bluuebunny/crossref_metadata_2025 huggingface dataset:
RiboProP: a probabilistic ribosome positioning algorithm for ribosome profiling
Authors: Zhao Dengke , Baez William D , Fredrick Kurt , Bundschuh Ralf
Published: October 2018

Motivation

Ribosome profiling has been widely used to study translation in a genome-wide fashion. It requires deep sequencing of ribosome protected mRNA fragments followed by mapping of fragments to the reference genome. For applications such as identification of ribosome pausing sites, it is not enough to map a fragment to a given gene, but the exact position of the ribosome represented by the fragment must be identified for each mRNA fragment. The assignment of the correct ribosome position is complicated by the broad length distribution of the ribosome protected fragments caused by the known sequence bias of micrococcal nuclease (MNase), the most widely used nuclease for digesting mRNAs in bacteria. Available mapping algorithms suffer from either MNase bias or low accuracy in characterizing the ribosome pausing kinetics.

Results

In this paper, we introduce a new computational method for mapping the ribosome protected fragments to ribosome locations. We first develop a mathematical model of the interplay between MNase digestion and ribosome protection of the mRNAs. We then use the model to reconstruct the ribosome occupancy profile on a per gene level. We demonstrate that our method has the capability of mitigating the sequence bias introduced by MNase and accurately locating ribosome pausing sites at codon resolution. We believe that our method can be broadly applied to ribosome profiling studies on bacteria where codon resolution is necessary.

Availability and implementation

Source code implementing our approach can be downloaded under GPL3 license at http://bioserv.mps.ohio-state.edu/RiboProP.

Supplementary information

Supplementary data are available at Bioinformatics online.
CANDI: an R package and Shiny app for annotating radiographs and evaluating computer-aided diagnosis
Authors: Badgeley Marcus A , Liu Manway , Glicksberg Benjamin S , Shervey Mark , Zech John , Shameer Khader , Lehar Joseph , Oermann Eric K , McConnell Michael V , Snyder Thomas M , Dudley Joel T
Published: October 2018

Motivation

Radiologists have used algorithms for Computer-Aided Diagnosis (CAD) for decades. These algorithms use machine learning with engineered features, and there have been mixed findings on whether they improve radiologists’ interpretations. Deep learning offers superior performance but requires more training data and has not been evaluated in joint algorithm-radiologist decision systems.

Results

We developed the Computer-Aided Note and Diagnosis Interface (CANDI) for collaboratively annotating radiographs and evaluating how algorithms alter human interpretation. The annotation app collects classification, segmentation, and image captioning training data, and the evaluation app randomizes the availability of CAD tools to facilitate clinical trials on radiologist enhancement.

Availability and implementation

Demonstrations and source code are hosted at (https://candi.nextgenhealthcare.org), and (https://github.com/mbadge/candi), respectively, under GPL-3 license.

Supplementary information

Supplementary material is available at Bioinformatics online.
TIVAN: tissue-specific cis-eQTL single nucleotide variant annotation and prediction
Authors: Chen Li , Wang Ye , Yao Bing , Mitra Amit , Wang Xu , Qin Xiao
Published: October 2018

Predicting genetic regulatory variants, most of which locate in non-coding genomic regions, still remain a challenge in genetic research. Among all non-coding regulatory variants, cis-eQTL single nucleotide variants (SNVs) are of particular interest for their crucial role in regulating gene expression. Since different gene expression patterns are believed to contribute to the etiologies of different phenotypes, it is desirable to characterize the impact of cis-eQTL SNVs in a context-specific manner. Though computational methods for predicting the potential of variants being pathogenic or deleterious are well-established, methods for annotating and predicting cis-eQTL SNVs are under-developed. Here, we present TIVAN (TIssue-specific Variant ANnotation and prediction), an ensemble method of decision trees, to predict tissue-specific cis-eQTL SNVs. TIVAN is trained based on a comprehensive collection of features, including genome-wide genomic and epigenomic profiling data. As a result, TIVAN has been shown to accurately discriminate cis-eQTL SNVs from non-eQTL SNVs and perform favorably to other methods by obtaining higher five-fold cross-validation AUC values (CV-AUC) and Leave-One-Chromosome-Out predicted AUC values (LOCO-AUC) across 44 different tissues belonging to 27 different tissue classes. Finally, TIVAN consistently maintains top performance on an independent testing dataset, which includes 7 tissues in 11 studies.

Availability and implementation

TIVAN software is available at https://github.com/lichen-lab/TIVAN.

Supplementary information

Supplementary data are available at Bioinformatics online.
Characterization of cell fusion in an experimental mouse model of endometriosis†
Authors: Tal A , Tal R , Shaikh S , Gidicsin S , Mamillapalli R , Taylor H S
Published: October 2018

Cell fusion is involved in the development of some adult organs, is implicated in the pathogenesis of specific types of cancer, and is known to participate in repair/regeneration processes mediated by bone-marrow-derived cells (BMDCs). Endometriosis is a disease characterized by growth of functional endometrial tissue outside of the uterine cavity. Endometriosis shares some molecular properties with cancer and BMDCs home to endometriosis lesions in a mouse model. Our objective was to determine if cell fusion can occur in endometriosis and establish whether bone-marrow-derived cells participate in cell fusion events in lesions. We employed a Cre-Lox system to identify cell fusion events in a mouse model of endometriosis. Fused cells were detected in endometriotic lesions, albeit at a low frequency (∼1 in 400 cells), localized to the stromal compartment, and displayed restricted proliferation. Using 5-fluorouracil-based nongonadotoxic bone marrow transplantation model, we demonstrate that bone marrow cells represent a principal cell source for fusion events in lesions. Cell fusion progeny uniformly lacked expression of selected markers of hematopoietic, endothelial, and epithelial markers, though they expressed the mesenchymal/stromal markers Sca-1 and CD29. This study is the first to describe the phenomenon of cell fusion in endometriosis and points to a mesenchymal population derived from cell fusion events with limited proliferative activity, properties previously attributed to endometrial stem cells. Their putative role in the pathogenesis of the disease remains to be elucidated.
Featured Article: Bidirectional Effects of Sleep and Sedentary Behavior Among Toddlers: A Dynamic Multilevel Modeling Approach
Authors: Armstrong Bridget , Covington Lauren B , Unick George J , Black Maureen M
Published: October 2018

Objective

To examine the bidirectional effects of objectively measured nighttime sleep and sedentary activity among toddlers.

Method

Actical accelerometer data were analyzed for 195 toddlers participating in an obesity prevention trial (mean age = 27 months). Toddlers wore the accelerometers for up to 7 consecutive days. Nighttime sleep was defined as the number of minutes asleep between the hours of 8 pm and 8 am the following morning. Sedentary behavior (in minutes) was defined using previously established Actical cut points for toddlers. Variables were lagged and parsed into latent within- and between-person components, using dynamic structural equation modeling (DSEM).

Results

Toddlers spent an average of 172 min (∼3 hr) in sedentary activity and slept an average of 460 min (∼8 hr) per night. An autoregressive cross-lagged multilevel model revealed significant autoregression for both sleep and sedentary activity. Cross-lagged values revealed that decreased sleep predicted increased next-day sedentary activity, and sedentary activity predicted that night’s sleep. For 89% of the sample, the within-person standardized cross-lagged effects of sleep on sedentary were larger than the cross-lagged effects of sedentary on sleep.

Conclusions

Results suggest that, on average, nighttime sleep is a stronger predictor of subsequent sedentary behavior (compared with the reverse), and this is the case for the majority of toddlers. Findings highlight the importance of interindividual associations between sleep and sedentary activity. The present study is an example of how DSEM methods can be used to ask questions about Granger-causal cross-lagged relations between variables, both within and between individuals.
Applications of chemical imaging techniques in paleontology
Authors: Pan Yanhong , Hu Liang , Zhao Tao
Published: October 2018

Chemical imaging techniques, based on a combination of microscopy and spectroscopy, are designed to analyse the composition and spatial distribution of heterogeneous chemical complexes within a sample. Over the last few decades, it has become an increasingly popular tool for characterizing trace elements, isotopic information and organic biomarkers (molecular biosignatures) found in fossils. Here, we introduce the analytical principle of each technique and the interpretation of the chemical signals, followed by a review of the main applications of these techniques in paleontology. We also demonstrate that each technique is associated with pros and cons, and the current limitations and obstacles associated with the use of each specific technique should be taken into account before being applied to fossil samples. Finally, we propose that, due to the rapid advances in the available technology and overall trends towards more multi-disciplinary studies in paleontology, chemical imaging techniques can be expected to have broader applications in paleontology in the near future.
Gender Wage Inequalities Between Historical Heritage and Structural Adjustments: A German–German Comparison Over Time
Authors: Minkus Lara , Busch-Heizmann Anne
Published: October 2018

While research on the gender pay gap (GPG) is growing, there is little evidence on the stability or convergence of GPGs against the backdrop of sudden historical changes. Taking advantage of German reunification, after which western male-breadwinner policies were superimposed on the hitherto gender egalitarian East, we illuminate this research gap. Using decompositions on the Socio-economic Panel, we examine how historically grown gender arrangements influence the GPG in eastern and western Germany 1990–2013. We find support for the concept of a stalled gender revolution and a continued influence of pre-unification gender arrangements on the German GPG.
Effect of different dosages of PG-600 on ovulation and pregnancy rates in ewes during the breeding season
Authors: Habeeb Hayder Mohammed Hassan , Hazzard Timothy M , Stormshak Fred , Kutzler Michelle A
Published: October 2018

This study compared the reproductive effects of different dosages of PG-600 (Intervet/Merck Animal Health, Madison, NJ) during the breeding season of ewes. PG-600 is a single-dose injectable product labeled for estrous induction in swine, containing equine chorionic gonadotropin (80 IU/mL) and human chorionic gonadotropin (40 IU/mL). PG-600 is routinely used off-label for out-of-season estrous induction in sheep. However, at the most common dose administered to ewes (5 mL), PG-600 is likely to overstimulate the ovaries, resulting in reduced pregnancy rates. Following estrous synchronization with intravaginal progesterone and cloprostenol, Polypay ewes were treated with 5 mL PG-600 (T1; n = 8), 1.5 mL PG-600 (T2; n = 8), or 5 mL saline (C; n = 8) and then mated to rams. Jugular vein samples were collected prior to the PG-600 injection (0 hr) and at 2, 4, 8, 12, and 24 hr after injection. Serum estradiol-17β was determined by chemiluminescence and among groups using repeated measures analysis of covariance. Ovulation and pregnancy rates were determined by transrectal ultrasonography and compared by one-way ANOVA and chi-square, respectively. Estradiol-17β concentrations were greater in T1 compared to T2 and C (P < 0.001). Ovulation rate was greater (P < 0.001) but pregnancy rate was lower (P < 0.001) in the T1 compared to C and T2. These data confirm that a 5 mL dose of PG-600 administered to ewes during the breeding season overstimulates the ovaries, which may then reduce fertilization or embryo survival. Future research will focus on the effects of different dosages of PG-600 on pregnancy rate of ewes during the nonbreeding season.
Development of Action Threshold to Manage Common Leaf Spot and Black Seed Disease of Strawberry Caused by Mycosphaerella fragariae
Authors: Carisse Odile , McNealis Vanessa
Published: October 2018

The fungus Mycosphaerella fragariae is responsible for two strawberry diseases: common leaf spot (CLS) and black seed disease (BSD). In June-bearing strawberry plantings, CLS influences vigor, yield, and winter survival. During production years, BSD causes black lesions around strawberry seeds, reducing the market value of the berries. The objective of this study was to characterize the relationships between CLS and BSD and to develop action thresholds for the management of BSD. Data on the number of lesions per leaf, number of black seeds per berry, and percentage of diseased berries were collected at two experimental and six commercial sites from 2000 to 2011, corresponding to 50 farm-years. First, logistic regression was used to model the relationship between BSD occurrence in its binary data form and the number of lesions per leaf assessed at 7, 14, 21, and 28 days before 10% bloom. Second, linear regression was used to model the relationship between BSD severity, BSD incidence, and number of lesions per leaf assessed at 7, 14, 21, and 28 days before 10% bloom. Resulting action thresholds of 15, 25, or 33 lesions per leaf at 21, 14, or 7 days before 10% bloom, respectively, were compared with the recommended practice at three commercial sites in 2014, 2015, and 2016. The percentage of diseased berries was significantly (P = 0.0016; least significant difference = 7.140) higher in the sections of the fields that were not managed for BSD, with an average of 15.22% diseased berries, in comparison with 3.22 and 2.44% diseased berries in sections managed according to the recommendations and the thresholds, respectively. Overall, 40% less fungicide was used when the thresholds were applied. Hence, these thresholds can be used as an additional decision tool to optimize fungicide applications during the prebloom period.
Biomechanical Assessment of Torsional Stiffness in a Supracondylar Humerus Fracture Model
Authors: Wallace Melissa , Johnson David B. , Pierce William , Iobst Christopher , Riccio Anthony , Wimberly R. Lane
Published: October 2018

Background:

We assessed the effect on the torsional stability by different pin diameters and varied pin configurations in a biomechanical supracondylar humerus fracture model.

Methods:

After scanning a model of a pediatric humerus, the image was imported into software. Variable pin trajectories were planned. Acrylonitrile butadiene styrene plastic models were 3-dimensionally printed with predetermined pin trajectories. Models were osteotomized and potted with a polyurethane resin. Five-pin configurations were designed to test coronal and sagittal patterns of pin placement. Each included 3 lateral pins and a medial pin. Pin diameters of 1.6, 2.0, and 2.4 mm were tested in all configurations. Three models for each pin diameter/configuration were tested to ensure uniformity. Stability of the construct was tested to determine the torque needed to deflect the osteotomy 10 degrees in internal/external rotation. Each model was tested 3 times.

Results:

In all models/configurations, the 2.4 mm pin diameter was statistically stiffer than 1.6 mm diameter pins; this lost statistical significance in certain patterns when comparing 2.0- and 2.4-mm pins. When comparing a divergent to a parallel configuration in the coronal plane, there was no significant difference in stability when pin diameter or number were controlled. The convergent pin configuration was, in general, the least stable pattern. Use of a medial pin conferred statistically significant stiffness throughout most models as demonstrated with pin deletion. Use of 2 pins was significantly less stiff than most 3-pin models.

Conclusions:

Larger pin diameters confer greater stiffness among all patterns. The use of 3 lateral and 1 medial pin was not statistically different than 2 lateral and 1 medial pin in our models. Both patterns were stiffer than 3 lateral pins only or other fewer pin constructs. The alignment of pins in the sagittal plane did not affect overall construct stiffness.
Therapeutic Management of the Posttraumatic Stiff Elbow After Open Osteocapsular Release
Authors: Cancio Jill M. , Rhee Peter
Published: October 2018

Arthrofibrosis is an inevitable consequence of elbow trauma that oftentimes requires surgical release to restore range of motion and function. Although the surgical procedure for elbow osteocapsular release can result in marked improvement in elbow motion, postrelease rehabilitation is paramount to maintaining and even improving the gains achieved in surgery. There are a variety of rehabilitation protocols and modalities that can be implemented that can be divided into an early versus late stage of rehabilitation after surgery. Irrespectively, patient ownership in the rehabilitative process and effective communication between surgeon and therapist are integral in achieving successful outcomes.
Tenodesis of the Ulnotriquetrum Ligament to the Fovea for a Triangular Fibrocartilage Complex Tear
Authors: Moritomo Hisao , Arimitsu Sayuri
Published: October 2018

We developed a novel procedure to treat a triangular fibrocartilage complex (TFCC) foveal tear, namely tenodesis of the ulnotriquetrum ligament (UTL) to the fovea. We attempted to reestablish the tension of the palmar radioulnar ligament by the procedure specifically in cases with palmar radius instability relative to the ulna. We used a palmar surgical approach to expose the palmar aspect of TFCC in which the ulnocarpal ligament merges with the palmar radioulnar ligament. UTL was distally excised at a 4 mm width from the triquetrum without disrupting its ligamentous connection to the palmar radioulnar ligament proximally. We pulled out the distal UTL through the bone tunnel from the fovea to ulnar neck. The UTL graft was fixed to the fovea with an interference screw. In 13 cases, this procedure effectively decreased ulnar wrist pain, improved distal radioulnar joint instability, and restored wrist motion and grip strength.
Tissue-selective estrogen complex for women who experience breast discomfort or vaginal bleeding when on hormone therapy
Authors: Kim Sung Eun , Lee Dong-Yun , Choi DooSeok
Published: October 2018

Objective:

The objective of this study was to evaluate the effects of switching from hormone therapy to tissue-selective estrogen complex (TSEC) in women who experience vaginal bleeding or breast discomfort.

Methods:

This retrospective cohort study included 82 postmenopausal women who received TSEC after switching from another hormone therapy due to adverse events. Changes in symptoms and imaging after switching to TSEC were evaluated.

Results:

The mean age was 56.9 years. The women were switched to TSEC due to vaginal bleeding in 56.1% and breast discomfort in 47.6% (multiple choices were allowed). After the switch, almost all women (97.6%) experienced an improvement in adverse events. However, 27% of the women had worsening of vasomotor symptoms, which was more common when hormone therapy was changed from 2 mg of estradiol (41.7%) compared with 1 mg of estradiol (16.7%), 0.625 mg of conjugated estrogen (30%), or tibolone (12.5%). Images of breast lesions and fibroids before the switch were assessed, showing no change in most women.

Conclusions:

This study suggests that TSEC is a good option for women who have breast discomfort or persistent bleeding during other hormone therapy when taking into account the differences in estrogen dose.
ULTRASOUND IN VITRECTOMY
Authors: Rizzo Stanislao , Fantoni Gualtiero , Mucciolo Dario Pasquale , Giorni Andrea , Volpi Lorenzo , Pierallini Michele , Mazzoni Andrea , Faraldi Francesco
Published: October 2018

Purpose:

To study a prototype of an ultrasound-based vitrector, and to try to understand the physical phenomena underlying this new technology.

Methods:

We tested the ultrasound-based vitrector prototype (UV) (ultrasonically-driven handpiece obtained from a modified version of the Alcon CONSTELLATION Vision System [Alcon]) using an automatic experimental setup. Balanced saline solution (BSS) and vitreous (from fresh postmortem enucleated porcine eyes) flow rates were analyzed using three different tips.

Results:

In general, BSS solution flow rates increased with increasing aspiration levels and decreased when we used % US power. Vitreous flow rates were influenced by aspiration levels, % US power, and ultrasound-related phenomena: cavitation phenomenon and “jet streaming.”

Conclusion:

Ultrasound-based vitrectomy may represent an important alternative to traditional vitrectomy. Such a tool, capable of liquefying and excising the vitreous body using ultrasound, could overcome all the limits of the guillotine-based technique (GV). Knowledge of the physical phenomena underlying ultrasound-based technology is a necessary prerequisite for further development of this new technology.
CHANGES OF AQUEOUS HUMOR MÜLLER CELLS' BIOMARKERS IN HUMAN PATIENTS AFFECTED BY DIABETIC MACULAR EDEMA AFTER SUBTHRESHOLD MICROPULSE LASER TREATMENT
Authors: Midena Edoardo , Bini Silvia , Martini Ferdinando , Enrica Convento , Pilotto Elisabetta , Micera Alessandra , Esposito Graziana , Vujosevic Stela
Published: October 2018

Purpose:

To evaluate the changes in activity of biomarkers of Müller cells (MC) in aqueous humor of patients with diabetic macular edema after subthreshold micropulse laser, over 1 year.

Methods:

Patients with untreated diabetic macular edema and central retinal thickness ≤ 400 μm were enrolled. Best-corrected visual acuity, full ophthalmic examination, and optical coherence tomography were performed. Subthreshold micropulse laser was applied every 3 months. Glial fibrillary acidic protein and inwardly rectifying potassium channel (Kir 4.1), MC activity markers, and vascular endothelial growth factor were quantified in the aqueous humor collected at baseline and at 1, 3, and 12 months after laser. Changes in the macular thickness and inner nuclear layer thickness, where MC bodies are located, were measured.

Results:

Ten eyes of 10 patients were included. Best-corrected visual acuity improved at 3 months (P = 0.047) and remained stable. Inner nuclear layer thickness significantly reduced at 12 months (P = 0.012). Glial fibrillary acidic protein, Kir 4.1, and vascular endothelial growth factor decreased at 1 and/or 3 and/or 12 months compared with baseline (P < 0.05).

Conclusion:

Subthreshold micropulse laser improves visual function in diabetic macular edema. Kir 4.1 and glial fibrillary acidic protein decrease and inner nuclear layer thickness reduction demonstrate that subthreshold micropulse laser may restore MC function. Subthreshold micropulse laser also reduces vascular endothelial growth factor concentration. The effect of subthreshold micropulse laser in diabetic macular edema may in part be due to changes of MC metabolic activity.
PNEUMATIC COMPACTION TREATMENT OF ACUTE SUBFOVEAL HEMORRHAGE AFTER BLUNT TRAUMA IN A PATIENT WITH ANGIOID STREAKS ASSOCIATED WITH PSEUDOXANTHOMA ELASTICUM
Authors: Colucciello Michael
Published: October 2018

Purpose:

To report a case of photoreceptor restitution and vision improvement with pneumatic compaction treatment of acute subfoveal hemorrhage in a patient with angioid streaks associated with pseudoxanthoma elasticum, observed by sequential fundus photography, spectral domain optical coherence tomography, and fundus autofluorescence.

Methods:

Findings on initial and sequential clinical examinations, fundus autofluorescence, and spectral domain optical coherence tomography are presented, before and after pneumatic compaction, demonstrating the course of compaction and resolution of subfoveal hemorrhage and status of the foveal ellipsoid zone and external limiting membrane. Sequential improvements in oxygen and nutrient diffusion are calculated using Fick's law of diffusion. Findings are compared with previous reports regarding the natural history of similar patients.

Results:

Rapid compaction of subfoveal hemorrhage occurred, resulting in an 89% improvement in oxygen diffusion in 15 days. No centrifugal movement of subfoveal hemorrhage occurred, potentially minimizing photoreceptor-shearing injury. Ultimately, resorption of all hemorrhage occurred with reestablishment of the foveal ellipsoid zone and external limiting membrane and minimal juxtafoveal subretinal fibrosis; best-corrected visual acuity improved to 20/40: an advantage over natural history based on published reports.

Conclusion:

Pneumatic compaction in patients with acute subfoveal hemorrhage secondary to angioid streaks associated with pseudoxanthoma elasticum compacts subfoveal hemorrhage, therefore improving oxygen and nutrient diffusion. This potentially spares foveal photoreceptors of ischemic and shearing injury, theoretically reducing subfoveal fibrosis and improving vision prognosis in these patients.
Age Impacts Olanzapine Exposure Differently During Use of Oral Versus Long-Acting Injectable Formulations
Authors: Tveito Marit , Smith Robert L. , Molden Espen , Haslemo Tore , Refsum Helge , Hartberg Cecilie , Correll Christoph U. , Høiseth Gudrun
Published: October 2018

Purpose

Olanzapine is a commonly prescribed antipsychotic available as oral and long-acting injectable (LAI) formulations. Data are lacking on the use and safety of olanzapine-LAI in older patients. The aim of this study was to investigate the effect of increasing age on olanzapine exposure during oral versus LAI administration in a real-life setting.

Methods

This observational study was based on routine therapeutic drug monitoring data collected during 2005–2017. As a measure of exposure, absolute concentrations and concentration/dose ratios of olanzapine were defined as outcome variables. Linear mixed-model analyzes were used to allow for inclusion of multiple samples per patient and adjustment for covariate effects.

Results

Olanzapine concentrations and doses from 8,288 patients (21,378 measurements) were included. The number of patients on oral treatment was 7,893 (42%, 50 years or older), while 395 were using olanzapine-LAI (27%, 50 years or older). In contrast to oral use, where the dose-adjusted concentration of olanzapine increased significantly for patients 50 years or older (P < 0.001), increasing age had no effect on olanzapine concentration following LAI administration (P = 0.550). The effects of smoking habits and gender were equal in oral and olanzapine-LAI users.

Conclusion

While the dose-adjusted systemic exposure of olanzapine increases by age after oral administration, these novel findings from a large patient population show that systemic exposure of olanzapine-LAI is unaffected by age, probably due to the lacking influence of age-related changes in gastrointestinal absorption and/or presystemic metabolism. From a pharmacokinetic point of view, it is therefore no reason to restrict the use of olanzapine-LAI in older patients requiring long-term treatment.
Selected Case From the Arkadi M. Rywlin International Pathology Slide Seminar: Atypical Thymoma With Rhabdomyomatous Differentiation
Authors: Suster David , Epstein Howard D. , Pearlstein Daryl , Suster Saul
Published: October 2018

Thymic epithelial neoplasms with foci of rhabdomyomatous differentiation are rare. A case is presented of a primary thymic epithelial neoplasm showing the features of an atypical spindle cell thymoma that contained foci of bland-appearing rhabdomyomatous cells. The histologic and immunohistochemical features of this tumor are discussed along with a review of the literature and the comments from the AMR members to the case.
Measuring the Impact of Research Using Conventional and Alternative Metrics
Authors: Knowlton Sasha E. , Paganoni Sabrina , Niehaus William , Verduzco-Gutierrez Monica , Sharma Raman , Iaccarino Mary A. , Hayano Todd , Schneider Jeffrey C. , Silver Julie K.
Published: October 2018

Bibliometrics use statistical methods to measure the scholarly impact of publications. Bibliometrics are categorized as conventional metrics or alternative metrics. Conventional metrics have often been considered the standard to measure the impact of publication-related scholarship. With the growing popularity of social media and ease of instantaneous distribution of information globally, alternative metrics have become an important complementary measure of scholarly activity. Bibliometrics may provide a standard performance measurement that may be used for tenure and/or promotion among academic institutions. The alternative metric industry has shown considerable growth with increasingly improved algorithms working towards standardization. Together, conventional metrics and alternative metrics may synergistically complement each other to provide an accelerated translation from research to clinical care that may lead to tremendous benefits in patients. All physicians and other healthcare professionals should receive training in bibliometrics and understand the potential impact of professional social media use.
Electrical Stimulation in the Treatment of Hemiplegic Shoulder Pain
Authors: Qiu Huaide , Li Jiahui , Zhou Ting , Wang Hongxing , Li Jianan
Published: October 2018

Objective

The aim of the study was to determine the effect of electrical stimulation in the treatment of hemiplegic shoulder pain.

Design

Eight databases were systematically searched for randomized controlled trials with a treatment duration of at least 2 wks comparing electrical stimulation with sham stimulation or no stimulation for patients with hemiplegic shoulder pain. Shoulder pain on the hemiplegic side after stroke at baseline was required at study selection. The overall effects of electrical stimulation were calculated using a meta-analytic method.

Results

Six studies were included. The pooled data indicated that electrical stimulation may have a positive effect for patients with hemiplegic shoulder pain on pain reduction (n = 193, standardized mean difference = −1.89, 95% confidence interval = −3.05 to −0.74) and pain-free external rotation (n = 164, weighted mean difference = 18.92, 95% confidence interval = 7.00 to 30.84). Meta-analysis also showed better recovery of activities of daily living independence in patient groups receiving electrical stimulation (n = 167, weighted mean difference = 8.96, 95% confidence interval = 5.26 to 12.66).

Conclusions

Electrical stimulation may be an effective pain management methodology for hemiplegic shoulders and may contribute to pain-free range of external rotation as well as activities of daily living recovery. However, these results should be interpreted with caution, given the low number of selected studies and risk of potential bias.
Computerized Exposure Therapy for Spider Phobia: Effects of Cardiac Timing and Interoceptive Ability on Subjective and Behavioral Outcomes
Authors: Watson David R. , Garfinkel Sarah N. , Gould van Praag Cassandra , Willmott Daniel , Wong Katherine , Meeten Frances , Critchley Hugo D.
Published: October 2018

Objective

Spider phobia is a common form of anxiety disorder for which exposure therapy is an effective first-line treatment. Motivated by the observed modulation of threat processing by afferent cardiac signals, we tested the hypothesis that interoceptive information concerning cardiovascular arousal can influence the outcomes of computerized exposure therapy for spider phobia.

Method

Fifty-three normal healthy participants with high spider phobia scores underwent one of the following three modified computerized exposure protocols, defined by the timing of exposure to brief spider stimuli within the cardiac cycle: systole (during afferent baroreceptor firing); diastole (during baroreceptor-quiescent interbeat interval); random (noncontingent on cardiac cycle). Outcomes were judged on phobic and anxiety measures and physiological data (skin conductance). Individuals were also rated on interoceptive accuracy.

Results

MANCOVA analysis showed that timing group affected the outcome measures (F(10,80) = 2.405,p= .015) and there was a group interaction with interoception ability (F(15,110) = 1.808,p= .045). Subjective symptom reduction was greatest in the systolic group relative to the other two groups (diastolic (t= 3.115,ptukey= .009); random (t= 2.438,ptukey= .048)), with greatest reductions in those participants with lower interoceptive accuracy. Behavioral aversion reduced more in cardiac-contingent groups than the noncontingent (random) group (diastolic (t= 3.295,ptukey= .005); systolic (t= 2.602,ptukey= .032)). Physiological (skin conductance response) responses remained strongest for spider stimuli presented at cardiac systole.

Conclusions

Interoceptive information influences exposure benefit. The reduction in the subjective expression of fear/phobia is facilitated by “bottom-up” afferent signals, whereas improvement in the behavioral expression is further dependent on “top-down” representation of self-related physiology (heart rhythm). Individual interoceptive differences moderate these effects, suggesting means to personalize therapy.
Splenosis of the Liver Capsule
Authors: Budak Emine , Oral Aylin , Yazici Bulent , Guler Ezgi , Omur Ozgur
Published: October 2018

Splenosis, a form of ectopic splenic tissue, is generally caused by heterotopic autotransplantation of splenic tissues after traumatic splenic rupture or splenectomy. The implants are often localized intraperitoneally, mostly in the left upper quadrant and splenic region. Hepatic foci are seen only on rare occasions. The differential diagnosis of splenosis foci from malignant masses can be challenging by conventional imaging and lead to unnecessary invasive procedures. This manuscript presents radiological and scintigraphic images of splenosis foci located in the peritoneal cavity and liver capsule of a 46-year-old man who underwent splenectomy due to traumatic splenic rupture 30 years ago.
Occult Giant Cell Arteritis Concurrent With Pancreatic Carcinoma Revealed by 18F-FDG PET/CT
Authors: Fu Zhanli , Chen Xueqi , Yang Xing , Li Qian
Published: October 2018

An 18F-FDG PET/CT was performed on a 74-year-old woman with pancreatic carcinoma and liver metastases. Occult giant cell arteritis, involving the aorta, truncus brachiocephalicus, subclavian arteries, axillaries, external carotid arteries, vertebral arteries, and superficial temporal arteries, was accidentally revealed.
Individual Treatment of Delayed Distal Biceps Tendon Rupture
Authors: Yao Chenglun , Weng Weidong , Zhou Xijie , Poonit Keshav , Yang Jingquan , Lin Damu , Sun Chao , Yan Hede
Published: October 2018

Introduction

Complicated elbow injuries (elbow injuries with bone and soft tissue injury) with distal biceps tendon ruptures (DBTRs) are not uncommon. There are several treatment modalities in different situations of injuries. In this article, we reported 3 successful individual treatments of delayed DBTR with complicated elbow injuries.

Materials and Methods

Three cases of complicated elbow injuries treated between 2010 and 2016 were reviewed. The delayed DBTR cases were summarized and treated. Mayo Elbow Performance Score value, range of motion, and visual analog scale score were used to assess outcomes after a minimum follow-up of 12 months.

Results

All 3 patients were male, aged 47 to 54 years (mean, 49.6 years). Patients received surgical treatments. After a mean follow-up of 13.7 months, in cases 1 and 2, Mayo Elbow Performance Score values improved by 50% and 100%, elbow flexion-extension arc were 115 degrees and 110 degrees, pronation-supination arc were 130 degrees and 120 degrees. Arthrodesis case reported pain relief; visual analog scale score for pain was 0 to 1. No postoperative complications were observed, and all patients were satisfied with the results.

Conclusions

Individual treatment is advised in DBTR with complicated elbow injuries. Secondary treatment of DBTR can achieve satisfactory results using individual strategies depending on patients' overall condition.
Effect of Long-Term Polytrauma on Ventilator-Induced Diaphragmatic Dysfunction in a Piglet Model
Authors: Breuer Thomas , Bruells Christian S. , Horst Klemens , Thiele Christoph , Hildebrand Frank , Linnartz Stephan , Siegberg Tom , Frank Nadine , Gayan-Ramirez Ghislaine , Martin Lukas , Ostareck Dirk H. , Marx Gernot , Simon Tim-Philipp
Published: October 2018

Introduction:

Mechanical ventilation is known to activate oxidative stress and proteolytic pathways in the diaphragm. Trauma by inducing inflammation and activating proteolytic pathways may potentiate the effects of mechanical ventilation on the diaphragm. In a blunt chest trauma with concomitant injuries we tested the hypothesis that trauma via inflammation further activates the proteolytic pathways and worsens atrophy in the diaphragm.

Material and Methods:

Piglets were separated into two groups and underwent 72 h of mechanical ventilation. One group received a polytrauma (PT) by unilateral femur fracture, blunt chest trauma with lung contusion, laparotomy with standardized liver incision, and a predefined hemorrhagic shock. The second mechanically ventilated group (MV) did not receive any trauma. A non-ventilated group (Con) served as control.

Diaphragmatic fiber dimensions, Western Blot analyses of proteolytic pathways, and lipid peroxidation and messenger ribonucleic acid (mRNA) levels of cytokines and nuclear factor kappa b subunit p65 were measured.

Results:

Active Caspase-3 was significantly increased in MV (P = 0.019), and in PT (P = 0.02) compared with Con. Nuclear factor kappa b subunit p65, was upregulated in PT (P = 0.010) compared with Con. IL-6 mRNA increased significantly in PT compared with Con (P = 0.0024) but did not differ between Con and MV.

Conclusion:

Trauma and mechanical ventilation induced proteolysis and atrophy in the diaphragm, but only polytrauma induced an inflammatory response in the diaphragm. The additional traumatic inflammatory stimulus did not increase the levels of the prementioned variables. These data underline that inflammation is not a major contributor to ventilator-induced diaphragmatic dysfunction.

Trial registry number:

AZ 84–02.04.2014.A265 (Landesamt für Natur-, Umwelt- und Verbraucherschutz, LANUV NRW, Germany).
A New Echocardiographic Tool for Cardiac Output Evaluation: An Experimental Study
Authors: Bobbia Xavier , Muller Laurent , Claret Pierre-Géraud , Vigouroux Laure , Perez-Martin Antonia , de La Coussaye Jean Emmanuel , Lefrant Jean Yves , Louart Guillaume , Roger Claire , Markarian Thibaut
Published: October 2018

Background:

The correlation between cardiac output (CO) evaluated by echocardiography and CO measured by thermodilution (COth) varies according to different studies. A new transthoracic echocardiography (TTE) tool allows automatic calculation of the subaortic velocity time index (VTIauto) and CO (COauto). The main objective was to evaluate the correlation between COth and COauto in an anesthetized, ventilated piglet hemorrhagic shock (HS) model. The secondary objectives were to evaluate the correlation between COth and CO evaluated by manual measurements of VTI, and the preload-dependency of VTIvaresp.

Methods:

Eighteen piglets were bled until mean arterial pressure reached 40 mm Hg. Controlled hemorrhage was maintained for 30 min before a resuscitation phase. CO was measured by Pulse index Contour Cardiac Output thermodilution methods. At each time of the experiment, three VTI values were measured (min, med, max) and the average value was calculated. COs were calculated by TTE (COmax, COmed, COmin, COave).

Results:

For the 204 measures attempted, the success rate was 197 (97%) manually and 122 (60%) automatically (P < 0.01). The correlation coefficients (r) between COth and, respectively, COauto, COave, COmax, COmed, and COmin were: 0.83 (95% CI [0.76; 0.88]; P < 0.01), 0.54 (95% CI [0.43; 0.63]; P < 0.01), 0.43 (95% CI [0.31; 0.54]; P < 0.01), 0.58 (95% CI [0.48; 0.67]; P < 0.01), and 0.52 (95% CI [0.41; 0.62]; P < 0.01).

Conclusion:

In an experimental model of HS, a new ultrasound tool, COauto, seems better correlated with COth than manual echocardiographic measurements.
Is whole-brain radiotherapy still a standard treatment for primary central nervous system lymphomas?
Authors: Schlegel Uwe , Korfel Agnieszka
Published: October 2018

Purpose of review

In primary central nervous system lymphomas (PCNSL), optimal therapy remains to be established, and the role of whole-brain radiotherapy (WBRT) is a matter of debate. With radiation alone, transient responses and clinical improvement are frequent, but long-term disease control is exceptional. WBRT has been considered possible consolidation therapy after high-dose methotrexate (HDMTX)-based initial chemotherapy. This strategy has been questioned due to a high risk of delayed neurotoxicity after combined treatment. This review analyses the current role of WBRT in PCNSL.

Recent findings

Neither in retrospective analyses nor in randomized trials, an overall survival benefit with WBRT in addition to HDMTX-based initial chemotherapy could be found. On the other hand, a recent randomized trial did not show superiority of consolidation with high-dose chemotherapy followed by autologous stem-cell transplantation to consolidation WBRT after initial HDMTX-based polychemotherapy. This finding, however, is probably due to an intense initial therapy and to a small number of patients having reached consolidation and randomization to WBRT vs. high-dose chemotherapy followed by autologous stem-cell transplantation.

The current role of WBRT in PCNSL is confined to patients who cannot tolerate chemotherapy or have failed it. WBRT should not routinely be used for consolidation of HDMTX-based chemotherapy due to lack of evidence of efficacy as additional treatment and due to a high risk of neurotoxicity.
IgE-mediated regulation of IL-10 and type I interferon enhances rhinovirus-induced Th2 priming by primary human monocytes
Authors: Rowe Regina K. , Pyle David M. , Farrar J. David , Gill Michelle A.
Published: October 2018

Rhinovirus infections are linked to the development and exacerbation of allergic diseases including allergic asthma. IgE, another contributor to atopic disease pathogenesis, has been shown to regulate dendritic cell antiviral functions and influence T cell priming by monocytes. We previously demonstrated that IgE-mediated stimulation of monocytes alters multiple cellular functions including cytokine secretion, phagocytosis, and influenza-induced Th1 priming. In this study, we investigate the effects of IgE-mediated allergic stimulation on monocyte-driven, RV-induced T cell priming utilizing primary human monocyte-T cell co-cultures. We demonstrate that IgE crosslinking of RV-exposed monocytes enhances monocyte-driven Th2 priming. This increase in RV-induced Th2 differentiation was regulated by IgE-mediated inhibition of type I interferon and induction of IL-10. These findings suggest an additional mechanism by which two clinically significant risk factors for allergic disease exacerbations – IgE-mediated stimulation and rhinovirus infection, may synergistically promote Th2 differentiation and allergic inflammation.
Network-aware mutation clustering of cancer
Authors: Pattnaik Swetansu , Vacher Catherine , Lee Hong Ching , Kaplan Warren , Thomas David M. , Wu Jianmin , Pinese Mark
Published: October 2018

The grouping of cancers across tissue boundaries is central to precision oncology, but remains a difficult problem. Here we present EPICC (Experimental Protein Interaction Clustering of Cancer), a novel technique to cluster cancer patients based on DNA mutation profile, that leverages knowledge of protein-protein interactions to reduce noise and amplify biological signal. We applied EPICC to data from The Cancer Genome Atlas (TCGA), and both recapitulated known cancer clusterings, and identified new cross-tissue cancer groups that may indicate novel cancer molecular subtypes. Investigation of EPICC clusters revealed new protein modules which were recurrently mutated across cancers, and indicate new avenues for research into cancer biology. EPICC leveraged the Vodafone DreamLab citizen science platform, and we provide our results as a resource for researchers to investigate the role of protein modules in cancer.
Genome-wide meta-analysis of depression identifies 102 independent variants and highlights the importance of the prefrontal brain regions
Authors: Howard David M. , Adams Mark J. , Clarke Toni-Kim , Hafferty Jonathan D. , Gibson Jude , Shirali Masoud , Coleman Jonathan R. I. , Hagenaars Saskia P. , Ward Joey , Wigmore Eleanor M. , Alloza Clara , Shen Xueyi , Barbu Miruna C. , Xu Eileen Y. , Whalley Heather C. , Marioni Riccardo E. , Porteous David J. , Davies Gail , Deary Ian J. , Hemani Gibran , Berger Klaus , Teismann Henning , Rawal Rajesh , Arolt Volker , Baune Bernhard T. , Dannlowski Udo , Domschke Katharina , Tian Chao , Hinds David A. ,   23andMe Research Team,   Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium, Trzaskowski Maciej , Byrne Enda M. , Ripke Stephan , Smith Daniel J. , Sullivan Patrick F. , Wray Naomi R. , Breen Gerome , Lewis Cathryn M. , McIntosh Andrew M.
Published: October 2018

Major depression is a debilitating psychiatric illness that is typically associated with low mood, anhedonia and a range of comorbidities. Depression has a heritable component that has remained difficult to elucidate with current sample sizes due to the polygenic nature of the disorder. To maximise sample size, we meta-analysed data on 807,553 individuals (246,363 cases and 561,190 controls) from the three largest genome-wide association studies of depression. We identified 102 independent variants, 269 genes, and 15 gene-sets associated with depression, including both genes and gene-pathways associated with synaptic structure and neurotransmission. Further evidence of the importance of prefrontal brain regions in depression was provided by an enrichment analysis. In an independent replication sample of 1,306,354 individuals (414,055 cases and 892,299 controls), 87 of the 102 associated variants were significant following multiple testing correction. Based on the putative genes associated with depression this work also highlights several potential drug repositioning opportunities. These findings advance our understanding of the complex genetic architecture of depression and provide several future avenues for understanding aetiology and developing new treatment approaches.