

Methods:
RBCs were hemolyzed and deproteinized using perchloric acid, followed by heating for the hydrolysis of nucleotides, and the resultant base was measured using LC-MS/MS. Precision, recovery, linearity, matrix effect, and limit of quantification was validated for clinical application. Our results were compared with another institution's established LC-MS/MS assay. We measured the concentrations of 6TG and 6MMP in RBCs of pediatric patients with acute lymphoblastic leukemia (ALL), and the clinical impact of those metabolites was investigated.

Results:
The imprecision coefficient of variations of 6TG and 6MMP were 5.7%–8.1%, and the bias was within 5%. Lower limits of quantification were set at 54 ng/mL for 6TG and 1036 ng/mL for 6MMP. Correlation coefficients for 6TG and 6MMP were 0.997 and 1.0 in a comparison study. For clinical proof-of-concept, 74 blood samples were collected from 37 pediatric ALL patients receiving maintenance therapy. Concentration of 6TG ranged from 16.1 to 880 pmol/8 × 108 RBCs and that of 6MMP from 55 to 20,937 pmol/8 × 108 RBCs. The 6MP metabolites were not correlated with WBC or absolute neutrophil count. On the other hand, the higher 6MMP level was associated with elevated alanine aminotransferase and aspartate aminotransferase.

Conclusions:
In this study, an assay for the quantification of 6TG and 6MMP in RBCs was established and applied to pediatric ALL patients. Interindividual variability in 6MP metabolite concentrations was considerable and associated with elevation of liver enzymes, which may be useful in the clinical monitoring of 6MP maintenance therapy in pediatric ALL patients.
Concentration–Effect Relationships of Psychoactive Drugs and the Problem to Calculate Therapeutic Reference Ranges
Authors: Hiemke Christoph 
Published: November 2018

Background:
Despite the obvious potential of Therapeutic Drug Monitoring (TDM) as a tool to optimize psychopharmacotherapy, especially treatment with mood-stabilizing, antidepressant and antipsychotic drugs, acceptance of TDM as a routine tool is still limited. A serious scientific argument against the regular use of TDM is the lack of evidence for a concentration-dependent clinical effect. The aim of this review was to highlight methodological problems leading to poor or even negative concentration–effect relationships and to show how therapeutically effective concentrations of psychoactive drugs can be determined using routine TDM databases.

Methods:
Reports on concentration–effect relationships of psychoactive drugs were analyzed with regard to applied methods. From routine TDM databases of patients who had been treated with antidepressant or antipsychotic drugs and whose improvement was measured by the clinical global impressions scale, mean and median drug concentrations were calculated and compared with reference ranges recommended by TDM guidelines.

Results:
Few fixed-dose studies with adequate design and data analysis demonstrated a correlation between drug concentration and clinical effect for psychoactive drugs. Most studies, however, mostly retrospective analyses of TDM databases, failed to find significant concentration–effect relationships because of flexible dosing. They were not suitable for the determination of therapeutically effective drug concentrations. Using TDM databases of antidepressant and antipsychotic drug concentrations in blood of patients who were categorized as responders by the clinical global impressions score, the interquartile ranges of drug concentrations (25th–75th percent range) can be shown to be very close to the therapeutic reference ranges recommended in guidelines for TDM in psychiatry.

Conclusions:
This review provides a discussion on why simple correlation analyses of psychoactive drug concentrations in blood and clinical effects are obsolete for flexible-dose studies or TDM databases. TDM databases, however, can and should be used to calculate drug concentrations in blood of patients who had responded to the drugs. Interquartile ranges can be regarded and used as preliminary therapeutic reference ranges.
Molecular characterization of endometrial cancer and therapeutic implications
Authors: Chang Zenas , Talukdar Shobhana , Mullany Sally A. , Winterhoff Boris 
Published: November 2018

Purpose of review
The present article reviews genomic subtyping of endometrial carcinoma and new molecular markers with therapeutic and prognostic implications.

Recent findings
Endometrial cancer has historically been classified through histology into endometrioid (type 1) and nonendometrioid (type II, mainly serous) subtypes. Molecular classification through genomic analysis now allows for a major advance in characterization; four distinct subgroups have been identified: polymerase ε (POLE) ultramutated, microsatellite unstable, copy number low/microsatellite stable, and copy number high/'serous-like’. These subtypes have prognostic implications and may aid in the identification of early-stage patients who are at high risk for recurrence. Through analysis of surrogate markers (POLE, MSI, and p53) and other validated molecular alterations (L1CAM), it may be possible to obtain an integrated molecular risk profile. Ongoing studies are utilizing this risk profile in order to identify patients who may benefit from additional treatment for early-stage disease.

Summary
Molecular characterization of endometrial cancer into subgroups has prognostic and therapeutic implications. Further development of an integrated molecular risk profile may identify patients who could benefit from additional treatment because of a higher risk of recurrence.
Single-cell sequencing in ovarian cancer: a new frontier in precision medicine
Authors: Winterhoff Boris , Talukdar Shobhana , Chang Zenas , Wang Jinhua , Starr Timothy K. 
Published: November 2018

Purpose of review
This article discusses the advances, applications and challenges of using single-cell RNA sequencing data in guiding treatment decisions for ovarian cancer.

Recent findings
Genetic heterogeneity is a hallmark of ovarian cancer biology and underlies treatment resistance. Defining the different cell types present within a single ovarian cancer is difficult, but could ultimately lead to improvements in diagnosis and treatment. Next-generation sequencing technologies have rapidly increased our understanding of the molecular landscape of epithelial ovarian cancers, but the majority of these studies are conducted on bulk samples, resulting in data that represents an ‘average’ of all cells present. Single-cell sequencing provides a means to characterize heterogeneity with a tumor tissue in ovarian cancer patients and opens up opportunity to determine key molecular properties that influence clinical outcomes, including prognosis and treatment response.

Summary
Single-cell sequencing provides a powerful tool in improving our understanding of tumor cell heterogeneity for the purpose of informing personalized cancer treatment.
Growth, pubertal development, and skeletal health in boys with Duchenne Muscular Dystrophy
Authors: Ward Leanne M. , Weber David R. 
Published: November 2018

Purpose of review
Glucocorticoid therapy is currently the most widely used treatment for Duchenne muscular dystrophy (DMD), having consistently shown to prolong ambulation by 2 years, reduce the frequency of scoliosis, and improve cardiorespiratory function. Among the most frequent side effects of glucocorticoids are fractures due to osteoporosis, linear growth retardation or arrest, and pubertal delay, the subjects of this review.

Recent findings
The diagnosis of osteoporosis has shifted in recent years away from a bone mineral density-centric to a fracture-focused approach, with particular emphasis on early vertebral fracture identification (one of the key triggers for osteoporosis intervention). Delayed puberty should be addressed in an age-appropriate manner, with numerous options available for sex steroid replacement. Growth impairment, however, is a more challenging complication of glucocorticoid-treated DMD, one that is most likely best addressed through growth-sparing therapies that target the dystrophinopathy.

Summary
With glucocorticoid prescription an increasingly prevalent component of DMD care, early attention to management of osteoporosis and delayed puberty are important components of multidisciplinary and anticipatory care. The treatment of short stature remains controversial, with no accepted therapy currently available to over-ride the toxic effects of glucocorticoids on the growth axis.
Ethical issues with early genitoplasty in children with disorders of sex development
Authors: Harris Rebecca M. , Chan Yee-Ming 
Published: November 2018

Purpose of review
Genitoplasty in children with disorders of sex development (DSD) is an ethically complex issue. From a surgical perspective, genitoplasty in early childhood is preferred because it is felt to be associated with improved tissue healing, decreased risk of complications, and reduced psychological impact of genital surgery. However, advocacy groups and recent ethics literature have argued for deferring genitoplasty until a child reaches decisional maturity. This article reviews these arguments using an ethical framework and discusses the application and challenges of recent disorders of sex development research.

Recent findings
Recent ethics literature and advocacy groups have argued for deferring genitoplasty until a child reaches decisional maturity. As a counterpoint, urological societies have published arguments supporting the practice of early genitoplasty. Data from DSD research lends some guidance but also has a wide range of outcomes, which makes generalizability difficult. A retrospective, multicenter study of 21 individuals with congenital adrenal hyperplasia who underwent feminizing surgery showed no difference between cases and controls in social functioning, parent–child relationships, or sexual fulfillment. Ninety percent of patients thought genitoplasty should occur within the first year of life. In a study of 52 patients with 46,XY and 46,XX DSDs who underwent masculinizing genitoplasty, 57% thought their physical appearance was ‘fair’ or ‘poor,’ and problems with sexual function, urinary incontinence, and short penile length were common.

Summary
Early genitoplasty in children with DSDs is ethically complex, and discordant results in DSD research makes generalizability difficult. There is unlikely to be a universal solution to the issue of early genitoplasty in children with DSDs; families must be supported while they weigh both parental decision-making and the objective of ensuring an open future for their child.
Undernutrition and growth in the developing world
Authors: Nijjar Jasreena K. , Stafford Diane 
Published: November 2018

Purpose of review
Despite targeted interventions, an estimated 150.8 million children under 5 years globally are still stunted, of which more than half live in Asia and more than one-third live in Africa. This review summarizes our current knowledge regarding how longitudinal bone growth is regulated by nutritional intake in the developing world. Dietary macronutrients and micronutrients necessary for growth are also briefly reviewed.

Recent findings
Recent advances include investigations of nutritionally sensitive regulators of growth as well as prospective evaluations of the role of specific dietary components on growth in order to better assess their impact.

Summary
Further investigation is required to understand how nutrition impacts growth, the mechanisms underlying stunting and to optimize therapeutic strategies for children who are at risk for growth attenuation or are stunted in low and middle-income countries (LMICs).