bluuebunny/crossref_metadata_2025_split huggingface dataset:
Tissue specificity of in vitro drug sensitivity
Authors: Yao Fupan , Madani Tonekaboni Seyed Ali , Safikhani Zhaleh , Smirnov Petr , El-Hachem Nehme , Freeman Mark , Manem Venkata Satya Kumar , Haibe-Kains Benjamin 
Published: July 2017

AbstractObjectivesWe sought to investigate the tissue specificity of drug sensitivities in large-scale pharmacological studies and compare these associations to those found in drug clinical indications.Materials and MethodsWe leveraged the curated cell line response data from PharmacoGx and applied an enrichment algorithm on drug sensitivity values’ area under the drug dose-response curves (AUCs) with and without adjustment for general level of drug sensitivity.ResultsWe observed tissue specificity in 63% of tested drugs, with 8% of total interactions deemed significant (false discovery rate &lt;0.05). By restricting the drug-tissue interactions to those with AUC &gt; 0.2, we found that in 52% of interactions, the tissue was predictive of drug sensitivity (concordance index &gt; 0.65). When compared with clinical indications, the observed overlap was weak (Matthew correlation coefficient, MCC = 0.0003, P &gt; .10).DiscussionWhile drugs exhibit significant tissue specificity in vitro, there is little overlap with clinical indications. This can be attributed to factors such as underlying biological differences between in vitro models and patient tumors, or the inability of tissue-specific drugs to bring additional benefits beyond gold standard treatments during clinical trials.ConclusionOur meta-analysis of pan-cancer drug screening datasets indicates that most tested drugs exhibit tissue-specific sensitivities in a large panel of cancer cell lines. However, the observed preclinical results do not translate to the clinical setting. Our results suggest that additional research into showing parallels between preclinical and clinical data is required to increase the translational potential of in vitro drug screening.
Decidability of interpretability logics ILM0 and ILW*
Authors: Mikec Luka , Perkov Tin , Vuković Mladen 
Published: July 2017

Abstract
The finite model property is a key step in proving decidability of modal logics. By adapting the filtration method to the generalized Veltman semantics for interpretability logics, we have been able to prove the finite model property of interpretability logic ILM0 w.r.t. generalized Veltman models. We use the same technique to prove the finite model property of interpretability logic ILW* w.r.t. generalized Veltman models. The missing link needed to prove the decidability of ILM0 was completeness w.r.t. generalized Veltman models, which we obtain in this article. Thus, we prove the decidability of ILM0, which was an open problem. Using the same technique, we prove that ILW* is also decidable.
Technologic Distractions (Part 1): Summary of Approaches to Manage Alert Quantity With Intent to Reduce Alert Fatigue and Suggestions for Alert Fatigue Metrics
Authors: Kane-Gill Sandra L. , O’Connor Michael F. , Rothschild Jeffrey M. , Selby Nicholas M. , McLean Barbara , Bonafide Christopher P. , Cvach Maria M. , Hu Xiao , Konkani Avinash , Pelter Michele M. , Winters Bradford D. 
Published: July 2017

Objective:
To provide ICU clinicians with evidence-based guidance on tested interventions that reduce or prevent alert fatigue within clinical decision support systems.

Design:
Systematic review of PubMed, Embase, SCOPUS, and CINAHL for relevant literature from 1966 to February 2017.

Patients:
Focus on critically ill patients and included evaluations in other patient care settings, as well.

Interventions:
Identified interventions designed to reduce or prevent alert fatigue within clinical decision support systems.

Measurements and Main Results:
Study selection was based on one primary key question to identify effective interventions that attempted to reduce alert fatigue and three secondary key questions that covered the negative effects of alert fatigue, potential unintended consequences of efforts to reduce alert fatigue, and ideal alert quantity. Data were abstracted by two reviewers independently using a standardized abstraction tool. Surveys, meeting abstracts, “gray” literature, studies not available in English, and studies with non-original data were excluded. For the primary key question, articles were excluded if they did not provide a comparator as key question 1 was designed as a problem, intervention, comparison, and outcome question. We anticipated that reduction in alert fatigue, including the concept of desensitization may not be directly measured and thus considered interventions that reduced alert quantity as a surrogate marker for alert fatigue. Twenty-six articles met the inclusion criteria.

Conclusion:
Approaches for managing alert fatigue in the ICU are provided as a result of reviewing tested interventions that reduced alert quantity with the anticipated effect of reducing fatigue. Suggested alert management strategies include prioritizing alerts, developing sophisticated alerts, customizing commercially available alerts, and including end user opinion in alert selection. Alert fatigue itself is studied less frequently, as an outcome, and there is a need for more precise evaluation. Standardized metrics for alert fatigue is needed to advance the field. Suggestions for standardized metrics are provided in this document.
Empirically Identified Subgroups of Children Served in Part C Early Intervention Programs
Authors: Elbaum Batya , Celimli-Aksoy Seniz 
Published: July 2017

ABSTRACT:

Objective:
Early intervention (EI) programs under Part C of the Individuals with Disabilities Education Act serve a developmentally heterogeneous population of infants and toddlers with or at risk of developmental delays or disabilities. The aim of this study was to identify empirically distinct subgroups of children in EI so as to inform early prognosis and service planning.

Methods:
We applied mixture modeling to developmental assessment data from 1513 children who enrolled in a large, urban EI program between 2009 and 2013. The observed variables were children's EI-entry developmental quotients (DQs) in 5 domains (communication, cognitive, motor, adaptive, and personal–social) as assessed by the Battelle Developmental Inventory, Second Edition.

Results:
A 4-class model showed the best fit to the data, revealing subgroups with distinct developmental profiles. Children in the first subgroup showed a severe delay in communication with less severe delays in the other domains. Children in the second subgroup likewise showed a severe delay in communication, but with comparably severe delays in the cognitive and motor domains. Profiles for the third and fourth subgroups showed the same overall patterns as those for the first and second subgroups, respectively, but to a less severe degree. Developmental trajectories differed by subgroup.

Conclusion:
Consideration of subgroups based on children's developmental assessment scores provides insight into underlying commonalities among children with different presenting diagnoses on entry into EI. The subgroups also have clinical relevance in terms of both practitioners' and parents' understanding of children's likely service needs and developmental trajectories.
Validation of Risk Factors for Fecal Incontinence in Patients With Crohn’s Disease
Authors: Vollebregt Paul F. , Visscher Arjan P. , van Bodegraven Adriaan A. , Felt-Bersma Richelle J. F. 
Published: July 2017

BACKGROUND:
Fecal incontinence has a great impact on daily life, and many patients are reluctant to report it.

OBJECTIVE:
The purpose of this study was to estimate the prevalence of fecal incontinence in patients with Crohn’s disease, validate risk factors, and relate outcome with quality of life.

DESIGN:
The design was cross-sectional.

SETTINGS:
The study was conducted at an academic tertiary center.

PATIENTS:
Consecutive patients with Crohn’s disease treated between 2003 and 2013 were included in this study.

MAIN OUTCOME MEASURES:
A questionnaire was sent out in October 2013 to evaluate perianal disease, current symptoms of fecal incontinence, and its impact on quality of life (Fecal Incontinence Quality of Life questionnaire). Risk factors were validated with univariate and multivariate analyses.

RESULTS:
The questionnaire was responded by 325 (62%) of 528 patients. Median age was 42 years (range, 18–91 y), 215 (66%) were women, and a diagnosis of Crohn’s disease was established for a median period of 12 years (interquartile range, 6–21 y). Fecal incontinence was reported by 65 patients (20%). Fecal incontinence was associated with liquid stools (p = 0.0001), previous IBD-related bowel resections (p = 0.001), stricturing behavior of disease (p = 0.02), and perianal disease (p = 0.03). Quality of life (lifestyle, coping, depression, and embarrassment) was poor in patients with fecal incontinence, particularly in patients with more frequent episodes of incontinence.

LIMITATIONS:
There was no correction for disease activity in the multivariate regression analysis.

CONCLUSIONS:
The prevalence of fecal incontinence in a tertiary population with Crohn’s disease is substantially higher than in the community-dwelling population. Considering the reduced quality of life in incontinent patients, active questioning to identify fecal incontinence is recommended in those with liquid stools, perianal disease, or previous (intestinal or perianal) surgery. See Video Abstract at http://journals.lww.com/dcrjournal/Pages/videogallery.aspx.
Evaluation of the Novel Methotrexate Architect Chemiluminescent Immunoassay: Clinical Impact on Pharmacokinetic Monitoring
Authors: Aumente Maria D. , López-Santamaría Julia , Donoso-Rengifo María Concepción , Reyes-Torres Inmaculada , Montejano Hervás Pablo 
Published: July 2017

Background:
Fluorescence polarization immunoassay (FPIA) has probably been the most widely used technique for the determination of methotrexate (MTX) concentrations in clinical laboratories. After its replacement by a novel architect chemiluminescent microparticle immunoassay (CMIA), it is essential to verify that there are no differences between the methods that can induce an error in leucovorin rescue with dire consequences for the patient. The objective of our study was to compare plasma/serum MTX measurements between CMIA and FPIA (reference method in this study) in the work conditions of a clinical pharmacokinetics unit to determine whether any difference would affect clinical decisions on the management of this drug.

Methods:
FPIA on TDx/FLx and CMIA on Architect ci8200 were simultaneously used to evaluate 127 clinical samples. Within-run (20 repetitions on same day) and between-run (20 repetitions on different days) imprecision was evaluated using 6 control samples provided by the manufacturer and diluting 2 of them by 50% for 0.03 and 0.22 μmol/L, respectively. The Passing–Bablok regression method, Bland–Altman plot, and concordance correlation coefficient (CCC) were used in the statistical analysis.

Results:
Within-run imprecision was <5% (3.6%–4.39%) and between-run imprecision <11% (2.42%–10.65%). Between-assay correlation for the studied concentration range (0.05–250 μmol/L) was CMIA = −0.026 + 1.033 FPIA (n = 127), r = 0.9963, and CCC = 0.9946. For samples <1.5 μmol/L (nondiluted) included in the assay calibration curve, the correlation was CMIA = −0.009 + 0.955 FPIA (n = 54), r = 0.9819, and CCC = 0.9807. No significant difference was observed between the measurements by the 2 assays, given that the 95% confidence interval of the ordinate at the origin included “0” (−0.020 to 0.0007), and the 95% confidence interval of the slope included 1 (0.923–1.020). The interchangeability of these assays was confirmed by Bland–Altman plot results, which showed a mean difference insignificant at concentrations <10 μmol/L.

Conclusions:
The correlation between methods was excellent, and Passing–Bablok regression analysis detected no virtually difference in their results. Utilization of the CMIA-Architect assay to measure MTX concentrations would therefore not affect clinical decisions on MTX management, supporting its employment in routine MTX monitoring.
Contraception counseling for adolescents
Authors: Raidoo Shandhini , Kaneshiro Bliss 
Published: July 2017

Purpose of review
In recent years, pregnancy and birth rates among adolescents in the United States have declined to all-time lows, although adolescents in the United States continue to have the highest rate of unintended pregnancy among developed countries. Contraception is a key component in the prevention of unintended pregnancy. In this review, we outline unique barriers to reproductive healthcare for adolescents and strategies to optimally address the contraceptive needs of adolescents.

Recent findings
Adolescents face barriers such as confidentiality, cost, and access when seeking contraception. Counseling about options for contraception may involve parents or guardians when appropriate, but an adolescent's autonomy should be respected in the decision-making process. Contraceptive counseling for adolescents must not be coercive in nature. Adolescents are at an increased risk for acquisition of sexually transmitted infections, and dual use, the use of condoms and an additional method of contraception, is highly recommended. Initiatives that remove the common barriers of cost and access have demonstrated significant success in increasing the use of long-acting reversible contraceptive methods and reducing the rates of unintended pregnancy among adolescents.

Summary
Counseling adolescents about contraception requires acknowledgement of the unique barriers that adolescents face and facilitating decision-making about contraceptive methods in a manner that prioritizes the adolescent's autonomy.
MACULAR ATROPHY AND MACULAR MORPHOLOGY IN AFLIBERCEPT-TREATED NEOVASCULAR AGE-RELATED MACULAR DEGENERATION
Authors: Kuroda Yoshimasa , Yamashiro Kenji , Ooto Sotaro , Tamura Hiroshi , Oishi Akio , Nakanishi Hideo , Miyata Manabu , Hata Masayuki , Takahashi Ayako , Wakazono Tomotaka , Yoshimura Nagahisa , Tsujikawa Akitaka 
Published: July 2017

Purpose:
To investigate the incidence and predictors of macular atrophy during treatment with aflibercept for neovascular age-related macular degeneration in Japanese patients.

Methods:
This study included patients with treatment-naive subfoveal neovascular age-related macular degeneration treated from December 2012 through January 2015. Patients were treated with bi-monthly aflibercept injections after 3 monthly loading injections for the first year. Diagnosis of retinal pigment epithelial atrophy was made based on color fundus photography, spectral-domain optical coherence tomography, and fundus autofluorescence. Baseline characteristics and morphological features were analyzed for their association with the development of macular atrophy.

Results:
This study included 123 eyes that had no baseline macular atrophy and treated with aflibercept injections for 12 months. Thirteen eyes (10.6%) developed new macular atrophy at 12 months. Logistic regression analysis showed that the presence of intraretinal fluid and thinner subfoveal choroidal thickness at baseline were associated with the development of macular atrophy after aflibercept treatment.

Conclusion:
Macular atrophy developed in about 10% of eyes with neovascular age-related macular degeneration during 12 months of treatment with a fixed regimen of aflibercept. Intraretinal fluid and subfoveal choroidal thickness seem to be predictors for development of macular atrophy after anti-vascular endothelial growth factor (VEGF) therapy.
Visceral pain as a triggering factor for fibromyalgia symptoms in comorbid patients
Authors: Costantini Raffaele , Affaitati Giannapia , Wesselmann Ursula , Czakanski Peter , Giamberardino Maria Adele 
Published: July 2017

Abstract
Fibromyalgia syndrome (FMS) is a central sensitization syndrome; however, peripheral pain sources potentially exacerbate its symptoms of chronic diffuse musculoskeletal pain and hyperalgesia. This prospective study evaluated visceral pain as a possible triggering factor for FMS pain and hyperalgesia in comorbid patients. Women with (1) FMS + irritable bowel syndrome (IBS); (2) FMS + primary dysmenorrhea (Dys); (3) FMS + Dys secondary to endometriosis (Endo); (4) FMS + colon diverticulosis (Div) were compared with FMS-only women, for fibromyalgia pain (number and intensity of episodes and analgesic consumption) over comparable periods and for somatic hyperalgesia (electrical and pressure pain thresholds) in painful (tender points) and control areas (trapezius, deltoid, quadriceps muscles, and overlying subcutis and skin). In comorbid subgroups, FMS symptoms were also reassessed after treatment of the visceral condition or no treatment. All comorbid groups vs FMS-only had significantly higher FMS pain (number/intensity of episodes and analgesic consumption) and hyperalgesia in deep somatic tissues (subcutis and muscle) at all sites (0.05 < P < 0.0001). Visceral pain (number of IBS days, painful menstrual cycles, and abdominal pain episodes from diverticulitis) correlated directly with all parameters of FMS pain and inversely with muscle pain thresholds at all sites (0.03 < P < 0.0001). Fibromyalgia syndrome pain and hyperalgesia in all tissues and all sites significantly decreased in patients after visceral comorbidity treatment (dietary for 6 months [IBS], hormonal for 6 months [dysmenorrhea], laser [endometriosis], and surgery [diverticulosis]) (0.05 < P < 0.0001) vs no change in untreated patients. Visceral pain enhances FMS symptoms, probably augmenting the level of central sensitization typical of the syndrome. Systematic assessment and treatment of visceral pain comorbidities should be a part of FMS management strategy.
Bidirectional association between fibromyalgia and gastroesophageal reflux disease: two population-based retrospective cohort analysis
Authors: Wang Jia-Chi , Sung Fung-Chang , Men Mauranda , Wang Kevin A. , Lin Cheng-Li , Kao Chia-Hung 
Published: July 2017

Abstract
Fibromyalgia (FM) tends to coexist with gastroesophageal reflux disease (GERD). This retrospective cohort study was conducted to determine the bidirectional association between FM and GERD, using a nationwide database, the National Health Insurance of Taiwan. We established 2 study arms, including 35,117 patients with FM in arm 1 and 34,630 patients with GERD in arm 2, newly diagnosed between 2000 and 2010. For each study arm, we randomly selected 4-fold subjects with neither FM nor GERD from the same database, frequency matched by sex, age, and diagnosis date, as the respective control cohorts. Incidence of GERD in arm 1 and incidence of FM in arm 2 were estimated by the end of 2011. The overall incidence of GERD was 1.6-fold greater in the FM cohort than in the non-FM cohort (12.0 and 7.61 per 1000 person-years, crude hazard ratio [HR] = 1.58, 95% confidence interval [CI] = 1.51-1.66), with an adjusted HR (aHR) of 1.27 (95% CI = 1.22-1.33) after controlling for sex, age, comorbidities, and medications. The GERD cohort ultimately had a 1.5-fold higher incidence of FM than the non-GERD cohort (5.76 vs 3.96 per 1000 person-years), with an aHR of 1.44 (95% CI = 1.29-1.60). The present study suggests a bidirectional relationship between FM and GERD. There is a greater risk of developing GERD for patients with FM than developing FM for patients with GERD.
Longitudinal change in parent and child functioning after internet-delivered cognitive-behavioral therapy for chronic pain
Authors: Law Emily F. , Fisher Emma , Howard Waylon J. , Levy Rona , Ritterband Lee , Palermo Tonya M. 
Published: July 2017

Abstract
Theoretical models of pediatric chronic pain propose longitudinal associations between children's pain experiences and parent and family factors. A large body of cross-sectional research supports these models, demonstrating that greater parent distress and maladaptive parenting behaviors are associated with greater child disability. Family-based cognitive-behavioral therapy interventions have been developed for youth with chronic pain which aim to improve child disability and reduce maladaptive parenting behaviors. However, little is known about temporal, longitudinal associations between parent and child functioning in this population. In the present study, we conducted a secondary analysis of data from 138 families of youth with chronic pain aged 11 to 17 years old who received family-based cognitive-behavioral therapy delivered through the Internet as part of a randomized controlled trial. Measures of child disability, parent protective behavior, and parent distress were obtained at pretreatment, immediate posttreatment, 6-month follow-up, and 12-month follow-up. Latent growth modeling indicated that child disability, parent protective behavior, and parent distress improved with treatment over the 12-month study period. Latent growth modeling for parallel processes indicated that higher parent distress at pretreatment predicted less improvement in child disability over 12 months. No other predictive paths between parent and child functioning were significant. These findings indicate that parent distress may increase the risk of poor response to psychological pain treatment among youth with chronic pain. At present, parent distress is not routinely targeted in psychological interventions for pediatric chronic pain. Research is needed to determine optimal strategies for targeting parent and family factors in the treatment of pediatric chronic pain.
Evaluation and management of nonsyndromic congenital hearing loss
Authors: Funamura Jamie L. 
Published: July 2017

Purpose of review
Nonsyndromic congenital hearing loss represents the largest proportion of paediatric sensorineural hearing loss. The optimal evaluation and management of affected patients remains clinically challenging. Current controversies in the diagnostic work-up of nonsyndromic congenital hearing loss are presented in this review.

Recent findings
The improved diagnostic yield of comprehensive genetic testing due to new sequencing technologies is changing the diagnostic for congenital hearing loss. Concerns for both ionizing radiation and general anaesthetic exposure are also driving shifts in imaging modality preferences for infants and toddlers.

Summary
A thoughtful systematic, targeted approach taking into consideration the audiologic phenotype of the patient is recommended for the work-up of nonsyndromic congenital hearing loss.
Development of Adaptive Coping From Mid to Late Life
Authors: Martin-Joy John S. , Malone Johanna C. , Cui Xing-Jia , Johansen Pål-Ørjan , Hill Kevin P. , Rahman M. Omar , Waldinger Robert J. , Vaillant George E. 
Published: July 2017

Abstract
The present study examines changes in defense maturity from mid to late life using data from an over 70-year longitudinal study. A sample of 72 men was followed beginning in late adolescence. Participants' childhoods were coded for emotional warmth. Defense mechanisms were coded by independent raters using the Q-Sort of Defenses (Roston et al., 1992, Ego mechanisms of defense: A guide for clinicians and researchers 217–233) based on interview data gathered at approximately ages 52 and 75. We examined psychosocial correlates of defenses at midlife, late life, and changes in defense from mid to late life. Overall, defenses grew more adaptive from midlife to late life. However, results differed on the basis of the emotional warmth experienced in the participants' childhoods. In midlife, men who experienced warm childhoods used more adaptive (mature) defenses; yet by late life, this difference in defensive maturity had disappeared. Men who experienced less childhood warmth were more likely to show an increase in adaptive defenses during the period from mid to late life.