bluuebunny/crossref_metadata_2025 huggingface dataset:
Bladder Artery Embolization for Massive Hematuria Treatment in a Patient With Ataxia-Telangiectasia Acute Lymphoblastic Leukemia
Authors: Bahadir Aysenur , Oguz Şükrü , Erduran Erol , Dinç Hasan , Yalçin Cömert Hatice S. , Bahat Özdogan Elif , Kaya Gülay
Published: April 2019

Ataxia-telangiectasia (AT) is a hereditary recessive autosomal disorder following a course of progressive cerebellar ataxia, and oculocutaneous telangiectasia. Disease-specific telangiectasias are generally localized in the oculocutaneous region, while telangiectasias located within the bladder are rarely seen in patients with AT. The patient who had been followed-up with a diagnosis of AT since the age of 3 years was later diagnosed with acute lymphoblastic leukemia at the age of 8 years. The patient developed hematuria approximately in the 29th month of treatment. The cystoscopy revealed regions of extensive hemorrhagic telangiectasis, which was interpreted as the bladder involvement of AT. The case presented here underwent several cycles of intravesical steroid and tranexamic acid treatments and intravesical cauterization procedures, but the patient was unresponsive to all medical treatment approaches. The patient was consequently evaluated by an interventional radiology unit for a selective arterial embolization. The patient’s hematuria resolved after embolization. Bladder wall telangiectasia may, on rare occasions, develop in patients with AT, and can result in life-threatening hemorrhages. We also suggest that a selective arterial embolectomy can be safely carried out in pediatric patients with treatment-resistant intravesical bleeding.
Predictors of functional and motor outcomes following upper limb robot-assisted therapy after stroke
Authors: Leem Min Jeong , Kim Gyu Seong , Kim Kee Hoon , Yi Tae Im , Moon Hyun Im
Published: April 2019

Robot-assisted therapy is an effective treatment for stroke patients and has recently gained popularity. Clinicians and researchers are trying to identify predictors to stratify patients for ensuring better stroke rehabilitation outcomes. However, previous studies have reported controversial results regarding the predictors of upper limb recovery after robot-assisted therapy. Our objective was to determine whether the demographic and clinical characteristics of stroke patients influence the motor and functional outcomes after robot-assisted therapy. We conducted a retrospective analysis of 48 hemiplegic patients who performed upper limb goal-directed tasks using RAPAEL Smart Glove (Neofect, Gyeonggi-do, Republic of Korea). Robot-assisted therapy was administered for 5 days a week over 4 weeks, and each session was for 30 minutes. The parameters of the primary outcomes after robot-assisted therapy were measured with the manual function test and functional independence measure. Correlation analysis showed that age, initial cognitive function, and the initial manual function test and the Modified Ashworth Scale for upper extremity scores were significant factors for independently predicting functional outcomes after robot-assisted therapy. Linear regression analysis revealed that the initial Mini-Mental State Examination (P< 0.001) and initial manual function test (P< 0.001) scores were significant predictors of the primary outcomes. In conclusion, our study suggests that stroke patients presenting with less spasticity, better initial cognitive function, and better initial motor function have a significant correlation with the functional outcomes after robot-assisted therapy.
Surgical Resection Margin Classifications for High-grade Pleomorphic Soft Tissue Sarcomas of the Extremity or Trunk After Neoadjuvant Cytotoxic Therapy
Authors: Cates Victoria M. , Cates Justin M.M.
Published: April 2019

Soft tissue sarcomas of the extremities or trunk are often resected after treatment with neoadjuvant radiotherapy. Adequate surgical resection margins for sarcomas after neoadjuvant cytotoxic therapy are not well characterized. Minimum surgical resection margins required for local control of primary, high-grade, pleomorphic soft tissue sarcomas treated with neoadjuvant therapy was assessed by competing risk regression in a series of 166 cases. Optimal tumor clearance was determined to be ≥1 mm. Predictive accuracy of three commonly used resection margin classification schemes (American Joint Committee on Cancer, Musculoskeletal Tumor Society, and the margin distance method) were comparable. However, diagnostic performance of a binary system (positive vs. negative) was more specific than margin distance classification (positive or <1 vs. ≥1 mm from tumor), but less sensitive in predicting local recurrence. The American Joint Committee on Cancer R classification (R0 vs. R1/R2) seems to adequately stratify patients by risk for local recurrence after neoadjuvant therapy and subsequent surgical resection. Furthermore, close but negative resection margins (<1 mm from tumor) appear sufficient for local control of high-grade pleomorphic soft tissue sarcomas of the extremity or trunk in this clinical setting, with minimal reduction in the risk of local recurrence with increasing margin width or surgical clearance.
Prognostic Value of Tumor Heterogeneity and SUVmax of Pretreatment 18F-FDG PET/CT for Salivary Gland Carcinoma With High-Risk Histology
Authors: Cheng Nai-Ming , Hsieh Cheng-En , Liao Chun-Ta , Ng Shu-Hang , Wang Hung-Ming , Fang Yu-Hua Dean , Chou Wen-Chi , Lin Chien-Yu , Yen Tzu-Chen
Published: April 2019

Purpose

Previous studies have shown that SUVmax on 18F-FDG PET/CT predicts prognosis in patients with salivary gland carcinoma (SGC). Here, we sought to evaluate whether texture features extracted from 18F-FDG PET/CT images may provide additional prognostic information for SGC with high-risk histology.

Methods

We retrospectively examined pretreatment 18F-FDG PET/CT images obtained from 85 patients with nonmetastatic SGC showing high-risk histology. All patients were treated with curative intent. We used the fixed threshold of 40% of SUVmax for tumor delineation. PET texture features were extracted by using histogram analysis, normalized gray-level co-occurrence matrix, and gray-level size zone matrix. Optimal cutoff points for each PET parameter were derived from receiver operating characteristic curve analyses. Recursive partitioning analysis was used to construct a prognostic model for overall survival (OS).

Results

Receiver operating characteristic curve analyses revealed that SUVmax, SUV entropy, uniformity, entropy, zone-size nonuniformity, and high-intensity zone emphasis were significantly associated with OS. The strongest associations with OS were found for high SUVmax (>6.67) and high SUV entropy (>2.50). Multivariable Cox analysis identified high SUVmax, high SUV entropy, performance status, and N2c–N3 stage as independent predictors of survival. A prognostic model derived from multivariable analysis revealed that patients with high SUVmax and SUV entropy or with the presence of poor performance status or N2c–N3 were associated with worse OS.

Conclusions

A prognostic model that includes SUVmax and SUV entropy is useful for risk stratification and supports the additional benefit of texture analysis for SGC with high-risk histology.
68Ga-PSMA Uptake in Fibrous Dysplasia
Authors: Reale Maria Lucia , Buttigliero Consuelo , Tucci Marcello , Giardino Roberto , Poti Carlo
Published: April 2019

Prostate cancer is one of the most common malignancies. Imaging tools play an important role throughout the entire process of the disease. The scenario, however, is going to change. Thanks to a higher sensitivity and specificity, the use of the prostate-specific membrane antigen (PSMA) PET is of increasing importance, particularly at the time of diagnosis and in case of biochemical recurrence. Nevertheless, previous reports have described false-positive findings, as tracer-avid physiological findings or benign processes, potential pitfalls for interpretation of 68Ga-PSMA PET/CT. Here we report a case of PSMA uptake in a histologically proven fibrous dysplasia.
Tuberculosis Presenting as Cutaneous Erythema Nodosum on 18F-FDG PET/CT
Authors: Jain Tarun Kumar
Published: April 2019

The present article presented a 47-year-old woman with areas of nodular swelling and discoloration involving bilateral lower limbs since 12 months. Biopsy from skin lesions revealed erythema nodosum. As erythema nodosum can be secondary to multiple etiologies, whole-body 18F-FDG PET/CT was performed to assess the disease distribution and guide the site of biopsy. 18F-FDG PET/CT revealed metabolically active mediastinal lymphadenopathy in addition to the skin lesions. Endobronchial ultrasound–guided biopsy from subcarinal lymph node revealed tuberculosis.
18F–Prostate-Specific Membrane Antigen 1007 and 18F-FCH PET/CT in Local Recurrence of Prostate Cancer
Authors: Witkowska-Patena Ewa , Giżewska Agnieszka , Miśko Jolanta , Dziuk Mirosław
Published: April 2019

18F–prostate-specific membrane antigen (PSMA) 1007 is one of the most promising radiotracers for PET imaging of relapsing prostate cancer. Minimal urinary clearance seems to be its most valuable and outstanding feature. We present images of biochemically relapsed prostate cancer where 18F-PSMA-1007 PET/CT (performed to verify an ambiguous finding adjacent to the urinary bladder found in 18F-FCH PET/CT) proved superior to radiocholine and precisely visualized site of local recurrence.
Gut Microbiota and Cardiometabolic Risk Factors in Hemodialysis Patients
Authors: Biruete Annabel , Allen Jacob M. , Kistler Brandon M. , Jeong Jin Hee , Fitschen Peter J. , Swanson Kelly S. , Wilund Kenneth R.
Published: April 2019

The gut microbiota has been implicated in the pathogenesis and progression of kidney disease. However, little is known about the gut microbiota in hemodialysis (HD) patients. We assessed the gut microbiota and its relationship with clinical variables in 10 HD patients. We found that the Firmicutes-to-Bacteroidetes ratio was positively associated with traditional risk factors for cardiovascular disease. Furthermore, Faecalibacterium was positively associated with carbohydrate intake and negatively associated with arterial stiffness. Finally, endotoxemia was inversely associated with butyrate producers. Future studies should assess whether targeting the gut microbiota results in a lower burden for cardiovascular disease in HD patients.
“It's Good, It's Delicious, It's Great”
Authors: Santiago Elena , Eck Kaitlyn M. , Delaney Colleen , Famodu Oluremi A. , Olfert Melissa D. , Shelnutt Karla P. , Byrd-Bredbenner Carol
Published: April 2019

Fruit and vegetable (F/V)–related cognitions of parents (n = 36) and children (aged 6-11 years; n = 41) were investigated via focus groups. Participants regarded F/Vs as important for health. Parents identified busy schedules, picky eating, and cost as F/V intake barriers. To overcome barriers, parents suggested scheduling time for F/V preparation and using time-saving forms of F/Vs and involving children in F/V selection/preparation. Kids identified disliking F/Vs as a barrier, recommending parents stock a variety of F/Vs and encourage kids to eat them. Considering F/V cognitions during intervention development may improve intervention effectiveness.
Temporal Distribution of Carbohydrate and Calorie Intake Is Not Associated With Hemoglobin A1c in Persons With Type 2 Diabetes Mellitus
Authors: Petr Jane Erin , Keim Kathryn S. , Chapman-Novakofski Karen M. , Rasmussen Heather
Published: April 2019

The aim of this study was to examine the temporal distribution of carbohydrate and energy intake over 24 hours in individuals with type 2 diabetes mellitus and determine the association with hemoglobin A1C (A1C). Up to four 24-hour food recalls were collected from 98 subjects with type 2 diabetes mellitus. Temporal macronutrient distribution was operationalized by dividing each day into four, 6-hour time periods and calculating the percentage of total intake in each period. Linear regression was conducted to determine the extent to which these distribution patterns predicted A1C. The temporal distribution of calories and carbohydrate was not associated with A1C in this sample.
Transient absorption spectroscopy using high harmonic generation: a review of ultrafast X-ray dynamics in molecules and solids
Authors: Geneaux Romain , Marroux Hugo J. B. , Guggenmos Alexander , Neumark Daniel M. , Leone Stephen R.
Published: April 2019

Attosecond science opened the door to observing nuclear and electronic dynamics in real time and has begun to expand beyond its traditional grounds. Among several spectroscopic techniques, X-ray transient absorption spectroscopy has become key in understanding matter on ultrafast time scales. In this review, we illustrate the capabilities of this unique tool through a number of iconic experiments. We outline how coherent broadband X-ray radiation, emitted in high-harmonic generation, can be used to follow dynamics in increasingly complex systems. Experiments performed in both molecules and solids are discussed at length, on time scales ranging from attoseconds to picoseconds, and in perturbative or strong-field excitation regimes.

This article is part of the theme issue ‘Measurement of ultrafast electronic and structural dynamics with X-rays’.
Chemical interactions and dynamics with femtosecond X-ray spectroscopy and the role of X-ray free-electron lasers
Authors: Wernet Philippe
Published: April 2019

X-ray free-electron lasers with intense, tuneable and short-pulse X-ray radiation are transformative tools for the investigation of transition-metal complexes and metalloproteins. This becomes apparent in particular when combining the experimental observables from X-ray spectroscopy with modern theoretical tools for calculations of electronic structures and X-ray spectra from first principles. The combination gives new insights into how charge and spin densities change in chemical reactions and how they determine reactivity. This is demonstrated for the investigations of structural dynamics with metal K-edge absorption spectroscopy, spin states in excited-state dynamics with metal 3p-3d exchange interactions, the frontier-orbital interactions in dissociation and substitution reactions with metal-specific X-ray spectroscopy, and studies of metal oxidation states with femtosecond pulses for ‘probe-before-destroy’ spectroscopy. The role of X-ray free-electron lasers is addressed with thoughts about how they enable ‘bringing back together’ different aspects of the same problem and this is thought to go beyond a conventional review paper where these aspects are formulated in italic font type in a prequel, an interlude and in a sequel.

This article is part of the theme issue ‘Measurement of ultrafast electronic and structural dynamics with X-rays'.
Photochemical pathways in nucleobases measured with an X-ray FEL
Authors: Wolf Thomas J. A. , Gühr Markus
Published: April 2019

The conversion of light energy into other molecular energetic degrees of freedom is often dominated by ultrafast, non-adiabatic processes. Femtosecond spectroscopy with optical pulses has helped in shaping our understanding of crucial processes in molecular energy-conversion. The advent of new, ultrashort and bright X-ray free electron laser sources opens the possibility to use X-ray-typical element and site sensitivity for ultrafast molecular research. We present two types of spectroscopy, ultrafast Auger and ultrafast X-ray absorption spectroscopy, and discuss their sensitivity to molecular processes. While Auger spectroscopy is able to monitor bond distance changes in the vicinity of an X-ray created core hole, near-edge absorption spectroscopy can deliver high-fidelity information on non-adiabatic transitions involving lone-pair orbitals. We demonstrate these features on the example of the UV-excited nucleobase thymine, investigated at the oxygen K-edge. We find a C–O bond elongation in the Auger data in addition to
ππ*
/
nπ*
non-adiabatic transition in X-ray near-edge absorption. We compare the results from both methods and draw a conclusive scenario of non-adiabatic molecular relaxation after UV excitation.

This article is part of the theme issue ‘Measurement of ultrafast electronic and structural dynamics with X-rays’.
Domain-specific quantification of prion protein in cerebrospinal fluid by targeted mass spectrometry
Authors: Minikel Eric Vallabh , Kuhn Eric , Cocco Alexandra R , Vallabh Sonia M , Hartigan Christina R , Reidenbach Andrew G , Safar Jiri G , Raymond Gregory J , McCarthy Michael D , O’Keefe Rhonda , Llorens Franc , Zerr Inga , Capellari Sabina , Parchi Piero , Schreiber Stuart L , Carr Steven A
Published: April 2019

Therapies currently in preclinical development for prion disease seek to lower prion protein (PrP) expression in the brain. Trials of such therapies are likely to rely on quantification of PrP in cerebrospinal fluid (CSF) as a pharmacodynamic biomarker and possibly as a trial endpoint. Studies using PrP ELISA kits have reproducibly shown that CSF PrP is lowered in the symptomatic phase of disease, a potential confounder for reading out the effect of PrP-lowering drugs in symptomatic patients. To date it has been unclear whether the reduced abundance of PrP in CSF results from its incorporation into plaques, retention in intracellular compartments, downregulation as a function of the disease process, or other factors. Because misfolding or proteolytic cleavage could potentially render PrP invisible to ELISA even if its concentration were constant or increasing in disease, we sought to establish an orthogonal method for CSF PrP quantification. We developed a targeted mass spectrometry method based on multiple reaction monitoring (MRM) of nine PrP tryptic peptides quantified relative to known concentrations of isotopically labeled standards. Analytical validation experiments showed process replicate coefficients of variation below 15%, good dilution linearity and recovery, and suitable performance for both CSF and brain homogenate and across humans as well as preclinical species of interest. InN=55 CSF samples from individuals referred to prion surveillance centers with rapidly progressive dementia, all six human PrP peptides, spanning the N- and C-terminal domains of PrP, were uniformly reduced in prion disease cases compared to individuals with non-prion diagnoses. This confirms the findings from ELISA studies, demonstrating that lowered CSF PrP concentration in prion disease is a genuine result of the disease process and not merely an artifact of ELISA-based measurement. We provide a targeted mass spectrometry-based method suitable for preclinical and clinical quantification of CSF PrP as a tool for drug development.
Characterization of LINE-1 transposons in a human genome at allelic resolution
Authors: Yang Lei , Metzger Genevieve A. , McLaughlin Richard N.
Published: April 2019

The activity of the retrotransposon LINE-1 has created a substantial portion of the human genome. Most of this sequence comprises fractured and debilitated LINE-1s. An accurate approximation of the number, location, and sequence of the LINE-1 elements present in any single genome has proven elusive due to the difficulty of assembling and phasing the repetitive and polymorphic regions of the human genome. Through an in-depth analysis of publicly-available, deep, long-read assemblies of nearly homozygous human genomes, we defined the location and sequence of all intact LINE-1s in these assemblies. We found 148 and 142 intact LINE-1s in two nearly homozygous assemblies. A combination of these assemblies suggests a diploid human genome contains at least 50% more intact LINE-1s than previous estimates – in this case, 290 intact LINE-1s at 194 loci. We think this is the best approximation, to date, of the number of intact LINE-1s in a single diploid human genome. In addition to counting intact LINE-1 elements, we resolved the sequence of each element, including some LINE-1 elements in unassembled, presumably centromeric regions of the genome. A comparison of the intact LINE-1s in each assembly shows the specific pattern of variation between these genomes, including LINE-1s that remain intact in only one genome, allelic variation in shared intact LINE-1s, and LINE-1s that are unique (presumably young) insertions in only one genome. We found that many old elements (> 6 million years old) remain intact, and comparison of the young and intact LINE-1s across assemblies reinforces the notion that only a small portion of all LINE-1 sequences that may be intact in the genomes of the human population has been uncovered. This dataset provides the first nearly comprehensive estimate of LINE-1 diversity within an individual, an important dataset in the quest to understand the functional consequences of sequence variation in LINE-1 and the complete set of LINE-1s in the human population.
Integrating multiple data sources to fit matrix population models for interacting species
Authors: Barraquand Frédéric , Gimenez Olivier
Published: April 2019

Inferring interactions between populations of different species is a challenging statistical endeavour, which requires a large amount of data. There is therefore some incentive to combine all available sources of data into a single analysis to do so. In demography and single-population studies, Integrated Population Models combine population counts, capture-recapture and reproduction data to fit matrix population models. Here, we extend this approach to the community level in a stage-structured predator-prey context. We develop Integrated Community Models (ICMs), implemented in a Bayesian framework, to fit multispecies nonlinear matrix models to multiple data sources. We assessed the value of the different sources of data using simulations of ICMs under different scenarios contrasting data availability. We found that combining all data types (capture-recapture, counts, and reproduction) allows the estimation of both demographic and interaction parameters, unlike count-only data which typically generate high bias and low precision in interaction parameter estimates for short time series. Moreover, reproduction surveys informed the estimation of interactions particularly well when compared to capture-recapture programs, and have the advantage of being less costly. Overall, ICMs offer an accurate representation of stage structure in community dynamics, and foster the development of efficient observational study designs to monitor communities in the field.
Parallel Group ICA + ICA: Joint Estimation of Linked Functional Network Variability and Structural Covariation with Application to Schizophrenia
Authors: Qi Shile , Sui Jing , Chen Jiayu , Liu Jingyu , Jiang Rongtao , Silva Rogers , Iraji Armin , Damaraju Eswar , Salman Mustafa , Lin Dongdong , Fu Zening , Zhi Dongmei , Turner Jessica A. , Bustillo Juan , Ford Judith M. , Mathalon Daniel H. , Voyvodic James , McEwen Sarah , Preda Adrian , Belger Aysenil , Potkin Steven G. , Mueller Bryon A. , Adali Tulay , Calhoun Vince D.
Published: April 2019

There is growing evidence that rather than using a single brain imaging modality to study its association with physiological or symptomatic features, the field is paying more attention to fusion of multimodal information. However, most current multimodal fusion approaches that incorporate functional magnetic resonance imaging (fMRI) are restricted to second-level 3D features, rather than the original 4D fMRI data. This trade-off is that the valuable temporal information is not utilized during the fusion step. Here we are motivated to propose a novel approach called “parallel group ICA+ICA” that incorporates temporal fMRI information from GICA into a parallel ICA framework, aiming to enable direct fusion of first-level fMRI features with other modalities (e.g.structural MRI), which thus can detect linked functional network variability and structural covariations. Simulation results show that the proposed method yields accurate inter-modality linkage detection regardless of whether it is strong or weak. When applied to real data, we identified one pair of significantly associated fMRI-sMRI components that show group difference between schizophrenia and controls in both modalities. Finally, multiple cognitive domain scores can be predicted by the features identified in the linked component pair by our proposed method. We also show these multimodal brain features can predict multiple cognitive scores in an independent cohort. Overall, results demonstrate the ability of parallel GICA+ICA to estimate joint information from 4D and 3D data without discarding much of the available information up front, and the potential for using this approach to identify imaging biomarkers to study brain disorders.
Is the addition of higher-order interactions in ecological models increasing the understanding of ecological dynamics?
Authors: AlAdwani Mohammad , Saavedra Serguei
Published: April 2019

Recent work has shown that higher-order interactions can increase the stability, promote the diversity, and better explain the dynamics of ecological communities. Yet, it remains unclear whether the perceived benefits of adding higher-order terms into population dynamics models come from fundamental principles or a simple mathematical advantage given by the nature of multivariate polynomials. Here, we develop a general method to quantify the mathematical advantage of adding higher-order interactions in ecological models based on the number of free-equilibrium points that can be engineered in a system (i.e., equilibria that can be feasible or unfeasible by tunning model parameters). We apply this method to calculate the number of free-equilibrium points in Lotka-Volterra dynamics. While it is known that Lotka-Volterra models without higher-order interactions only have one free-equilibrium point regardless of the number of parameters, we find that by adding higher-order terms this number increases exponentially with the dimension of the system. Our results suggest that while adding higher-order interactions in ecological models may be good for prediction purposes, they cannot provide additional explanatory power of ecological dynamics if model parameters are not ecologically restricted.
Moiety Modeling Framework for Deriving Moiety Abundances from Mass Spectrometry Measured Isotopologues
Authors: Jin Huan , Moseley Hunter N.B.
Published: April 2019

Background

Stable isotope tracing can follow individual atoms through metabolic transformations through the detection of the incorporation of stable isotope within metabolites. This resulting data can be interpreted in terms related to metabolic flux. However, detection of a stable isotope in metabolites by mass spectrometry produces a profile of isotopologue peaks that requires deconvolution to ascertain the localization of isotope incorporation.

Results

To aid the interpretation of the mass spectroscopy isotopologue profile, we have developed a moiety modeling framework for deconvoluting metabolite isotopologue profiles involving single and multiple isotope tracers. This moiety modeling framework provides facilities for moiety model representation, moiety model optimization, and moiety model selection. The moiety_modeling package was developed from the idea of metabolite decomposition into moiety units based on metabolic transformations, i.e. a moiety model. A SAGA-optimize package, solving a boundary-value inverse problem through a combined simulated annealing and genetic algorithm, was developed for model optimization. Additional optimization methods from the Python scipy library are utilized as well. Several forms of the Akaike information criterion and Bayesian information criterion are provided for selecting between moiety models. Moiety models and associated isotopologue data are defined in the JSON format.

By testing the moiety modeling framework on the timecourses of 13C isotopologue data for UDP-N-acetyl-D-glucosamine (UDP-GlcNAc) in human prostate cancer LnCaP-LN3 cells, we were able to confirm its robust performance in isotopologue deconvolution and moiety model selection.

Conclusions

SAGA-optimize is a useful Python package for solving boundary-value inverse problems, and the moiety_modeling package is an easy-to-use tool for mass spectroscopy isotopologue profile deconvolution involving single and multiple isotope tracers. Both packages are freely freely available on GitHub and via the Python Package Index.
Inertial Measurement Unit-Based Estimation of Foot Trajectory for Clinical Gait Analysis
Authors: Ono Yumi , Hori Koyu , Ora Hiroki , Hirobe Yuki , Mao Yufeng , Sawada Hiroyuki , Inaba Akira , Orimo Satoshi , Miyake Yoshihiro
Published: April 2019

Gait analysis is used widely in clinical practice for the evaluation of abnormal gait caused by disease. Conventionally, medical professionals use motion capture systems or make visual observations to evaluate a patient’s gait. Recent biomedical engineering studies have proposed easy-to-use gait analysis methods involving wearable sensors with inertial measurement units (IMUs). IMUs placed on the shanks just above the ankles allow for the long-term monitoring of gait because the participant can walk with or without shoes during the analysis. As far as the authors know, there is no report of the gait analysis method that estimates stride length, gait speed, stride duration, stance duration, and swing duration at the same time. In this study, we tested a proposed gait analysis method that uses IMUs attached on the shanks to estimate foot trajectory and temporal gait parameters. We evaluated this proposed method by analyzing the gait of 10 able-bodied participants (mean age 23.1 years, nine men and one woman). Wearable sensors were attached to the participants’ shanks, and we measured three-axis acceleration and three-axis angular velocity with the sensors to estimate foot trajectory during walking. We compared gait parameters estimated from the foot trajectory obtained with the proposed method and those measured with a motion capture system. Mean accuracy (mean ± standard deviation) was –0.046 ± 0.026 m for stride length, –0.036 ± 0.026 m/s for gait speed, –0.002 ± 0.019 s for stride duration, –0.000 ± 0.016 s for stance duration, and –0.002 ± 0.022 s for swing duration. These results suggest that the proposed method is useful for evaluation of clinical gait parameters.
Chemogenetic activation of excitatory neurons alters hippocampal neurotransmission in a dose-dependent manner
Authors: Pati Sthitapranjya , Salvi Sonali S. , Kallianpur Mamata , Banerjee Antara , Maiti Sudipta , Clement James P. , Vaidya Vidita A.
Published: April 2019

Designer Receptors Exclusively Activated by Designer Drugs (DREADD)-based chemogenetic tools are extensively used to manipulate neuronal activity in a cell-type specific manner. Whole-cell patch-clamp recordings indicate membrane depolarization, coupled with increased neuronal firing rate, following administration of the DREADD ligand, Clozapine-N-Oxide (CNO) to activate the Gq-coupled DREADD, hM3Dq. Although hM3Dq has been used to enhance neuronal firing in order to manipulate diverse behaviors, often within thirty minutes to an hour post-CNO administration, the physiological effects on excitatory neurotransmission remain poorly understood. We investigated the influence of CNO-mediated hM3Dq DREADD activation on distinct aspects of hippocampal excitatory neurotransmission at the Schaffer collateral-CA1 synapse in hippocampal slices derived from mice expressing hM3Dq in Ca2+/calmodulin dependent protein kinase α (CamKIIα)-positive excitatory neurons. Our results indicate a clear dose-dependent effect on fEPSP slope, with no change noted at the lower dose of CNO (1 µM) and a significant, long-term decline in fEPSP slope observed at higher doses (5-20 µM). Further, we noted a robust theta burst stimulus (TBS) induced long-term potentiation (LTP) in the presence of the lower CNO (1 µM) dose, which was significantly attenuated at the higher CNO (20 µM) dose. Whole-cell patch clamp recording revealed both complex dose-dependent regulation of excitability, and spontaneous and evoked activity of CA1 pyramidal neurons in response to hM3Dq activation across CNO concentrations. Our data indicate that CNO-mediated activation of the hM3Dq DREADD results in dose-dependent regulation of excitatory hippocampal neurotransmission, and highlight the importance of careful interpretation of behavioral experiments involving chemogenetic manipulation.
Display of malaria transmission-blocking antigens on chimeric duck hepatitis B virus-derived virus-like particles produced inHansenula polymorpha
Authors: Wetzel David , Chan Jo-Anne , Suckow Manfred , Barbian Andreas , Weniger Michael , Jenzelewski Volker , Reiling Linda , Richards Jack S , Anderson David A , Kouskousis Betty , Palmer Catherine , Hanssen Eric , Schembecker Gerhard , Merz Juliane , Beeson James G , Piontek Michael
Published: April 2019

1.

Background

Malaria caused byPlasmodium falciparumis one of the major threats to human health globally. Despite huge efforts in malaria control and eradication, highly effective vaccines are urgently needed, including vaccines that can block malaria transmission. Chimeric virus-like particles (VLP) have emerged as a promising strategy to develop new malaria vaccine candidates.

Methods

We developed yeast cell lines and processes for the expression of malaria transmission-blocking vaccine candidates Pfs25 and Pfs230 as VLP and VLP were analyzed for purity, size, protein incorporation rate and expression of malaria antigens.

Results

In this study, a novel platform for the display ofPlasmodium falciparumantigens on chimeric VLP is presented. Leading transmission-blocking vaccine candidates Pfs25 and Pfs230 were genetically fused to the small surface protein (dS) of the duck hepatitis B virus (DHBV). The resulting fusion proteins were co-expressed in recombinantHansenula polymorpha(syn.Pichia angusta, Ogataea polymorpha) strains along with the wild-type dS as the VLP scaffold protein. Through this strategy, chimeric VLP containing Pfs25 or the Pfs230-derived fragments Pfs230c or Pfs230D1M were purified. Up to 100 mg chimeric VLP were isolated from 100 g dry cell weight with a maximum protein purity of 90 % on the protein level. Expression of the Pfs230D1M construct was more efficient than Pfs230c and enabled VLP with higher purity. VLP showed reactivity with transmission-blocking antibodies and supported the surface display of the malaria antigens on the native VLP.

Conclusion

The incorporation of leadingPlasmodium falciparumtransmission-blocking antigens into the dS-based VLP scaffold is a promising novel strategy for their display on nano-scaled particles. Competitive processes for efficient production and purification were established in this study.
Sex-specific transcriptomic responses to changes in the nutritional environment
Authors: Camus M. Florencia , Piper Matthew D.W. , Reuter Max
Published: April 2019

Males and females typically pursue divergent reproductive strategies and accordingly require different dietary compositions to maximise their fitness. Here we move from identifying sex-specific optimal diets to understanding the molecular mechanisms that underlie male and female responses to dietary variation. We examine male and female gene expression on male-optimal (carbohydrate-rich) and female-optimal (protein-rich) diets. We find that the sexes share a large core of metabolic genes that are concordantly regulated in response to dietary composition. However, we also observe smaller sets of genes with divergent and opposing regulation, most notably in reproductive genes which are over-expressed on each sex’s optimal diet. Our results suggest that nutrient sensing output emanating from a shared metabolic machinery are reversed in males and females, leading to opposing diet-dependent regulation of reproduction in males and females. Further analysis and experiments suggest that this reverse regulation occurs within the IIS/TOR network.
Thyroid hormone levels associate with insulin resistance in obese women with metabolic syndrome in Saudi Arabia: A cross-sectional study
Authors: Binobead Manal Abdulaziz , Al Badr Nawal Abdullah , Al-Qahtani Wahidah Hazzaa , AlSedairy Sahar Abdulaziz , Albrahim Tarfa Ibrahim , Alhussain Maha Hussain , Aljurbua Tahani Ali , Arzoo Shaista , Al-Qahtani Wedad Saeed
Published: April 2019

Background

The obesity epidemic is a pressing global health concern, as obesity rates continue to climb worldwide. The current study was aimed mainly to evaluate the correlation between thyroid hormones and homeostatic model assessment of insulin resistance in Saudi obese women with metabolic syndrome.

Methods

100 obese women aged 25 to 55 years were clinically evaluated, from which 72 women were diagnosed with the metabolic syndrome and 28 without metabolic syndrome. Insulin resistance was quantified using the homeostatic model assessment of insulin resistance method and the resulting values were analyzed for association with demographic, clinical, and metabolic parameters.

Results

This analysis revealed that body mass index, systolic blood pressure, and biochemical parameters and fasting insulin showed statistically higher levels in the group with metabolic syndrome compared to the group without metabolic syndrome. Similarly, values of waist circumference, fat ratio, cholesterol, free thyroxine, free triiodothyronine and homeostatic model assessment of insulin resistance results were higher in the group with metabolic syndrome as compared to the group without metabolic syndrome. Correlation analysis revealed positive association of thyroid-stimulating hormone with waist circumference (P=0.01), total cholesterol (P=0.002), fasting insulin (P=0.03) and homeostatic model assessment of insulin resistance results (P<0.01), and negatively associated with diastolic blood pressure (P=0.013) and age (P=0.05). Free thyroxine was positively associated with triglyceride level (P=0.003) and negatively associated with homeostatic model assessment of insulin resistance values (P=0.035) and fasting insulin. Free triiodothyronine was positively associated with body mass index (P=0.032) and waist circumference (P= 0.006) and negatively with age (P=0.004) and total cholesterol (P=0.001).

Homeostatic model assessment of insulin resistance test revealed elevated level with positive association of body mass index, waist circumference, biochemical parameters and thyroid-stimulating hormone in insulin resistant obese women. Higher level of free triiodothyronine was found to be associated with low insulin sensitivity.
LightDock goes information-driven
Authors: Roel-Touris Jorge , Bonvin Alexandre M.J.J. , Jiménez-García Brian
Published: April 2019

The use of experimental information has been demonstrated to increase the success rate of computational macromolecular docking. Many methods use information to post-filter the simulation output while others drive the simulation based on experimental restraints, which can become problematic for more complex scenarios such as multiple binding interfaces. We present a novel two-step method for including interface information into protein docking simulations within the LightDock framework. Prior to the simulation, irrelevant regions from the receptor are excluded for sampling (filter of initial swarms) and initial ligand poses are pre-oriented based on ligand input information. We demonstrate the applicability of this approach on the new 55 cases of the Protein-Protein Docking Benchmark 5, using different amounts of information. Even with incomplete information, a significant improvement in performance is obtained compared to blind ab initio docking.

The software is supported and freely available fromhttps://github.com/brianjimenez/lightdockand analysis data fromhttps://github.com/brianjimenez/lightdock_bm5.
On the energetics and stability of a minimal fish school
Authors: Li Gen , Kolomenskiy Dmitry , Liu Hao , Thiria Benjamin , Godoy-Diana Ramiro
Published: April 2019

The physical basis for fish schooling is examined using three-dimensional numerical simulations of a pair of swimming fish, with kinematics and geometry obtained from experimental data. Energy expenditure and efficiency are evaluated using a cost of transport function, while the effect of schooling on the stability of each swimmer is examined by probing the lateral force and the lateral and longitudinal force fluctuations. We construct full maps of the aforementioned quantities as functions of the spatial pattern of the swimming fish pair and show that both energy expenditure and stability can be invoked as possible reasons for the swimming patterns and tail-beat synchronization observed in real fish. Our results suggest that high cost of transport zones should be avoided by the fish. Wake capture may be energetically unfavorable in the absence of kinematic adjustment. We hereby hypothesize that fish may restrain from wake capturing and, instead, adopt side-to-side configuration as a conservative strategy, when the conditions of wake energy harvesting are not satisfied. To maintain a stable school configuration, compromise between propulsive efficiency and stability, as well as between school members, ought to be considered.
SSD1suppresses phenotypes induced by the lack of Elongator-dependent tRNA modifications
Authors: Xu Fu , Byström Anders S. , Johansson Marcus J.O.
Published: April 2019

The Elongator complex promotes formation of 5-methoxycarbonylmethyl (mcm5) and 5-carbamoylmethyl (ncm5) side-chains on uridines at the wobble position of cytosolic eukaryotic tRNAs. In all eukaryotic organisms tested to date, the inactivation of Elongator not only leads to the lack of mcm5/ncm5groups in tRNAs, but also a wide variety of phenotypes. Although the phenotypes are most likely caused by a translational defect induced by reduced functionality of the hypomodified tRNAs, the mechanism(s) underlying individual phenotypes are poorly understood. In this study, we show that the genetic background modulates the phenotypes induced by the lack of mcm5/ncm5groups inSaccharomyces cerevisiae. We show that the stress-induced growth defects of Elongator mutants are stronger in the W303 than in the closely related S288C genetic background and that the phenotypic differences are caused by the known polymorphism at the locus for the mRNA binding protein Ssd1. Moreover, the mutantssd1allele found in W303 cells is required for the reported histone H3 acetylation and telomeric gene silencing defects of Elongator mutants. The difference at theSSD1locus also partially explains why the simultaneous lack of mcm5and 2-thio groups at wobble uridines is lethal in the W303 but not in the S288C background. Collectively, our results demonstrate that theSSD1locus modulates phenotypes induced by the lack of Elongator-dependent tRNA modifications.

Author Summary

Modified nucleosides in the anticodon region of tRNAs are important for the efficiency and fidelity of translation. The Elongator complex promotes formation of several related modified uridine residues at the wobble position of eukaryotic tRNAs. In yeast, plants, worms, mice and humans, mutations in genes for Elongator subunits lead to a wide variety of different phenotypes. Here, we show that the genetic background modulates the phenotypic consequences of the inactivation of budding yeast Elongator. This background effect is largely a consequence of a polymorphism at theSSD1locus, encoding a RNA binding protein that influences translation, stability and/or localization of mRNAs. We show that several phenotypes reported for yeast Elongator mutants are either significantly stronger or only detectable in strains harboring a mutantssd1allele. Thus,SSD1is a suppressor of the phenotypes induced by the hypomodification of tRNAs.
The accessible chromatin landscape of the murine hippocampus at single-cell resolution
Authors: Sinnamon John R. , Torkenczy Kristof A. , Linhoff Michael W. , Vitak Sarah A. , Mulqueen Ryan M. , Pliner Hannah A. , Trapnell Cole , Steemers Frank J. , Mandel Gail , Adey Andrew C.
Published: April 2019

Here we present a comprehensive map of the accessible chromatin landscape of the mouse hippocampus at single-cell resolution. Substantial advances of this work include the optimization of a single-cell combinatorial indexing assay for transposase accessible chromatin (sci-ATAC-seq); a software suite, scitools, for the rapid processing and visualization of single-cell combinatorial indexing data sets; and a valuable resource of hippocampal regulatory networks at single-cell resolution. We used sci-ATAC-seq to produce 2346 high-quality single-cell chromatin accessibility maps with a mean unique read count per cell of 29,201 from both fresh and frozen hippocampi, observing little difference in accessibility patterns between the preparations. By using this data set, we identified eight distinct major clusters of cells representing both neuronal and nonneuronal cell types and characterized the driving regulatory factors and differentially accessible loci that define each cluster. Within pyramidal neurons, we identified four major clusters, including CA1 and CA3 neurons, and three additional subclusters. We then applied a recently described coaccessibility framework, Cicero, which identified 146,818 links between promoters and putative distal regulatory DNA. Identified coaccessibility networks showed cell-type specificity, shedding light on key dynamic loci that reconfigure to specify hippocampal cell lineages. Lastly, we performed an additional sci-ATAC-seq preparation from cultured hippocampal neurons (899 high-quality cells, 43,532 mean unique reads) that revealed substantial alterations in their epigenetic landscape compared with nuclei from hippocampal tissue. This data set and accompanying analysis tools provide a new resource that can guide subsequent studies of the hippocampus.
BCR-NTRK2 fusion in a low-grade glioma with distinctive morphology and unexpected aggressive behavior
Authors: Jones Karra A. , Bossler Aaron D. , Bellizzi Andrew M. , Snow Anthony N.
Published: April 2019

A 52-yr-old man was found to have a 6.6-cm left frontotemporal mass. Biopsy revealed a low-grade astrocytic neoplasm with significant infiltration and an unusual morphologic appearance. Only rare mitotic figures were seen and the Ki-67 proliferative index was very low. Unexpectedly, the low-grade astrocytoma showed rapid progression within a short time, but subsequent resection showed similar histologic findings to the original biopsy with only slightly more mitoses and a marginally increased Ki-67 proliferative index. Molecular testing performed on the tumor showed no alterations in the IDH1, IDH2, EGFR, or BRAF genes by sequencing, intact 1p/19q by FISH, and a novel BCR-NTRK2 fusion transcript by reverse transcription and anchored multiplex PCR. The patient underwent standard-of-care therapy, both first and second line, for a high-grade glioma because of the aggressive behavior, but the glioma continued to progress despite treatment, and the patient died within 13.5 mo of the original diagnosis. At the time of diagnosis, the BCR-NTRK2 fusion transcript had not been described in solid tumors; however, a recent publication described this fusion transcript in two glioblastomas. Although no approved therapy was available for this patient, FDA approval has now been given for solid tumors with any NTRK gene family fusions. This unexpected molecular finding in a deceptively low-grade-appearing glioma supports the use of expanded molecular testing in gliomas and solid tumors, particularly in instances where targeted therapies are available.
X-ray scattering from a thickness-modulated phase of lipid membranes
Authors: Madhukar S. , Raghunathan V. A.
Published: April 2019

An electron density model for small-angle X-ray scattering from a novel thickness-modulated phase of lipid membranes is presented, and analytical expressions are derived for the intensities of the diffraction peaks. Structural parameters of the membranes in this phase have been determined from a least-squares fit of the calculated intensities to the observed ones. The amplitude of the thickness modulation is found to be about an order of magnitude smaller than the membrane thickness, which accounts for the very small number and very weak intensities of the peaks arising from these modulations.