bluuebunny/crossref_metadata_2025 huggingface dataset:
Intracerebral Injection of Graphene Oxide Nanosheets Mitigates Microglial Activation Without Inducing Acute Neurotoxicity: A Pilot Comparison to Other Nanomaterials
Authors: Portioli Corinne , Bussy Cyrill , Mazza Mariarosa , Lozano Neus , Jasim Dhifaf A. , Prato Maurizio , Bianco Alberto , Bentivoglio Marina , Kostarelos Kostas
Published: November 2020

Carbon‐based nanomaterials (CNMs) are being explored for neurological applications. However, systematic in vivo studies investigating the effects of CNM nanocarriers in the brain and how brain cells respond to such nanomaterials are scarce. To address this, functionalized multiwalled carbon nanotubes and graphene oxide (GO) sheets are injected in mice brain and compared with charged liposomes. The induction of acute neuroinflammatory and neurotoxic effects locally and in brain structures distant from the injection site are assessed up to 1 week postadministration. While significant neuronal cell loss and sustained microglial cell activation are observed after injection of cationic liposomes, none of the tested CNMs induces either neurodegeneration or microglial activation. Among the candidate nanocarriers tested, GO sheets appear to elicit the least deleterious neuroinflammatory profile. At molecular level, GO induces moderate activation of proinflammatory markers compared to vehicle control. At histological level, brain response to GO is lower than after vehicle control injection, suggesting some capacity for GO to reduce the impact of stereotactic injection on brain. While these findings are encouraging and valuable in the selection and design of nanomaterial‐based brain delivery systems, they warrant further investigations to better understand the mechanisms underlying GO immunomodulatory properties in brain.
CCCDTD5: Individual and community‐based psychosocial and other non‐pharmacological interventions to support persons living with dementia and their caregivers
Authors: Vedel Isabelle , Sheets Debra , McAiney Carrie , Clare Linda , Brodaty Henry , Mann James , Anderson Nicole , Liu‐Ambrose Teresa , Rojas‐Rozo Laura , Loftus Lynn , Gauthier Serge , Sivananthan Saskia
Published: November 2020

Introduction

Current pharmacological therapies for dementia have limited efficacy. Thus it is important to provide recommendations on individual and community‐based psychosocial and non‐pharmacological interventions for persons living with dementia (PLWDs) and their caregivers.

Methods

Phase 1: A systematic review for developing recommendations on psychosocial and non‐pharmacological interventions at the individual and community level for PLWDs and their caregivers. Phase 2: Rating of recommendations using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) guidelines. Phase 3: Delphi process (>50 dementia experts) for approving recommendations by the 5th Canadian Consensus Conference on the Diagnosis and Treatment of Dementia (CCCDTD5).

Results

The CCCDTD5 approved the following recommendations: Exercise (1B) and group cognitive stimulation for PLWDs (2B), psychosocial and psychoeducational interventions for caregivers (2C), development of dementia friendly organization and communities (2C), and case management for PLWDs (2B).

Discussion

The CCCDTD5 provides for the first time, evidence‐based recommendations on psychosocial and non‐pharmacological interventions for PLWDs and their caregivers that can inform evidence‐based policies for PLWDs in Canada.
A review on RNAi therapy for NSCLC: Opportunities and challenges
Authors: Kumar Vignesh , Yadavilli Sairam , Kannan Raghuraman
Published: November 2020

Non‐small cell lung cancer (NSCLC) is the primary cause of cancer death worldwide. Despite developments in chemotherapy and targeted therapies, the 5‐year survival rate has remained at approximately 16% for the last four decades. NSCLC is a heterogeneous group of tumors that, through mutations and drivers, also demonstrate intra‐tumor heterogeneity. Thus, current treatment approaches revolve around targeting these oncogenes, often using small molecule inhibitors and chemotherapeutics. However, the efficacy of these therapies has been crippled by acquired and inherent drug‐resistance in the tumor, accompanied by increased therapeutic dosages and subsequent devastating off‐target effects for patients. Evidently, there is a critical need for developing treatment methodologies more effective than the current standard of care. Fortunately, RNA interference, particularly small interfering RNA (siRNA), presents an alternative of silencing specific oncogenes to control tumor growth. Although siRNA therapy is subject to rapid degradation and poor internalization in vivo, nanoparticles can serve as nontoxic and efficient delivery vehicles, even introducing combinational delivery of multiple therapeutic agents. Indeed, siRNA‐nanoconstructs possess extraordinary potential as an innovative modality to address clinical needs. This state‐of‐the‐art review summarizes the recent advancements in the development of novel nanosystems for delivering siRNA to NSCLC tumors and analyzes the efficacy of representative examples. By illuminating the most promising biomarkers for silencing, we hope to streamline current therapeutic efforts and highlight powerful translational opportunities to combat NSCLC.

This article is categorized under:

Therapeutic Approaches and Drug Discovery > Emerging Technologies

Biology‐Inspired Nanomaterials > Lipid‐Based Structures

Therapeutic Approaches and Drug Discovery > Nanomedicine for Oncologic Disease
Bis‐cyclometalated Iridium Complexes Containing Modified Phenanthroline Ligands and Evaluation of their Cytotoxic Activities
Authors: Graf Marion , Böttcher Hans‐Christian , Sünkel Karlheinz , Thavalingam Sugina , Metzler‐Nolte Nils , Czerwieniec Rafał
Published: November 2020

The synthesis and characterization of new bis‐cyclometalated complex salts [Ir(ptpy)2(Lphen)]PF6 with Lphen = 2,9‐dimethyl‐4,7‐bis(pentyloxy)‐1,10‐phenanthroline (1) and Lphen = 2,9‐dimethyl‐4,7‐bis(2‐ethoxyethoxyl)‐1,10‐phenanthroline (2) are described. Compounds 1 and 2 were obtained by the reaction of the corresponding phenanthroline ligands with [{Ir(μ‐Cl)(ptpy)2}2] in a refluxing CH2Cl2/MeOH mixture. The molecular structure of compound 2 was confirmed by single‐crystal X‐ray structure determination. Complex 2 was crystallized from dichloromethane/methanol/iso‐hexane in the monoclinic space group P21/c. The biological activity of both new compounds was examined, and they exhibit significant cytotoxicity against human cancer cell lines with the IC50 values around 2 μM, significantly better than the established anticancer drug cisplatin under identical conditions.
ADJUNCTION FOR VARIETIES WITH A ℂ* ACTION
Authors: ROMANO ELEONORA A. , WIŚNIEWSKI JAROSŁAW A.
Published: November 2020

Let X be a complex projective manifold, L an ample line bundle on X, and assume that we have a ℂ* action on (X;L). We classify such triples (X; L;ℂ*) for which the closure of a general orbit of the ℂ* action is of degree ≤ 3 with respect to L and, in addition, the source and the sink of the action are isolated fixed points, and the ℂ* action on the normal bundle of every fixed point component has weights ±1. We treat this situation by relating it to the classical adjunction theory. As an application, we prove that contact Fano manifolds of dimension 11 and 13 are homogeneous if their group of automorphisms is reductive of rank ≥ 2.
Do you really want to deactivate your sacral neuromodulation device during pregnancy? A single center case series
Authors: Agnello Marco , Vottero Mario , Bertapelle Paola
Published: November 2020

Introduction and hypothesis

The main objective of the study is to assess the efficacy and safety of sacral neuromodulation (SNM) during pregnancy.

Methods

We retrospectively enrolled patients who underwent SNM implantation in our center and subsequently became pregnant. The indication for SNM, timing of device de-activation (if performed), course of pregnancy and urological complications, duration of labor, childbirth term, delivery mode, congenital abnormalities and SNM dysfunctions after delivery were recorded.

Results

Fourteen pregnancies were recorded among 11 women undergoing SNM. Indications for device implantation were urinary retention (7 cases) and dysfunctional voiding (4 cases). Two patients carried on two and three pregnancies, respectively, with the device turned off since the first trimester. They both had to return to self-catheterization and developed recurring urinary tract infections. No major urological complications were recorded among the remaining nine women that kept the device on during pregnancy. A cesarean section was performed in four cases for obstetric reasons, and in seven cases it was planned by the urologist and gynecologist to avoid lead damage/displacement. Three pregnancies resulted in a vaginal delivery, and no association with term of delivery or duration of labor was observed. No congenital abnormalities related to SNM or lead displacement are reported, and only one patient required device removal because of significant loss of efficacy after childbirth.

Conclusions

The use of SNM during pregnancy appears to be safe, without morbidity for the fetus. Moreover, risks associated with switching the device off may be greater than benefits and justify maintaining the electrical stimulation throughout pregnancy.
Optimal sampling strategies for darunavir and external validation of the underlying population pharmacokinetic model
Authors: Stillemans Gabriel , Belkhir Leila , Vandercam Bernard , Vincent Anne , Haufroid Vincent , Elens Laure
Published: November 2020

Purpose

A variety of diagnostic methods are available to validate the performance of population pharmacokinetic models. Internal validation, which applies these methods to the model building dataset and to additional data generated through Monte Carlo simulations, is often sufficient, but external validation, which requires a new dataset, is considered a more rigorous approach, especially if the model is to be used for predictive purposes. Our first objective was to validate a previously published population pharmacokinetic model of darunavir, an HIV protease inhibitor boosted with ritonavir or cobicistat. Our second objective was to use this model to derive optimal sampling strategies that maximize the amount of information collected with as few pharmacokinetic samples as possible.

Methods

A validation dataset comprising 164 sparsely sampled individuals using ritonavir-boosted darunavir was used for validation. Standard plots of predictions and residuals, NPDE, visual predictive check, and bootstrapping were applied to both the validation set and the combined learning/validation set in NONMEM to assess model performance. D-optimal designs for darunavir were then calculated in PopED and further evaluated in NONMEM through simulations.

Results

External validation confirmed model robustness and accuracy in most scenarios but also highlighted several limitations. The best one-, two-, and three-point sampling strategies were determined to be pre-dose (0 h); 0 and 4 h; and 1, 4, and 19 h, respectively. A combination of samples at 0, 1, and 4 h was comparable to the optimal three-point strategy. These could be used to reliably estimate individual pharmacokinetic parameters, although with fewer samples, precision decreased and the number of outliers increased significantly.

Conclusions

Optimal sampling strategies derived from this model could be used in clinical practice to enhance therapeutic drug monitoring or to conduct additional pharmacokinetic studies.
Outcomes of Laparoscopic Splenectomy for Treatment of Splenomegaly: A Systematic Review and Meta‐analysis
Authors: Rodríguez‐Luna María Rita , Balagué Carmen , Fernández‐Ananín Sonia , Vilallonga Ramon , Targarona Soler Eduardo María
Published: November 2020

Objectives

To review the evidence regarding the outcomes of laparoscopic techniques in cases of splenomegaly.

Background

Endoscopic approaches such as laparoscopic, hand‐assisted laparoscopic, and robotic surgery are commonly used for splenectomy, but the advantages in cases of splenomegaly are controversial.

Review methods

We conducted a systematic review using PRISMA guidelines. PubMed/MEDLINE, ScienceDirect, Scopus, Cochrane Library, and Web of Science were searched up to February 2020.

Results

Nineteen studies were included for meta‐analysis. In relation to laparoscopic splenectomy (LS) versus open splenectomy (OS), 12 studies revealed a significant reduction in length of hospital stay (LOS) of 3.3 days (p = <0.01) in the LS subgroup. Operative time was higher by 44.4 min (p < 0.01) in the LS group. Blood loss was higher in OS 146.2 cc (p = <0.01). No differences were found regarding morbimortality. The global conversion rate was 19.56%. Five studies compared LS and hand‐assisted laparosocpic splenectomy (HALS), but no differences were observed in LOS, blood loss, or complications. HALS had a significantly reduced conversion rate (p < 0.01). In two studies that compared HALS and OS (n = 66), HALS showed a decrease in LOS of 4.5 days (p < 0.01) and increase of 44 min in operative time (p < 0.01), while OS had a significantly higher blood loss of 448 cc (p = 0.01). No differences were found in the complication rate.

Conclusion

LS is a safe approach for splenomegaly, with clear clinical benefits. HALS has a lower conversion rate. Higher‐quality confirmatory trials with standardized splenomegaly grading are needed before definitive recommendations can be provided.

Prospero registration number: CRD42019125251.
Development of image quality related reference doses called acceptable quality doses (AQD) in paediatric CT exams in Qatar
Authors: Kharita Mohammad Hassan , AlNaemi Huda , Kini Vishwanatha , Alkhazzam Shady , Rehani Madan M.
Published: November 2020

Objectives

To describe first experience of integrating assessment of image quality in paediatric X-ray computed tomography (CT) with analysis of the radiation dose indices to develop reference doses called acceptable quality dose (AQD).

Methods

Image quality was scored by the radiologists at a tertiary care hospital in Qatar on a scale of 0 to 4 using the recently published scoring criteria. The patients undergoing head, chest and abdomen CT were divided in different weight groups as follows: < 5 kg, 5–< 15 kg, 15–< 30 kg, 30–< 50 kg, 50–< 80 kg and > 80 kg. The images that were clinically acceptable (score of 3) were included for assessment of median values of CTDIvol and DLP to obtain AQDs in different weight groups.

Results

After initial training in image quality scoring of CT images of 49 patients by three radiologists, the study on 715 patients indicated 665 studies (93%) were clinically acceptable as per scoring criteria. The median CTDIvol values for the above weight groups were 16, 20, 22, 22, 27 and 27 mGy and the median DLP values for these weight groups were 271, 377, 463, 486, 568 and 570 mGy cm, respectively, for head CT. Similar values are presented for chest and abdomen CTs.

Conclusions

The first ever experience of starting with image quality assessment and integrating it with analysis of dose indices to obtain AQD values shall provide a workable model for others and values for comparison within the facility and in other facilities leading to optimisation.

Key Points

• The first study to integrate image quality assessment with analysis of patient dose indices shows feasibility for routine practice in other centres.

• The values of acceptable quality dose (AQD) were provided for head, chest and abdomen CT of children divided into weight groups rather than age. They shall act as reference values for future studies.

• Verification of our findings on proportional increase in exposure parameters (CTDIvol and DLP) with weight by other investigators shall be helpful.
Extension of WRF-Chem for birch pollen modelling—a case study for Poland
Authors: Werner Małgorzata , Guzikowski Jakub , Kryza Maciej , Malkiewicz Małgorzata , Bilińska Daria , Skjøth Carsten Ambelas , Rapiejko Piotr , Chłopek Kazimiera , Dąbrowska-Zapart Katarzyna , Lipiec Agnieszka , Jurkiewicz Dariusz , Kalinowska Ewa , Majkowska-Wojciechowska Barbara , Myszkowska Dorota , Piotrowska-Weryszko Krystyna , Puc Małgorzata , Rapiejko Anna , Siergiejko Grzegorz , Weryszko-Chmielewska Elżbieta , Wieczorkiewicz Andrzej , Ziemianin Monika
Published: November 2020

In recent years, allergies due to airborne pollen allergens have shown an increasing trend, along with the severity of allergic symptoms in most industrialized countries, while synergism with other common atmospheric pollutants has also been identified as affecting the overall quality of citizenly life. In this study, we propose the state-of-the-art WRF-Chem model, which is a complex Eulerian meteorological model integrated on-line with atmospheric chemistry. We used a combination of the WRF-Chem extended towards birch pollen, and the emission module based on heating degree days, which has not been tested before. The simulations were run for the moderate season in terms of birch pollen concentrations (year 2015) and high season (year 2016) over Central Europe, which were validated against 11 observational stations located in Poland. The results show that there is a big difference in the model’s performance for the two modelled years. In general, the model overestimates birch pollen concentrations for the moderate season and highly underestimates birch pollen concentrations for the year 2016. The model was able to predict birch pollen concentrations for first allergy symptoms (above 20 pollen m−3) as well as for severe symptoms (above 90 pollen m−3) with probability of detection at 0.78 and 0.68 and success ratio at 0.75 and 0.57, respectively for the year 2015. However, the model failed to reproduce these parameters for the year 2016. The results indicate the potential role of correcting the total seasonal pollen emission in improving the model’s performance, especially for specific years in terms of pollen productivity. The application of chemical transport models such as WRF-Chem for pollen modelling provides a great opportunity for simultaneous simulations of chemical air pollution and allergic pollen with one goal, which is a step forward for studying and understanding the co-exposure of these particles in the air.
Neuromodulation of the subthalamic nucleus in Parkinson’s disease: the effect of fiber tract stimulation on tremor control
Authors: Abdulbaki Arif , Kaufmann Jörn , Galazky Imke , Buentjen Lars , Voges Jürgen
Published: November 2020

Background

Therapeutic effects of deep brain stimulation (DBS) of the subthalamic nucleus (STN) in Parkinson’s disease (PD) may in parts be attributed to the stimulation of white matter near the targeted structure. The dentato-rubro-thalamic (DRT) tract supposed to improve tremor control in patients with essential tremor could be one candidate structure. The aim of this study was to investigate the effect of stimulation proximity to the DRT on tremor control in PD patients treated with STN-DBS.

Methods

For this retrospective analysis, we included 36 consecutive patients (median age 65.5 years) treated with STN-DBS for disabling motor symptoms including tremor. Stereotactic implantation of DBS electrodes into the motor area of the STN was performed using direct MRI-based targeting and intraoperative microelectrode recording. Tremor severity was assessed preoperatively and at regular intervals postoperatively (Unified Parkinson’s Disease Rating Scale III). The DRT was visualized in 60 hemispheres after probabilistic fiber tracking (3-T MRI). The position of active electrode contacts was verified on intraoperative stereotactic X-rays and postoperative CT images after co-registration with 3D treatment planning MRI/CT images. We determined the shortest distance of active contacts to the ipsilateral DRT tracts on perpendicular view slices and correlated this value with tremor change percentage.

Results

Twelve patients had unilateral tremor only, and accordingly, 12 hemispheres were excluded from further imaging analysis. The remaining 60 hemispheres were associated with contralateral resting tremor. Active brain electrode contacts leading to resting tremor improvement (46 hemispheres) had a significantly shorter distance to the DRT (1.6 mm (0.9–2.1) [median (25th–75th percentiles)]) compared with contacts of non-responders (14 hemispheres, distance: 2.8 mm (2–4.6), p < 0.001).

Conclusion

This retrospective analysis suggests that in STN-DBS, better tremor control in PD patients correlates with the distance of active electrode contacts to the DRT. Tractography may optimize both individually DBS targeting and postoperative adjustment of stimulation parameters.
Plasma free amino acid profiling as metabolomic diagnostic and prognostic biomarker in paediatric cancer patients: a follow-up study
Authors: Synakiewicz Anna , Stanislawska-Sachadyn Anna , Sawicka-Zukowska Malgorzata , Galezowska Grazyna , Ratajczyk Joanna , Owczarzak Anna , Skuza Malgorzata , Wolska Lidia , Stachowicz-Stencel Teresa
Published: November 2020

Amino acids (AAs) play a crucial role in cancer cell metabolism. Levels of 22 plasma AAs at the time of diagnosis and after treatment were established among 39 pediatric cancer patients and 33 healthy children. Glutamic acid levels decreased and tryptophan levels increased during treatment. Cancer patients presented significantly lower levels of glutamine and leucine post-treatment while levels of 12 other AAs were higher comparing to controls. Results suggest that plasma free AA profile may serve as a prognostic biomarker.
Saliva substitute mouthwash in nasopharyngeal cancer survivors with xerostomia: a randomized controlled trial
Authors: Marimuthu Dayaabaran , Han Kong Min , Mohamad Mohd Shawal Firdaus , Azman Mawaddah
Published: November 2020

Objectives

Xerostomia is a prevalent sequelae among nasopharyngeal cancer (NPC) survivors; yet, effective treatment protocols have been elusive. This study was a prospective randomized clinical trial to compare the effects of saliva substitute mouthwash in nasopharyngeal cancer survivors with xerostomia, between two treatment arms, conducted in a tertiary center.

Materials and methods

This study measured the effects within 4 weeks in relation to summated xerostomia inventory (SXI) and unstimulated whole saliva (UWS). Patients randomized into the interventional arm were prescribed an immunologically active saliva substitute (IASS), while patients in the control arm were prescribed a non-immunologically active mouthwash as placebo.

Results

The study population consisted of 94 patients. There was a significant difference in SXI difference (p< 0.0001) and UWS difference (p< 0.0001) between control and interventional arms. No harmful side effects associated with the use of either mouthwash encountered throughout the study duration.

Conclusion

IASS mouthwash significantly reduces subjective xerostomia scores measured using SXI and improves objective measurement of salivary flow using UWS among nasopharyngeal cancer survivors with xerostomia.

Clinical relevance

IASS is significantly more effective in improving subjective and objective xerostomia measurements compared to non-immunologically active mouthwash. Additionally, this treatment is very safe, with superior side effect profiles.

Trial registration

ClinicalTrials.govIdentifier: NCT04491435
Allergenic fungal spores in the air of urban parks
Authors: Kasprzyk Idalia , Grinn-Gofroń Agnieszka , Ćwik Agata , Kluska Katarzyna , Cariñanos Paloma , Wójcik Tomasz
Published: November 2020

Urban green spaces, especially urban parks, are essential for the proper functioning of cities, but they can be a serious source of airborne fungal spores. Aerobiological monitoring was carried out in urban parks of different typology to estimate the risk associated with fungal spores for citizens. Volumetric method was applied with the use of portable Burkard Sampler. In the air of the studied parks, the most dominant spores are strong allergenic or considered as potentially allergenic. Cladosporium spores were found in enormous concentrations in all studied parks, and it affected the low biodiversity of fungal spores in the parks. Compared to Cladosporium, concentrations of Alternaria spores in the air were several dozen times lower, but still a risk for people who are allergic. The fungal spores spectra and their seasonal occurrence in each park were similar. The highest similarities in the patterns of the season were found in the case of Cladosporium, Alternaria, Epicoccum, and the lowest in the case of Torula and Drechslera type. Due to the fact that allergy sufferers are most often polysensitized, the period when they should limit long visits in the urban parks is July–August, when the concentration of allergenic fungal spores of many taxa is the highest.
Metabolic rate and resource depletion in the tick Ixodes ricinus in response to temperature
Authors: Alasmari Saeed , Wall Richard
Published: November 2020

Understanding the effects of temperature on the metabolic activity and the rate of depletion of energy reserves by Ixodes ricinus can represent an important contribution to explaining patterns of tick activity and the likely impacts of environmental change on tick and tick-borne disease risk. Here, a cohort of I. ricinus nymphs, males, and females was collected and placed into incubators at temperatures of between 5 and 30 °C. The protein, carbohydrate, total lipid, neutral lipid, and glycogen levels were measured for nymphs for up to 70 days and adults up to 42 days. In nymphs, at day 0, glycogen was the most abundant metabolite followed by carbohydrate, with relatively low concentrations of protein and lipids. For males, the concentrations of different metabolites were relatively similar. In contrast, for females, concentrations of glycogen and carbohydrate were relatively low compared to those of protein and neutral lipids. Significant exponential declines in metabolite concentrations of all metabolites were detected over time for all life-cycle stages and at all temperatures. Nymphs generally showed lower rates of resource depletion than adults at all temperatures. The lower thresholds for metabolic activity were estimated to be between −10 and −5 °C. The Q10 values, which describe the thermal sensitivity of metabolic rate, were estimated to be relatively low (1.5 for nymphs, 1.71 for males, and 1.63 for females) compared to insects where they are typically around 2.5 (range: 1.5–3), and this is considered to be an adaptation to increase survival during the extended inter-feed intervals.
Proof-of-Concept Study: a Mobile Application to Derive Clinical Outcome Measures from Expression and Speech for Mental Health Status Evaluation
Authors: Siena Francesco Luke , Vernon Michael , Watts Paul , Byrom Bill , Crundall David , Breedon Philip
Published: November 2020

This proof-of-concept study aimed to assess the ability of a mobile application and cloud analytics software solution to extract facial expression information from participant selfie videos. This is one component of a solution aimed at extracting possible health outcome measures based on expression, voice acoustics and speech sentiment from video diary data provided by patients. Forty healthy volunteers viewed 21 validated images from the International Affective Picture System database through a mobile app which simultaneously captured video footage of their face using the selfie camera. Images were intended to be associated with the following emotional responses: anger, disgust, sadness, contempt, fear, surprise and happiness. Both valence and arousal scores estimated from the video footage associated with each image were adequate predictors of the IAPS image scores (p < 0.001 and p = 0.04 respectively). 12.2% of images were categorised as containing a positive expression response in line with the target expression; with happiness and sadness responses providing the greatest frequency of responders: 41.0% and 21.4% respectively. 71.2% of images were associated with no change in expression. This proof-of-concept study provides early encouraging findings that changes in facial expression can be detected when they exist. Combined with voice acoustical measures and speech sentiment analysis, this may lead to novel measures of health status in patients using a video diary in indications including depression, schizophrenia, autism spectrum disorder and PTSD amongst other conditions.
18F-FDG PET/CT of off-target lymphoid organs in CD19-targeting chimeric antigen receptor T-cell therapy for relapsed or refractory diffuse large B-cell lymphoma
Authors: Derlin Thorsten , Schultze-Florey Christian , Werner Rudolf A. , Möhn Nora , Skripuletz Thomas , David Sascha , Beutel Gernot , Eder Matthias , Ross Tobias L. , Bengel Frank M. , Ganser Arnold , Koenecke Christian
Published: November 2020

Objective

The interplay between systemic inflammation, activity of lymphoid organs and lymphoma activity in CD19-targeting chimeric antigen receptor (CAR)-T-cell immunotherapy, and its significance for response and toxicity, is not well defined.

Methods

Using serial 18F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT), metabolic parameters of lymphoma and lymphoid organs were analyzed in ten patients receiving Tisagenlecleucel (an autologous CD19 CAR-T cell product) for relapsed or refractory diffuse large B-cell lymphoma. The prevalence and severity of toxicity (e.g., neurotoxicity) were noted.

Results

Achieving remission required early metabolic response (P = 0.0476). Early suppression of metabolic activity of lymphoid organs (spleen, P = 0.0368; lymph nodes, P = 0.0470) was associated with poor outcome. Lymphoma metabolic activity was significantly higher in patients with neurotoxicity (P = 0.0489).

Conclusions

Early metabolic changes in lymphoma lesions and off-target lymphoid organs parallel medium-term response to CAR-T-cell therapy. PET can identify patients at risk for severe toxicity.
Layer entanglement in multiplex, temporal multiplex, and coupled multilayer networks
Authors: Škrlj Blaž , Renoust Benjamin
Published: November 2020

Complex networks, such as transportation networks, social networks, or biological networks, capture the complex system they model by often representing only one type of interactions. In real world systems, there may be many different aspects that connect entities together. These can be captured using multilayer networks, which combine different modalities of interactions in a single model. Coupling in multilayer networks may exhibit different properties which can be related to the very nature of the data they model (or to events in time-dependent data). We hypothesise that such properties may be reflected in the way layers are intertwined. In this paper, we investigated these through the prism of layer entanglement in coupled multilayer networks. We test over 30 real-life networks in 6 different disciplines (social, genetic, transport, co-authorship, trade, and neuronal networks). We further propose a random generator, displaying comparable patterns of elementary layer entanglement and transition coupling entanglement across 1,329,696 synthetic coupled multilayer networks. Our experiments demonstrate difference of layer entanglement across disciplines, and even suggest a link between entanglement intensity and homophily. We additionally study entanglement in 3 real world temporal datasets displaying a potential rise in entanglement activity prior to other network activity.
The Politics of Productivity: Differences in Exporting Firms Across Domestic Contexts
Authors: Roosevelt Megan
Published: November 2020

Political economists have paid increasing attention to distinctions between exporting and nonexporting firms, particularly with regard to their preferences on trade policy liberalization. A multitude of past studies focusing on economically advanced democracies characterized exporters as a small, elite group of large and highly productive firms, but this profile of a prototypical exporter is not necessarily representative of the body of firms operating under different domestic contexts. Using current and methodologically consistent cross-national surveys of firms conducted by the World Bank, this paper re-evaluates the link between certain firm-level characteristics and firms’ propensity to export, taking into account how national-level political, economic, and geographic conditions affect these relationships. The pooled sample of firms from approximately 100 countries spanning different political regimes and levels of development confirms that, generally speaking, exporters are large, productive, and innovative. However, in less democratic and less developed settings, productivity and innovation do not appear to be a prerequisite to export orientation. When developing generalizable theories of firms’ participation in the policymaking process, we must therefore be careful not to treat export behavior as an unqualified predictor of pro-free-trade attitudes.
India Antimicrobial Stewardship and Resistance (INTEREST) 2018: A needs assessment survey
Authors: Shah Aditya , Vijayvargiya Prakhar , O’Horo John C. , Shah Varun , Shah Sanjiv , Dutt Taru , Bansal Vikas , Kashyap Rahul
Published: November 2020

Antimicrobial resistance is a major problem in India with limited understanding of whether this issue is related to systems, prescriber characteristics, patient characteristics, or diagnostic technologies. In our survey, most of the issues lie in the easy availability of antimicrobials and the lack of electronic storage of medical and microbiological records.
Lattice Studies of Gerrymandering Strategies
Authors: Gatesman Kyle , Unwin James
Published: November 2020

A new theoretical method for examining gerrymandering is presented based on lattice models of voters, in which districts are constructed by partitioning the lattice. We propose three novel algorithms for constructing equal-population, connected districts which favor the gerrymanderer and incorporate the spatial distribution of voters. Due to the probabilistic population fluctuations inherent to our voter models, Monte Carlo techniques can be applied to study the impact of gerrymandering. We use the method developed here to compare our different gerrymandering algorithms, show approaches which ignore spatial data lead to (legally prohibited) disconnected districts, and examine the effectiveness of isoperimetric quotient tests.
Umbilicaria orientalis– a new species ofUmbilicariasubg.Papillophorawith an East Asian distribution: morphological delimitation and molecular evidence
Authors: Davydov Evgeny A. , Yakovchenko Lidia S. , Urbanavichene Irina , Konoreva Liudmila , Chesnokov Sergey , Kharpukhaeva Tatiana , Obermayer Walter
Published: November 2020

Umbilicaria orientalisDavydov sp. nov. is described and phylogenetic analysis (ITS, mtLSU andRPB2) confirmed its distinctness and indicated a sister relationship withU. trabeculatawithin theU.velleagroup. The species is morphologically similar toU. velleabut differs by simple, cylindrical or strap-like rhizinomorphs and by thalloconidia, developing both on the lower surface and on rhizinomorphs, that are 1–2 (rarely 4)–celled or in aggregates of up to 5–6 cells.Umbilicaria orientalisis described from the Russian Far East and is currently known from a wide range of localities in East Asia, from the Far East to South Siberia and Mongolia in the north, to Hebei and Tibet in the south. New sequences ofU. americanawere obtained; the species represents an independent phylogenetic lineage withinUmbilicariasubg.Papillophora. Diagnostic traits and variability of different developmental stages ofU. orientalis, as well as its East Asian distribution pattern, are discussed.
A molecular study of the lichen genus Byssoloma Trevisan (Pilocarpaceae) with descriptions of three new species from China
Authors: Wang Wei-Cheng , van den Boom Pieter , Sangvichien Ek , Wei Jiang-Chun
Published: November 2020

A molecular phylogeny of the genus Byssoloma is inferred from mtSSU sequences using Bayesian and maximum likelihood phylogenetic analyses. Byssoloma subdiscordans is resolved as sister to B. citricola rather than to the B. leucoblepharum clade, the B. subundulatum group (species with a compact apothecial margin) is shown to be a monophyletic group, and three species belonging to this group are described as new to science from Hainan Province in China: B. brunneodiscum W. C. Wang & J. C. Wei, with dark brown apothecia, crystals in the excipulum and the presence of 2,5,7-trichloro-3-O-methylnorlichexanthone; B. rubrofuscum W. C. Wang & J. C. Wei, with red-brown apothecia, 3–6-septate ascospores and the presence of 5,7-dichloro-3-O-methylnorlichexanthone; B. melanodiscocarpum W. C. Wang & J. C. Wei, with pure black apothecia, a K+ olive-black hypothecium and the presence of thiophanic acid.
MONARCHS, TRAVELLERS AND EMPIRE IN THE PACIFIC'S AGE OF REVOLUTIONS
Authors: Sivasundaram Sujit
Published: November 2020

The Pacific has often been invisible in global histories written in the UK. Yet it has consistently been a site for contemplating the past and the future, even among Britons cast on its shores. In this lecture, I reconsider a critical moment of globalisation and empire, the ‘age of revolutions’ at the end of the eighteenth century and the start of the nineteenth century, by journeying with European voyagers to the Pacific Ocean. The lecture will point to what this age meant for Pacific islanders, in social, political and cultural terms. It works with a definition of the Pacific's age of revolutions as a surge of indigeneity met by a counter-revolutionary imperialism. What was involved in undertaking a European voyage changed in this era, even as one important expedition was interrupted by news from revolutionary Europe. Yet more fundamentally vocabularies and practices of monarchy were consolidated by islanders across the Pacific. This was followed by the outworkings of counter-revolutionary imperialism through agreements of alliance and alleged cessation. Such an argument allows me, for instance, to place the 1806 wreck of the Port-au-Prince within the Pacific's age of revolutions. This was an English ship used to raid French and Spanish targets in the Pacific, but which was stripped of its guns, iron, gunpowder and carronades by Tongans. To chart the trajectory from revolution and islander agency on to violence and empire is to appreciate the unsettled paths that gave rise to our modern world. This view foregrounds people who inhabited and travelled through the earth's oceanic frontiers. It is a global history from a specific place in the oceanic south, on the opposite side of the planet to Europe.
CHILDREN AGAINST SLAVERY: JUVENILE AGENCY AND THE SUGAR BOYCOTTS IN BRITAIN
Authors: Gleadle Kathryn , Hanley Ryan
Published: November 2020

In late eighteenth- and early nineteenth-century Britain, many contemporaries observed a striking phenomenon: that children were especially active in the boycotts of sugar produced by enslaved people. First-hand accounts often suggested that children's activism was unilateral and unmediated, whereas historians of British abolitionism have tended to assume that children were passive recipients of antislavery literature and adult influence. Engaging with both the historiography on British abolitionism and the new histories of childhood, this article examines the nature of juvenile engagement within the sugar boycotts. Collecting together some of the extensive but dispersed evidence of juvenile antislavery across the country, and focusing upon a case study of the Plymley household of Shropshire during the early 1790s, we explore the intricacies of children's involvement. Children's agency, we argue, needs to be understood as a specific, historicised phenomenon. Adults often chose to represent children's abolitionist activities as self-determined, for their participation in the boycotts affirmed both adult positions and their own child-rearing practices. However, whilst adults frequently solicited particular types of juvenile response, children often responded independently and in unexpected ways, negotiating their own positions in relation to their parents, siblings, and peers. We situate juvenile antislavery as a recursive process, operating within complex, intergenerational interactions.
THE ‘MARTYRDOM OF THINGS’: ICONOCLASM AND ITS MEANINGS IN THE SPANISH CIVIL WAR
Authors: Vincent Mary
Published: November 2020

The anticlerical violence of the Spanish Civil War has received significant scholarly attention in recent years. However, there has been relatively little focus on the iconoclasm, even though the destruction of objects was easily the most common form of anticlerical violence. Nor has the effect of iconoclastic violence on those who treasured or venerated these objects been examined. This article looks at the emotional significance of the material artefacts that came under attack during the Civil War. It argues that, while some objects were treated simply as the material of which they were made, most provoked more complex interactions. In contrast to most earlier episodes of iconoclasm, these also left a visual record, which shows how the memory of the violence was shaped not only by textual accounts but also by photographs that memorialised and aestheticised it.
Preschoolers benefit from a clear sound-referent mapping to acquire nonnative phonology
Authors: Esteve-Gibert Núria , Muñoz Carmen
Published: November 2020

Previous studies have shown that visual information is a crucial input in early language learning. In the present study we examine what type of visual input helps preschoolers in acquiring nonnative phonological contrasts. Catalan/Spanish-speaking children (4–5 years, N = 47) participated in a task to assess their phonological discrimination abilities before and after a training. Three training conditions were presented: one with clear oral/visual speech information, one with an ostensive object-sound mapping, and one with a rich social interaction. Children’s looking patterns were tracked to examine their focus of interest while being trained. Results revealed that preschoolers’ discrimination abilities increase in all trained conditions, but the condition where the speaker created an ostensive object–sound mapping led to higher long-term gains (especially for younger children). Eye-tracking results further showed that children looked to the object of reference while being exposed to the novel phonological input, which may explain the higher learning gains in this condition. Our results indicate that preschoolers’ learning of nonnative phonological contrasts is particularly boosted when the speech input is accompanied by an object of reference that is signaled ostensively and contingently in the visual space, compared to when the visual space only contains clear oral/visual speech information or social interactivity cues.
The ‘Question of Palestine’: From liminality to emancipation
Authors: Mason Victoria
Published: November 2020

While the gravity of the injustice and inequality experienced by Palestinians is now widely documented, evidenced, and acknowledged, when it comes toactionthe situation appears ‘impervious’ to international law and norms of global politics, with Israel largely enjoying impunity. This article argues that this state of affairs can be most coherently understood through a critical interdisciplinary emancipatory framework centred on ‘liminality’. Referring to situations and actors ‘betwixt and between’, the framework of liminality offers significant potential for understanding how particular actors and spaces are intentionally marginalised, disempowered, and silenced within global politics and international law. Furthermore, in revealing the root causes of liminality, and the inherent vulnerability of such spaces to contestation and subversion, the framework also opens up potential pathways of transformative emancipation. Applying the lens of liminality to Palestine, it is demonstrated that Palestinians have been deliberately corralled to a liminal space within international law and global politics in order to enable an expansionist Zionist/Israeli settler colonial enterprise. After exploring how Palestinian liminality manifests in global politics and international law, the article turns to a range of efforts to subvert Palestinian liminality and assesses prospects for a teleological emancipation for Palestinians.
Assessment of the cognitive attentional syndrome in children: an adaptation of the CAS-1
Authors: Normann Nicoline , Reinholdt-Dunne Marie Louise , Stolpe Andersen Martin , Esbjørn Barbara Hoff
Published: November 2020

Background:

Research suggests that the metacognitive model is applicable to clinical child populations. However, few measures related to the model are available for younger age groups. A key concept of the model is the cognitive attentional syndrome (CAS), which encompasses the individual’s worry and rumination, maladaptive coping strategies, and metacognitive beliefs. While the CAS has been successfully measured in adults, this has not yet been attempted in children.

Aims:

The aim of this study was to adapt a measure of the CAS for use with children and investigate the measure’s associations with anxiety, worry, depression and metacognitions.

Methods:

Our study included 127 children with anxiety disorders aged 7–13 years. The adult measure of CAS was adapted for use with children and administered at pre- and post-treatment. We examined the correlations between variables and the ability of the CAS measure to explain variance in anxious symptomatology, as well as the measure’s sensitivity to treatment change.

Results:

The adapted measure, CAS-1C, displayed strong associations with overall anxiety, depression, worry and metacognitions. The CAS-1C explained an additional small amount of variance in anxiety and worry symptoms after accounting for metacognitions, which may be due to the measure also assessing thinking styles and coping strategies. Furthermore, the measure displayed sensitivity to treatment change.

Conclusions:

The child measure of the CAS is a brief tool for collecting information on metacognitive beliefs and strategies that maintain psychopathology according to the metacognitive model, and it can be used to monitor treatment changes in these components.
Students Learn New Skills with Scientist-in-Training Programs
Authors: Kornei Katherine
Published: November 2020

AGU’s Bright STaRS offers a model for programs to give middle and high school students a taste of what a career in science can offer.
Shaping the Future of Science
Authors: Goss Heather
Published: November 2020

As Earth and space scientists gather this December for AGU’s annual Fall Meeting, Eos looks at the ways in which the community is reimagining itself to create a more diverse and adaptable future.