bluuebunny/crossref_metadata_2025_split huggingface dataset:
A proof‐of‐concept of parallel single‐drop microextraction for the rapid and sensitive biomonitoring of pesticides in urine
Authors: Mafra Gabriela , Will Camila , Huelsmann Ricardo , Merib Josias , Carasek Eduardo 
Published: February 2021

AbstractIn this study, a lab‐made parallel single‐drop microextraction methodology using the magnetic ionic liquid trihexyltetradecylphosphonium tetrachloromanganate (II) as extraction solvent was developed to determine the pesticides tebuconazole, pendimethalin, dichlorodiphenyltrichloroethane, and dichlorodiphenyldichloroethylene in human urine samples. The experimental setup consisted of a 96‐well plate system containing a set of magnetic pins that allowed for the manipulation of up to 96 samples simultaneously, providing an enhanced drop stability compared to traditional single‐drop microextraction approaches. The optimal conditions employed 5.38 ± 0.55 mg of extraction solvent, 1.5 mL of diluted urine samples (1:10), extraction time of 130 min, and subsequent dilution in 20 μL of acetonitrile. The method exhibited satisfactory analytical performance, with limits of detection of 7.5 μg/L for all analytes and coefficients of determination higher than 0.9955. Intraday and interday precisions ranged from 3 to 17% (n = 3) and 15 to 18% (n = 9), respectively, with relative recovery of analytes ranging from 70 to 122%. The method proposed was successfully applied in two human urine samples and no sign of the analytes was detected. The results demonstrated that the proposed method allowed for cost‐effective and high‐throughput methodology to be explored as a valuable tool in bioanalytical applications.
Substrate inhibition versus product feedback inhibition: In the perspective of single molecule enzyme kinetics
Authors: Dhatt Sharmistha , Nandi Mintu , Chaudhury Pinaki 
Published: February 2021

AbstractIn this work, we study the origin of dynamic disorder in a simple reaction network of substrate inhibition and product feedback inhibition loop. It is well established that dynamic disorder arises in a biochemical reaction network not only due to enzymatic fluctuations influencing the catalytic rate but also due to the physical presence of inhibitors owing to their transition between active and inhibited states of enzymes. But we show here, for networks, where there is explicitly no physical presence of an inhibitor but either the reactant or the product in time course of the reaction possesses to be the one. There is a strikingly noticeable dependence of the randomness parameter on the substrate concentration that can discriminate between both the phenomena under consideration.
Non‐Motor Fluctuations in Parkinson's Disease: Validation of the Non‐Motor Fluctuation Assessment Questionnaire
Authors: Kleiner Galit , Fernandez Hubert H. , Chou Kelvin L. , Fasano Alfonso , Duque Kevin R. , Hengartner Diana , Law Albie , Margolius Adam , Poon Yu‐Yan , Sáenz Farret Michel , Saleh Philip , Vizcarra Joaquin A. , Stebbins Glenn T. , Espay Alberto J. ,   PSG NoMoFA Study Group
Published: February 2021

ABSTRACTBackgroundIn patients with Parkinson's disease (PD), sleep, mood, cognitive, autonomic, and other non‐motor symptoms may fluctuate in a manner similar to motor symptoms.ObjectivesTo validate a final version of a patient‐rated questionnaire that captures the presence and severity of non‐motor fluctuations in levodopa‐treated PD patients (NoMoFA).MethodsWe recruited PD subjects from five movement disorders centers across the US and Canada. We assessed the internal consistency, floor and ceiling effects, test–retest reliability, and concurrent validity of NoMoFA. Classical test theory and item response theory methods informed item reduction and Delphi process yielded a final questionnaire.ResultsTwo hundred subjects and their care‐partners participated in the study (age: 66.4 ± 9.6 years; disease duration: 9 ± 5.5 years; median Hoehn and Yahr [H&Y] OFF: 3 [range 1−5]; mean Unified Parkinson's Disease Rating Scale (UPDRS) III ON score: 27.4 ± 14.9). Acceptability of the scale was adequate. There were floor effects in 8/28 items. Cronbach's alpha was 0.894. While eight items had “item‐to‐total” correlations below the cutoff of 0.4, removing these items did not improve Cronbach's alpha. Test–retest reliability was acceptable (intraclass correlation coefficient [ICC] 0.73; 95% confidence interval, 0.64−0.80). Concurrent validity was adequate with all Spearman's rho values comparing NoMoFA score to other measures of parkinsonian severity showing significance and in the expected direction. A final Delphi panel eliminated one item to avoid redundancy.ConclusionsThe final 27‐item self‐administered NoMoFA is a valid and reliable questionnaire, capturing both static and fluctuating non‐motor symptoms in PD. © 2021 International Parkinson and Movement Disorder Society
Technical Note: Patient‐morphed mesh‐type phantoms to support personalized nuclear medicine dosimetry — a proof of concept study
Authors: Carter Lukas M. , Camilo Ocampo Ramos Juan , Bolch Wesley E. , Lewis Jason S. , Kesner Adam L. 
Published: February 2021

PurposeCurrent standard practice for clinical radionuclide dosimetry utilizes reference phantoms, where defined organ dimensions represent population averages for a given sex and age. Greater phantom personalization would support more accurate dose estimations and personalized dosimetry. Tailoring phantoms is traditionally accomplished using operator‐intensive organ‐level segmentation of anatomic images. Modern mesh phantoms provide enhanced anatomical realism, which has motivated their integration within Monte Carlo codes. Here, we present an automatable strategy for generating patient‐specific phantoms/dosimetry using intensity‐based deformable image registration between mesh reference phantoms and patient CT images. This work demonstrates a proof‐of‐concept personalized dosimetry workflow, presented in comparison to the manual segmentation approach.MethodsA linear attenuation coefficient phantom was generated by resampling the PSRK‐Man reference phantom onto a voxel grid and defining organ regions with corresponding Hounsfield unit (HU) reference values. The HU phantom was co‐registered with a patient CT scan using Plastimatch B‐spline deformable registration. In parallel, major organs were manually contoured to generate a “ground truth” patient‐specific phantom for comparisons. Monte Carlo derived S‐values, which support nuclear medicine dosimetry, were calculated using both approaches and compared.ResultsApplication of the derived B‐spline transform to the polygon vertices comprising the PSRK‐Man yielded a deformed variant more closely matching the patient’s body contour and most organ volumes as‐evaluated by Hausdorff distance and Dice metrics. S‐values computed for fluorine‐18 for the deformed phantom using the Particle and Heavy Ion Transport code System showed improved agreement with those derived from the patient‐specific analog.ConclusionsDeformable registration techniques can be used to create a personalized phantom and better support patient‐specific dosimetry. This method is shown to be easier and faster than manual segmentation. Our study is limited to a proof‐of‐concept scope, but demonstrates that integration of personalized phantoms into clinical dosimetry workflows can reasonably be achieved when anatomical images (CT) are available.
Randomized, Double-Blind, Placebo-Controlled Phase II Study of Yeast-Brachyury Vaccine (GI-6301) in Combination with Standard-of-Care Radiotherapy in Locally Advanced, Unresectable Chordoma
Authors: DeMaria Peter Joseph , Bilusic Marijo , Park Deric M. , Heery Christopher R. , Donahue Renee N. , Madan Ravi A. , Bagheri Mohammad Hadi , Strauss Julius , Shen Victoria , Marté Jennifer L. , Steinberg Seth M. , Schlom Jeffrey , Gilbert Mark R. , Gulley James L. 
Published: February 2021

Abstract

Background
Brachyury is a transcription factor overexpressed in chordoma and is associated with chemotherapy resistance and epithelial-to-mesenchymal transition. GI-6301 is a recombinant, heat-killed Saccharomyces cerevisiae yeast-based vaccine targeting brachyury. A previous phase I trial of GI-6301 demonstrated a signal of clinical activity in chordomas. This trial evaluated synergistic effects of GI-6301 vaccine plus radiation.

Materials and Methods
Adults with locally advanced, unresectable chordoma were treated on a randomized, placebo-controlled trial. Patients received three doses of GI-6301 (80 × 107 yeast cells) or placebo followed by radiation, followed by continued vaccine or placebo until progression. Primary endpoint was overall response rate, defined as a complete response (CR) or partial response (PR) in the irradiated tumor site at 24 months. Immune assays were conducted to evaluate immunogenicity.

Results
Between May 2015 and September 2019, 24 patients enrolled on the first randomized phase II study in chordoma. There was one PR in each arm; no CRs were observed. Median progressive-free survival for vaccine and placebo arms was 20.6 months (95% confidence interval [CI], 5.7–37.5 months) and 25.9 months (95% CI, 9.2–30.8 months), respectively. Hazard ratio was 1.02 (95% CI, 0.38–2.71). Vaccine was well tolerated with no vaccine-related serious adverse events. Preexisting brachyury-specific T cells were detected in most patients in both arms. Most patients developed T-cell responses during therapy, with no difference between arms in frequency or magnitude of response.

Conclusion
No difference in overall response rate was observed, leading to early discontinuation of this trial due to low conditional power to detect statistical difference at the planned end of accrual.

Implications for Practice
Chordoma is a rare neoplasm lacking effective systemic therapies for advanced, unresectable disease. Lack of clinically actionable somatic mutations in chordoma makes development of targeted therapy quite challenging. While the combination of yeast-brachyury vaccine (GI-6301) and standard radiation therapy did not demonstrate synergistic antitumor effects, brachyury still remains a good target for developmental therapeutics in chordoma. Patients and their oncologists should consider early referral to centers with expertise in chordoma (or sarcoma) and encourage participation in clinical trials.
Metastatic Myxofibrosarcoma with Durable Response to Temozolomide Followed by Atezolizumab: A Case Report
Authors: Lambden Jason P. , Kelsten Max F. , Schulte Brian C. , Abbinanti Susan , Hayes John P. , Villaflor Victoria , Agulnik Mark 
Published: February 2021

Abstract

Myxofibrosarcoma (MFS) is a well-recognized histotype of soft tissue sarcomas that generally presents with localized disease. Herein, we describe the case of a patient with metastatic MFS who experienced durable response to sixth-line therapy with temozolomide. Upon further progression, his tumor was notable for a high tumor mutational burden, and he was subsequently treated with seventh-line immunotherapy, atezolizumab, achieving a second durable response. This case highlights the role of immunotherapy after administration of alkylating agents. Review of the literature indicates that recurrent tumors treated with alkylating agents often experience hypermutation as a means of developing resistance and that checkpoint inhibitors are subsequently effective in these tumors.

Key Points
Prospects and Applications of Palladium Nanoparticles in the Cross‐coupling of (hetero)aryl Halides and Related Analogues
Authors: Ayogu Jude I. , Onoabedje Efeturi A. 
Published: February 2021

AbstractDiscovering efficient methods for the formation of carbon‐carbon bonds is a central ongoing theme in organic synthesis. Cross‐coupling reactions catalysed by metal nanoparticles are attractive alternatives to the traditional use of metal counterparts due to the catalytic tunability, selectivity, recyclability and reusability of the nanoparticles. The ongoing search for sustainable processes demands that reusable and environmentally benign catalysts are used. While the advantages of nanoparticles catalysts over bulk catalysts cannot be overemphasised, the problem of sintering, agglomeration and leaching are drawbacks to their full industrial applications. Hence, efforts are being made towards advancing the efficiency of the catalytic nanoparticle systems over the years. This review presents the progress, the challenges and the prospects of palladium nanoparticle with focus on Heck, Suzuki, Hiyama and Sonogashira cross‐coupling reactions involving (hetero) aryl halides and the analogues.
Mechanical and thermal study of 3D printing composite filaments from wind turbine waste
Authors: Rahimizadeh Amirmohammad , Kalman Jordan , Fayazbakhsh Kazem , Lessard Larry 
Published: February 2021

AbstractThe subject of composite waste from the wind turbine blades has become more serious and challenging. Inspired by the recent popularity of the 3D printing industry, this work presents a step‐by‐step recycling solution to manufacture fiber reinforced filaments for fused filament fabrication. Polylactic acid filaments reinforced with 3, 5, and 10 wt% recyclate content are manufactured and tested using thermogravimetric analysis (TGA), and micro computed tomography (μCT). TGA results elucidate that an increase in the recyclate content translates into a reduction in the mean fiber length. Visualizing μCT results, it is confirmed that fibers are predominantly aligned along the filament length. Tensile specimens per ASTM D636 standard are manufactured and tested with results showing an improvement of, respectively, 20% and 28% in the specific tensile strength and modulus compared with pure PLA samples. The mechanical performance of the newly introduced recycled parts is also assessed through a coherent set of theoretical models, where an excellent agreement between the experiments and predictions is observed.
Intensity of usual care physical therapy during inpatient rehabilitation for people with neurologic diagnoses
Authors: DiPasquale Jake , Trammell Molly , Clark Kelly , Fowler Hayden , Callender Librada , Bennett Monica , Swank Chad 
Published: February 2021

AbstractBackgroundEarly, intense rehabilitation is essential to promote recovery after stroke, spinal cord injury (SCI), and traumatic brain injury (TBI). However, intensity of usual care rehabilitation interventions during inpatient rehabilitation are poorly characterized.ObjectiveTo describe the intensity of usual care rehabilitation interventions completed during the subacute phase of recovery from neurologic injury.DesignObservational.SettingInpatient rehabilitation facility.InterventionsTwenty‐two usual care physical therapy interventions were grouped into six categories: gait (four activities), functional (two), strengthening (four), aerobic (six), balance (four), and wheelchair (two).PatientsPatients admitted to inpatient rehabilitation with a primary diagnosis of stroke, SCI or TBI within 6 months of injury.Main Outcome Measure(s)Cardiovascular intensity (physiological and perceived) was recorded during rehabilitation activity sessions. Physiological intensity was assessed by heart rate reserve (HRR) via a Polar A370 Fitness Watch and characterized as very light (<30%), light (30–39%), moderate (40–59%), vigorous (60–89%), and near maximal (≥90%). Perceived intensity was assessed using the Rating of Perceived Exertion scale.ResultsPatients (stroke n = 16 [number of activity sessions = 338/average session duration = 16.4 min]; SCI n = 15 [299/27.4 min]; TBI n = 15 [340/14.2 min]) participated. For patients with stroke, moderate‐to‐vigorous HRR was attained between 42% (aerobic exercise) to 55% (wheelchair propulsion) of activity sessions. For patients with SCI, moderate‐to‐vigorous HRR was attained between 29% (strength training) to 46% (gait training) of activity sessions. For patients with TBI, moderate‐to‐vigorous HRR was attained between 29% (balance activities) to 47% (gait training) of activity sessions. Associations between HRR and rate of perceived exertion were very weak across stroke (r = 0.12), SCI (r = 0.18), and TBI (r = 0.27).ConclusionsPatients with stroke, SCI, and TBI undergoing inpatient rehabilitation achieve moderate‐to‐vigorous intensity during some usual care activities such as gait training. Patient perception of intensity was dissimilar to physiological response.
Revealing the changes of IgG subclass‐specific N‐glycosylation in colorectal cancer progression by high‐throughput assay
Authors: Liu Si , Yu Yuting , Liu Yuanyuan , Lin Jiajing , Fu Yang , Cheng Liming , Liu Xin 
Published: February 2021

AbstractPurposeThe changes of glycosylation of different IgG subclass in colorectal cancer (CRC) were rarely investigated. The authors aimed to use a simple and high‐throughput analytical method to explore the changes of subclass‐specific IgG glycosylation in CRC, and to find the specific glyco‐biomarkers for early detection of this disease.Experimental designSerum samples from 71 cancer patients and 22 benign patients with 50 age‐ and sex‐matched healthy controls were collected from two independent cohorts. Subclass‐specific IgG glycosylation was profiled by MALDI‐MS followed by the structural identification through MALDI‐MS/MS. The exported MS data was automatically and rapidly processed by the self‐developed MATLAB code.ResultsStatistical analysis suggested the significantly decreased galactosylation and remarkably increased agalactosylation of IgG1 or IgG2 in the malignant transformation of CRC, which enables the differentiation between cancer patients and healthy controls. The changes of glycan features were elucidated by the exploration of individual glycopeptides, showing the biantennary fucosylated glycan without galactose (H3N4F1) or with two galactose (H5N4F1) of IgG1 and IgG2 could distinguish cancer group from both benign and control groups.Conclusions and clinical relevanceThrough the simple and high‐throughput procedures, this study revealed the important role of IgG glycopeptides in the premature pathology of CRC.
The fractional energy balance equation
Authors: Lovejoy Shaun , Procyk Roman , Hébert Raphael , Del Rio Amador Lenin 
Published: February 2021

AbstractClassical Energy Balance Equations (EBEs) are differential equations of integer order (h = 1), here we generalize this to fractional orders: the Fractional EBE (FEBE, 0 < h ≤ 1). In the FEBE, when the Earth is perturbed by a forcing, the temperature relaxes to equilibrium via a slow power‐law process: h = 1 is the exceptional (but standard) exponential case. Our FEBE derivation is phenomenological, it complements derivations based on the classical continuum mechanics heat equation (that imply h = 1/2 for the surface temperature) and of the more general Fractional Heat Equation which allows for 0 < h < 2. Unlike some of the earlier “scale free” models based purely on scaling, the FEBE has an extra blackbody radiation term that allows for energy balance. It therefore has two scaling regimes (not one), it has the advantage of being stable to infinitesimal step‐function perturbations and it has a finite Equilibrium Climate Sensitivity. We solve the FEBE using Green's functions, whose high‐ and low‐frequency limits are power laws with a relaxation scale transition (several years). When stochastically forced, the high‐frequency parts of the internal variability are fractional Gaussian noises that can be used for monthly and seasonal forecasts; when deterministically forced, the low‐frequency response describes the consequences of anthropogenic forcing, it has been used for climate projections. The FEBE introduces complex climate sensitivities that are convenient for handling periodic (especially annual) forcing. The FEBE obeys Newton's law of cooling, but the heat flux crossing a surface nonetheless depends on the fractional time derivative of the temperature. The FEBE's ratio of transient to equilibrium climate sensitivity is compatible with GCM estimates. A simple ramp forcing model of the industrial‐epoch warming combining deterministic (external) with stochastic (internal) forcing is statistically validated against centennial‐scale temperature series.
Molecular trees with extremal values of Sombor indices
Authors: Deng Hanyuan , Tang Zikai , Wu Renfang 
Published: February 2021

AbstractBased on elementary geometry, a class of novel graph invariants was introduced by Gutman, of which the simplest is the Sombor index SO, defined as , where G = (V, E) is a simple graph and dG(v) denotes the degree of v in G. In this paper, the chemical importance of the Sombor index is investigated and it is shown that the new index is useful in predicting physico‐chemical properties with high accuracy compared to some well‐established and often used indices. We obtain a sharp upper bound for the Sombor index among all molecular trees with fixed numbers of vertices, and characterize those molecular trees achieving the extremal value. Also, we obtain the extremal values of the reduced Sombor index for molecular trees.
Emergent learning during crisis: A case study of the arctic circle border crossing at Storskog in Norway
Authors: Steen Riana , Rønningsbakk Bernt 
Published: February 2021

AbstractThis explorative study addresses emergent learning related to the refugee crisis in Norway in 2015. We define emergent learning as organizational learning that occurs as a benign by‐product of solving immediate problems as they arise. The study is based mainly on secondary data; media coverage, public evaluation report, and other public documentation. The results from empirical research confirm that emergent learning has had a profound influence on how the Storskog crisis in 2015 was managed. Our findings also reveal suboptimal problem solving, insufficient management capacity, and public organizations who were not prepared to respond fast enough.
Adaptive hierarchical sliding mode control for full nonlinear dynamics of uncertain ridable ballbots under input saturation
Authors: Do Van‐Thach , Lee Soon‐Geul , Van Mien 
Published: February 2021

AbstractThis research proposes a nonlinear adaptive controller based on a hierarchical sliding mode control (HSMC) framework to stabilize the operation of a ridable ballbot based on the full nonlinear dynamics (FND). The FND of ballbots is a multiple‐input‐multiple‐output underactuated system with a non‐invertible input matrix. By applying a novel approach to transform the FND into two subsystems, the invertibility of the input matrix of the transformed subsystems can be guaranteed. Thus, an HSMC scheme can be applied to control the ridable ballbot system based on stabilizing the transformed subsystems. In addition, to improve the robustness of HSMC, a new adaptive law is proposed to deal with the effects of exogenous disturbances and parameter variations on the modeled dynamics. Chattering and actuator saturation phenomena are also reduced or avoided with the proposed controller. Comparative simulations are conducted to demonstrate the merit features of the proposed approach and the robustness of the developed control algorithm.
Palladium‐ Catalyzed C−P Bond Forming Reactions: An Overview
Authors: Kanchana U. S. , Diana Elizabeth J. , Mathew Thomas V. , Anilkumar Gopinathan 
Published: February 2021

AbstractTransition metal catalyzed synthesis of organo‐phosphorus compounds show rapid advances. Due to the powerful bond‐forming ability under mild reaction conditions and wide functional group tolerance made palladium‐catalyzed reactions an inevitable tool for the synthesis of various structurally diversed complex molecules. This review is an account of palladium‐catalyzed Carbon‐Phosphorous bond forming reactions. For proving an insight into the synthetic and mechanistic knowledge of its chemistry some of the mechanisms of this type of catalysis are also added. This review focuses on the recent advances in Palladium‐catalyzed C−P bond forming reactions and covers literature from 2001 to 2020.