bluuebunny/crossref_metadata_2025 huggingface dataset:
Biofabrication of 3D breast cancer models for dissecting the cytotoxic response of human T cells expressing engineered MAIT cell receptors
Authors: Dey Madhuri , Kim Myong Hwan , Nagamine Momoka , Karhan Ece , Kozhaya Lina , Dogan Mikail , Unutmaz Derya , Ozbolat Ibrahim T
Published: September 2022

Immunotherapy has revolutionized cancer treatment with the advent of advanced cell engineering techniques aimed at targeted therapy with reduced systemic toxicity. However, understanding the underlying immune–cancer interactions require development of advanced three-dimensional (3D) models of human tissues. In this study, we fabricated 3D tumor models with increasing complexity to study the cytotoxic responses of CD8+ T cells, genetically engineered to express mucosal-associated invariant T (MAIT) cell receptors, towards MDA-MB-231 breast cancer cells. Homotypic MDA-MB-231 and heterotypic MDA-MB-231/human dermal fibroblast tumor spheroids were primed with precursor MAIT cell ligand 5-amino-6-D-ribitylaminouracil (5-ARU). Engineered T cells effectively eliminated tumors after a 3 d culture period, demonstrating that the engineered T cell receptor recognized major histocompatibility complex class I-related (MR1) protein expressing tumor cells in the presence of 5-ARU. Tumor cell killing efficiency of engineered T cells were also assessed by encapsulating these cells in fibrin, mimicking a tumor extracellular matrix microenvironment. Expression of proinflammatory cytokines such as interferon gamma, interleukin-13, CCL-3 indicated immune cell activation in all tumor models, post immunotherapy. Further, in corroborating the cytotoxic activity, we found that granzymes A and B were also upregulated, in homotypic as well as heterotypic tumors. Finally, a 3D bioprinted tumor model was employed to study the effect of localization of T cells with respect to tumors. T cells bioprinted proximal to the tumor had reduced invasion index and increased cytokine secretion, which indicated a paracrine mode of immune–cancer interaction. Development of 3D tumor-T cell platforms may enable studying the complex immune–cancer interactions and engineering MAIT cells for cell-based cancer immunotherapies.
Contact.engineering—Create, analyze and publish digital surface twins from topography measurements across many scales
Authors: Röttger Michael C , Sanner Antoine , Thimons Luke A , Junge Till , Gujrati Abhijeet , Monti Joseph M , Nöhring Wolfram G , Jacobs Tevis D B , Pastewka Lars
Published: September 2022

The optimization of surface finish to improve performance, such as adhesion, friction, wear, fatigue life, or interfacial transport, occurs largely through trial and error, despite significant advancements in the relevant science. There are three central challenges that account for this disconnect: (1) the challenge of integration of many different types of measurement for the same surface to capture the multi-scale nature of roughness; (2) the technical complexity of implementing spectral analysis methods, and of applying mechanical or numerical models to describe surface performance; (3) a lack of consistency between researchers and industries in how surfaces are measured, quantified, and communicated. Here we present a freely-available internet-based application (available athttps://contact.engineering) which attempts to overcome all three challenges. First, the application enables the user to upload many different topography measurements taken from a single surface, including using different techniques, and then integrates all of them together to create a digital surface twin. Second, the application calculates many of the commonly used topography metrics, such as root-mean-square parameters, power spectral density (PSD), and autocorrelation function (ACF), as well as implementing analytical and numerical calculations, such as boundary element modeling (BEM) for elastic and plastic deformation. Third, the application serves as a repository for users to securely store surfaces, and if they choose, to share these with collaborators or even publish them (with a digital object identifier) for all to access. The primary goal of this application is to enable researchers and manufacturers to quickly and easily apply cutting-edge tools for the characterization and properties-modeling of real-world surfaces. An additional goal is to advance the use of open-science principles in surface engineering by providing a FAIR database where researchers can choose to publish surface measurements for all to use.
Effect of extrusion ratio on microstructure and mechanical properties of Mg-6Sn-3Al-1Zn alloy
Authors: Zhou Shihao , Wei Fuan , Wang Jinhui , Jin Peipeng
Published: September 2022

The Mg–6Sn–3Al–1Zn (wt%) alloy was prepared by casting and then deformed by hot extrusion at 350 °C with different extrusion ratios (9:1, 13:1, 20:1), extrusion rate was 20 mm min−1. The microstructure of as-extruded alloy was analyzed by XRD and EBSD, the tensile properties were tested by a universal testing machine. The results showed that there underwent processing hardening and recrystallization softening simultaneously during the process thermal deformation. Dynamic recrystallization (DRX) mainly occurred at the grain boundary of the deformed grain, with the extrusion ratio increased, the volume fraction of the dynamic recrystallization grain of alloy increased. When the extrusion ratio was less than or equal to 13:1, the average grain size decreased with the extrusion ratio increased. When the extrusion ratio reached up to 20:1, the average grain size increased. {0001} basal plane texture formed after the alloy extruded, and it paralleled to the extrusion direction, the texture intensity decreased first and then increased as the extrusion ratio increased. With the extrusion ratio increased from 9:1 to 20:1, the tensile properties increased first and then declined. Among all the tested alloys, the alloy with the extrusion ratio of 13:1 exhibited the optimum mechanical properties, the yield strength, tensile strength and elongation of alloy was 320 MPa, 371 MPa and 13.5%, the texture strength of the alloy was 8.26, the average grain size was 1.5 μm.
Dementia—so much done, so much to do, so much to gain by doing so
Authors: Banerjee Sube
Published: September 2022

Background

it has been a busy 50 years for dementia, a complicated voyage from obscurity and neglect towards recognition, knowledge and action. This commentary sets out that path through research, practice and policy to examine what we have achieved, where we are now and what more there is to be done.

Findings

the main themes identified were as follows:

Conclusions

we have made substantial advances in cause, cure, and care research and practice. Moving to deliver solutions to improve dementia care would be of major value to the whole health and care system.
Successful in vitro fertilization in the horse: production of blastocysts and birth of foals after prolonged sperm incubation for capacitation
Authors: Felix Matheus R , Turner Regina M , Dobbie Tamara , Hinrichs Katrin
Published: September 2022

Methods for standard in vitro fertilization have been difficult to establish in the horse. We evaluated whether prolonged sperm pre-incubation would support subsequent fertilization. Fresh sperm were pre-incubated with penicillamine, hypotaurine, and epinephrine (PHE) for 22 h. Co-incubation of cumulus-oocyte complexes (COCs) for 6 h yielded 43% fertilization; culture of presumptive embryos yielded 21% blastocysts. Sperm incubated similarly, but without PHE, did not fertilize oocytes. Use of extended semen in the system yielded 54% blastocysts and was applied in subsequent experiments. Transfer of three in vitro fertilization-produced blastocysts to recipient mares resulted in birth of three normal foals. When sperm were pre-incubated for 22 h, 47–79% of oocytes were fertilized after 1 h of co-incubation. Sperm pre-incubated for 15 min or 6 h before co-incubation yielded no fertilization at 1 h, suggesting that capacitation in this system requires between 6 and 22 h. Sperm assessed after 15 min, 6 h, or 22 h pre-incubation showed increasing protein tyrosine phosphorylation of the midpiece, equatorial band, and apical head; this pattern differed from that induced by high pH conditions and may denote functional equine sperm capacitation. Use of the final devised system, i.e., extended semen, with 22 h of sperm pre-incubation and 3 h of COC co-incubation, yielded 90% fertilization with a blastocyst rate of 74%. This is the first report of efficient and repeatable standard in vitro fertilization in the horse and the first report of in vitro production of blastocysts and resulting foals after in vitro fertilization.
In Reply to Performance of Deep Learning in the Interpretation of Serum Protein Electrophoresis
Authors: Chabrun Floris , Dieu Xavier , Reynier Pascal , Mirebeau-Prunier Delphine
Published: September 2022

We thank He et al. for their comments on our article (1), which gives us the opportunity to clarify some methodological points.

1. Detection of abnormal patterns: mechanics.
Successful Dietary Therapy in Paediatric Crohn’s Disease is Associated with Shifts in Bacterial Dysbiosis and Inflammatory Metabotype Towards Healthy Controls
Authors: Verburgt Charlotte M , Dunn Katherine A , Ghiboub Mohammed , Lewis James D , Wine Eytan , Sigall Boneh Rotem , Gerasimidis Konstantinos , Shamir Raanan , Penny Susanne , Pinto Devanand M , Cohen Alejandro , Bjorndahl Paul , Svolos Vaios , Bielawski Joseph P , Benninga Marc A , de Jonge Wouter J , Van Limbergen Johan E
Published: September 2022

Background and aims

Nutritional therapy with the Crohn’s Disease Exclusion Diet + Partial Enteral Nutrition [CDED+PEN] or Exclusive Enteral Nutrition [EEN] induces remission and reduces inflammation in mild-to-moderate paediatric Crohn’s disease [CD]. We aimed to assess if reaching remission with nutritional therapy is mediated by correcting compositional or functional dysbiosis.

Methods

We assessed metagenome sequences, short chain fatty acids [SCFA] and bile acids [BA] in 54 paediatric CD patients reaching remission after nutritional therapy [with CDED + PEN or EEN] [NCT01728870], compared to 26 paediatric healthy controls.

Results

Successful dietary therapy decreased the relative abundance of Proteobacteria and increased Firmicutes towards healthy controls. CD patients possessed a mixture of two metabotypes [M1 and M2], whereas all healthy controls had metabotype M1. M1 was characterised by high Bacteroidetes and Firmicutes, low Proteobacteria, and higher SCFA synthesis pathways, and M2 was associated with high Proteobacteria and genes involved in SCFA degradation. M1 contribution increased during diet: 48%, 63%, up to 74% [Weeks 0, 6, 12, respectively.]. By Week 12, genera from Proteobacteria reached relative abundance levels of healthy controls with the exception of E. coli. Despite an increase in SCFA synthesis pathways, remission was not associated with increased SCFAs. Primary BA decreased with EEN but not with CDED+PEN, and secondary BA did not change during diet.

Conclusion

Successful dietary therapy induced correction of both compositional and functional dysbiosis. However, 12 weeks of diet was not enough to achieve complete correction of dysbiosis. Our data suggests that composition and metabotype are important and change quickly during the early clinical response to dietary intervention. Correction of dysbiosis may therefore be an important future treatment goal for CD.
Making Terrorism Thinkable: The Philosophy of the Act and Its Reception in German Thought, 1794–1845
Authors: Ries Klaus
Published: September 2022

This article challenges the widespread assumption that terrorist ideology was invented in the mid-nineteenth century by figures such as Pierre-Joseph Proudhon and Mikhail Bakunin. Instead, the article argues, the foundations of terrorism were laid at the end of the eighteenth century by the Enlightenment philosopher Johann Gottlieb Fichte and his disciples, who in turn exerted a strong influence on later radical thinkers. In showing how the intellectual reverberations of the French Revolution gave rise to anarchist ideology as well as actual acts of terrorism in Germany, the article traces the link between the state terror of the French Revolution and the emergence of insurgent terrorism.
Site-specific decreases in DNA methylation in replicating cells following exposure to oxidative stress
Authors: Seddon Annika R , Das Andrew B , Hampton Mark B , Stevens Aaron J
Published: September 2022

Oxidative stress is a common feature of inflammation-driven cancers, and it promotes genomic instability and aggressive tumour phenotypes. It is known that oxidative stress transiently modulates gene expression through the oxidation of transcription factors and associated regulatory proteins. Neutrophils are our most abundant white blood cells and accumulate at sites of infection and inflammation. Activated neutrophils produce hypochlorous acid and chloramines, which can disrupt DNA methylation by oxidizing methionine. The goal of the current study was to determine whether chloramine exposure results in sequence-specific modifications in DNA methylation that enable long-term alterations in transcriptional output. Proliferating Jurkat T-lymphoma cells were exposed to sublethal doses of glycine chloramine and differential methylation patterns were compared using Illumina EPIC 850 K bead chip arrays. There was a substantial genome-wide decrease in methylation 4 h after exposure that correlated with altered RNA expression for 24 and 48 h, indicating sustained impacts on exposed cells. A large proportion of the most significant differentially methylated CpG sites were situated towards chromosomal ends, suggesting that these regions are most susceptible to inhibition of maintenance DNA methylation. This may contribute to epigenetic instability of chromosomal ends in rapidly dividing cells, with potential implications for the regulation of telomere length and cellular longevity.
Reducing Blood Loss in a Burn Care Unit: A Review of Its Key Determinants
Authors: Souto João , Rodrigues Acacio Goncalves
Published: September 2022

Patients with a major burn injury differ considerably from the typical critical ill and trauma population. Very often, burn patients suffer from anemia throughout their hospital stay. This is caused both by combination of persistent blood loss with decreased erythropoiesis. Therefore, burn patients do have major transfusion requirements. However, transfusion is not devoid of risks or costs. We hereby review the best surgical techniques and medical approaches, aiming to reduce blood loss in a burn patient and optimize red cell production, so that we can reduce the need of RBC transfusion. The implementation of a combination of surgical techniques aiming to reduce blood loss and medical care approaches to prevent anemia, rather than single attitudes, should be adopted in burn care. There is an urgent need for clear guidelines that can easily be accepted, applied, and spread across different burn units to methodically implement measures to reduce blood loss and transfusion needs, and ultimately improve burn patients’ outcome and the health care financial status.
Abbreviated Molecular Breast Imaging: Feasibility and Future Considerations
Authors: Maimone Santo , Morozov Andrey P , Letter Haley P , Robinson Kristin A , Wasserman Martha C , Li Zhuo , Maxwell Robert W
Published: September 2022

Objective

Molecular breast imaging (MBI) is a supplemental screening modality consistently demonstrating incremental cancer detection over mammography alone; however, its lengthy duration may limit widespread utilization. The study purpose was to assess feasibility of an abbreviated MBI protocol, providing readers with mediolateral oblique (MLO) projections only and assessing performance in lesion detection and localization.

Methods

Retrospective IRB-exempt blinded reader study administered to 5 fellowship-trained breast imaging radiologists. Independent reads performed for 124 screening MBI cases, half abnormal and half negative/normal. Readers determined whether an abnormality was present, side of abnormality, and location of abnormality (medial/lateral). Abnormal cases had confirmatory biopsy or surgical pathology; normal cases had imaging follow-up ensuring true negative results. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were calculated to assess performance. A false negative result indicated that a reader failed to detect abnormal uptake; a false positive result indicated a reader incorrectly called an abnormality for a negative case. Tests for association included chi-square, Fisher-exact, and analysis of variance.

Results

Mean reader performance for detecting abnormal uptake: sensitivity 96.8%, specificity 98.7%, PPV 98.8%, and NPV 96.9%. Accuracy in localizing lesions to the medial or lateral breast was 100%. There were no associations in reader performance with reader experience, reader technique, lesion morphology, or lesion pathology. Median lesion size was 1.0 cm (range: 0.4–8.0 cm). All readers correctly identified 97.7% (42/43) of lesions with malignant or elevated risk pathology.

Conclusion

An abbreviated MBI protocol (MLO images only) maintained high accuracy in lesion detection and localization.
The mitochondrial genomes of Enoplolambrus validus (De Haan, 1837) and Jonas distinctus (De Haan, 1835) (Decapoda: Brachyura: Parthenopoidea, Corystoidea): a novel gene rearrangement and phylogenetic implications
Authors: Liu Cai-Xin , Gu Tian-Yu , Wang Lu-Yao , Shi Bo-Yang , Wang Ru-Xiao , Pan Da , Sun Hong-Ying
Published: September 2022

A complete mitochondrial genome (mitogenome) of Enoplolambrus validus (De Haan, 1837) (Parthenopoidea) and a near complete mitochondrial genome of Jonas distinctus (De Haan, 1835) (Corystoidea) were sequenced and characterized. Their lengths are 15,431 bp and 16,152 bp, respectively. Both mitogenomes comprise 13 protein-coding genes (PCGs), two ribosomal RNA genes, and 22 transfer RNA genes. A novel gene rearrangement pattern with seven rearranged genes was found in the mitogenome of J. distinctus. The nucleotide compositions of the two mitogenomes are biased towards A/T. The phylogenetic relationship of Brachyura from 57 mitogenomes was reconstructed with two species of Anomura as outgroups by both Bayesian inference and maximum likelihood methods using sequences of 13 protein coding genes. The freshwater crabs, (Gecarcinucoidea and Potamoidea) are sister to species of Thoracotremata. Our results do not support the monophyly of Heterotremata. Enoplolambrus validus and J. distinctus are clustered with species of six other superfamilies but the phylogenetic relationships among these superfamilies are largely unresolved. Our results provide valuable resources for understanding the mitogenome evolutionary pattern and phylogenetic relationships within Brachyura.
Toxicity and prosocial behaviors in massively multiplayer online games: The role of mutual dependence, power, and passion
Authors: Zhu Zicheng , Zhang Renwen , Qin Yuren
Published: September 2022

Understanding factors that predict toxic and prosocial behavior in massively multiplayer online (MMO) games has drawn a great deal of scholarly attention. Prior work on this topic has primarily focused on individual and technological factors while overlooking the role of interpersonal dynamics. To fill this gap, this study examines if and how players’ perceptions of mutual dependence and power in MMO games are related to toxicity and prosocial behavior in games. Results from a survey of 782 Chinese game players suggest that players’ perceived power is positively related to prosocial behavior in games. Perceived mutual dependence and power are also indirectly related to prosocial and toxic behaviors through players’ passion for games. This study has theoretical implications for scholarship on toxicity, prosocial behaviors, and gameplay, while also providing design and policy implications for MMO games.
Reference genome of the Woolly Sculpin,Clinocottus analis
Authors: Wright Daniel B , Escalona Merly , Marimuthu Mohan P A , Sahasrabudhe Ruta , Nguyen Oanh , Sacco Samuel , Beraut Eric , Toffelmier Erin , Miller Courtney , Shaffer H Bradley , Bernardi Giacomo
Published: September 2022

Sculpins (Family Cottidae) are generally cold-temperate intertidal reef fishes most commonly found in the North Pacific. As part of the California Conservation Genomics Project (CCGP), we sequenced the genome of the Woolly Sculpin, Clinocottus analis, to establish a genomic model for understanding phylogeographic structure of inshore marine taxa along the California coast. These patterns, in turn, should further inform the design of marine protected areas using dispersal models based on genomic data. The small genome of C. analis is typical of marine fishes at less than 1 Gb (genome size = 538 Mb), and our assembly is near-chromosome level (contig N50 = 9.1 Mb, scaffold N50 = 21 Mb, BUSCO completeness = 97.9%). Within the context of the CCGP, the Woolly Sculpin genome will be used as a reference for future whole-genome resequencing projects aimed at enhancing our knowledge of the population structure of the species, and efficacy of marine protected areas across the state.
Europe’s Human Rights Court rules for the first time on a breach of a copyright holder’s right to property in a private dispute
Authors: Izyumenko Elena
Published: September 2022

The European Court of Human Rights has recently ruled that the domestic courts’ failure to justify the grounds for dismissing the applicant’s copyright infringement claim in a private-party dispute concerning the unauthorized online reproduction of the applicant’s book breached the latter’s human right to property. Notably, the Court was not satisfied with the fact that the national courts had not persuasively explained their conclusions regarding the applicability in the applicant’s case of digital exhaustion and of copyright exceptions for libraries and private copying.
Forest disturbance and occupancy patterns of American ermine (Mustela richardsonii) and long-tailed weasel (Neogale frenata): results from a large-scale natural experiment in Maine, United States
Authors: Evans Bryn E , Mortelliti Alessio
Published: September 2022

Weasels are small mustelid carnivores that play an important role as predators of small mammals in a wide array of ecosystems. However, their response to land use, such as forest harvest for timber products, is seldom the subject of focused research and management projects. Both the American ermine, also known as the short-tailed weasel (Mustela richardsonii), and the long-tailed weasel (Neogale frenata) are native to Maine, United States, where commercial timber harvesting is widespread. The effects of this forest disturbance on weasels are poorly understood, so to contribute toward filling this knowledge gap, we conducted a 4-year, large-scale field study: specifically, our objective was to assess the effects of forest disturbance caused by timber harvest on occupancy patterns of ermines and long-tailed weasels occupancy patterns in Maine. We collected data from 197 survey sites (three camera traps each) over 4 years and analyzed over 7,000 images of weasels using dynamic false-positive occupancy models. We found that American ermines were widely distributed across the state (naïve occupancy at 54% of sites), while long-tailed weasels were rarer (naïve occupancy at 16% of sites). Both species responded positively to forest disturbance, with higher occupancy probabilities as disturbance increased, especially at the larger scales. American ermines were more likely to occupy stands with a higher percentage of conifer trees, while no such relationship was found for long-tailed weasels. We conclude that current forest harvest practices in Maine are not detrimental to weasel populations, but that the two species warrant continued monitoring.
Attitudes towards adherence and deprescribing among polypharmacy patients: a cross-sectional study
Authors: Nusair Mohammad B , Khasawneh Rawand , Al-azzam Sayer , Al-Shuqairat Tala , Khair Zaid M , Arabyat Rasha
Published: September 2022

Objectives

Deprescribing is the process of optimization of medication regimens through cessation of potentially inappropriate or unnecessary medications or adjustment of doses with the goal of managing polypharmacy and improving outcomes. Deprescribing potentially improves adherence by reducing polypharmacy. This study aimed to assess polypharmacy patients’ adherence attitudes and their attitudes towards deprescribing.

Methods

A cross-sectional study that targeted polypharmacy patients at outpatient clinics at King Abdullah University Hospital. The inclusion criteria were (1) patients ≥18 years old, (2) patients taking five or more medications, and (3) patients who do not require a caregiver or assistance at home. We excluded patients that showed any signs of moderate or severe cognitive impairment. Patients who met the inclusion/exclusion criteria were interviewed by a clinical pharmacist and completed two survey instruments: revised Patients’ Attitudes Toward Deprescribing (rPATD) and Adherence Attitude Inventory (AAI).

Key findings

In total, 501 patients took part in this study. Over half of the participants were not satisfied with their current medicines and over 70% of them perceived that their current medications are a burden to them and would like their prescribers to initiate deprescribing. The majority of the participants have low to medium adherence attitudes primarily due to ineffective patient–provider communication. Logistic regression analysis revealed that self-efficacy, commitment to adherence, education and age were significantly associated with participants’ willingness to stop one or more of their medications.

Conclusions

Our findings suggest that polypharmacy patients have negative attitudes towards their medication therapy and favour deprescribing. These reported attitudes had been associated with negative adherence attitudes. Study findings offer schematic direction for future investigations of the role of adherence on key health-related outcomes in patients on polypharmacy. Furthermore, research is warranted to investigate the impact of deprescribing on polypharmacy patients’ medication adherence.
Analysis of the influence of perceived self-efficacy on organizational performance among pharmaceutical managers: a structural equation study
Authors: Ehidiamen Oamen Theophilus
Published: September 2022

Objective

To investigate the influence of perceived self-efficacy on organizational performance among operational, product and strategic managers in the pharmaceutical marketing industry.

Method

A cross-sectional study with a literature-based questionnaire administered to 241 managers proportioned across operational, product and strategic managerial roles using stratified random sampling. Structural equation modeling techniques in the analysis of moment structures software were used to examine causal relations between predictor and outcome variables. Study hypotheses were tested using inferential statistical measures with a P-value of < 0.05.

Key findings

A large number of respondents were operational sales managers (n = 138, 57.3%), followed by strategic managers (n = 64, 25.6%), and the least was product managers (n = 39, 16.2%). The measurement models of self-efficacy, organizational performance constructs and structural models had acceptable measures of fit. Three first-order constructs were derived from the self-efficacy construct namely: self-adaptability (regression coefficient, β = 0.237, P < 0.025), self-efficiency (β = 0.574, P < 0.001), and self-creativity (β = 0.649, P < 0.003). Structural equation modelling revealed a significant positive effect of perceived self-efficacy on organizational performance (R2 = 0.65, β = 0.651, P < 0.003). Simple plot analysis revealed lower performance scores at a moderate level of self-efficacy with operational sales managers compared to strategic and product managers. Multigroup analysis revealed no confounding effect of gender and type of firm on the hypothesized relationship (P > 0.05).

Conclusions

This study contributed another dimension to extant research on the relationship between perceived self-efficacy and performance among pharmaceutical managers. The study suggests targeted management training and collaborative learning for managers to improve their level of self-efficacy. Focal and routine training to enhance work-based competencies, professional development and problem-solving skills of pharmaceutical managers are advocated.
Observations of the October Draconid outburst at different latitudes along 120°E
Authors: Li Yi , Li Guozhu , Hu Lianhuan , Zhao Xiukuan , Sun Wenjie , Xie Haiyong , Yang Sipeng , Ning Baiqi
Published: September 2022

The observations of short-duration meteor showers at different geographic locations are important for well understanding of their outbursts. Using the four all-sky interferometric meteor radars at Mohe (53.49°N, 122.34°E), Beijing (40.3°N, 116.19°E), Wuhan (30.54°N, 114.34°E), and Ledong (18.44°N, 108.97°E) in China, four outbursts (2011, 2012, 2018, and 2019) of the October Draconid meteor shower were observed between 2011 and 2021. The October Draconid meteor velocity was concentrated around 22∼23 km s−1, with an active duration of 6∼9 h and a main peak around the solar longitude 194.73°∼195.63°. When comparing the hourly rates of the October Draconid meteor shower for different years at Mohe, a maximum (minimum) of peak flux was observed in 2012 (2011). The radiants and orbit parameters of the October Draconid meteors derived from the radars at different latitudes are consistent, except that the weighted mean echo height during the peak activity at Mohe was always lower than that at other stations.
Non-gravitational parameters and orbital stability of asteroids in retrograde orbits
Authors: Wlodarczyk I
Published: September 2022

We studied the dynamical evolution of all numbered and selected unnumbered asteroids in a retrograde orbit. We computed the absolute magnitude, size range, and non-gravitational parameters A2 and $Lyapunov\, times$ during the 2 Myr forward and backward orbital evolution of all 21 studied retrograde asteroids. We also studied non-gravitation parameters of 10 unnumbered retrograde asteroids brighter than 18.1 mag. It turns out that the values of A2 are of a similar order as for comets, i.e. on average, a few orders more than in the case of asteroids that are moving in prograde orbits. We investigated how the change of the non-gravitational effect influences the Lyapunov time and the evolution of the semimajor-axis-selected retrograde orbits during the forward and backward integration. We also indicated the roles of Lidov–Kozai resonance in the orbital evolution of the retrograde asteroid.
On the origin and characteristic features of the V1 layer in Venus ionosphere using Akatsuki radio science experiment and the one-dimensional photochemical model
Authors: Ambili K M , Tripathi K R , Choudhary R K , Imamura T
Published: September 2022

Using the radio science experiment onboard the Akatsuki spacecraft and an in-house developed one-dimensional photochemical model (1D-PCM) characteristic features of the V1 layer in Venus ionosphere, which peaks ∼125 km, have been studied. The shape of a V1 layer is highly variable; it can appear from mere as a slope change below the V2 layer to a clear prominent layer peak. We simulated the observations using 1D-PCM and found that the model solar X-ray flux at 1.5–3 nm and 5–10 nm bands need to be enhanced by a factor of 2–4 to reproduce a V1 layer. The model simulations also show that major ions below 135 km are O$_2^+$ and NO+ with O$_2^+$ increasing linearly up to ∼135 km, while NO+ peaks at around 127 km. Our analysis shows that for a case when the V1 layer appears as a slope change below the V2 layer, O$_2^+$ ions are the dominant ions, whereas the NO+ ions are the major ion when a clear V1 peak appears. When both the ion densities are comparable, the layer appears as a ledge.
Mepolizumab administration for eosinophilic granulomatosis with polyangiitis in an elderly patient with an abrupt onset of limb ischaemia and peripheral neuropathy: A case-based literature review
Authors: Terashima Seika , Yamaguchi Makoto , Ishihara Tomomi , Hagita Junichiro , Katsuno Takayuki , Ito Mayumi , Sugiyama Hirokazu , Iwagaitsu Shiho , Nobata Hironobu , Kinashi Hiroshi , Ishimoto Takuji , Banno Shogo , Ito Yasuhiko
Published: September 2022

Eosinophilic granulomatosis with polyangiitis (EGPA) is a type of anti-neutrophil cytoplasmic antibody-associated vasculitis characterised by small- to medium-sized vessel vasculitis and is typically associated with eosinophilic granulomatous inflammation. EGPA can affect any organ system, most commonly the lungs, skin, and the nervous system. However, limb ulcers are rare complications and have only been described in few case reports. Furthermore, no documented cases of EGPA have been treated with mepolizumab. Herein, we report a case of an 86-year-old Japanese woman with anti-neutrophil cytoplasmic antibody-negative EGPA, who had an abrupt onset of upper limb ulcers and bilateral foot drop due to multiple mononeuropathy. Clinicopathological sural nerve biopsy showed eosinophil-associated vascular damage. The patient was administered steroids, intravenous immunoglobulin, vasodilators, and mepolizumab; this resulted in clinical improvement of her finger ulcers and peripheral neuropathy without any adverse effects. In cases of an abrupt onset of limb ischaemia and peripheral neuropathy, physicians should consider the possibility of EGPA as a differential diagnosis. Furthermore, the early administration of mepolizumab might yield better outcomes in terms of improving limb ischaemia and peripheral neuropathy.
High-throughput identification of RNA localization elements in neuronal cells
Authors: Arora Ankita , Castro-Gutierrez Roberto , Moffatt Charlie , Eletto Davide , Becker Raquel , Brown Maya , Moor Andreas E , Russ Holger A , Taliaferro J Matthew
Published: September 2022

Hundreds of RNAs are enriched in the projections of neuronal cells. For the vast majority of them, though, the sequence elements that regulate their localization are unknown. To identify RNA elements capable of directing transcripts to neurites, we deployed a massively parallel reporter assay that tested the localization regulatory ability of thousands of sequence fragments drawn from endogenous mouse 3′ UTRs. We identified peaks of regulatory activity within several 3′ UTRs and found that sequences derived from these peaks were both necessary and sufficient for RNA localization to neurites in mouse and human neuronal cells. The localization elements were enriched in adenosine and guanosine residues. They were at least tens to hundreds of nucleotides long as shortening of two identified elements led to significantly reduced activity. Using RNA affinity purification and mass spectrometry, we found that the RNA-binding protein Unk was associated with the localization elements. Depletion of Unk in cells reduced the ability of the elements to drive RNAs to neurites, indicating a functional requirement for Unk in their trafficking. These results provide a framework for the unbiased, high-throughput identification of RNA elements and mechanisms that govern transcript localization in neurons.
Targeting the TREM1-positive myeloid microenvironment in glioblastoma
Authors: Filippova Natalia , Grimes Jeffrey M , Leavenworth Jianmei W , Namkoong David , Yang Xiuhua , King Peter H , Crowley Michael , Crossman David K , Nabors L Burt
Published: September 2022

Background

Tumor cellular and molecular heterogeneity is a hallmark of glioblastoma and underlies treatment resistance and recurrence. This manuscript investigated the myeloid-derived microenvironment as a driver of glioblastoma heterogeneity and provided a pharmacological pathway for its suppression.

Methods

Transcriptomic signatures of glioblastoma infiltrated myeloid-derived cells were assessed using R2: genomic platform, Ivy Glioblastoma Spatial Atlas, and single-cell RNA-seq data of primary and recurrent glioblastomas. Myeloid-derived cell prints were evaluated in five PDX cell lines using RNA-seq data. Two immunocompetent mouse glioblastoma models were utilized to isolate and characterize tumor-infiltrated myeloid-derived cells and glioblastoma/host cell hybrids. The ability of an inhibitor of HuR dimerization SRI42127 to suppress TREM1+-microenvironment and glioblastoma/myeloid-derived cell interaction was assessed in vivo and in vitro.

Results

TREM1+-microenvironment is enriched in glioblastoma peri-necrotic zones. TREM1 appearance is enhanced with tumor grade and associated with poor patient outcomes. We confirmed an expression of a variety of myeloid-derived cell markers, including TREM1, in PDX cell lines. In mouse glioblastoma models, we demonstrated a reduction in the TREM1+-microenvironment and glioblastoma/host cell fusion after treatment with SRI42127. In vitro assays confirmed inhibition of cell fusion events and reduction of myeloid-derived cell migration towards glioblastoma cells by SRI42127 and TREM1 decoy peptide (LP17) versus control treatments.

Conclusions

TREM1+-myeloid-derived microenvironment promulgates glioblastoma heterogeneity and is a therapeutic target. Pharmacological inhibition of HuR dimerization leads to suppression of the TREM1+-myeloid-derived microenvironment and the neoplastic/non-neoplastic fusogenic cell network.
Determinants of tumor treating field usage in patients with primary glioblastoma: A single institutional experience
Authors: Ballo Matthew T , Qualls Kaitlin W , Michael L Madison , Sorenson Jeffrey M , Baughman Brandon , Karri-Wellikoff Saradasri , Pandey Manjari
Published: September 2022

Background

Determinates of tumor treating fields (TTFields) usage in patients receiving combined modality therapy for primary IDH wild-type glioblastoma are currently unknown.

Methods

Ninety-one patients underwent maximal debulking surgical resection, completed external beam radiotherapy with concurrent Temozolomide (TMZ), and initiated adjuvant TMZ with or without TTFields. We performed a retrospective analysis of patient, tumor, and treatment-related factors that affected TTFields usage.

Results

We identified three TTFields usage subgroups: 32 patients that declined TTFields, 40 patients that started, but had monthly compliance of less than 75% or used it for less than 2 months, and 19 patients who used TTFields for 2 or more months and maintained average monthly compliance greater than 75%. With 26.5 months median follow-up for surviving patients, the 1- and 3-year actuarial overall survival for all patients was 80% and 18%, respectively. On multivariate analysis TTFields use (P = .03), extent of surgical resection (P = 0.02), and MGMT methylation status (P = .01) were significantly associated with overall survival. TTFields usage was explored as a continuous variable and higher average usage was associated with longer overall survival (P = .03). There was no relationship between patient, tumor, or treatment-related factors and a patient’s decision to use TTFields.

Conclusions

No subgroup of patients was more or less likely to initiate TTFields therapy and no subgroup was more or less likely to use TTFields as prescribed. The degree of TTFields compliance may be associated with improved survival independent of other factors.
Soft, biocompatible materials and skin-like electronics as wearable devices: an interview with John A. Rogers
Authors: Song By Enming
Published: September 2022

Recent advances in active materials, micro-fabrication techniques, ultra-miniaturized design approaches and hybrid device layouts form the foundations for emerging classes of unusual systems that can capture physiological signals from the human body in a physically imperceptible fashion at nearly any anatomical location, external on the skin or internal on vital organ systems. Of particular interest with these technologies are their thin geometries, flexible/stretchable physical properties and unique form factors, to enable conformal and gentle contacts with soft, curved and dynamic surfaces of living tissues. Commercial embodiments of skin-integrated devices with clinical-grade monitoring capabilities are just now becoming widely available not only in developed countries but also in the most resource-constrained areas of the globe. A specific example is in skin-like—sometimes referred to as ‘epidermal’—wireless electronics for continuous monitoring of essential markers of physiological health status, with accuracy and reliability comparable to that of expensive, wired-based systems currently used with patients in intensive care units, but cost-effectively and applicable in any setting—in hospitals, health clinics, work environments or in the home. These technologies have the potential to revolutionize diagnostic and therapeutic approaches for the care of patients.

NSR spoke to one of the scientific leaders in this field—a 2009 MacArthur Fellow, the winner of the 2022 US National Academy of Sciences James Prize in Science and Technology Integration and one of the few individuals in history to be elected to all three US National Academies, namely the National Academy of Engineering, the National Academy of Science and the National Academy of Medicine, Professor John A. Rogers, the Director of the Querrey-Simpson Institute of Bioelectronics at Northwestern University on the recent advancements and the prospects of soft, biocompatible electronic systems and skin-like wearable devices.
Standardization of Epidemiological Surveillance of Rheumatic Heart Disease
Authors: Scheel Amy , Miller Kate M , Beaton Andrea , Katzenellenbogen Judith , Parks Tom , Cherian Thomas , Van Beneden Chris A , Cannon Jeffrey W , Moore Hannah C , Bowen Asha C , Carapetis Jonathan R ,   for the Strep A Vaccine Global Consortium (SAVAC) Burden of Disease Working Group
Published: September 2022

Rheumatic heart disease (RHD) is a long-term sequela of acute rheumatic fever (ARF), which classically begins after an untreated or undertreated infection caused by Streptococcus pyogenes (Strep A). RHD develops after the heart valves are permanently damaged due to ARF. RHD remains a leading cause of morbidity and mortality in young adults in resource-limited and low- and middle-income countries. This article presents case definitions for latent, suspected, and clinical RHD for persons with and without a history of ARF, and details case classifications, including differentiating between definite or borderline according to the 2012 World Heart Federation echocardiographic diagnostic criteria. This article also covers considerations specific to RHD surveillance methodology, including discussions on echocardiographic screening, where and how to conduct active or passive surveillance (eg, early childhood centers/schools, households, primary healthcare), participant eligibility, and the surveillance population. Additional considerations for RHD surveillance, including implications for secondary prophylaxis and follow-up, RHD registers, community engagement, and the negative impact of surveillance, are addressed. Finally, the core elements of case report forms for RHD, monitoring and audit requirements, quality control and assurance, and the ethics of conducting surveillance are discussed.
Open-Label Placebo for the Treatment of Cancer-Related Fatigue in Patients with Advanced Cancer: A Randomized Controlled Trial
Authors: Yennurajalingam Sriram , Azhar Ahsan , Lu Zhanni , Rodriguez Ashley J , Arechiga Adrienne B , Guerra-Sanchez Maria , Stanton Penny , Andersen Clark R , Urbauer Diana L , Bruera Eduardo
Published: September 2022

Background

The purpose of this study was to determine the effects of an open-labeled placebo (OLP) compared to a waitlist control (WL) in reducing cancer-related fatigue (CRF) in patients with advanced cancer using Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F).

Materials and Methods

In this randomized controlled trial, patients with fatigue ≥4/10 on Edmonton Symptom Assessment Scale (ESAS) were randomized to OLP one tablet twice a day or WL for 7 days. On day 8, patients of both arms received a placebo for 3 weeks. Changes in FACIT-F from baseline to day 8 (primary outcome) and at day 29, were assessed. Secondary outcomes included FACT-G, Multidimensional Fatigue Symptom Inventory-SF, Fatigue cluster (defined as a composite of ESAS fatigue, pain, and depression), Center for epidemiologic studies-depression, Godin leisure-time physical activity questionnaire, and global symptom evaluation.

Results

A total of 84/90 (93%) patients were evaluable. The mean (SD) FACIT-F change at day 8 was 6.6 (7.6) after OLP, vs. 2.1 (9.4) after WL (P = .016). On days 15 and 29, when all patients received OLP, there was a significant improvement in CRF and no difference between arms. There was also a significant improvement in ESAS fatigue, and fatigue cluster score in the OLP arm on day 8 of the study (0.029, and 0.044, respectively). There were no significant differences in other secondary outcomes and adverse events between groups.

Conclusions

Open-labeled placebo was efficacious in reducing CRF and fatigue clusters in fatigued advanced cancer patients at the end of 1 week. The improvement in fatigue was maintained for 4 weeks. Further studies are needed.
On Powers BSAs
Authors: Friend Toby
Published: September 2022

Can the desire for efficiently systematised theories in science be explained from within a powers metaphysics? It is plausible that the traditional ‘Powers Theory of Laws’, endorsed by many friends of powers, does not alone provide such an explanation. This has led a number of recent authors to argue that a ‘Powers Best System Account’ of laws would be a preferable alternative. This account borrows a method for determining laws from the Humean and applies it to a reality of powers. Here I claim, to the contrary, that this account is both internally unworkable and, anyway, completely undermotivated when compared with the traditional view. Apart from some brief suggestions for alternative accounts, I’ll conclude that the powers theorist still has their work cut out to explain systematising in science.
Successful stopping of biologic therapy for remission in children and young people with juvenile idiopathic arthritis
Authors: Kearsley-Fleet Lianne , Baildam Eileen , Beresford Michael W , Douglas Sharon , Foster Helen E , Southwood Taunton R , Hyrich Kimme L , Ciurtin Coziana
Published: September 2022

Objectives

Clinicians concerned about long-term safety of biologics in JIA may consider tapering or stopping treatment once remission is achieved despite uncertainty in maintaining drug-free remission. This analysis aims to (i) calculate how many patients with JIA stop biologics for remission, (ii) calculate how many later re-start therapy and after how long, and (iii) identify factors associated with re-starting biologics.

Methods

Patients starting biologics between 1 January 2010 and 7 September 2021 in the UK JIA Biologics Register were included. Patients stopping biologics for physician-reported remission, those re-starting biologics and factors associated with re-starting, were identified. Multiple imputation accounted for missing data.

Results

Of 1451 patients with median follow-up of 2.7 years (IQR 1.4, 4.0), 269 (19%) stopped biologics for remission after a median of 2.2 years (IQR 1.7, 3.0). Of those with follow-up data (N = 220), 118 (54%) later re-started therapy after a median of 4.7 months, with 84% re-starting the same biologic. Patients on any-line tocilizumab (prior to stopping) were less likely to re-start biologics (vs etanercept; odds ratio [OR] 0.3; 95% CI: 0.2, 0.7), while those with a longer disease duration prior to biologics (OR 1.1 per year increase; 95% CI: 1.0, 1.2) or prior uveitis were more likely to re-start biologics (OR 2.5; 95% CI: 1.3, 4.9).

Conclusions

This analysis identified factors associated with successful cessation of biologics for remission in JIA as absence of uveitis, prior treatment with tocilizumab and starting biologics earlier in the disease course. Further research is needed to guide clinical recommendations.