bluuebunny/crossref_metadata_2025 huggingface dataset:
Teaching repertoires and pedagogical improvisation in music teacher practices
Authors: Espeland Åsmund , Stige Brynjulf
Published: March 2021

In this article, we describe the characteristics of repertoires in music teaching and discuss how these repertoires are related to pedagogical improvisation. The empirical background for the article is classroom observations and interviews with two experienced music teachers. Video-taped examples of teacher repertoires and improvisational teaching practices are included in the article, where we argue that repertoires should be viewed as emerging practices. They can be identified and categorised as ‘techniques’ and ‘teaching acts’ performed by the teachers in constant interplay with the pupils within the context of overall learning activities in the music classroom.
Identification of patient variables that are associated with ventricular end-diastolic pressure before the bidirectional Glenn operation
Authors: Schwartz Matthew C. , Karunanandaa Aravinth , Anderson William E. , Herlong J. Rene , Paolillo Joseph , Wallis Gonzalo , Kirshbom Paul , Maxey Thomas S.
Published: March 2021

Introduction:

Systemic ventricular end-diastolic pressure is important in patients with single ventricle heart disease. Predictors of an elevated systemic ventricular end-diastolic pressure prior to bidirectional Glenn operation have been incompletely identified.

Methods:

All patients who underwent bidirectional Glenn operation operation at our centre between January 2007 and March 2017 were retrospectively identified and patient variables were extracted. For patients who had undergone Fontan operation at the time of this study, post-Fontan patient variables were also extracted.

Results:

One-hundred patients were included with a median age at pre-bidirectional Glenn operation catheterisation of 4.5 months. In total, 71 (71%) patients had a systemic right ventricle. At the pre-bidirectional Glenn operation catheterisation, the mean systemic ventricular end-diastolic pressure was higher amongst those with systemic right ventricle compared to left ventricle (9.1 mmHg ± 2.1 versus 7.7 ± 2.7 mmHg, p < 0.01). On univariate analysis, pre-bidirectional Glenn operation systemic ventricular end-diastolic pressure was positively associated with the presence of a systemic right ventricle (p < 0.01), history of recoarctation (p = 0.03), history of Norwood operation (p = 0.04), and ventricular systolic pressure (p < 0.01). On multivariate analysis, systemic ventricular end-diastolic pressure was positively associated with the presence of a systemic right ventricle (p < 0.01) and ventricular systolic pressure (p < 0.01). Amongst those who had undergone Fontan operation at the time of study (n = 49), those with a higher pre-bidirectional Glenn operation systemic ventricular end-diastolic pressure were more likely to have experienced death, transplantation, or listed for transplantation (p = 0.02) and more likely to have had heart failure symptoms (p = 0.04) at a mean time from Fontan of 5.2 years ± 1.3.

Conclusions:

In patients undergoing bidirectional Glenn operation operation, the volume-loaded, pre-bidirectional Glenn operation state may expose diastolic dysfunction that has prognostic value.
Comparison of motor outcomes between preschool children with univentricular and biventricular critical heart disease not diagnosed with cerebral palsy or acquired brain injury
Authors: Ricci M. Florencia , Fung Alastair , Moddemann Diane , Micek Victoria , Bond Gwen Y. , Guerra Gonzalo G. , Day Chelsea , Robertson Charlene M.T. ,   for the Western Canadian Complex Pediatric Therapies Follow-up Program
Published: March 2021

This comparison study of two groups within an inception cohort aimed to compare the frequency of motor impairment between preschool children with univentricular and biventricular critical congenital heart disease (CHD) not diagnosed with cerebral palsy/acquired brain injury, describe and compare their motor profiles and explore predictors of motor impairment in each group.

Children with an intellectual quotient <70 or cerebral palsy/acquired brain injury were excluded. Motor skills were assessed with the Movement Assessment Battery for Children-2. Total scores <5th percentile indicated motor impairment. Statistical analysis included χ2 test and multiple logistic regression analysis.

At a mean age of 55.4 (standard deviation 3.77) months, motor impairment was present in 11.8% of those with biventricular critical CHD, and 32.4% (p < 0.001) of those with univentricular critical CHD. The greatest difference between children with biventricular and univentricular CHD was seen in total test scores 8.73(2.9) versus 6.44(2.8) (p < 0.01) and in balance skills, 8.84 (2.8) versus 6.97 (2.5) (p = 0.001). Manual dexterity mean scores of children with univentricular CHD were significantly below the general population mean (>than one standard deviation). Independent odds ratio for motor impairment in children with biventricular critical CHD was presence of chromosomal abnormality, odds ratio 10.9 (CI 2.13–55.8) (p = 0.004); and in children with univentricular critical CHD odds ratio were: postoperative day 1–5 highest lactate (mmol/L), OR: 1.65 (C1.04–2.62) (p = 0.034), and dialysis requirement any time before the 4.5-year-old assessment, OR: 7.8 (CI 1.08–56.5) (p = 0.042).

Early assessment of motor skills, particularly balance and manual dexterity, allows for intervention and supports that can address challenges during the school years.
The Historical Rawls: Introduction
Authors: Smith Sophie , Bejan Teresa M. , Zimmermann Annette
Published: March 2021

John Rawls (1921–2002) and his work are now squarely a subject for history. In the more than fifteen years since his death, a rich body of scholarship has emerged which attempts, in different ways, to understand the nature, development, and impact of Rawls's thought from a variety of historical perspectives. With 2021 marking fifty years since A Theory of Justice (1971) was first published, this special forum examines what we here call the “historical Rawls.”
Historicizing Rawls
Authors: Smith Sophie
Published: March 2021

The opening, in 2004, of John Rawls's personal archive prompted a new wave of Rawls scholarship. This work has deepened our understanding of the development and impact of Rawls's ideas and of the broader contours of twentieth-century analytical political philosophy. This article places these recent archival histories, for the first time, in the context of the longer history of attempts to historicize Rawls, beginning with the publication ofA Theory of Justicefifty years ago. Doing so does three things. First, it shows that early readers were more interested in how to think historically about Rawls than is sometimes assumed. Second, it reveals that partisan accounts of Rawls's place in history, popularized by those close to him, have sometimes made their way into the archival studies. Third and finally, it offers an opportunity to rethink how the twentieth-century history of political philosophy and political theory is often told.
John Rawls and Oxford Philosophy
Authors: Krishnan Nikhil
Published: March 2021

Scholarship historicizing John Rawls has put paid to the view that his work was without precedent. This article sets out to find out why, then, ATheory of Justicestirred such philosophical excitement, even among British philosophers in a position to recognize its antecedents. I advance the view that his work is helpfully understood as fulfilling the promise of the “naturalist” revival in ethics begun at Oxford by Philippa Foot and Elizabeth Anscombe. After briefly surveying the development of analytic philosophy, I argue that Rawls's contribution was to reconceive ethics so that it was an investigation neither of an independent ethical reality nor of the logic of moral language. Rather, it was concerned with a class of facts about ourselves. Rawls's practice of ethics adopts as its central focus the ongoing human practice of justification. I place Rawls's turn from religious faith to justification between persons alongside similar shifts in Plato'sEuthyphroand in the biographies of Kant and Sidgwick. I try to show the distinctiveness of Rawls's focus by contrasting his search for human self-understanding with the project of R. M. Hare, his most prominent non-naturalist critic, who charged Rawls with offering an inadequate account of the authority of ethics.
Photochemical and Microbial Degradation of Chromophoric Dissolved Organic Matter Exported From Tidal Marshes
Authors: Logozzo Laura , Tzortziou Maria , Neale Patrick , Clark J. Blake
Published: March 2021

Wetlands export chromophoric dissolved organic matter (CDOM) to estuaries, where CDOM is removed and transformed through biotic and abiotic process, subsequently impacting nutrient cycling, light availability, ecosystem metabolism, and phytoplankton activity. We examined the bioavailability and photoreactivity of CDOM exported from four Chesapeake Bay tidal marshes across three seasons and along an estuarine salinity gradient using three incubation treatments: 14‐day microbial (MD), 7‐day combined photochemical/microbial (PB + MD), and 7‐day microbial incubation after photobleaching (MD after PB). CDOM absorption at 300 nm (aCDOM300) and dissolved organic carbon (DOC) concentrations showed strong seasonality, with minima in winter, but CDOM quality (absorption spectral slopes, fluorescence component ratios) was less variable seasonally. PB + MD over 7 days decreased aCDOM300 (−56.0%), humic‐like fluorescence (−67.6%), and DOC (−17.8%), but increased the spectral slope ratio SR (=S275–295/S300–350) (+94.8%), suggesting a decrease in CDOM molecular weight. Photochemistry dominated the PB + MD treatment. Photoreactivity was greater during the winter and in marsh/watershed versus down‐estuary sites, likely due to less previous light exposure. Prior photobleaching increased the bioavailability of marsh‐exported CDOM, resulting in a greater loss of aCDOM300 and DOC, and a greater increase in humic‐like fluorescence (−6.0%, −5.9%, and +18.4% change, respectively, over 7‐day MD after PB incubations, vs. −2.8%, −5.5%, and +2.6% change, respectively, over 14‐day MD incubations). CDOM exported from a marsh downstream of a major wastewater treatment plant showed the greatest photoreactivity and bioavailability. This highlights the significance of human activity on estuarine CDOM quality and biogeochemical cycles.
Non‐Gaussian Parameter Inference for Hydrogeological Models Using Stein Variational Gradient Descent
Authors: Ramgraber Maximilian , Weatherl Robin , Blumensaat Frank , Schirmer Mario
Published: March 2021

The sustainable management of groundwater demands a faithful characterization of the subsurface. This, in turn, requires information which is generally not readily available. To bridge the gap between data need and availability, numerical models are often used to synthesize plausible scenarios not only from direct information but also from additional, indirect data. Unfortunately, the resulting system characterizations will rarely be unique. This poses a challenge for practical parameter inference: computational limitations often force modelers to resort to methods based on questionable assumptions of Gaussianity, which do not reproduce important facets of ambiguity such as Pareto fronts or multimodality. In search of a remedy, an alternative could be found in Stein Variational Gradient Descent (SVGD), a recent development in the field of statistics. This ensemble‐based method iteratively transforms a set of arbitrary particles into samples of a potentially non‐Gaussian posterior, provided the latter is sufficiently smooth. A prerequisite for this method is knowledge of the Jacobian, which is usually exceptionally expensive to evaluate. To address this issue, we propose an ensemble‐based, localized approximation of the Jacobian. We demonstrate the performance of the resulting algorithm in two cases: a simple, bimodal synthetic scenario, and a complex numerical model based on a real world, prealpine catchment. Promising results in both cases—even when the ensemble size is smaller than the number of parameters—suggest that SVGD can be a valuable addition to hydrogeological parameter inference.
Recovery of logged forest fragments in a human-modified tropical landscape during the 2015-16 El Niño
Authors: Nunes Matheus Henrique , Jucker Tommaso , Riutta Terhi , Svátek Martin , Kvasnica Jakub , Rejžek Martin , Matula Radim , Majalap Noreen , Ewers Robert M. , Swinfield Tom , Valbuena Rubén , Vaughn Nicholas R. , Asner Gregory P. , Coomes David A.
Published: March 2021

The past 40 years in Southeast Asia have seen about 50% of lowland rainforests converted to oil palm and other plantations, and much of the remaining forest heavily logged. Little is known about how fragmentation influences recovery and whether climate change will hamper restoration. Here, we use repeat airborne LiDAR surveys spanning the hot and dry 2015-16 El Niño Southern Oscillation event to measure canopy height growth across 3,300 ha of regenerating tropical forests spanning a logging intensity gradient in Malaysian Borneo. We show that the drought led to increased leaf shedding and branch fall. Short forest, regenerating after heavy logging, continued to grow despite higher evaporative demand, except when it was located close to oil palm plantations. Edge effects from the plantations extended over 300 metres into the forests. Forest growth on hilltops and slopes was particularly impacted by the combination of fragmentation and drought, but even riparian forests located within 40 m of oil palm plantations lost canopy height during the drought. Our results suggest that small patches of logged forest within plantation landscapes will be slow to recover, particularly as ENSO events are becoming more frequent.
A self-sustainable wearable multi-modular E-textile bioenergy microgrid system
Authors: Yin Lu , Kim Kyeong Nam , Lv Jian , Tehrani Farshad , Lin Muyang , Lin Zuzeng , Moon Jong-Min , Ma Jessica , Yu Jialu , Xu Sheng , Wang Joseph
Published: March 2021

Despite the fast development of various energy harvesting and storage devices, their judicious integration into efficient, autonomous, and sustainable wearable systems has not been widely explored. Here, we introduce the concept and design principles of e-textile microgrids by demonstrating a multi-module bioenergy microgrid system. Unlike earlier hybrid wearable systems, the presented e-textile microgrid relies solely on human activity to work synergistically, harvesting biochemical and biomechanical energy using sweat-based biofuel cells and triboelectric generators, and regulating the harvested energy via supercapacitors for high-power output. Through energy budgeting, the e-textile system can efficiently power liquid crystal displays continuously or a sweat sensor-electrochromic display system in pulsed sessions, with half the booting time and triple the runtime in a 10-min exercise session. Implementing “compatible form factors, commensurate performance, and complementary functionality” design principles, the flexible, textile-based bioenergy microgrid offers attractive prospects for the design and operation of efficient, sustainable, and autonomous wearable systems.
Apparent nosocomial adaptation of Enterococcus faecalis predates the modern hospital era
Authors: Pöntinen Anna K. , Top Janetta , Arredondo-Alonso Sergio , Tonkin-Hill Gerry , Freitas Ana R. , Novais Carla , Gladstone Rebecca A. , Pesonen Maiju , Meneses Rodrigo , Pesonen Henri , Lees John A. , Jamrozy Dorota , Bentley Stephen D. , Lanza Val F. , Torres Carmen , Peixe Luisa , Coque Teresa M. , Parkhill Julian , Schürch Anita C. , Willems Rob J. L. , Corander Jukka
Published: March 2021

Enterococcus faecalis is a commensal and nosocomial pathogen, which is also ubiquitous in animals and insects, representing a classical generalist microorganism. Here, we study E. faecalis isolates ranging from the pre-antibiotic era in 1936 up to 2018, covering a large set of host species including wild birds, mammals, healthy humans, and hospitalised patients. We sequence the bacterial genomes using short- and long-read techniques, and identify multiple extant hospital-associated lineages, with last common ancestors dating back as far as the 19th century. We find a population cohesively connected through homologous recombination, a metabolic flexibility despite a small genome size, and a stable large core genome. Our findings indicate that the apparent hospital adaptations found in hospital-associated E. faecalis lineages likely predate the “modern hospital” era, suggesting selection in another niche, and underlining the generalist nature of this nosocomial pathogen.
Evolution of the locomotor skeleton in Anolis lizards reflects the interplay between ecological opportunity and phylogenetic inertia
Authors: Feiner Nathalie , Jackson Illiam S. C. , Stanley Edward L. , Uller Tobias
Published: March 2021

Anolislizards originated in continental America but have colonized the Greater Antillean islands and recolonized the mainland, resulting in three major groups (Primary and Secondary Mainland and Greater Antillean). The adaptive radiation in the Greater Antilles has famously resulted in the repeated evolution of ecomorphs. Yet, it remains poorly understood to what extent this island radiation differs from diversification on the mainland. Here, we demonstrate that the evolutionary modularity between girdles and limbs is fundamentally different in the Greater Antillean and Primary MainlandAnolis. This is consistent with ecological opportunities on islands driving the adaptive radiation along distinct evolutionary trajectories. However, Greater AntilleanAnolisshare evolutionary modularity with the group that recolonized the mainland, demonstrating a persistent phylogenetic inertia. A comparison of these two groups support an increased morphological diversity and faster and more variable evolutionary rates on islands. These macroevolutionary trends of the locomotor skeleton inAnolisillustrate that ecological opportunities on islands can have lasting effects on morphological diversification.
Time-resolved single-cell analysis of Brca1 associated mammary tumourigenesis reveals aberrant differentiation of luminal progenitors
Authors: Bach Karsten , Pensa Sara , Zarocsinceva Marija , Kania Katarzyna , Stockis Julie , Pinaud Silvain , Lazarus Kyren A. , Shehata Mona , Simões Bruno M. , Greenhalgh Alice R. , Howell Sacha J. , Clarke Robert B. , Caldas Carlos , Halim Timotheus Y. F. , Marioni John C. , Khaled Walid T.
Published: March 2021

It is unclear how genetic aberrations impact the state of nascent tumour cells and their microenvironment. BRCA1 driven triple negative breast cancer (TNBC) has been shown to arise from luminal progenitors yet little is known about how BRCA1 loss-of-function (LOF) and concomitant mutations affect the luminal progenitor cell state. Here we demonstrate how time-resolved single-cell profiling of genetically engineered mouse models before tumour formation can address this challenge. We found that perturbing Brca1/p53 in luminal progenitors induces aberrant alveolar differentiation pre-malignancy accompanied by pro-tumourigenic changes in the immune compartment. Unlike alveolar differentiation during gestation, this process is cell autonomous and characterised by the dysregulation of transcription factors driving alveologenesis. Based on our data we propose a model where Brca1/p53 LOF inadvertently promotes a differentiation program hardwired in luminal progenitors, highlighting the deterministic role of the cell-of-origin and offering a potential explanation for the tissue specificity of BRCA1 tumours.
Naturally acquired blocking human monoclonal antibodies to Plasmodium vivax reticulocyte binding protein 2b
Authors: Chan Li-Jin , Gandhirajan Anugraha , Carias Lenore L. , Dietrich Melanie H. , Vadas Oscar , Visentin Remy , França Camila T. , Menant Sebastien , Soldati-Favre Dominique , Mueller Ivo , King Christopher L. , Tham Wai-Hong
Published: March 2021

Plasmodium vivax preferentially invades reticulocytes and recognition of these cells is mediated by P. vivax Reticulocyte Binding Protein 2b (PvRBP2b) binding to human Transferrin receptor 1 (TfR1) and Transferrin (Tf). Longitudinal cohort studies in Papua New Guinea, Thailand and Brazil show that PvRBP2b antibodies are correlated with protection against P. vivax infection and disease. Here, we isolate and characterize anti-PvRBP2b human monoclonal antibodies from two individuals in Cambodia with natural P. vivax infection. These antibodies bind with high affinities and map to different regions of PvRBP2b. Several human antibodies block PvRBP2b binding to reticulocytes and inhibit complex formation with human TfR1-Tf. We describe different structural mechanisms for functional inhibition, including either steric hindrance with TfR1-Tf or the reticulocyte membrane. These results show that naturally acquired human antibodies against PvRBP2b can inhibit its function which is important for P. vivax invasion.
RALYL increases hepatocellular carcinoma stemness by sustaining the mRNA stability of TGF-β2
Authors: Wang Xia , Wang Jin , Tsui Yu-Man , Shi Chaoran , Wang Ying , Zhang Xin , Yan Qian , Chen Miao , Jiang Chen , Yuan Yun-Fei , Wong Chun-Ming , Liu Ming , Feng Zeng-yu , Chen Honglin , Ng Irene Oi Lin , Jiang Lingxi , Guan Xin-Yuan
Published: March 2021

Growing evidences suggest that cancer stem cells exhibit many molecular characteristics and phenotypes similar to their ancestral progenitor cells. In the present study, human embryonic stem cells are induced to differentiate into hepatocytes along hepatic lineages to mimic liver development in vitro. A liver progenitor specific gene, RALY RNA binding protein like (RALYL), is identified. RALYL expression is associated with poor prognosis, poor differentiation, and metastasis in clinical HCC patients. Functional studies reveal that RALYL could promote HCC tumorigenicity, self-renewal, chemoresistance, and metastasis. Moreover, molecular mechanism studies show that RALYL could upregulate TGF-β2 mRNA stability by decreasing N6-methyladenosine (m6A) modification. TGF-β signaling and the subsequent PI3K/AKT and STAT3 pathways, upregulated by RALYL, contribute to the enhancement of HCC stemness. Collectively, RALYL is a liver progenitor specific gene and regulates HCC stemness by sustaining TGF-β2 mRNA stability. These findings may inspire precise therapeutic strategies for HCC.
Tumor-penetrating therapy for β5 integrin-rich pancreas cancer
Authors: Hurtado de Mendoza Tatiana , Mose Evangeline S. , Botta Gregory P. , Braun Gary B. , Kotamraju Venkata R. , French Randall P. , Suzuki Kodai , Miyamura Norio , Teesalu Tambet , Ruoslahti Erkki , Lowy Andrew M. , Sugahara Kazuki N.
Published: March 2021

Pancreatic ductal adenocarcinoma (PDAC) is characterized by marked desmoplasia and drug resistance due, in part, to poor drug delivery to extravascular tumor tissue. Here, we report that carcinoma-associated fibroblasts (CAFs) induce β5 integrin expression in tumor cells in a TGF-β dependent manner, making them an efficient drug delivery target for the tumor-penetrating peptide iRGD. The capacity of iRGD to deliver conjugated and co-injected payloads is markedly suppressed when β5 integrins are knocked out in the tumor cells. Of note, β5 integrin knock-out in tumor cells leads to reduced disease burden and prolonged survival of the mice, demonstrating its contribution to PDAC progression. iRGD significantly potentiates co-injected chemotherapy in KPC mice with high β5 integrin expression and may be a powerful strategy to target an aggressive PDAC subpopulation.
A noncanonical AR addiction drives enzalutamide resistance in prostate cancer
Authors: He Yundong , Wei Ting , Ye Zhenqing , Orme Jacob J. , Lin Dong , Sheng Haoyue , Fazli Ladan , Jeffrey Karnes R. , Jimenez Rafael , Wang Liguo , Wang Liewei , Gleave Martin E. , Wang Yuzhuo , Shi Lei , Huang Haojie
Published: March 2021

Resistance to next-generation anti-androgen enzalutamide (ENZ) constitutes a major challenge for the treatment of castration-resistant prostate cancer (CRPC). By performing genome-wide ChIP-seq profiling in ENZ-resistant CRPC cells we identify a set of androgen receptor (AR) binding sites with increased AR binding intensity (ARBS-gained). While ARBS-gained loci lack the canonical androgen response elements (ARE) and pioneer factor FOXA1 binding motifs, they are highly enriched with CpG islands and the binding sites of unmethylated CpG dinucleotide-binding protein CXXC5 and the partner TET2. RNA-seq analysis reveals that both CXXC5 and its regulated genes including ID1 are upregulated in ENZ-resistant cell lines and these results are further confirmed in patient-derived xenografts (PDXs) and patient specimens. Consistent with the finding that ARBS-gained loci are highly enriched with H3K27ac modification, ENZ-resistant PCa cells, organoids, xenografts and PDXs are hyper-sensitive to NEO2734, a dual inhibitor of BET and CBP/p300 proteins. These results not only reveal a noncanonical AR function in acquisition of ENZ resistance, but also posit a treatment strategy to target this vulnerability in ENZ-resistant CRPC.
Author Correction: Recursive patterns in online echo chambers
Authors: Brugnoli Emanuele , Cinelli Matteo , Quattrociocchi Walter , Scala Antonio
Published: March 2021

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
A study of quantum Berezinskii–Kosterlitz–Thouless transition for parity-time symmetric quantum criticality
Authors: Sarkar Sujit
Published: March 2021

The Berezinskii–Kosterlitz–Thouless (BKT) mechanism governs the critical behavior of a wide range of many-body systems. We show here that this phenomenon is not restricted to conventional many body system but also for the strongly correlated parity-time (PT) symmetry quantum criticality. We show explicitly behaviour of topological excitation for the real and imaginary part of the potential are different through the analysis of second order and third order renormalization group (RG). One of the most interesting feature that we observe from our study the presence of hidden QBKT and also conventional QBKT for the real part of the potential whereas there is no such evidence for the imaginary part of the potential. We also present the exact solution for the RG flow lines. We show explicitly how the physics of single field double frequencies sine-Gordon Hamiltonian effectively transform to the dual field double frequencies sine-Gordon Hamiltonian for a certain regime of parameter space. This is the first example in any quantum many body systems. We present the results of second order and third order RG flow results explicitly for the real and imaginary part of the potential. This PT symmetric system can be experimentally tested in ultra-cold atoms. This work provides a new perspective for the PT symmetric quantum criticality.
Mathematical model for the thermal enhancement of radiation response: thermodynamic approach
Authors: De Mendoza Adriana M. , Michlíková Soňa , Berger Johann , Karschau Jens , Kunz-Schughart Leoni A. , McLeod Damian D.
Published: March 2021

Radiotherapy can effectively kill malignant cells, but the doses required to cure cancer patients may inflict severe collateral damage to adjacent healthy tissues. Recent technological advances in the clinical application has revitalized hyperthermia treatment (HT) as an option to improve radiotherapy (RT) outcomes. Understanding the synergistic effect of simultaneous thermoradiotherapy via mathematical modelling is essential for treatment planning. We here propose a theoretical model in which the thermal enhancement ratio (TER) relates to the cell fraction being radiosensitised by the infliction of sublethal damage through HT. Further damage finally kills the cell or abrogates its proliferative capacity in a non-reversible process. We suggest the TER to be proportional to the energy invested in the sensitisation, which is modelled as a simple rate process. Assuming protein denaturation as the main driver of HT-induced sublethal damage and considering the temperature dependence of the heat capacity of cellular proteins, the sensitisation rates were found to depend exponentially on temperature; in agreement with previous empirical observations. Our findings point towards an improved definition of thermal dose in concordance with the thermodynamics of protein denaturation. Our predictions well reproduce experimental in vitro and in vivo data, explaining the thermal modulation of cellular radioresponse for simultaneous thermoradiotherapy.
Functional connectivity and upper limb function in patients after pediatric arterial ischemic stroke with contralateral corticospinal tract wiring
Authors: Steiner Leonie , Homan Stephanie , Everts Regula , Federspiel Andrea , Kamal Sandeep , Rodriguez Juan Antonio Delgado , Kornfeld Salome , Slavova Nedelina , Wiest Roland , Kaelin-Lang Alain , Steinlin Maja , Grunt Sebastian
Published: March 2021

To develop individualized motor rehabilitation, knowledge of the relationship between neuroplastic reorganization and motor recovery after pediatric arterial ischemic stroke (AIS) is crucial. Thus, we investigated functional connectivity in patients after AIS with good motor outcome and in patients with hemiparesis compared with typically developing peers. We included 18 patients (n = 9 with hemiparesis, n = 9 with good motor outcome) with pediatric AIS in the chronic phase (≥ 2 years after diagnosis, diagnosed > 16 years) and 18 peers matched by age and gender. Participants underwent a standardized motor assessment, single-pulse transcranial magnetic stimulation to determine the type of corticospinal tract wiring, and resting-state functional magnetic resonance imaging to examine motor network connectivity. Corticospinal tract wiring was contralateral in all participants. Patients with hemiparesis had lower interhemispheric connectivity strength compared with patients with good clinical outcome and peers. Patients with good clinical outcome had higher intrahemispheric connectivity strength compared with peers. Further, higher intrahemispheric connectivity was related to better motor outcome in patients. Our findings suggest that better motor outcome after pediatric AIS is related to higher motor network connectivity strength. Thus, resting-state functional connectivity might be predictive for motor recovery after pediatric AIS.
Human cerebral organoids as a therapeutic drug screening model for Creutzfeldt–Jakob disease
Authors: Groveman Bradley R. , Ferreira Natalia C. , Foliaki Simote T. , Walters Ryan O. , Winkler Clayton W. , Race Brent , Hughson Andrew G. , Zanusso Gianluigi , Haigh Cathryn L.
Published: March 2021

Creutzfeldt–Jakob Disease (CJD) is a fatal, currently incurable, neurodegenerative disease. The search for candidate treatments would be greatly facilitated by the availability of human cell-based models of prion disease. Recently, an induced pluripotent stem cell derived human cerebral organoid model was shown to take up and propagate human CJD prions. This model offers new opportunities to screen drug candidates for the treatment of human prion diseases in an entirely human genetic background. Here we provide the first evidence that human cerebral organoids can be a viable model for CJD drug screening by using an established anti-prion compound, pentosan polysulfate (PPS). PPS delayed prion propagation in a prophylactic-like treatment paradigm and also alleviated propagation when applied following establishment of infection in a therapeutic-like treatment paradigm. This study demonstrates the utility of cerebral organoids as the first human 3D cell culture system for screening therapeutic drug candidates for human prion diseases.
Effects of white Gaussian noise on dynamic balance in healthy young adults
Authors: Zhou Ziyou , Wu Can , Hu Zhen , Chai Yujuan , Chen Kai , Asakawa Tetsuya
Published: March 2021

It has been known that short-time auditory stimulation can contribute to the improvement of the balancing ability of the human body. The present study aims to explore the effects of white Gaussian noise (WGN) of different intensities and frequencies on dynamic balance performance in healthy young adults. A total of 20 healthy young participants were asked to stand at a dynamic balance force platform, which swung along the x-axis with an amplitude of ± 4° and frequency of 1 Hz. Their center of pressure (COP) trajectories were recorded when they were stimulated by WGN of different intensities (block 1) and different frequencies (block 2). A traditional method and detrended fluctuation analysis (DFA) were used for data preprocessing. The authors found that only with 75–85 dB WGN, the COP parameters improved. WGN frequency did not affect the dynamic balance performance of all the participants. The DFA results indicated stimulation with 75 dB WGN enhanced the short-term index and reduced the crossover point. Stimulation with 500 Hz and 2500 Hz WGN significantly enhanced the short-term index. These results suggest that 75 dB WGN and 500 Hz and 2500 Hz WGN improved the participants’ dynamic balance performance. The results of this study indicate that a certain intensity of WGN is indispensable to achieve a remarkable improvement in dynamic balance. The DFA results suggest that WGN only affected the short-term persistence, indicating the potential of WGN being considered as an adjuvant therapy in low-speed rehabilitation training.
Magnitude of the 8.2 ka event freshwater forcing based on stable isotope modelling and comparison to future Greenland melting
Authors: Aguiar Wilton , Meissner Katrin J. , Montenegro Alvaro , Prado Luciana , Wainer Ilana , Carlson Anders E. , Mata Mauricio M.
Published: March 2021

The northern hemisphere experienced an abrupt cold event ~ 8200 years ago (the 8.2 ka event) that was triggered by the release of meltwater into the Labrador Sea, and resulting in a weakening of the poleward oceanic heat transport. Although this event has been considered a possible analogue for future ocean circulation changes due to the projected Greenland Ice Sheet (GIS) melting, large uncertainties in the amount and rate of freshwater released during the 8.2 ka event make such a comparison difficult. In this study, we compare sea surface temperatures and oxygen isotope ratios from 28 isotope-enabled model simulations with 35 paleoproxy records to constrain the meltwater released during the 8.2 ka event. Our results suggest that a combination of 5.3 m of meltwater in sea level rise equivalent (SLR) released over a thousand years, with a short intensification over ~ 130 years (an additional 2.2 m of equivalent SLR) due to routing of the Canadian river discharge, best reproduces the proxy anomalies. Our estimate is of the same order of magnitude as projected future GIS melting rates under the high emission scenario RCP8.5.
Hair and salivary cortisol and their relationship with lifestyle, mood and cognitive outcomes in premanifest Huntington’s disease
Authors: Cruickshank Travis , Porter Tenielle , Laws Simon M. , Ziman Mel , Bartlett Danielle M.
Published: March 2021

Salivary cortisol dysrhythmias have been reported in some, but not all studies assessing hypothalamic–pituitary–adrenal (HPA) axis function in Huntington’s disease (HD). These differences are presumed to be due to environmental influences on temporal salivary cortisol measurement. Further exploration of HPA-axis function using a more stable and longer-term measure, such as hair cortisol, is needed to confirm earlier findings. This study aimed to evaluate hair and salivary cortisol concentrations and their associations with clinical and lifestyle outcomes in individuals with premanifest HD (n = 26) compared to healthy controls (n = 14). Participants provided saliva and hair samples and data were collected on clinical disease outcomes, mood, cognition, physical activity, cognitive reserve, sleep quality and social network size to investigate relationships between clinical and lifestyle outcomes and cortisol concentrations. Hair and salivary cortisol concentrations did not significantly differ between the premanifest HD and control groups. No significant associations were observed between hair or salivary cortisol concentrations and cognitive, mood or lifestyle outcomes. However, hair cortisol concentrations were significantly associated with disease outcomes in individuals with premanifest HD. Significant associations between hair cortisol concentrations and measures of disease burden and onset may suggest a potential disease marker and should be explored longitudinally in a larger sample of individuals with HD.
Ex vivo characterization of Breg cells in patients with chronic Chagas disease
Authors: Girard Magalí C. , Acevedo Gonzalo R. , Ossowski Micaela S. , Fernández Marisa , Hernández Yolanda , Chadi Raúl , Gómez Karina A.
Published: March 2021

Despite the growing importance of the regulatory function of B cells in many infectious diseases, their immunosuppressive role remains elusive in chronic Chagas disease (CCD). Here, we studied the proportion of different B cell subsets and their capacity to secrete IL-10 ex vivo in peripheral blood from patients with or without CCD cardiomyopathy. First, we immunophenotyped peripheral blood mononuclear cells from patients according to the expression of markers CD19, CD24, CD38 and CD27 and we showed an expansion of total B cell and transitional CD24highCD38high B cell subsets in CCD patients with cardiac involvement compared to non-infected donors. Although no differences were observed in the frequency of total IL-10 producing B cells (B10) among the groups, CCD patients with cardiac involvement showed an increased proportion of naïve B10 cells and a tendency to a higher frequency of transitional B10 cells compared to non-infected donors. Our research demonstrates that transitional B cells are greatly expanded in patients with the cardiac form of CCD and these cells retain the ability to secrete IL-10. These findings provide insight into the phenotypic distribution of regulatory B cells in CCD, an important step towards new strategies to prevent cardiomyopathy associated with T. cruzi infection.
COVID-19-related school closing aggravate obesity and glucose intolerance in pediatric patients with obesity
Authors: Kim Eun Sil , Kwon Yiyoung , Choe Yon Ho , Kim Mi Jin
Published: March 2021

It is important to pay attention to the indirect effects of the social distancing implemented to prevent the spread of coronavirus disease 2019 (COVID-19) pandemic on children and adolescent health. The aim of the present study was to explore impacts of a reduction in physical activity caused by COVID-19 outbreak in pediatric patients diagnosed with obesity. This study conducted between pre-school closing and school closing period and 90 patients aged between 6- and 18-year-old were included. Comparing the variables between pre-school closing period and school closing period in patients suffering from obesity revealed significant differences in variables related to metabolism such as body weight z-score, body mass index z-score, liver enzymes and lipid profile. We further evaluated the metabolic factors related to obesity. When comparing patients with or without nonalcoholic fatty liver disease (NAFLD), only hemoglobin A1c (HbA1c) was the only difference between the two time points (p < 0.05). We found that reduced physical activity due to school closing during COVID-19 pandemic exacerbated obesity among children and adolescents and negatively affects the HbA1C increase in NAFLD patients compared to non-NAFLD patients.
Bombyx mori β1,4-N-acetylgalactosaminyltransferase possesses relaxed donor substrate specificity in N-glycan synthesis
Authors: Kajiura Hiroyuki , Miyauchi Ryousuke , Kakudo Akemi , Ohashi Takao , Misaki Ryo , Fujiyama Kazuhito
Published: March 2021

N-Glycosylation is one of the most important post-translational protein modifications in eukaryotic cells. Although more than 200 N-glycogenes contributing to N-glycan biosynthesis have been identified and characterized, the information on insect N-glycosylation is still limited. Here, focusing on insect N-glycosylation, we characterized Bombyx mori N-acetylgalactosaminyltransferase (BmGalNAcT) participating in complex N-glycan biosynthesis in mammals. BmGalNAcT localized at the Golgi and was ubiquitously expressed in every organ and in the developmental stage of the middle silk gland of fifth instar larvae. Analysis of recombinant BmGalNAcT expressed in Sf9 cells showed that BmGalNAcT transferred GalNAc to non-reducing terminals of GlcNAcβ1,2-R with β1,4-linkage. In addition, BmGalNAcT mediated transfer of galactose and N-acetylglucosamine residues but not transfer of either glucose or glucuronic acid from the UDP-sugar donor substrate to the N-glycan. Despite this tri-functional sugar transfer activity, however, most of the endogenous glycoproteins of insect cells were present without GalNAc, Gal, or GlcNAc residues at the non-reducing terminal of β1,2-GlcNAc residue(s). Moreover, overexpression of BmGalNAcT in insect cells had no effect on N-acetylgalactosaminylation, galactosylation, or N-acetylglucosaminylation of the major N-glycan during biosynthesis. These results suggested that B. mori has a novel multifunctional glycosyltransferase, but the N-glycosylation is highly and strictly regulated by the endogenous N-glycosylation machineries.
Brain fMRI during orientation selective epidural spinal cord stimulation
Authors: Canna Antonietta , Lehto Lauri J. , Wu Lin , Sang Sheng , Laakso Hanne , Ma Jun , Filip Pavel , Zhang Yuan , Gröhn Olli , Esposito Fabrizio , Chen Clark C. , Lavrov Igor , Michaeli Shalom , Mangia Silvia
Published: March 2021

Epidural spinal cord stimulation (ESCS) is widely used for chronic pain treatment, and is also a promising tool for restoring motor function after spinal cord injury. Despite significant positive impact of ESCS, currently available protocols provide limited specificity and efficiency partially due to the limited number of contacts of the leads and to the limited flexibility to vary the spatial distribution of the stimulation field in respect to the spinal cord. Recently, we introduced Orientation Selective (OS) stimulation strategies for deep brain stimulation, and demonstrated their selectivity in rats using functional MRI (fMRI). The method achieves orientation selectivity by controlling the main direction of the electric field gradients using individually driven channels. Here, we introduced a similar OS approach for ESCS, and demonstrated orientation dependent brain activations as detected by brain fMRI. The fMRI activation patterns during spinal cord stimulation demonstrated the complexity of brain networks stimulated by OS-ESCS paradigms, involving brain areas responsible for the transmission of the motor and sensory information. The OS approach may allow targeting ESCS to spinal fibers of different orientations, ultimately making stimulation less dependent on the precision of the electrode implantation.
Omics data integration identifies ELOVL7 and MMD gene regions as novel loci for adalimumab response in patients with Crohn’s disease
Authors: Gorenjak Mario , Zupin Mateja , Jezernik Gregor , Skok Pavel , Potočnik Uroš
Published: March 2021

Response to anti-TNF therapy is of pivotal importance in patients with Crohn’s disease (CD). Here we integrated our and previously reported PBMC derived transcriptomic and genomic data for identification of biomarkers for discrimination between responders and non-responders to anti-TNF therapy. CD patients, who were naïve with respect to the treatment with biologicals, were enrolled in the study. DNA and RNA were extracted from peripheral blood mononuclear cells. RNA-seq was performed using BGISEQ-500. Genotyping was performed using Infinium Global Screening Array. Association regressions were carried out with 12 week response to adalimumab as an outcome variable. RNA-seq analysis confirmed 7 out of 65 previously suggested genes involved in anti-TNF response. Subsequently, analysis of single nucleotide variants in regions of confirmed genes identified 5 variants near MMD and two in ELOVL7 intronic regions associated with treatment response to anti-TNF. Functional analysis has shown that rs1465352, rs4422035 and rs78620886 are listed at H3K9ac_Pro histone modification epigenetic mark. The present study confirmed MMD and ELOVL7 involvement in anti-TNF response and revealed that the regulation of MMD and ELOVL7 gene regions in ADA response may be a part of a complex interplay extending from genetic to epigenetic and to transcriptomic level.
Development of multifunctional nanocomposites for controlled drug delivery and hyperthermia
Authors: Hovhannisyan Vladimir , Siposova Katarina , Musatov Andrey , Chen Shean-Jen
Published: March 2021

Magnetic nano/micro-particles based on clinoptilolite-type of natural zeolite (CZ) were fabricated and were expected to act as carriers for controlled drug delivery/release, imaging and local heating in biological systems. Adsorption of rhodamine B, sulfonated aluminum phthalocyanine and hypericin by magnetic CZ nano/micro-particles was investigated, as was the release of hypericin. Using an alternating magnetic field, local temperature increase by 10 °C in animal tissue with injected magnetic CZ particles was demonstrated. In addition, the CZ-based particles have been found to exhibit an anti-amyloidogenic effect on the amyloid aggregation of insulin and lysozyme in a dose- and temperature-dependent manner. Therefore, the mesoporous structure of CZ particles provided a unique platform for preparation of multifunctional magnetic and optical probes suitable for optical imaging, MRI, thermo- and phototherapy and as effective containers for controlled drug delivery. We concluded that magnetic CZ nano/micro-particles could be evaluated for further application in cancer hyperthermia therapy and as anti-amyloidogenic agents.
Author Correction: Quantitative determination and toxicity evaluation of 2,4-dichlorophenol using poly(eosin Y)/hydroxylated multi-walled carbon nanotubes modified electrode
Authors: Zhu Xiaolin , Zhang Kexin , Wang Chengzhi , Guan Jiunian , Yuan Xing , Li Baikun
Published: March 2021

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Self-assembled graphene-based microfibers with eclectic optical properties
Authors: Ghamsari Mahdi , Madrakian Tayyebeh , Afkhami Abbas , Ahmadi Mazaher
Published: March 2021

The construction of graphene-based microfibers with reinforced mechanical and electrical properties has been the subject of numerous researches in recent years. However, the fabrication of graphene-based fibers with remarkable optical features still remains a challenge and has not been addressed so far. This paper aims to report a series of flexible self-assembled fibers, synthesized through a few-minute sonication of thermally oxidized graphene oxide nanosheets, so-called Nanoporous Over-Oxidized Graphene (NOG), in an acidic medium. These free-standing glassy fibers were classified into four distinct morphological structures and displayed a collection of intriguing optical properties comprising high transparency, strong birefringence, fixed body colorations (e.g. colorless, blue, green, and red), tunable interference marginal colorations, UV–visible-near IR fluorescence, and upconversion emissions. Moreover, they exhibited high chemical stability in strongly acidic, basic, and oxidizing media. The foregoing notable attributes introduce the NOG fiber as a promising candidate both for the construction of graphene-based photoluminescent textiles and the development of a wide variety of optical applications.