bluuebunny/crossref_metadata_2025_split huggingface dataset:
Nonrapid eye movement sleep characteristics and relations with motor, memory, and cognitive ability from infancy to preadolescence
Authors: Page Jessica M. , Wakschlag Lauren S. , Norton Elizabeth S. 
Published: November 2021

AbstractSleep plays a critical role in neural neurodevelopment. Hallmarks of sleep reflected in the electroencephalogram during nonrapid eye movement (NREM) sleep are associated with learning processes, cognitive ability, memory, and motor functioning. Research in adults is well‐established; however, the role of NREM sleep in childhood is less clear. Growing evidence suggests the importance of two NREM sleep features: slow‐wave activity and sleep spindles. These features may be critical for understanding maturational change and the functional role of sleep during development. Here, we review the literature on NREM sleep from infancy to preadolescence to provide insight into the network dynamics of the developing brain. The reviewed findings show distinct relations between topographical and maturational aspects of slow waves and sleep spindles; however, the direction and consistency of these relationships vary, and associations with cognitive ability remain unclear. Future research investigating the role of NREM sleep and development would benefit from longitudinal approaches, increased control for circadian and homeostatic influences, and in early childhood, studies recording daytime naps and overnight sleep to yield increased precision for detecting age‐related change. Such evidence could help explicate the role of NREM sleep and provide putative physiological markers of neurodevelopment.
DHHC5 facilitates oligodendrocyte development by palmitoylating and activating STAT3
Authors: Ma Yanchen , Liu Huiqing , Ou Zhimin , Qi Chen , Xing Rui , Wang Shiyun , Han Yinuo , Zhao Tong‐Jin , Chen Ying 
Published: November 2021

AbstractMyelin sheath is an important structure to maintain functions of the nerves in central nervous system. Protein palmitoylation has been established as a sorting determinant for the transport of myelin‐forming proteins to the myelin membrane, however, its function in the regulation of oligodendrocyte development remains unknown. Here, we show that an Asp‐His‐His‐Cys (DHHC) motif‐containing palmitoyl acyltransferases, DHHC5, is involved in the control of oligodendrocyte development. Loss of Zdhhc5 in oligodendrocytes inhibits myelination and remyelination by reducing total myelinating oligodendrocyte population. STAT3 is the primary substrate for DHHC5 palmitoylation in oligodendrocytes. Zdhhc5 ablation reduces STAT3 palmitoylation and suppresses STAT3 phosphorylation and activation. As a result, the transcription of the myelin‐related and anti‐apoptosis genes is inhibited, leading to suppressed oligodendrocyte development and myelination. Our findings demonstrate a key role DHHC5 in controlling myelinogenesis.
Safety, pharmacokinetic, pharmacodynamic and clinical activity of molibresib for the treatment of nuclear protein of the testis carcinoma and other cancers: Results of a Phase I/II open‐label, dose escalation study
Authors: Cousin Sophie , Blay Jean‐Yves , Garcia Irene Braña , de Bono Johann S. , Le Tourneau Christophe , Moreno Victor , Trigo Jose , Hann Christine L. , Azad Arun A. , Im Seock‐Ah , Cassier Philippe A. , French Christopher A. , Italiano Antoine , Keedy Vicki L. , Plummer Ruth , Sablin Marie‐Paule , Hemming Matthew L. , Ferron‐Brady Geraldine , Wyce Anastasia , Khaled Ahmed , Datta Antara , Foley Shawn W. , McCabe Michael T. , Wu Yuehui , Horner Thierry , Kremer Brandon E. , Dhar Arindam , O'Dwyer Peter J. , Shapiro Geoffrey I. , Piha‐Paul Sarina A. 
Published: November 2021

AbstractMolibresib is an orally bioavailable, selective, small molecule BET protein inhibitor. Results from a first time in human study in solid tumors resulted in the selection of a 75 mg once daily dose of the besylate formulation of molibresib as the recommended Phase 2 dose (RP2D). Here we present the results of Part 2 of our study, investigating safety, pharmacokinetics, pharmacodynamics and clinical activity of molibresib at the RP2D for nuclear protein in testis carcinoma (NC), small cell lung cancer, castration‐resistant prostate cancer (CRPC), triple‐negative breast cancer, estrogen receptor‐positive breast cancer and gastrointestinal stromal tumor. The primary safety endpoints were incidence of adverse events (AEs) and serious AEs; the primary efficacy endpoint was overall response rate. Secondary endpoints included plasma concentrations and gene set enrichment analysis (GSEA). Molibresib 75 mg once daily demonstrated no unexpected toxicities. The most common treatment‐related AEs (any grade) were thrombocytopenia (64%), nausea (43%) and decreased appetite (37%); 83% of patients required dose interruptions and 29% required dose reductions due to AEs. Antitumor activity was observed in NC and CRPC (one confirmed partial response each, with observed reductions in tumor size), although predefined clinically meaningful response rates were not met for any tumor type. Total active moiety median plasma concentrations after single and repeated administration were similar across tumor cohorts. GSEA revealed that gene expression changes with molibresib varied by patient, response status and tumor type. Investigations into combinatorial approaches that use BET inhibition to eliminate resistance to other targeted therapies are warranted.
Improved Sensitivity of Ultrasound‐Based Subharmonic Aided Pressure Estimation Using Monodisperse Microbubbles
Authors: van Hoeve Wim , de Vargas Serrano Miguel , te Winkel Lisa , Forsberg Flemming , Dave Jaydev K. , Sarkar Kausik , Wessner Corinne E. , Eisenbrey John R. 
Published: November 2021

ObjectivesSubharmonic aided pressure estimation (SHAPE) has been shown effective for noninvasively measuring hydrostatic fluid pressures in a variety of clinical applications. The objective of this study was to explore potential improvements in SHAPE sensitivity using monodisperse microbubbles.MethodsPopulations of monodisperse microbubbles were created using a commercially available microfluidics device (Solstice Pharmaceuticals). Size distributions were assessed using a Coulter Counter and stability of the distribution following fabrication was evaluated over 24 hours. Attenuation of the microbubble populations from 1 to 10 MHz was then quantified using single element transducers to identify each formulation's resonance frequency. Frequency spectra over increasing driving amplitudes were investigated to determine the nonlinear phases of subharmonic signal generation. SHAPE sensitivity was evaluated in a hydrostatic pressure‐controlled water bath using a Logiq E10 scanner (GE Healthcare).ResultsMonodisperse lipid microbubble suspensions ranging from 2.4 to 5.3 μm in diameter were successfully created and they showed no discernable change in size distribution over 24 hours following activation. Calculated resonance frequencies ranged from 2.1 to 6.3 MHz and showed excellent correlation with microbubble diameter (R2 > 0.99). When investigating microbubble frequency response, subharmonic signal occurrence was shown to begin at 150 kPa peak negative pressure, grow up to 225 kPa, and saturate at approximately 250 kPa. Using the Logiq E10, monodisperse bubbles demonstrated a SHAPE sensitivity of −0.17 dB/mmHg, which was nearly twice the sensitivity of the commercial polydisperse microbubble currently being used in clinical trials.ConclusionsMonodisperse microbubbles have the potential to greatly improve the sensitivity of SHAPE for the noninvasive measurement of hydrostatic pressures.
The Effect of Povidone‐Iodine Nasal Spray on Nasopharyngeal SARS‐CoV‐2 Viral Load: A Randomized Control Trial
Authors: Zarabanda David , Vukkadala Neelaysh , Phillips Katie M. , Qian Z. Jason , Mfuh Kenji O. , Hatter Matthew J. , Lee Ivan T. , Rao Vidya K. , Hwang Peter H. , Domb George , Patel Zara M. , Pinsky Benjamin A. , Nayak Jayakar V. 
Published: November 2021

Objectives/HypothesisTo determine the effect of povidone‐iodine (PVP‐I) nasal sprays on nasopharyngeal (NP) viral load as assessed by cycle threshold (Ct) on quantitative polymerase chain reaction (qPCR) of SARS‐CoV‐2 in outpatients.Study DesignThree arm, triple blinded, randomized, placebo‐controlled clinical trial.MethodsParticipants were randomized within 5 days of testing positive for COVID‐19 to receive nasal sprays containing placebo (0.9% saline), 0.5% PVP‐I, or 2.0% PVP‐I. NP swabs for qPCR analysis were taken at baseline, 1‐hour post‐PVP‐I spray (two sprays/nostril), and 3 days post‐PVP‐I spray (20 sprays/nostril). Symptom and adverse event questionnaires were completed at baseline, day 3, and day 5. University of Pennsylvania Smell Identification Tests (UPSIT) were completed at baseline and day 30.ResultsMean Ct values increased over time in all groups, indicating declining viral loads, with no statistically significant difference noted in the rate of change between placebo and PVP‐I groups. The 2.0% PVP‐I group showed statistically significant improvement in all symptom categories; however, it also reported a high rate of nasal burning. Olfaction via UPSIT showed improvement by at least one category in all groups. There were no hospitalizations or mortalities within 30 days of study enrollment.ConclusionsSaline and low concentration PVP‐I nasal sprays are well tolerated. Similar reductions in SARS‐CoV‐2 NP viral load were seen over time in all groups. All treatment groups showed improvement in olfaction over 30 days. These data suggest that dilute versions of PVP‐I nasal spray are safe for topical use in the nasal cavity, but that PVP‐I does not demonstrate virucidal activity in COVID‐19 positive outpatients.Level of Evidence2 Laryngoscope, 132:2089–2095, 2022
Identification of modes of tumor regression in non‐small cell lung cancer patients during radiotherapy
Authors: Amugongo Lameck Mbangula , Green Andrew , Cobben David , van Herk Marcel , McWilliam Alan , Osorio Eliana Vasquez 
Published: November 2021

AbstractPurposeObserved gross tumor volume (GTV) shrinkage during radiotherapy (RT) raises the question of whether to adapt treatment to changes observed on the acquired images. In the literature, two modes of tumor regression have been described: elastic and non‐elastic. These modes of tumor regression will affect the safety of treatment adaptation. This study applies a novel approach, using routine cone‐beam computed tomography (CBCT) and deformable image registration to automatically distinguish between elastic and non‐elastic tumor regression.MethodsIn this retrospective study, 150 locally advanced non‐small cell lung cancer patients treated with 55 Gray of radiotherapy were included. First, the two modes of tumor regression were simulated. For each mode of tumor regression, one timepoint was simulated. Based on the results of simulated data, the approach used for analysis in real patients was developed. CBCTs were non‐rigidly registered to the baseline CBCT using a cubic B‐spline algorithm, NiftyReg. Next, the Jacobian determinants were computed from the deformation vector fields. To capture local volume changes, 10 Jacobian values were sampled perpendicular to the surface of the GTV, across the lung‐tumor boundary. From the simulated data, we can distinguish elastic from non‐elastic tumor regression by comparing the Jacobian values samples between 5 and 12.5 mm inside and 5 and 12.5 mm outside the planning GTV. Finally, morphometric results were compared between tumors of different histologies.ResultsMost patients (92.3%) in our cohort showed stable disease in the first week of treatment and non‐elastic shrinkage in the later weeks of treatment. At week 2, 125 patients (88%) showed stable disease, three patients (2.1%) disease progression, and 11 patients (8%) regression. By treatment completion, 91 patients (64%) had stable disease, one patient (0.7%) progression and 46 patients (32%) regression. A slight difference in the mode of tumor change was observed between tumors of different histologies.ConclusionOur novel approach shows that it may be possible to automatically quantify and identify global changes in lung cancer patients during RT, using routine CBCT images. Our results show that different regions of the tumor change in different ways. Therefore, careful consideration should be taken when adapting RT.
Cutaneous silent period in ulnar neuropathy at the elbow
Authors: Mondelli Mauro , Aretini Alessandro 
Published: November 2021

AbstractIntroduction/AimsThe cutaneous silent period (CSP) reflects the function of A‐delta sensory fibers. There are few studies on CSP in nerve entrapment syndromes. This study aims to evaluate the neurophysiological abnormalities of small‐diameter sensory fibers in ulnar neuropathy at the elbow (UNE) by means of CSP.MethodsWe consecutively evaluated UNE patients at one electrodiagnostic laboratory. The CSP was obtained upon stimulating the fifth (D5) and third digits, recording from the first dorsal interosseous (FDI) and abductor pollicis brevis (APB) muscles.ResultsWe enrolled 37 UNE patients (mean age 55.4 ± 11.2 y) and 30 controls (mean age 51.2 ± 11.1 y). The combinations of the D5‐APB and D5‐FDI mean onset latencies of CSP were significantly more prolonged in patients (83.7 ± 6.8 and 84.5 ± 8 ms, respectively) than in controls (78.2 ± 8.1 and 79.4 ± 7.6 ms, respectively). The D5‐FDI duration of CSP was shorter in patients (52.2 ± 8.3 ms) than in controls (55.8 ± 7 ms). The mean of the onset latencies of D5‐FDI and D5‐APB was related to the clinical severity (P = .013 and .0025, respectively). D5‐APB and D5‐FDI onset latencies were more prolonged and the duration was shorter in the UNE group with absent ulnar sensory nerve action potentials (SNAPs) and axonal motor damage than in patients with preserved SNAPs and with demyelinating damage.DiscussionCSP was able to demonstrate abnormalities of small‐diameter myelinated sensory fibers. This damage was directly related to UNE severity and to axonal damage of motor fibers. Absence of a sensory large‐diameter fiber response did not exclude preserved residual small fiber conduction.
Gurgeltests an der Universität
Authors: Zbikowski Frauke 
Published: November 2021

AbstractKonstanzer Wissenschaftler haben ein PCR‐Testverfahren entwickelt, und die Universität hat es zum Wintersemester 2020/2021 eingeführt. Die Hintergründe erläutert Daniel Dietrich vom Fachbereich Biologie.
Material modeling for parametric, anisotropic finite strain hyperelasticity based on machine learning with application in optimization of metamaterials
Authors: Fernández Mauricio , Fritzen Felix , Weeger Oliver 
Published: November 2021

AbstractMechanical metamaterials such as open‐ and closed‐cell lattice structures, foams, composites, and so forth can often be parametrized in terms of their microstructural properties, for example, relative densities, aspect ratios, material, shape, or topological parameters. To model the effective constitutive behavior and facilitate efficient multiscale simulation, design, and optimization of such parametric metamaterials in the finite deformation regime, a machine learning‐based constitutive model is presented in this work. The approach is demonstrated in application to elastic beam lattices with cubic anisotropy, which exhibit highly nonlinear effective behaviors due to microstructural instabilities and topology variations. Based on microstructure simulations, the relevant material and topology parameters of selected cubic lattice cells are determined and training data with homogenized stress‐deformation responses is generated for varying parameters. Then, a parametric, hyperelastic, anisotropic constitutive model is formulated as an artificial neural network, extending a recent work of the author extending a recent work of the author, Comput Mech., 2021;67(2):653‐677. The machine learning model is calibrated with the simulation data of the parametric unit cell. The authors offer public access to the simulation data through the GitHub repository
https://github.com/CPShub/sim‐data. For the calibration of the model, a dedicated sample weighting strategy is developed to equally consider compliant and stiff cells and deformation scenarios in the objective function. It is demonstrated that this machine learning model is able to represent and predict the effective constitutive behavior of parametric lattices well across several orders of magnitude. Furthermore, the usability of the approach is showcased by two examples for material and topology optimization of the parametric lattice cell.
Liquid–liquid phase separation in aqueous solutions of poly(ethylene glycol) methacrylate homopolymers
Authors: Constantinou Anna P. , Tall Amy , Li Qian , Georgiou Theoni K. 
Published: November 2021

AbstractHere, the liquid–liquid phase separation (LLPS) in aqueous solutions containing poly(ethylene glycol) (PEG) methacrylate homopolymers is reported for the first time. In this study, the thermoresponse of concentrated solutions of DEGMA60 (two ethylene glycol, EG, groups) TEGMA71 (three EG groups), OEGMA300x (4.5 in average EG groups) of varying molar masses (MM), and OEGMA50028 (nine in average EG groups) is discussed. Interestingly, the temperature of LLPS (TLLPS) is controlled by the length of the PEG side chain, the MM of the OEGMA300x and the polymer concentration. More specifically, the transition temperature decreases with: (i) Decrease in the length of the PEG side chain, (ii) increase in MM of the OEGMA300x, and increase in concentration. In addition, LLPS is also observed in mixtures of OEGMA300x with Pluronic® F127. In conclusion, these systems present a thermally induced LLPS, with the transition temperature being finely tuned to room temperature when DEGMA is used. These systems find potential use in numerous applications, varying from purification to “water‐in‐water” emulsions.
3D Arrangement of Magnetic Particles in Thin Polymer Films Assisted by Magnetically Patterned Exchange Bias Layer Systems
Authors: Koch Iris , Langner Markus , Holzinger Dennis , Merkel Maximilian , Reginka Meike , Huhnstock Rico , Tomiţa Andreea , Jauregui Caballero Claudia , Greiner Andreas , Ehresmann Arno 
Published: November 2021

AbstractThe possibility to arrange and embed magnetic micro‐ and nanoparticles in thin polymer film systems using flat magnetically patterned substrate templates is investigated. In contrast to self‐organized particle rows forming by applying a homogeneous magnetic field, particles adapt to the magnetic field landscape of the substrate's magnetic pattern prior to polymer crosslinking. Crosslinking then fixes the particle positions in the polymer. The process is tested for composites of hydrophobic polydimethylsiloxane (PDMS) and maghemite nanoparticles as well as for hydrophilic polyvinyl alcohol (PVOH) and hydrophilic functionalized, superparamagnetic core–shell microspheres. The substrate template is an exchange bias layer system magnetically patterned into parallel‐stripe domains with in‐plane magnetizations and head‐to‐head/tail‐to‐tail remanent magnetization orientation in adjacent magnetic domains. A high occupancy percentage of magnetic beads on a domain wall as well as anisotropic actuation of the composite is achieved.
Bortezomib is significantly beneficial for de novo pediatric AML patients with low phosphorylation of the NF‐κB subunit RelA
Authors: van Dijk Anneke D. , Hoff Fieke W. , Qiu Yihua , Gerbing Robert B. , Gamis Alan S. , Aplenc Richard , Kolb E. Anders , Alonzo Todd A. , Meshinchi Soheil , Jenkins Gaye N. , de Bont Eveline S. J. M. , Kornblau Steven M. , Horton Terzah M. 
Published: November 2021

AbstractPurpose: The addition of the proteasome inhibitor (PI) bortezomib to standard chemotherapy (ADE: cytarabine [Ara‐C], daunorubicin, and etoposide) did not improve overall outcome of pediatric AML patients in the Children's Oncology Group AAML1031 phase 3 randomized clinical trial (AAML1031) . Bortezomib prevents protein degradation, including RelA via the intracellular NF‐kB pathway. In this study, we hypothesized that subgroups of pediatric AML patients benefitting from standard therapy plus bortezomib (ADEB) could be identified based on pre‐treatment RelA expression and phosphorylation status.Experimental design: RelA‐total and phosphorylation at serine 536 (RelA‐pSer536) were measured in 483 patient samples using reverse phase protein array technology.Results: In ADEB‐treated patients, low‐RelA‐pSer536 was favorably prognostic when compared to high‐RelA‐pSer536 (3‐yr overall survival (OS): 81% vs. 68%, p = 0.032; relapse risk (RR): 30% vs. 49%, p = 0.004). Among low‐RelA‐pSer536 patients, RR significantly decreased with ADEB compared to ADE (RR: 30% vs. 44%, p = 0.035). Correlation between RelA‐pSer536 and 295 other assayed proteins identified a strong correlation with HSF1‐pSer326, another protein previously identified as modifying ADEB response. The combination of low‐RelA‐pSer536 and low‐HSF1‐pSer326 was a significant predictor of ADEB response (3‐yr OS: 86% vs. 67%, p = 0.013).Conclusion and clinical relevance: Bortezomib may improve clinical outcome in a subgroup of AML patients identified by low‐RelA‐pSer536 and low‐HSF1‐pSer326.
Electronic and magnetic properties of one‐dimensional sandwich transition metal‐anthracene molecular wires
Authors: Yang Guang , Zhang Huiyang , Yang Yijun , Wang Yudi , Xv Xinzi , Zhao Xinli , Meng Lijuan , Yao Xiaojing , Zhang Xiuyun , Liu Yongjun 
Published: November 2021

AbstractOrganometallic sandwich complexes have been attracting interest for their potential applications in electronics and spintronics. Here, we systematically studied the structures, electronic and magnetic properties of one‐dimensional (1D) transition metal (TM)‐anthracene (Ant) sandwich molecular wires (SMWs), [TM2Ant]∞, and [TM3Ant]∞ (TM = Ti, V, Cr, Mn), based on density functional theory calculations. Our results show that all the 1D SMWs display normal sandwich configurations with their binding energies closely related to the choice of TM atoms. Excepting 1D [Mn2Ant]∞ and [Fe3Ant]∞ favoring antiferromagnetic ordering, most 1D [TM2Ant]∞ and [TM3Ant]∞ SMWs display robust ferromagnetic (FM) features. Particularly, 1D [Cr3Ant]∞ SMW is revealed to be FM half‐metal (HM), and 1D [Cr2Ant]∞, [Fe2Ant]∞ and [Mn3Ant]∞ SMWs are FM quasi HMs. Of which, high magnetic transform temperature up to 310 and 220 K are identified for 1D [V2Ant]∞ and [Fe2Ant]∞, respectively. Further spintransport calculations demonstrated that 1D Cr2‐Ant and Cr3‐Ant molecule lines are good spintransport devices. Our findings shed light on the properties of 1D Ant based SMWs and propose a new way to design potential electronic and spintronic devices.