bluuebunny/crossref_metadata_2025 huggingface dataset:
Differentiating dural metastases from meningioma: role of 68Ga DOTA-NOC PET/CT
Authors: Purandare Nilendu C. , Puranik Ameya , Shah Sneha , Agrawal Archi , Gupta Tejpal , Moiyadi Aliasgar , Shetty Prakash , Shridhar Epari , Patil Vijay , Rangarajan Venkatesh
Published: January 2020

Objective

To assess the ability of 68Ga DOTA-NOC PET/computed tomography (CT) to differentiate dural metastases from meningioma.

Patients and methods

Patients who underwent a 68Ga DOTA-NOC PET/CT for differentiating meningiomas from dural metastases were included in the study. A visual score was assigned to the dural lesions (visual score – 1 to 3) in relation to the uptake in liver and spleen and variation in the visual score was evaluated. SUVmax of the dural lesions was also noted and difference in the values of the two pathologies were compared for statistical significance using nonparametric statistical tests. Final diagnosis was decided by histopathological confirmation whenever available.

Results

Imaging, histopathology or follow-up data of 42 patients was available for analysis. Meningioma was the final diagnosis in 31 (73.8%) patients, whereas dural metastases were diagnosed in 9 (21.4%) patients. In two patients, histopathology revealed inflammatory pseudotumor and hemangioblastoma. Meningiomas showed intense tracer uptake in 30/31 patients (visual score 3). All metastatic lesions showed some degree of tracer uptake though the intensity was lesser compared to meningioma (visual score 1, 2). Meningiomas showed a significantly higher median SUV max value compared to metastases (12.7 vs. 6.0, P = 0.001).

Conclusion

Meningiomas can be differentiated from dural metastases by virtue of their higher uptake of 68Ga-labeled DOTA peptides reflecting higher SSTR expression. An asymptomatic meningeal based lesion with a high visual score (Visual score 3) has a very high probability to be a meningioma rather than dural metastasis.
Educating Students About Opioid Use Disorder and Treatments in the Community Using an Educational Video
Authors: Williams Kristiann T. , Baron Kristy A. , Gee Julie P. , Chan Julian
Published: January 2020

Background

A treatment gap exists for people in the community with opioid use disorders (OUDs). Stigma and lack of knowledge of how to access community resources contribute to this gap. One valuable resource that may help fill this gap is nursing students.

Purpose

This study examined the impact of an educational video on prelicensure and postlicensure nursing students' knowledge and attitudes toward people with OUD.

Methods

A pre-post study design was used to examine whether 406 nursing students' knowledge and attitudes changed after viewing an educational video. Knowledge and attitudes were measured by an online survey, consisting of demographics, an 8-item Knowledge and Attitudes survey, and the Drug and Drug Problems Perceptions Questionnaire.

Results

The educational video produced a statistically significant positive improvement on nursing students' knowledge and attitudes.

Conclusion

Educating nursing students about OUD and treatment options can help reduce stigma and improve care toward people with OUD.
Self-efficacy and Satisfaction With Teaching in Online Courses
Authors: Hampton Debra , Culp-Roche Amanda , Hensley Angie , Wilson Jessica , Otts Jo Ann , Thaxton-Wiggins Amanda , Fruh Sharon , Moser Debra K.
Published: January 2020

Background

Growth of online education has increased the demand for satisfied educators with perceived self-efficacy in online teaching. Teaching self-efficacy is an indicator of the belief that one can make a difference in student learning outcomes.

Purpose

The aim of this study was to examine the level of teaching self-efficacy and satisfaction of online nursing faculty.

Methods

This study used a descriptive cross-sectional survey design. Faculty satisfaction was measured by the Online Instructor Satisfaction Measure, and self-efficacy for online teaching was measured by the Michigan Nurse Educator's Sense of Efficacy for Online Teaching instrument.

Results

The sample included 100 faculty in multiple schools of nursing who taught at least 1 online course in RN to BSN or graduate nursing programs. Overall, participants had relatively high levels of online teaching self-efficacy and satisfaction.

Conclusions

Teacher self-efficacy can be facilitated through faculty development and increased experience teaching online.
Effect of Ultra High-Resolution Computed Tomography and Model-Based Iterative Reconstruction on Detectability of Simulated Submillimeter Artery
Authors: Morisaka Hiroyuki , Shimizu Yuta , Adachi Takuya , Fukushima Keita , Arai Takahiro , Yamamura Wataru , Koyanagi Masamichi , Kariyasu Toshiya , Machida Haruhiko , Sano Katsuhiro , Yokoyama Kenichi , Ichikawa Tomoaki
Published: January 2020

Objective

To evaluate the effect of ultra high-resolution computed tomography (UHRCT) and model-based iterative reconstruction (MBIR) on the detectability of simulated submillimeter artery.

Methods

A small vessel phantom ranging from 0.4 to 2.0 mm in diameter and edge phantoms of low to high attenuation values were scanned by UHRCT (super-high-resolution mode and normal-resolution-mode) and conventional CT, and data were reconstructed by MBIR and filtered back projection (FBP). Vessel detectability was assessed subjectively and the effective size at which 50% of response was achieved (ES50 [mm]) was calculated. Modulation transfer function (MTF) was calculated by an edge spread function method.

Results

ES50 of super high-resolution mode (0.36 mm for MBIR and 0.50 mm for FBP) was significantly smaller than those of normal-resolution mode (P < 0.01). In the MTF analysis, the MTF of MBIR improved as the edge phantom attenuation increased, whereas that of FBP was stable.

Conclusions

Both UHRCT and MBIR are effective for the detectability of simulated submillimeter artery.
Quantitative Assessment of Extracellular Volume in Doxorubicin-Induced Liver Injury in Beagle Models by Equilibrium Computed Tomography
Authors: Han Pengxi , Zhou Zhen , Wang Rui , Wang Hui , Sun Zhonghua , Wang Ximing , Xu Lei
Published: January 2020

Purpose

The purpose of this study was to determine whether liver extracellular volume (ECV) measured using equilibrium computed tomography (EQ-CT) can be used to quantitatively assess doxorubicin-induced liver injury (DILI).

Methods

The ethical approval was obtained from the Institutional Animal Care and Use Committee regulations. Thirteen dogs administered with doxorubicin for 0 to 24 weeks were imaged by contrast-enhanced EQ-CT. The dogs were divided into 3 groups: the baseline (13 dogs), 16-week (10 dogs), and 24-week (7 dogs) groups. Pathological analysis of the liver was performed using hematoxylin-eosin and Masson staining. Liver ECV uptake was calculated for each group and correlated with the histopathological and serological findings of hepatic fibrosis (hyaluronic acid and procollagen type III).

Results

In the baseline group, the median ECVs of the right and left liver lobes were 21.78% (interquartile range [IQR], 16.78%–26.68%) and 20.91% (IQR, 16.39%–24.07%), respectively. In the 16- and 24-week groups, the median ECVs of these 2 liver lobes were 28.18% (IQR, 20.56%–34.61%) and 25.96% (IQR, 14.07%–41.38%) and 29.71% (IQR, 27.19%–35.25%) and 29.22% (IQR, 22.62%–38.67%), respectively. There were no significant differences in ECV between the left and right lobes in the 3 groups (P < 0.05). Both the 16- and 24-week groups showed significantly higher ECV than did the primary group (P = 0.001–0.0006). However, there were no significant differences in ECV between the 16-week group and 24-week group (P = 0.412). There was a positive correlation between the serum index and edema due to the inflammation and necrosis associated with DILI (R
2 = 0.6534, R
2 = 0.7129).

Conclusions

Extracellular volume measured by EQ-CT imaging can accurately predict the potential DILI through the quantification of ECV changes.
Safety and Efficacy of Early Tube Removal Following Percutaneous Transhepatic Gallbladder Drainage: an Observational Study
Authors: Kamezaki Hidehiro , Tsuyuguchi Toshio , Shimura Kenji , Sakamoto Dai , Senoo Junichi , Mizumoto Hideaki , Kubota Michio , Yoshida Yu , Azemoto Ryosaku , Sugiyama Harutoshi , Kato Naoya
Published: January 2020

Background:

There are currently no guidelines concerning the advisability and timing of tube removal following percutaneous transhepatic gallbladder drainage (PTGBD). The present study aimed to assess the feasibility and risks of early removal of the PTGBD tube under the scenario of subsiding inflammation, patent cystic and common bile ducts, and absence of intraperitoneal leakage.

Methods:

Patient background and outcomes were assessed retrospectively in 701 cases of acute cholecystitis treated with PTGBD. The median times until tube removal and tube dislodgement and the cumulative rates of tube dislodgement were calculated.

Results:

Tube removal was performed in 275 patients after a median time of 16 days (range: 6 to 213 d); biliary peritonitis was observed in 2 patients following tube removal. Tubes were removed in 8 and 35 patients within 7 and 10 days, respectively. Tube dislodgement was observed in 82 patients after a median time of 12 days (range: 1 to 125 d).

Conclusion:

The present study suggests that drainage tube removal is safe and effective when performed after a short drainage period of 7 to 10 days if the criteria for the removal of the drainage tube were met.
Evaluation of measurement properties of health-related quality of life instruments for burns: A systematic review
Authors: Legemate Catherine M. , Spronk Inge , Mokkink Lidwine B. , Middelkoop Esther , Polinder Suzanne , van Baar Margriet E. , van der Vlies Cornelis H.
Published: January 2020

BACKGROUND

Health-related quality of life (HRQL) is a key outcome in the evaluation of burn treatment. Health-related quality of life instruments with robust measurement properties are required to provide high-quality evidence to improve patient care. The aim of this review was to critically appraise the measurement properties of HRQL instruments used in burns.

METHODS

A systematic search was conducted in Embase, MEDLINE, CINAHL, Cochrane, Web of Science, and Google scholar to reveal articles on the development and/or validation of HRQL instruments in burns. Measurement properties were assessed using the Consensus-based Standards for the selection of health Measurement Instruments methodology. A modified Grading of Recommendations, Assessment, Development, and Evaluation analysis was used to assess risk of bias (prospero ID, CRD42016048065).

RESULTS

Forty-three articles covering 15 HRQL instruments (12 disease-specific and 3 generic instruments) were included. Methodological quality and evidence on measurement properties varied widely. None of the instruments provided enough evidence on their measurement properties to be highly recommended for routine use; however, two instruments had somewhat more favorable measurement properties. The Burn-Specific Health Scale—Brief (BSHS-B) is easy to use, widely accessible, and demonstrated sufficient evidence for most measurement properties. The Brisbane Burn Scar Impact Profiles were the only instruments with high-quality evidence for content validity.

CONCLUSION

The Burn Specific Health Scale—Brief (burn-specific HRQL) and the Brisbane Burn Scar Impact Profile (burn scar HRQL) instruments have the best measurement properties. There is only weak evidence on the measurement properties of generic HRQL instruments in burn patients. Results of this study form important input to reach consensus on a universally used instrument to assess HRQL in burn patients.

LEVEL OF EVIDENCE

Systematic review, level III.
Mapping the increasing interest in acute care surgery—Who, why and which fellowship?
Authors: Gayed Benjamin N. , Zarzaur Ben L. , Livingston David H. , Chiu William C. , Davis Kimberly A. , Tisherman Samuel A. , Alam Hasan B. , Spain David A.
Published: January 2020

BACKGROUND

Interest in acute care surgery (ACS) has increased over the past 10 years as demonstrated by the linear increase in fellowship applicants to the different fellowships leading to ACS careers. It is unclear why interest has increased, whether various fellowship pathways attract different applicants or whether fellowship choice correlates with practice patterns after graduation.

METHODS

An online survey was distributed to individuals previously registered with the Surgical critical care and Acute care surgery Fellowship Application Service. Fellowship program directors were also asked to forward the survey to current and former fellows to increase the response rate. Data collected included demographics, clinical interests and motivations, publications, and postfellowship practice patterns. Fisher's exact and Pearson's χ2 were used to determine significance.

RESULTS

Trauma surgery was the primary clinical interest for all fellowship types (n = 273). Fellowship type had no impact on academic productivity or practice patterns. Most fellows would repeat their own fellowship. The 2-year American Association for the Surgery of Trauma–approved fellowship was nearly uniformly reported as the preferred choice among those who would perform a different fellowship. Career motivations were similar across fellowships and over time though recent trainees were more likely to consider predictability of schedule a significant factor in career choice. Respondents reported graduated progression to full responsibility, further exposure to trauma care and additional operative technical training as benefits of a second fellowship year.

CONCLUSION

American Association for the Surgery of Trauma–approved 2-year fellows appear to be the most satisfied with their fellowship choice. No differences were noted in academic productivity or practice between fellowships. Future research should focus on variability in trauma training and operative experience during residency and in practice to better inform how a second fellowship year would improve training for ACS careers.

LEVEL OF EVIDENCE

Descriptive, mixed methods, Level IV.
Emerging Microbiology Diagnostics for Transplant Infections: On the Cusp of a Paradigm Shift
Authors: Azar Marwan M. , Gaston David C. , Kotton Camille N. , Malinis Maricar F.
Published: January 2020

In light of the heightened risk for infection associated with solid organ and hematopoietic stem cell transplantation, rapid and accurate microbiology diagnostics are essential to the practice of transplant clinicians, including infectious diseases specialists. In the last decade, diagnostic microbiology has seen a shift toward culture-independent techniques including single-target and multiplexed molecular testing, mass-spectrometry, and magnetic resonance-based methods which have together greatly expanded the array of pathogens identified, increased processing speed and throughput, allowed for detection of resistance determinants, and ultimately improved the outcomes of infected transplant recipients. More recently, a newer generation of diagnostics with immense potential has emerged, including multiplexed molecular panels directly applicable to blood and blood culture specimens, next-generation metagenomics, and gas chromatography mass spectrometry. Though these methods have some recognized drawbacks, many have already demonstrated improved sensitivity and a positive impact on clinical outcomes in transplant and immunocompromised patients.
The Impact of Biliary Reconstruction Methods on Small Partial Liver Grafts
Authors: Yoshikawa Junichi , Hata Koichiro , Nakamura Kojiro , Okamura Yusuke , Uemoto Shinji
Published: January 2020

Background.

Graft recipient weight ratios are lower in adult-to-adult living-donor liver transplantation than in adult-to-adult deceased-donor liver transplantation. Rapid liver regeneration is essential for increased recipient survival rates in adult-to-adult living-donor liver transplantation. However, the influence of biliary reconstruction methods, including choledocho-choledochostomy and choledocho-jejunostomy, on small partial liver grafts remains unknown. Herein, we investigate the impact of these biliary reconstruction methods on small partial liver grafts.

Methods.

Male Lewis rats underwent isogenic arterialized 30% partial liver transplantation with small partial grafts, either via choledocho-jejunostomy or choledocho-choledochostomy.

Results.

The 7-day survival rates of the choledocho-choledochostomy and choledocho-jejunostomy groups were 100% and 50%, respectively (P = 0.011). Choledocho-jejunostomy provoked reflux cholangitis, as confirmed by neutrophil infiltration around the bile ducts; suppressed and delayed liver regeneration in grafts, as confirmed by significant increases in intrahepatic interleukin-1β level, significant decreases in the graft weight increase ratios, hepatocyte proliferation, and intrahepatic mRNA expression of vascular endothelial growth factor; and induced graft dysfunction, as confirmed by the presence of massive ascites, significantly decreased bile production, and prolonged elevation of total bilirubin, aspartate aminotransferase, and alanine aminotransferase.

Conclusions.

Choledocho-jejunostomy predisposed grafts to cholangitis, impaired liver regeneration, and aggravated animal survival, suggesting that choledocho-choledochostomy may be preferable over choledocho-jejunostomy in adult-to-adult living-donor liver transplantation.
Pre- and post-copulatory traits working in concert: sexual dichromatism in passerines is associated with sperm morphology
Authors: Durrant Kate L. , Reader Tom , Symonds Matthew R. E.
Published: January 2020

Passerine birds produce costly traits under intense sexual selection, including elaborate sexually dichromatic plumage and sperm morphologies, to compete for fertilizations. Plumage and sperm traits vary markedly among species, but it is unknown if this reflects a trade-off between pre- and post-copulatory investment under strong sexual selection producing negative trait covariance, or variation in the strength of sexual selection among species producing positive covariance. Using phylogenetic regression, we analysed datasets describing plumage and sperm morphological traits for 278 passerine species. We found a significant positive relationship between sperm midpiece length and male plumage elaboration and sexual dichromatism. We did not find a relationship between plumage elaboration and testes mass. Our results do not support a trade-off between plumage and sperm traits, but may be indicative of variance among species in the strength of sexual selection to produce both brightly coloured plumage and costly sperm traits.
Gustav Victor Rudolph Born. 29 July 1921—16 April 2018
Authors: Flower Rod
Published: January 2020

Gustav Born (Gus) made fundamental contributions to the study of blood platelets and their role in thrombogenesis. Working first on the biochemistry of these cells and their granules, Gus later devised an extremely effective method to measure their dynamic responses when stimulated to aggregate by pro-thrombotic stimuli. ‘The Born Aggregometer’, as it is known, revolutionized the study of platelets and the diagnosis of platelet-related disorders. Gus was elected a Fellow of the Royal Society in 1972 for his work and subsequently awarded the Royal Medal. He received numerous other accolades and awards for his contributions to cardiovascular medicine.
Mathematical deconvolution of CAR T-cell proliferation and exhaustion from real-time killing assay data
Authors: Sahoo Prativa , Yang Xin , Abler Daniel , Maestrini Davide , Adhikarla Vikram , Frankhouser David , Cho Heyrim , Machuca Vanessa , Wang Dongrui , Barish Michael , Gutova Margarita , Branciamore Sergio , Brown Christine E. , Rockne Russell C.
Published: January 2020

Chimeric antigen receptor (CAR) T-cell therapy has shown promise in the treatment of haematological cancers and is currently being investigated for solid tumours, including high-grade glioma brain tumours. There is a desperate need to quantitatively study the factors that contribute to the efficacy of CAR T-cell therapy in solid tumours. In this work, we use a mathematical model of predator–prey dynamics to explore the kinetics of CAR T-cell killing in glioma: the Chimeric Antigen Receptor T-cell treatment Response in GliOma (CARRGO) model. The model includes rates of cancer cell proliferation, CAR T-cell killing, proliferation, exhaustion, and persistence. We use patient-derived and engineered cancer cell lines with an
in vitro
real-time cell analyser to parametrize the CARRGO model. We observe that CAR T-cell dose correlates inversely with the killing rate and correlates directly with the net rate of proliferation and exhaustion. This suggests that at a lower dose of CAR T-cells, individual T-cells kill more cancer cells but become more exhausted when compared with higher doses. Furthermore, the exhaustion rate was observed to increase significantly with tumour growth rate and was dependent on level of antigen expression. The CARRGO model highlights nonlinear dynamics involved in CAR T-cell therapy and provides novel insights into the kinetics of CAR T-cell killing. The model suggests that CAR T-cell treatment may be tailored to individual tumour characteristics including tumour growth rate and antigen level to maximize therapeutic benefit.
Finding hotspots: development of an adaptive spatial sampling approach
Authors: Andrade-Pacheco Ricardo , Rerolle Francois , Lemoine Jean , Hernandez Leda , Aboulaye Meïté , Juziwelo Lazarus , Bibaut Aurelien , van der Laan Mark , Arnold Benjamin , Sturrock Hugh
Published: January 2020

The identification of disease hotspots is an increasingly important public health problem. While geospatial modeling offers an opportunity to predict the locations of hotspots using suitable environmental and climatological data, little attention has been paid to optimizing the design of surveys used to inform such models. Here we introduce an adaptive sampling scheme optimized to identify hotspot locations where prevalence exceeds a relevant threshold. Our approach incorporates ideas from Bayesian optimization theory to adaptively select sample batches. We present an experimental simulation study based on survey data of schistosomiasis and lymphatic filariasis across four countries. Results across all scenarios explored show that adaptive sampling produces superior results and suggest that similar performance to random sampling can be achieved with a fraction of the sample size.
Protocol for Project Recovery: Cardiac Surgery - Leveraging Digital Platform for Efficient Collection of Longitudinal Patient-Reported Outcome Data Towards Improving Postoperative Recovery
Authors: Mori Makoto , Brooks Cornell , Spatz Erica , Mortazavi Bobak J , Dhruva Sanket S. , Linderman George C. , Grab Lawrence A. , Zhang Yawei , Geirsson Arnar , Chaudhry Sarwat I. , Krumholz Harlan M.
Published: January 2020

Introduction

Improving postoperative patient recovery after cardiac surgery is a priority, but our current understanding of individual variations in recovery and factors associated with poor recovery is limited. We are using a health-information exchange platform to collect patient-reported outcome measures (PROMs) and wearable device data to phenotype recovery patterns in the 30-day period after cardiac surgery hospital discharge, to identify factors associated with these phenotypes and to investigate phenotype associations with clinical outcomes.

Methods and analysis

We designed a prospective cohort study to enroll 200 patients undergoing valve, coronary artery bypass graft, or aortic surgery at a tertiary center in the U.S. We are enrolling patients postoperatively after the intensive care unit (ICU) discharge, and delivering electronic surveys directly to patients every 3 days for 30 days after hospital discharge. We will conduct medical record reviews to collect patient demographics, comorbidity, operative details and hospital course using the Society of Thoracic Surgeons (STS) data definitions. We will use phone interview and medical record review data for adjudication of survival, readmission, and complications. We will apply group-based trajectory modeling to the time-series PROM and device data to classify patients into distinct categories of recovery trajectories. We will evaluate whether certain recovery pattern predicts death or hospital readmissions, as well as whether clinical factors predict a patient having poor recovery trajectories. We will evaluate whether early recovery patterns predict the overall trajectory at the patient-level.

Ethics and dissemination

The Yale Institutional Review Board approved this study. Following the description of the study procedure, we obtain written informed consent from all study participants. The consent form states that all personal information, survey response, and any medical records are confidential, will not be shared, and are stored in an encrypted database.

Strengths and limitations of this study

This study will assess the patient perspective on recovery after cardiac surgery at a high frequency within the 30-day postoperative period with surveys and activity monitoring via a health information platform and wearable devices.

Using longitudinal patient-reported outcomes measure (PROM) data, this study will define recovery patterns and factors associated with different recovery trajectories and guide the development interventions to improve recovery and support expansion of the study to additional sites.

The study is single center and the sample size is limited.
Effective connectivity of the hippocampus can differentiate patients with schizophrenia from healthy controls: a spectral DCM approach
Authors: Uscătescu Lavinia Carmen , Kronbichler Lisa , Stelzig-Schöler Renate , Pearce Brandy-Gale , Said-Yürekli Sarah , Reich Luise Antonia , Weber Stefanie , Aichhorn Wolfgang , Kronbichler Martin
Published: January 2020

We applied spectral dynamic causal modelling (spDCM; Friston et al., 2014) to analyze the effective connectivity differences between the nodes of three resting state networks (i.e. Default mode network/DMN, Salience network/SAN and Dorsal attention network/DAN) in a dataset of 31 healthy controls (HC) and 25 patients with schizophrenia (SZ), all male. Patients showed increased connectivity from the left hippocampus (LHC) to the dorsal anterior cingulate cortex (DACC), right anterior insula (RAI), left frontal eye fields (LFEF) and the bilateral inferior parietal sulcus (LIPS & RIPS), as well as increased connectivity from the right hippocampus (RHC) to the bilateral anterior insula (LAI & RAI), right frontal eye fields (RFEF) and RIPS. Moreover, negative symptoms predicted the connectivity strengths from the LHC to the DACC, the left inferior parietal sulcus (LIPAR) and the RHC, while positive symptoms predicted the connectivity strengths from the LHC to the LIPAR and from the RHC to the LHC. These results reinforce the crucial role of hippocampus dysconnectivity in SZ pathology and its potential as a biomarker of disease severity.
Dicer- and BSC-dependent miRNAs during murine anagen development
Authors: Vishlaghi Neda , Lisse Thomas S.
Published: January 2020

MicroRNAs (miRNAs) are a major class of conserved non-coding RNAs that have a wide range of functions during development and disease. Biogenesis of canonical miRNAs depend on the cytoplasmic processing of pre-miRNAs to mature miRNAs by the Dicer endoribonuclease. Once mature miRNAs are generated, the miRNA-induced silencing complex, or miRISC, incorporates one strand of miRNAs as a template for recognizing complementary target messenger RNAs (mRNAs) to dictate post-transcriptional gene expression. Besides regulating miRNA biogenesis, Dicer is also part of miRISC to assist in activation of the complex. Dicer associates with other regulatory miRISC co-factors such as trans-activation responsive RNA-binding protein (Tarbp2) to regulate miRNA-based RNA interference. Although the functional role of miRNAs within epidermal keratinocytes have been extensively studied within embryonic and post-natal mouse skin, its contribution to the normal function of hair follicle bulge stem cells (BSCs) during post-natal hair follicle development is unknown. With this question in mind, we sought to ascertain whether Dicer-Tarpb2 plays a functional role within BSCs during induced anagen development by utilizing conditional knockout mouse models. Our findings suggest that Dicer, but not Tarbp2, functions within BSCs to regulate induced anagen (growth) development of post-natal hair follicles. These findings strengthen our understanding of miRNA-dependency within hair follicle cells to define a boundary for post-transcriptional gene regulation during anagen development.
Neuronal oscillatory activities in separate frequencies encode hierarchically distinct visual features
Authors: Date Hiroto , Kawasaki Keisuke , Hasegawa Isao , Okatani Takayuki
Published: January 2020

Although most previous studies in cognitive neuroscience have focused on the change of the neuronal firing rate under various conditions, there has been increasing evidence that indicates the importance of neuronal oscillatory activities in cognition. In the visual cortex, specific time-frequency bands are thought to have selectivity to visual stimuli. Furthermore, several recent studies have shown that several time-frequency bands are related to frequency-specific feedforward or feedback processing in inter-areal communication. However, few studies have investigated detailed visual selectivity of each time-frequency band, especially in the primate inferior temporal cortex (ITC). In this work, we analyze frequency-specific electrocorticography (ECoG) activities in the primate ITC by training encoding models that predict frequency-specific amplitude from hierarchical visual features extracted from a deep convolutional neural network (CNNs). We find that ECoG activities in two specific time-frequency bands, theta (around 5 Hz) and gamma (around 20-25 Hz) bands, are better predicted from CNN features than the other bands. Furthermore, theta- and gamma-band activities are better predicted from higher and lower layers in CNNs, respectively. Our visualization analysis using CNN-based encoding models qualitatively show that theta- and gamma-band encoding models have selectivity to higher- and lower-level visual features, respectively. Our results suggest that neuronal oscillatory activities in theta and gamma bands carry distinct information in the hierarchy of visual features, and that distinct levels of visual information are multiplexed in frequency-specific brain signals.
Pre-movement changes in sensorimotor beta oscillations predict motor adaptation drive
Authors: Darch Henry T , Cerminara Nadia L , Gilchrist Iain D , Apps Richard
Published: January 2020

Beta frequency oscillations in scalp electroencephalography (EEG) recordings over the primary motor cortex have been associated with the preparation and execution of voluntary movements. Here, we test whether changes in beta frequency are related to the preparation of adapted movements in human, and whether such effects generalise to other species (cat). Eleven healthy adult humans performed a joystick visuomotor adaptation task. Beta (15-25Hz) scalp EEG signals recorded over the motor cortex during a pre-movement preparatory phase were, on average, significantly reduced in amplitude during early adaptation trials compared to baseline or late adaptation trials (p=0.01). The changes in beta were not related to measurements of reaction time or duration of the reach. We also recorded LFP activity within the primary motor cortex of three cats during a prism visuomotor adaptation task. Analysis of these signals revealed similar reductions in motor cortical LFP beta frequencies during early adaptation. This effect was also present when controlling for any influence of the reaction time and reaching duration. Overall, the results are consistent with a reduction in pre-movement beta oscillations predicting an increase in adaptive drive in upcoming task performance when motor errors are largest in magnitude and the rate of adaptation is greatest.
Spatial and functional links between cellular virological state and progression of liver fibrosis in chronic hepatitis B
Authors: Zhang Xiaonan , Liu Danping , Lu Wei , Zheng Ye , Wu Min , Ding Jiahui , Xu Mingzhu , Zhou Xiaohui , Feng Yanling , Zhang Zhanqing , Yuan Zhenghong
Published: January 2020

Chronic Hepatitis B Virus (HBV) infection is strongly associated with the progression of liver fibrosis, cirrhosis and hepatocellular carcinoma. Despite intensive study, the detailed mechanisms leading to HBV induced liver disease have not been fully elucidated. Previously, we reported a mosaic distribution of viral antigens and nucleic acids at single-cell level in liver tissues of chronic hepatitis B (CHB) patients and proposed a ‘three-stage model’ of HBV infection in vivo. Here, we explored whether the different stages at cellular level is functionally linked with fibrogenesis. We observed a tight spatial relationship between the invasion of collagen fibers and transitions from S-rich to DNA-rich stage. While S-rich cells mainly localized within minimally fibrotic tissue, DNA-rich cells were often closely surrounded by a milieu of stiffened extracellular matrix (ECM). cDNA microarray and subsequent validation analyses revealed that S-rich cells manifested elevated ribosomal proteins and oxidative phosphorylation genes in a disease phase-dependent manner. On the other hand, DNA-rich cells exhibited gradually deteriorated expression of hepatocyte-specific antigen and transcriptional regulator in parallel with the progression of hepatic fibrosis. Finally, during fibrogenesis, inflammatory genes such as IP-10 were found to be expressed in both portal infiltrated cells and surrounding parenchymal cells which resulted in suppressed antigen expression. Taken together, we propose that liver inflammation and accompanying fibrogenesis is spatially and functionally linked with the transition of virological stages at cellular level. These transitions occur possibly due to an altered hepatocyte transcription profile in response to a transformed ECM environment. The collective viral and host activities shape the histological alterations and progression of liver disease during CHB infection.
Sensory and Behavioral Components of Neocortical Signal Flow in Discrimination Tasks with Short-term Memory
Authors: Gallero-Salas Yasir , Laurenczy Balazs , Voigt Fabian F. , Gilad Ariel , Helmchen Fritjof
Published: January 2020

In neocortex, each sensory modality engages distinct primary and secondary areas that route information further to association areas. Where signal flow may converge for maintaining information in short-term memory and how behavior may influence signal routing remain open questions. Using wide-field calcium imaging, we compared cortex-wide neuronal activity in layer 2/3 for mice trained in auditory and whisker-based tactile discrimination tasks with delayed response. In both tasks, mice were either active or passive during stimulus presentation, engaging in body movements or sitting quietly. Irrespective of behavioral strategy, auditory and tactile stimulation activated spatially segregated subdivisions of posterior parietal cortex (areas A and RL, respectively). In the subsequent delay period, in contrast, behavioral strategy rather than sensory modality determined where short-term memory was located: frontomedially in active trials and posterolaterally in passive trials. Our results suggest behavior-dependent routing of sensory-driven cortical information flow from modality-specific PPC subdivisions to higher association areas.
Transcriptional regulation of theNε-fructoselysine metabolism inEscherichia coliby global and substrate-specific cues
Authors: von Armansperg Benedikt Graf , Koller Franziska , Gericke Nicola , Hellwig Michael , Jagtap Pravin Kumar Ankush , Heermann Ralf , Hennig Janosch , Henle Thomas , Lassak Jürgen
Published: January 2020

Thermally processed food is an important part of the human diet. Heat-treatment, however, promotes the formation of so-called Amadori rearrangement products (ARPs), such as fructoselysine. The gut microbiota includingEscherichia colican utilize these compounds as a nutrient source. While the degradation route for fructoselysine is well described, regulation of the corresponding pathway genesfrlABCDremained poorly understood. Here we use bioinformatics combined with molecular and biochemical analyses and show that inE. coli, fructoselysine metabolism is tightly controlled at the transcriptional level. The global regulator Crp (CAP), as well as the alternative sigma factor σ32 (RpoH) contribute to promoter activation at high cAMP-levels and heat stress, respectively. In addition, we identified and characterized a transcriptional regulator FrlR, encoded adjacent tofrlABCD, as fructoselysine-6-phosphate specific roadblock repressor. Our study provides profound evidence that the interplay of global and substrate-specific regulation is a perfect adaptation strategy to efficiently utilize unusual substrates within the human gut environment.

Abbreviated Summary

Thermal food processing promotes the formation of Amadori rearrangement products (ARPs), such as fructoselysine. The gut microbiota includingEscherichia colican utilize these compounds as a nutrient source. We show that inE. coli, fructoselysine metabolism is tightly controlled at the transcriptional level by global and substrate-specific regulators. Their interplay is a perfect adaptation strategy to efficiently utilize fructoselysine within the human gut environment.

Graphical Abstract
Optical microscopy reveals the dynamic nature ofB. pseudomalleimorphology during β-lactam antimicrobial susceptibility testing
Authors: McLaughlin Heather P. , Bugrysheva Julia , Sue David
Published: January 2020

Background

In Gram-negative species, β-lactam antibiotics target penicillin binding proteins (PBPs) resulting in morphological alterations of bacterial cells. Observations of antibiotic-induced cell morphology changes can rapidly and accurately differentiate drug susceptible from resistant bacterial strains; however, resistant cells do not always remain unchanged.Burkholderia pseudomalleiis a Gram-negative, biothreat pathogen and the causative agent of melioidosis, an often fatal infectious disease for humans.

Results

Here, we identified β-lactam targets inB. pseudomalleibyin silicoanalysis. Ten genes encoding putative PBPs, including PBP-1, PBP-2, PBP-3 and PBP-6, were detected in the genomes of susceptible and resistant strains. Real-time, live-cell imaging ofB. pseudomalleistrains demonstrated dynamic morphological changes in broth containing clinically relevant β-lactam antibiotics. At sub-inhibitory concentrations of ceftazidime (CAZ), amoxicillin-clavulanic acid (AMC), and imipenem (IPM), filamentation, varying in length and proportion, was an initial response of the multidrug-resistant strain Bp1651 in exponential phase. However, a dominant morphotype reemerged during stationary phase that resembled cells unexposed to antibiotics. Similar morphology dynamics were observed for AMC-resistant strains, MSHR1655 and 724644, when exposed to sub-inhibitory concentrations of AMC. For allB. pseudomalleistrains evaluated, increased exposure time and exposure to increased concentrations of AMC at and above minimal inhibitory concentrations (MICs) in broth resulted in cell morphology shifts from filaments to spheroplasts and/or cell lysis.B. pseudomalleimorphology changes were more consistent in IPM. Spheroplast formation followed by cell lysis was observed for all strains in broth containing IPM at concentrations greater than or equal to MICs, however, the time to cell lysis was variable. Length ofB. pseudomalleicells was strain-, drug- and drug concentration-dependent.

Conclusions

Both resistant and susceptibleB. pseudomalleistrains exhibited filamentation during early exposure to AMC and CAZ at concentrations used to interpret susceptibility (based on CLSI guidelines). While developing a rapid β-lactam antimicrobial susceptibility test based on cell-shape alone requires more extensive analyses, optical microscopy detectedB. pseudomalleigrowth attributes that lend insight into antibiotic response and antibacterial mechanisms of action.
Recent fluctuations in Mexican American genomes have altered the genetic architecture of biomedical traits
Authors: Spear Melissa L. , Diaz-Papkovich Alex , Ziv Elad , Yracheta Joseph M. , Gravel Simon , Torgerson Dara G. , Hernandez Ryan D.
Published: January 2020

People in the Americas represent a diverse group of populations with varying degrees of admixture among African, European, and Amerindigenous ancestries. In the United States, many populations with non-European ancestry remain understudied, and thus little is known about the genetic architecture of phenotypic variation in these populations. Using genome-wide genotype data from the Hispanic Community Health Study/Study of Latinos, we find that Amerindigenous ancestry has increased over time across Hispanic/Latino populations, particularly in Mexican Americans where Amerindigenous ancestry increased by an average of ∼20% over the 50-year period spanning 1940s-1990s. We find similar patterns across American cities, and replicate our observations in an independent sample of Mexican Americans. These dynamic ancestry patterns are a result of a complex interaction of several population and cultural factors, including strong ancestry-related assortative mating and subtle shifts in migration with differences in subcontinental Amerindigenous ancestry over time. These factors have shaped patterns of genetic variation, including an increase in runs of homozygosity in Amerindigenous ancestral tracts, and also influenced the genetic architecture of complex traits within the Mexican American population. We show for height, a trait correlated with ancestry, polygenic risk scores based on summary statistics from a European-based genome-wide association study perform poorly in Mexican Americans. Our findings reveal temporal changes in population structure within Hispanics/Latinos that may influence biomedical traits, demonstrating a crucial need to improve our understanding of the genetic diversity of admixed populations.
Factor VIII exhibits chaperone-dependent and glucose-regulated reversible amyloid formation in the endoplasmic reticulum
Authors: Poothong Juthakorn , Pottekat Anita , Siirin Marina , Campos Alexandre Rosa , Paton Adrienne W. , Paton James C. , Lagunas-Acosta Jacqueline , Chen Zhouji , Swift Mark , Volkmann Niels , Hanein Dorit , Yong Jing , Kaufman Randal J.
Published: January 2020

Factor VIII (FVIII) is the coagulation factor deficient in hemophilia A, which is treated by protein replacement. Unfortunately, this regimen is costly due to the expense of producing recombinant FVIII as a consequence of its low level secretion. FVIII expression activates the endoplasmic reticulum (ER) stress response, causes oxidative stress and induces apoptosis. Importantly, little is known about the factors that cause protein misfolding and aggregation in metazoans. Here we identified intrinsic and extrinsic factors that cause FVIII to form aggregates in the ER. We show that FVIII forms amyloid-like fibrils within the ER upon increased FVIII synthesis or inhibition of glucose metabolism. Significantly, FVIII amyloids can be dissolved upon restoration of glucose metabolism to produce functional secreted FVIII. Two ER chaperones and their co-chaperones, BiP and CANX/CRT, promote FVIII solubility in the ER, where the former is also required for disaggregation. A short aggregation motif in the FVIII A1 domain (termed Aggron) is necessary and sufficient to seed β-sheet polymerization and BiP binding to this Aggron prevents amyloidogenesis. Our findings provide novel insight into mechanisms that limit FVIII secretion and ER protein folding in general and have implication for ongoing hemophilia A gene therapy clinical trials.

Key Points

-

FVIII forms amyloid aggregates in the ER that are dissolved in a chaperone- and glucose-dependent manner to produce secreted active FVIII.

-

A short amino acid sequence in the A1 domain causes β sheet polymerization and ER chaperone BiP binding to this site prevents aggregation.
Fluidity of gender identity induced by illusory body-sex change
Authors: Tacikowski P. , Fust J. , Ehrsson H. H.
Published: January 2020

Gender identity is the inner sense of being male, female, both, or neither. How this sense is linked to the perception of one’s own masculine or feminine body remains unclear. Here, in a series of three behavioral experiments conducted on a large group of healthy volunteers (N=140), we show that a perceptual illusion of having the opposite-sex body was associated with a shift toward more balanced identification with both genders and less gender-stereotypical beliefs about one’s own personality characteristics, as indicated by subjective reports and implicit behavioral measures. These findings demonstrate that the ongoing perception of one’s own body affects the sense of one’s own gender in a dynamic, robust, and automatic manner.
Dietary Amino Acids Impact LRRK2-induced Neurodegeneration in Parkinson’s Disease Models
Authors: Chittoor-Vinod Vinita G. , Villalobos-Cantor Steffany , Roshak Hanna , Shea Kelsey , Martin Ian
Published: January 2020

The G2019S mutation in leucine-rich repeat kinase 2 (LRRK2) is a common cause of Parkinson’s disease (PD) and results in age-related dopamine neuron loss and locomotor dysfunction in Drosophila melanogaster through an aberrant increase in bulk neuronal protein synthesis. Under non-pathologic conditions, protein synthesis is tightly controlled by metabolic regulation. Whether nutritional and metabolic influences on protein synthesis can modulate the pathogenic effect of LRRK2 on protein synthesis and thereby impact neuronal loss is a key unresolved question. Here, we show that LRRK2 G2019S-induced neurodegeneration is critically dependent on dietary amino acid content. Low dietary amino acid concentration prevents aberrant protein synthesis and blocks LRRK2 G2019S-mediated neurodegeneration in Drosophila and rat primary neurons. Unexpectedly, a moderately high amino acid diet also blocks dopamine neuron loss and motor deficits in Drosophila through a separate mechanism involving stress-responsive activation of 5’-AMP-activated protein kinase (AMPK) and neuroprotective induction of autophagy, implicating the importance of protein homeostasis to neuronal viability. At the highest amino acid diet of the range tested, PD-related neurodegeneration occurs in an age-related manner, but is also observed in control strains, suggesting that it is independent of mutant LRRK2 expression. We propose that dietary influences on protein synthesis and autophagy are critical determinants of LRRK2 neurodegeneration, opening up possibilities for future therapeutic intervention.