bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evaluation of Syringomas by In Vivo Reflectance Confocal Microscopy: A Report of Two Cases
Authors: Jiménez Marcela R. , Rocchetto Helena , Ferreira Paula S. , Sangueza Martin , Lourenço Silvia V. , Nico Marcello M. S. 
Published: October 2016

Abstract:
Syringomas are benign adnexal tumors that are characterized histologically by the presence of small solid and cystic epithelial structures in the upper half of the reticular dermis. Reflectance confocal microscopy is a noninvasive diagnostic method that enables in vivo visualization of tissues with a resolution that approximates that of conventional histopathology. The use of this method in skin imaging over the past several years has improved dermatological diagnoses, creating the potential for its wide application in such diagnoses, especially for benign and malignant skin tumors. We describe its use in the diagnosis of syringoma in 2 patients and correlate the resulting clinical, histopathological, and digital reflectance confocal microscopy images.
A Rare Case of a Primary Cutaneous Desmoplastic Atypical Granular Cell Tumor
Authors: Nakamura Yasuhiro , Fujino Takashi , Nagata Koji , Imamura Taichi , Teramoto Yukiko , Asami Yuri , Arai Eiichi , Yamamoto Akifumi 
Published: October 2016

Abstract:
Granular cell tumors are uncommon neoplasms and a small number of these neoplasms have been reported as showing malignant behavior. Here, we report a rare case of a solitary granular cell tumor that exhibited atypical histology, including an extensive desmoplastic stroma, in a 69-year-old woman. The surgical specimen revealed localized areas of spindling cells, areas of cellular pleomorphism, and p53 overexpression. Based on previously published criteria, we classified this lesion as an atypical granular cell tumor. To date, only very few case reports have documented this desmoplastic variant of granular cell tumor. However, the classifications of benign, atypical, and malignant granular cell tumors are still controversial, owing to an overlap of morphological and immunohistochemical profiles and lack of consistent histological criteria. Additionally, it is unknown whether the histology of the desmoplastic variant in the present case is significant for the classification of granular cell tumors and prediction of patient prognosis. Regardless of these issues, awareness, and close follow-up are required because of potential recurrences of this rare variant of granular cell tumor.
Quantitative Method for Simultaneous Analysis of a 5-Probe Cocktail for Cytochrome P450 Enzymes
Authors: Lammers Laureen A. , Achterbergh Roos , Pistorius Marcel C. M. , Bijleveld Yuma , de Vries Emmely M. , Boelen Anita , Klümpen Heinz-Josef , Romijn Johannes A. , Mathôt Ron A. A. 
Published: October 2016

Background:
The metabolic activity of P450 enzymes in vivo can be determined using selective probe drugs. The simultaneous administration of multiple CYP-specific probe drugs is commonly known as the “cocktail approach.” Disadvantages of a cocktail are large volumes of samples required for analysis and time-consuming analyses. The aim of this study was to develop and validate a simplified but sensitive method for the simultaneous quantification of 5 probe drugs [caffeine (CYP1A2), metoprolol (CYP2D6), midazolam (CYP3A4), omeprazole (CYP2C19), and S-warfarin (CYP2C9)] in a previously validated cocktail using a liquid chromatography–tandem mass spectrometry (LC-MS/MS) method.

Methods:
The method entailed a single method for sample preparation that enables quick processing of the samples containing all 5 probe drugs in a small volume of blood (≥10 μL) followed by a chiral and nonchiral LC-MS/MS method. The method was validated for selectivity, specificity, resolution of racemic warfarin, linearity, accuracy, imprecision, recovery, process efficiency, ionization efficiency, and carryover effect.

Results:
The method showed good selectivity without matrix interferences and differentiated S- and R-warfarin enantiomers with adequate resolution (Rs = 1.55). For all analytes, the mean process efficiency was >95%, and the mean ionization efficiency was >97%. Furthermore, the accuracy was between 94.9% and 108% for all analytes, and the within- and between-run imprecision were <11.7% for the lower limit of quantification and <12.6% for the middle level and upper limit of quantification.

Conclusions:
The method presented here enables the simultaneous quantification of the 5 probes in a very small blood volume (≥10 μL). Furthermore, it is less time consuming than previously reported methods because it requires only 1 simple method for sample preparation followed by a nonchiral and chiral LC-MS/MS method that can be performed sequentially.
Gonorrhea Control, United States, 1972–2015, A Narrative Review
Authors: Peterman Thomas A. , O’Connor Kevin , Bradley Heather M. , Torrone Elizabeth A. , Bernstein Kyle T. 
Published: October 2016

Abstract
Gonorrhea is the second most commonly reported infection. It can lead to pelvic inflammatory disease, ectopic pregnancy, and infertility. Rates of gonorrhea decreased after the National Gonorrhea Control Program began in 1972, but stabilized in the mid 1990s. The emergence of antimicrobial resistant strains increases the urgency for enhanced gonorrhea control efforts. To identify possible approaches for improving gonorrhea control, we reviewed historic protocols, reports, and other documents related to the activities of the National Gonorrhea Control Program using Centers for Disease Control and Prevention records and the published literature. The Program was a massive effort that annually tested up to 9.3 million women, and treated up to 85,000 infected partners and 100,000 additional exposed partners. Reported gonorrhea rates fell by 74% between 1976 and 1996, then stabilized. Testing positivity was 1.6–4.2% in different settings in 1976. In 1999–2008, the test positivity of a random sample of 14- to 25-year-olds was 0.4%. Gonorrhea testing rates remain high, however, partner notification efforts decreased in the 1990s as attention shifted to human immunodeficiency virus and other sexually transmitted diseases. The decrease and subsequent stabilization of gonorrhea rates was likely also influenced by changes in behavior, such as increases in condom use in response to acquired immune deficiency syndrome. Renewed emphasis on partner treatment might lead to further decreases in rates of gonorrhea.
The Association of Health Seeking Behaviors With Human Papillomavirus Vaccination Status Among High-Risk Urban Youth
Authors: Fontenot Holly B. , Lee-St. John Terrence , Vetters Ralph , Funk Danielle , Grasso Chris , Mayer Kenneth H. 
Published: October 2016

Background
Vaccination is the primary strategy to reduce the burden of human papillomavirus (HPV) related diseases in the United States. Unvaccinated youth are at risk for HPV infection and associated diseases, and limited research has explored factors associated with HPV vaccination among those who are disadvantaged and at high risk, including lesbian, gay, bisexual, transgender and queer and/or homeless.

Methods
A retrospective electronic medical record review was conducted at an urban, homeless, and lesbian, gay, bisexual, transgender and queer focused health center in northeastern US logistic regression models examined the associations between HPV vaccination and demographic/social characteristics and health behaviors.

Results
A total of 1211 men and 1326 women (gender at birth) records were reviewed from patients (ages 13–26 years) who presented for care between January 2010 and June 2013. The sample was diverse, and about half identified as heterosexual and reported stable/secure housing. Approximately 8% of men and 29% of women had obtained ≥ 1 HPV vaccine dose. The strongest predictors of vaccine initiation were health-related behaviors: having an annual examination, obtaining a non-HPV vaccine, and engaging in oral sex. Additionally, for women only, having had a Pap test or a sexually transmitted infection visit were also associated with an increase in odds, whereas identifying as transmale decreased the odds of vaccination. Having private insurance was the only predictor of 3-dose completion (women only).

Conclusions
Among a high-risk adolescent sample, primarily health-seeking behaviors increased the odds of HPV vaccination, reinforcing the importance of providers using various routine preventative visits as opportunities/cues to vaccine.
Herpes Simplex Virus Type 1 Shedding in Tears and Nasal and Oral Mucosa of Healthy Adults
Authors: Ramchandani Meena , Kong Marlene , Tronstein Elizabeth , Selke Stacy , Mikhaylova Anna , Magaret Amalia , Huang Meei-Li , Johnston Christine , Corey Lawrence , Wald Anna 
Published: October 2016

Background
Herpes simplex virus type 1 (HSV-1) is prevalent worldwide and causes mucocutaneous infections of the oral area. We aimed to define the frequency and anatomic distribution of HSV-1 reactivation in the facial area in persons with a history of oral herpes.

Methods
Eight immunocompetent HSV-1 seropositive adults were evaluated for shedding of HSV-1 from 12 separate orofacial sites (8 from oral mucosa, 2 from nose, and 2 from conjunctiva) 5 days a week and from the oral cavity 7 days a week for approximately 5 consecutive weeks by a HSV DNA PCR assay. Symptoms and lesions were recorded by participants.

Results
Herpes simplex virus type 1 was detected at least from 1 site on 77 (26.5%) of 291 days. The most frequent site of shedding was the oral mucosa, with widespread shedding throughout the oral cavity. Lesional shedding rate was 36.4% (4 of 11 days with lesions), and the asymptomatic rate was 27.1% (65 of 240 nonlesional days). In individual participants, the median rate of HSV shedding by HSV PCR was 19.7% of days (range, 11%–63%).

Conclusions
Reactivation of HSV-1 on the oral mucosa is common and usually asymptomatic. However, HSV-1 is rarely found in tears and nasal mucosa. Frequent oral shedding of HSV-1 may increase the risk for transmitting the virus to both oral and genital mucosa of sexual partners.
Can Residents Assess Other Providers' Infant Lumbar Puncture Skills?
Authors: Braun Colleen , Kessler David O. , Auerbach Marc , Mehta Renuka , Scalzo Anthony J. , Gerard James M. 
Published: October 2016

ObjectivesThe aims of this study were to provide validity evidence for infant lumbar puncture (ILP) checklist and global rating scale (GRS) instruments when used by residents to assess simulated ILP performances and to compare these metrics to previously obtained attending rater data.MethodsIn 2009, the International Network for Simulation–based Pediatric Innovation, Research, and Education (INSPIRE) developed checklist and GRS scoring instruments, which were previously validated among attending raters when used to assess simulated ILP performances. Video recordings of 60 subjects performing an LP on an infant simulator were collected; 20 performed by subjects in 3 categories (beginner, intermediate, and expert). Six blinded pediatric residents independently scored each performance (3 via the GRS, 3 via the checklist). Four of the 5 domains of validity evidence were collected: content, response process, internal structure (reliability and discriminant validity), and relations to other variables.ResultsEvidence for content and response process validity is presented. When used by residents, the checklist performed similarly to what was found for attending raters demonstrating good internal consistency (Cronbach α = 0.77) and moderate interrater agreement (intraclass correlation coefficient = 0.47). Residents successfully discerned beginners (P< 0.01, effect size = 2.1) but failed to discriminate between expert and intermediate subjects (P= 0.68, effect size = 0.34). Residents, however, gave significantly higher GRS scores than attending raters across all subject groups (P< 0.001). Moderate correlation was found between GRS and total checklist scores (P= 0.49,P< 0.01).ConclusionsThis study provides validity evidence for the checklist instrument when used by pediatric residents to assess ILP performances. Compared with attending raters, residents appeared to over-score subjects on the GRS instrument.
A Case of Resistant Schizophrenia Successfully Treated With Clozapine/Long-acting Injectable Aripiprazole Combination
Authors: Sepede Gianna , Di Iorio Giuseppe , Spano Maria Chiara , Lorusso Marco , Sarchione Fabiola , Santacroce Rita , Salerno Rosa Maria , Di Giannantonio Massimo 
Published: October 2016

Background
Treatment-resistant schizophrenia (TRS) is a condition characterized by intense symptom severity and poor response to different antipsychotic agents. The first therapeutic option in TRS is clozapine, but often high/medium doses are not tolerated. Adding an oral antipsychotic to low doses of clozapine is a promising strategy in the management of TRS. On the contrary, there are few data on combined clozapine/long-acting injectable (LAI) medications, and none on clozapine/LAI-aripiprazole.

Case
A 21-year-old male schizophrenic patient, resistant to several oral and LAI medications, partially improved after clozapine 300 mg/d treatment. Unfortunately, he also reported excessive sedation and an episode of myoclonus, so clozapine was reduced to 150 mg/d, but no additional benefits were observed. Subsequently, LAI-aripiprazole (first 200 mg/mo, then 400 mg/mo) was added, and the patient's conditions dramatically improved over time. After 1 year of observation, symptoms reduction was 50% or greater, without significant adverse events.

Conclusions
Clozapine use in TRS is often reduced or delayed due to the fear of serious adverse effects. Adding LAI-aripiprazole to low doses of clozapine may be a useful therapeutic option to obtain a good efficacy/tolerability balance.
Functional MRI Correlates of Resting-State Temporal Theta and Delta EEG Rhythms
Authors: Marawar Rohit A. , Yeh Hsiang J. , Carnabatu Christopher J. , Stern John M. 
Published: October 2016

Purpose:
The EEG rhythms demonstrate changes in frequency and power with spontaneous changes in behavioral state that do not have well-understood metabolic correlates within the brain. To investigate this question and compare the temporal lobe theta and delta rhythms, resting-state functional MRI was obtained with simultaneous EEG.

Methods:
Simultaneous EEG–functional MRI was recorded from 14 healthy sleep-deprived subjects in awake and drowsy states. Scalp electrodes corresponding to bilateral temporal lobes were used to calculate delta and theta band power. The resulting time series was used as input in a general linear model, and the final power curves were convolved with the standard hemodynamic response function. Resulting images were thresholded at Z > 2.0.

Results:
Positive and negative correlations for unilateral theta and delta rhythms were present bilaterally in different structures and with differing correlation signs. Theta rhythm positive correlation was present in hindbrain, peri-opercular, and frontoparietal regions and subcortical gray structures, whereas negative correlation was present in parietooccipital cortex. Delta rhythm positive correlation was present in parietooccipital cortex, and negative correlation roughly resembled positive correlations for the theta rhythm.

Conclusions:
Temporal lobe theta and delta rhythms are correlated with functional MRI signal in an almost mutually exclusive distribution. The different distributions indicate different corresponding networks. These normal findings supplement the understanding of theta and delta rhythm significance.
Hierarchical Frequency Tagging reveals neural markers of predictive coding under varying uncertainty
Authors: Gordon Noam , Koenig-Robert Roger , Tsuchiya Naotsugu , van Boxtel Jeroen , Hohwy Jakob 
Published: October 2016

AbstractUnderstanding the integration of top-down and bottom-up signals is essential for the study of perception. Current accounts of predictive coding describe this in terms of interactions between state units encoding expectations or predictions, and error units encoding prediction error. However, direct neural evidence for such interactions has not been well established. To achieve this, we combined EEG methods that preferentially tag different levels in the visual hierarchy: Steady State Visual Evoked Potential (SSVEP at 10Hz, tracking bottom-up signals) and Semantic Wavelet-Induced Frequency Tagging (SWIFT at 1.3Hz tracking top-down signals). Importantly, we examined intermodulation components (IM, e.g., 11.3Hz) as a measure of integration between these signals. To examine the influence of expectation and predictions on the nature of such integration, we constructed 50-second movie streams and modulated expectation levels for upcoming stimuli by varying the proportion of images presented across trials. We found SWIFT, SSVEP and IM signals to differ in important ways. SSVEP was strongest over occipital electrodes and was not modified by certainty. Conversely, SWIFT signals were evident over temporo- and parieto-occipital areas and decreased as a function of increasing certainty levels. Finally, IMs were evident over occipital electrodes and increased as a function of certainty. These results link SSVEP, SWIFT and IM signals to sensory evidence, predictions, prediction errors and hypothesis-testing - the core elements of predictive coding. These findings provide neural evidence for the integration of top-down and bottom-up information in perception, opening new avenues to studying such interactions in perception while constraining neuronal models of predictive coding.SIGNIFICANCE STATEMENTThere is a growing understanding that both top-down and bottom-up signals underlie perception. But how do these signals interact? And how does this process depend on the signals’ probabilistic properties? ‘Predictive coding’ theories of perception describe this in terms how well top-down predictions fit with bottom-up sensory input. Identifying neural markers for such signal integration is therefore essential for the study of perception and predictive coding theories in particular. The novel Hierarchical Frequency Tagging method simultaneously tags top-down and bottom-up signals in EEG recordings, while obtaining a measure for the level of integration between these signals. Our results suggest that top-down predictions indeed integrate with bottom-up signals in a manner that is modulated by the predictability of the sensory input.
A two-state photoconversion model predicts the spectral response dynamics of optogenetic systems
Authors: Olson Evan J. , Tzouanas Constantine N. , Tabor Jeffrey J. 
Published: October 2016

AbstractIn optogenetics, light signals are used to control genetically engineered photoreceptors, and in turn manipulate biological pathways with unmatched precision. Recently, evolved photoreceptors with diversein vitro-measured wavelength and intensity-dependent photoswitching properties have been repurposed for synthetic control of gene expression, proteolysis, and numerous other cellular processes. However, the relationship between the input light spectrum andin vivophotoreceptor response dynamics is poorly understood, restricting the utility of these optogenetic tools. Here, we advance a classicin vitrotwo-state photoreceptor model to reflect thein vivoenvironment, and combine it with simplified mathematical descriptions of signal transduction and output gene expression through our previously engineered green/red and red/far red photoreversible bacterial two-component systems (TCSs). Additionally, we leverage our recent open-source optical instrument to develop a workflow of spectral and dynamical characterization experiments to parameterize the model for both TCSs. To validate our approach, we challenge the model to predict experimental responses to a series of complex light signals very different from those used during parameterization. We find that the model generalizes remarkably well, predicting the results of all categories of experiments with high quantitative accuracy for both systems. Finally, we exploit this predictive power to program two simultaneous and independent dynamical gene expression signals in bacteria expressing both TCSs. This multiplexed gene expression programming approach will enable entirely new studies of how metabolic, signaling, and decision-making pathways integrate multiple gene expression signals. Additionally, our approach should be compatible with a wide range of optogenetic tools and model organisms.Significance statementLight-switchable signaling pathways (optogenetic tools) enable precision studies of how biochemical networks underlie cellular behaviors. We have developed a versatile mathematical model based on a two-state photoconversion mechanism that we have applied to theE. coliCcaSR and Cph8-OmpR optogenetic tools. This model enables accurate prediction of the gene expression response to virtually any light source or mixture of light sources. We express both optogenetic tools in the same cell and apply our model to program two simultaneous and independent gene expression signals in the same cell. This method can be used to study how biological pathways integrate multiple inputs and should be extensible to other optogenetic tools and host organisms.