bluuebunny/crossref_metadata_2025 huggingface dataset:
Hate, amplified? Social media news consumption and support for anti-Muslim policies
Authors: Lajevardi Nazita , Oskooii Kassra A.R. , Walker Hannah
Published: July 2022

Research finds that social media platforms’ peer-to-peer structures shape the public discourse and increase citizens’ likelihood of exposure to unregulated, false, and prejudicial content. Here, we test whether self-reported reliance on social media as a primary news source is linked to racialised policy support, taking the case of United States Muslims, a publicly visible but understudied group about whom significant false and prejudicial content is abundant on these platforms. Drawing on three original surveys and the Nationscape dataset, we find a strong and consistent association between reliance on social media and support for a range of anti-Muslim policies. Importantly, reliance on social media is linked to policy attitudes across the partisan divide and for individuals who reported holding positive or negative feelings towards Muslims. These findings highlight the need for further investigation into the political ramification of information presented on contemporary social media outlets, particularly information related to stigmatised groups.
Cardiac involvement in multisystem inflammatory syndrome in children: single-centre experience
Authors: Atasayan Vildan , Akbay Özge P. , Çağlayan Şengül , Sözeri Betül , Hasbal Akkuş Canan , Vuran Alican , Öner Taliha , Karacan Mehmet
Published: July 2022

Background:

This study aimed to evaluate electrocardiographic and echocardiographic findings, Holter recordings of the multisystem inflammatory syndrome in children, and to identify prognostic factors for cardiac involvement.

Methods:

We retrospectively reviewed demographic characteristics, medical data, laboratory findings, electrocardiogram and echocardiographic findings, 24-hour Holter recordings, need for an ICU, and extracorporeal membrane oxygenation in multisystem inflammatory syndrome in children. Acute left ventricular systolic dysfunction was defined as left ventricular ejection fraction (EF) ≤%55 on echocardiography.

Results:

Sixty-seven children were included in the study. 24-hour Holters were recorded in 61.2% of the patients and 49.2% were normal. On echocardiographic examination, 14.9% of the patients had systolic dysfunction (EF ≤ 55%). While 32.8% of patients had mild mitral regurgitation, 3% had moderate mitral regurgitation, and 6% had mild aortic regurgitation. There was no statistically significant difference in EF values between the group with arrhythmia in Holter and the group with normal Holter results (p ≥ 0.05). B-type natriuretic peptide was positively correlated with C-reactive protein, ferritin, and fibrinogen. Significant effectivity of the B-type natriuretic peptide value was observed in the differentiation of those with EF ≤ and > 55%. Extracorporeal membrane oxygenation support was needed for three (4.5%) patients. One patient who died had systemic juvenile idiopathic arthritis.

Conclusions:

Neutrophil/lymphocyte ratio, C-reactive protein, D-dimer, ferritin, troponin, and B-type natriuretic peptide were found to be significantly higher in patients with systolic dysfunction. Also, the cut-off value of 1700 pg/ml for B-type natriuretic peptide was significantly effective. These parameters may indicate the severity of the disease but should be supported by prospective studies.
The macroeconomic effects of the tax cuts and jobs act
Authors: Occhino Filippo
Published: July 2022

This paper studies the macroeconomic effects of seven key TCJA provisions, including the tax cuts for individuals and businesses, the bonus depreciation of equipment, the amortization of R&D expenses, and the limits on interest deductibility. I use a dynamic general equilibrium model with interest deductibility and accelerated depreciation. I find that, initially, the tax reform had a small positive effect on output and investment. In the medium term, however, the effect on output will diminish, and the effect on investment will turn negative. The tax reform will depress investment in R&D. Government debt will surge.
Representing Cloud Mesoscale Variability in Superparameterized Climate Models
Authors: Jansson Fredrik , van den Oord Gijs , Pelupessy Inti , Chertova Maria , Grönqvist Johanna H. , Siebesma A. Pier , Crommelin Daan
Published: July 2022

In atmospheric modeling, superparameterization (SP) has gained popularity as a technique to improve cloud and convection representations in large‐scale models by coupling them locally to cloud‐resolving models. We show how the different representations of cloud water in the local and the global models in SP lead to a suppression of cloud advection and ultimately to a systematic underrepresentation of the cloud amount in the large‐scale model. We demonstrate this phenomenon in a regional SP experiment with the global model OpenIFS coupled to the local model Dutch Atmospheric Large Eddy Simulation, as well as in an idealized setup, where the large‐scale model is replaced by a simple advection scheme. As a starting point for mitigating the problem of suppressed cloud advection, we propose a scheme where the spatial variability of the local model's total water content is enhanced in order to match the global model's cloud condensate amount. The proposed scheme enhances the cloud condensate amount in the test cases, however a large discrepancy remains, caused by rapid dissipation of the clouds added by the proposed scheme.
A comparison of bacterial colonization between nasogastric and orogastric enteral feeding tubes in infants in the neonatal intensive care unit
Authors: Vongbhavit Kannikar , Salinero Lauren K. , Kalanetra Karen M. , Masarweh Chad , Yu Alice , Taft Diana H. , Mills David A. , Underwood Mark A.
Published: July 2022

Objective

Feeding tubes harbor microbial contaminants; studies to date have not explored differences between orogastric (OG) and nasogastric (NG) tube biofilms. We sought to extend a previous analysis by comparing bacterial colonization by location (OG v NG) and by evaluating clinical factors that may affect tube bacterial populations.

Study design

The pharyngeal segments of 41 infant feeding tubes (14 OG and 27 NG) from 41 infants were analyzed by next generation 16 S rRNA sequencing on the MiSeq platform.

Results

At the phylum level, Proteobacteria had the highest relative abundance of both OG and NG tubes. At the genus/species level, nine taxa differed significantly between OG and NG tubes. Alpha and beta diversity analyses showed significant differences between OG and NG tubes with relatively little contribution from clinical factors.

Conclusion

The route of feeding tube insertion (oral vs nasal) had a greater impact on bacterial colonization than the assessed clinical factors.
Radical cancer treatment is safe during COVID-19: the real-world experience of a large London-based Comprehensive Cancer Centre during the first wave
Authors: Russell Beth , Moss Charlotte , Monroy-Iglesias Maria , Roberts Graham , Dickinson Harvey , Haire Kate , Innes Kathryn , Mulji-Shah Bansi , Castell Fiona , Al-Salihi Omar , Lei Mary , Francis Angela , Dann Bill , Jogia Vikash , Hamid Hisham , Challacombe Ben , Simo Ricard , Fraser Stephanie , Gousis Charalampos , Sawyer Elinor , Tsotra Eirini , Roca Jose , Khan Muhammad , Josephs Debra , Enting Deborah , Van Hemelrijck Mieke , Harris Victoria , Dolly Saoirse
Published: July 2022

Background

During the COVID pandemic, there was a paucity of data to support clinical decision-making for anticancer treatments. We evaluated the safety of radical treatments which were delivered whilst mitigating the risks of concurrent COVID-19 infection.

Methods

Using descriptive statistics, we report on the characteristics and short-term clinical outcomes of patients undergoing radical cancer treatment during the first COVID-19 wave compared to a similar pre-pandemic period.

Results

Compared to 2019, the number of patients undergoing radical treatment in 2020 reduced by: 28% for surgery; 18% for SACT; and 10% for RT. Within SACT, 36% received combination therapy, 35% systemic chemotherapy, 23% targeted treatments, 5% immunotherapy and 2% biological therapy. A similar proportion of RT was delivered in 2019 and 2020 (53% vs. 52%). Oncological outcomes were also similar to pre-COVID-19. The COVID-19 infection rates were low: 12 patients were positive pre surgery (1%), 7 post surgery (<1%), 17 SACT patients (2%) and 3 RT patients (<1%). No COVID-19-related deaths were reported.

Conclusions

Whilst there were fewer patients receiving radical anticancer treatments, those who did receive treatment were treated in a safe environment. Overall, cancer patients should have the confidence to attend hospitals and be reassured of the safety measures implemented.
Loss-of-function of the hippo transducer TAZ reduces mammary tumor growth through a myeloid-derived suppressor cell-dependent mechanism
Authors: Shen He , Zhang Yuwen , Kramer Elliot D. , Katsuta Eriko , Wan Yin , Chen Yanmin , Wang Jianmin , Zhang Yali , Matsuzaki Junko , Frangou Costa , Abrams Scott I. , Zhang Jianmin
Published: July 2022

TAZ, one of the key effectors in the Hippo pathway, is often dysregulated in breast cancer, leading to cancer stemness, survival, and metastasis. However, the mechanistic bases of these tumor outcomes are incompletely understood and even less is known about the potential role played by the non-malignant cellular constituents of the tumor microenvironment (TME). Here, we revealed an inverse correlation between TAZ expression and survival in triple-negative breast cancer (TNBC), but not other subtypes of breast cancer. We found that TAZ knockdown in two murine TNBC tumor cell line models significantly inhibited tumor growth and metastasis in immune competent but not immune deficient hosts. RNA-seq analyses identified substantial alterations in immune components in TAZ knockdown tumors. Using mass cytometry analysis, we found that TAZ-deficiency altered the immune landscape of the TME leading to significant reductions in immune suppressive populations, namely myeloid-derived suppressor cells (MDSCs) and macrophages accompanied by elevated CD8+ T cell/myeloid cell ratios. Mechanistic studies demonstrated that TAZ-mediated tumor growth was MDSC-dependent in that MDSC depletion led to reduced tumor growth in control, but not TAZ-knockdown tumor cells. Altogether, we identified a novel non-cancer cell-autonomous mechanism by which tumor-intrinsic TAZ expression aids tumor progression. Thus, our findings advance an understanding of the crosstalk between tumor-derived TAZ expression and the immune contexture within the TME, which may lead to new therapeutic interventions for TNBC or other TAZ-driven cancers.
MicroRNA-21 guide and passenger strand regulation of adenylosuccinate lyase-mediated purine metabolism promotes transition to an EGFR-TKI-tolerant persister state
Authors: Zhang Wen Cai , Skiados Nicholas , Aftab Fareesa , Moreno Cerena , Silva Luis , Corbilla Paul Joshua Anthony , Asara John M. , Hata Aaron N. , Slack Frank J.
Published: July 2022

In EGFR-mutant lung cancer, drug-tolerant persister cells (DTPCs) show prolonged survival when receiving EGFR tyrosine kinase inhibitor (TKI) treatments. They are a likely source of drug resistance, but little is known about how these cells tolerate drugs. Ribonucleic acids (RNAs) molecules control cell growth and stress responses. Nucleic acid metabolism provides metabolites, such as purines, supporting RNA synthesis and downstream functions. Recently, noncoding RNAs (ncRNAs), such as microRNAs (miRNAs), have received attention due to their capacity to repress gene expression via inhibitory binding to downstream messenger RNAs (mRNAs). Here, our study links miRNA expression to purine metabolism and drug tolerance. MiR-21-5p (guide strand) is a commonly upregulated miRNA in disease states, including cancer and drug resistance. However, the expression and function of miR-21-3p (passenger strand) are not well understood. We found that upregulation of miR-21-5p and miR-21-3p tune purine metabolism leading to increased drug tolerance. Metabolomics data demonstrated that purine metabolism was the top pathway in the DTPCs compared with the parental cells. The changes in purine metabolites in the DTPCs were partially rescued by targeting miR-21. Analysis of protein levels in the DTPCs showed that reduced expression of adenylosuccinate lyase (ADSL) was reversed after the miR-21 knockdown. ADSL is an essential enzyme in the de novo purine biosynthesis pathway by converting succino-5-aminoimidazole-4-carboxamide riboside (succino-AICAR or SAICAR) to AICAR (or acadesine) as well as adenylosuccinate to adenosine monophosphate (AMP). In the DTPCs, miR-21-5p and miR-21-3p repress ADSL expression. The levels of top decreased metabolite in the DTPCs, AICAR was reversed when miR-21 was blocked. AICAR induced oxidative stress, evidenced by increased reactive oxygen species (ROS) and reduced expression of nuclear factor erythroid-2-related factor 2 (NRF2). Concurrently, miR-21 knockdown induced ROS generation. Therapeutically, a combination of AICAR and osimertinib increased ROS levels and decreased osimertinib-induced NRF2 expression. In a MIR21 knockout mouse model, MIR21 loss-of-function led to increased purine metabolites but reduced ROS scavenging capacity in lung tissues in physiological conditions. Our data has established a link between ncRNAs, purine metabolism, and the redox imbalance pathway. This discovery will increase knowledge of the complexity of the regulatory RNA network and potentially enable novel therapeutic options for drug-resistant patients.
Tumor treating fields affect mesothelioma cell proliferation by exerting histotype-dependent cell cycle checkpoint activations and transcriptional modulations
Authors: Mannarino Laura , Mirimao Federica , Panini Nicolò , Paracchini Lara , Marchini Sergio , Beltrame Luca , Amodeo Rosy , Grosso Federica , Libener Roberta , De Simone Irene , Ceresoli Giovanni L. , Zucali Paolo A. , Lupi Monica , D’Incalci Maurizio
Published: July 2022

Although clinical antitumor activity of Tumor Treating Fields (TTFields) has been reported in malignant pleural mesothelioma (MPM) patients, the mechanisms behind the different selectivity displayed by the various MPM histotypes to this physical therapy has not been elucidated yet. Taking advantage of the development of well characterized human MPM cell lines derived from pleural effusion and/or lavages of patients’ thoracic cavity, we investigated the biological effects of TTFields against these cells, representative of epithelioid, biphasic, and sarcomatoid histotypes. Growth inhibition and cell cycle perturbations caused by TTFields were investigated side by side with RNA-Seq analyses at different exposure times to identify pathways involved in cell response to treatment. We observed significant differences of response to TTFields among the cell lines. Cell cycle analysis revealed that the most sensitive cells (epithelioid CD473) were blocked in G2M phase followed by formation of polyploid cells. The least sensitive cells (sarcomatoid CD60) were only slightly affected by TTFields with a general delay in all cell cycle phases. Apoptosis was present in all samples, but while epithelioid cell death was already observed during the first 24 h of treatment, sarcomatoid cells needed longer times before they engaged apoptotic pathways. RNA-Seq experiments demonstrated that TTFields induced a transcriptional response already detectable at early time points (8 h). The number of differentially expressed genes was higher in CD473 than in CD60 cells, involving several pathways, such as those pertinent to cell cycle checkpoints, DNA repair, and histone modifications. Our data provide further support to the notion that the antitumor effects of TTFields are not simply related to a non-specific reaction to a physical stimulus, but are dependent on the biological background of the cells and the particular sensitivity to TTFields observed in epithelioid MPM cells is associated with a higher transcriptional activity than that observed in sarcomatoid models.
Insulin-like growth factor 1 receptor mediates photoreceptor neuroprotection
Authors: Rajala Ammaji , Teel Kenneth , Bhat Mohd A. , Batushansky Albert , Griffin Timothy M. , Purcell Lindsey , Rajala Raju V. S.
Published: July 2022

Insulin-like growth factor I (IGF-1) is a neurotrophic factor and is the ligand for insulin-like growth factor 1 receptor (IGF-1R). Reduced expression of IGF-1 has been reported to cause deafness, mental retardation, postnatal growth failure, and microcephaly. IGF-1R is expressed in the retina and photoreceptor neurons; however, its functional role is not known. Global IGF-1 KO mice have age-related vision loss. We determined that conditional deletion of IGF-1R in photoreceptors and pan-retinal cells produces age-related visual function loss and retinal degeneration. Retinal pigment epithelial cell-secreted IGF-1 may be a source for IGF-1R activation in the retina. Altered retinal, fatty acid, and phosphoinositide metabolism are observed in photoreceptor and retinal cells lacking IGF-1R. Our results suggest that the IGF-1R pathway is indispensable for photoreceptor survival, and activation of IGF-1R may be an essential element of photoreceptor and retinal neuroprotection.
Cutaneous and acral melanoma cross-OMICs reveals prognostic cancer drivers associated with pathobiology and ultraviolet exposure
Authors: Vicente Anna Luiza Silva Almeida , Novoloaca Alexei , Cahais Vincent , Awada Zainab , Cuenin Cyrille , Spitz Natália , Carvalho André Lopes , Evangelista Adriane Feijó , Crovador Camila Souza , Reis Rui Manuel , Herceg Zdenko , de Lima Vazquez Vinicius , Ghantous Akram
Published: July 2022

Ultraviolet radiation (UV) is causally linked to cutaneous melanoma, yet the underlying epigenetic mechanisms, known as molecular sensors of exposure, have not been characterized in clinical biospecimens. Here, we integrate clinical, epigenome (DNA methylome), genome and transcriptome profiling of 112 cutaneous melanoma from two multi-ethnic cohorts. We identify UV-related alterations in regulatory regions and immunological pathways, with multi-OMICs cancer driver potential affecting patient survival.TAPBP, the top gene, is critically involved in immune function and encompasses several UV-altered methylation sites that were validated by targeted sequencing, providing cost-effective opportunities for clinical application. The DNA methylome also reveals non UV-related aberrations underlying pathological differences between the cutaneous and 17 acral melanomas. Unsupervised epigenomic mapping demonstrated that non UV-mutant cutaneous melanoma more closely resembles acral rather than UV-exposed cutaneous melanoma, with the latter showing better patient prognosis than the other two forms. These gene-environment interactions reveal translationally impactful mechanisms in melanomagenesis.
AMEERA-1 phase 1/2 study of amcenestrant, SAR439859, in postmenopausal women with ER-positive/HER2-negative advanced breast cancer
Authors: Bardia Aditya , Chandarlapaty Sarat , Linden Hannah M. , Ulaner Gary A. , Gosselin Alice , Cartot-Cotton Sylvaine , Cohen Patrick , Doroumian Séverine , Paux Gautier , Celanovic Marina , Pelekanou Vasiliki , Ming Jeffrey E. , Ternès Nils , Bouaboula Monsif , Lee Joon Sang , Bauchet Anne-Laure , Campone Mario
Published: July 2022

AMEERA-1 is a Phase 1/2 open-label single-arm study evaluating once-daily (QD) amcenestrant, an orally bioavailable selective estrogen receptor (ER) degrader, in postmenopausal women with ER+/HER2− advanced breast cancer (NCT03284957), who were mostly heavily pretreated (including targeted therapies and fulvestrant). In the dose escalation phase (Part A: n = 16), patients received amcenestrant 20-600 mg QD. Based on absence of dose-limiting toxicities, paired functional 18F-fluoroestradiol positron emission tomography, and pharmacokinetics, 400 mg QD was selected as recommended Phase 2 dose (RP2D) for the dose expansion phase (Part B: n = 49). No Grade ≥3 treatment-related adverse events or clinically significant cardiac/eye toxicities were reported. The Part B primary endpoint, confirmed objective response rate (ORR) was 3/45 at the interim analysis and 5/46 (10.9%) at the final analysis. The overall clinical benefit rate (CBR) was 13/46 (28.3%). CBRs among patients with baseline wild-type and mutated ESR1 were 9/26 (34.6%) and 4/19 (21.1%), respectively. Paired tumor biopsy and cell-free DNA analyses revealed ER inhibition and degradation, and a reduction in detectable ESR1 mutations, including Y537S. In conclusion, amcenestrant at RP2D of 400 mg QD for monotherapy is well-tolerated with no dose-limiting toxicities, and demonstrates preliminary antitumor activity irrespective of baseline ESR1 mutation status.
Building programmable multicompartment artificial cells incorporating remotely activated protein channels using microfluidics and acoustic levitation
Authors: Li Jin , Jamieson William D. , Dimitriou Pantelitsa , Xu Wen , Rohde Paul , Martinac Boris , Baker Matthew , Drinkwater Bruce W. , Castell Oliver K. , Barrow David A.
Published: July 2022

Intracellular compartments are functional units that support the metabolism within living cells, through spatiotemporal regulation of chemical reactions and biological processes. Consequently, as a step forward in the bottom-up creation of artificial cells, building analogous intracellular architectures is essential for the expansion of cell-mimicking functionality. Herein, we report the development of a droplet laboratory platform to engineer complex emulsion-based, multicompartment artificial cells, using microfluidics and acoustic levitation. Such levitated models provide free-standing, dynamic, definable droplet networks for the compartmentalisation of chemical species. Equally, they can be remotely operated with pneumatic, heating, and magnetic elements for post-processing, including the incorporation of membrane proteins; alpha-hemolysin; and mechanosensitive channel of large-conductance. The assembly of droplet networks is three-dimensionally patterned with fluidic input configurations determining droplet contents and connectivity, whilst acoustic manipulation can be harnessed to reconfigure the droplet network in situ. The mechanosensitive channel can be repeatedly activated and deactivated in the levitated artificial cell by the application of acoustic and magnetic fields to modulate membrane tension on demand. This offers possibilities beyond one-time chemically mediated activation to provide repeated, non-contact, control of membrane protein function. Collectively, this expands our growing capability to program and operate increasingly sophisticated artificial cells as life-like materials.
Making marine image data FAIR
Authors: Schoening Timm , Durden Jennifer M. , Faber Claas , Felden Janine , Heger Karl , Hoving Henk-Jan T. , Kiko Rainer , Köser Kevin , Krämmer Christopher , Kwasnitschka Tom , Möller Klas Ove , Nakath David , Naß Andrea , Nattkemper Tim W. , Purser Autun , Zurowietz Martin
Published: July 2022

Underwater images are used to explore and monitor ocean habitats, generating huge datasets with unusual data characteristics that preclude traditional data management strategies. Due to the lack of universally adopted data standards, image data collected from the marine environment are increasing in heterogeneity, preventing objective comparison. The extraction of actionable information thus remains challenging, particularly for researchers not directly involved with the image data collection. Standardized formats and procedures are needed to enable sustainable image analysis and processing tools, as are solutions for image publication in long-term repositories to ascertain reuse of data. The FAIR principles (Findable, Accessible, Interoperable, Reusable) provide a framework for such data management goals. We propose the use of image FAIR Digital Objects (iFDOs) and present an infrastructure environment to create and exploit such FAIR digital objects. We show how these iFDOs can be created, validated, managed and stored, and which data associated with imagery should be curated. The goal is to reduce image management overheads while simultaneously creating visibility for image acquisition and publication efforts.
Light-induced asymmetries in embryonic retinal gene expression are mediated by the vascular system and extracellular matrix
Authors: Versace Elisabetta , Sgadò Paola , George Julia , Loveland Jasmine L. , Ward Joseph , Thorpe Peter , Jensen Lars Juhl , Spencer Karen A. , Paracchini Silvia , Vallortigara Giorgio
Published: July 2022

Left–right asymmetries in the nervous system (lateralisation) influence a broad range of behaviours, from social responses to navigation and language. The role and pathways of endogenous and environmental mechanisms in the ontogeny of lateralisation remains to be established. The domestic chick is a model of both endogenous and experience-induced lateralisation driven by light exposure. Following the endogenous rightward rotation of the embryo, the asymmetrical position in the egg results in a greater exposure of the right eye to environmental light. To identify the genetic pathways activated by asymmetric light stimulation, and their time course, we exposed embryos to different light regimes: darkness, 6 h of light and 24 h of light. We used RNA-seq to compare gene expression in the right and left retinas and telencephalon. We detected differential gene expression in right vs left retina after 6 h of light exposure. This difference was absent in the darkness condition and had already disappeared by 24 h of light exposure, suggesting that light-induced activation is a self-terminating phenomenon. This transient effect of light exposure was associated with a downregulation of the sensitive-period mediator geneDIO2(iodothyronine deiodinase 2) in the right retina. No differences between genes expressed in the right vs. left telencephalon were detected. Gene networks associated with lateralisation were connected to vascularisation, cell motility, and the extracellular matrix. Interestingly, we know that the extracellular matrix—including the differentially expressedPDGFRBgene—is involved in morphogenesis, sensitive periods, and in the endogenous chiral mechanism of primary cilia, that drives lateralisation. Our data show a similarity between endogenous and experience-driven lateralisation, identifying functional gene networks that affect lateralisation in a specific time window.
Impairing proliferation of glioblastoma multiforme with CD44+ selective conjugated polymer nanoparticles
Authors: Lubanska Dorota , Alrashed Sami , Mason Gage T. , Nadeem Fatima , Awada Angela , DiPasquale Mitchell , Sorge Alexandra , Malik Aleena , Kojic Monika , Soliman Mohamed A. R. , deCarvalho Ana C. , Shamisa Abdalla , Kulkarni Swati , Marquardt Drew , Porter Lisa A. , Rondeau-Gagné Simon
Published: July 2022

Glioblastoma is one of the most aggressive types of cancer with success of therapy being hampered by the existence of treatment resistant populations of stem-like Tumour Initiating Cells (TICs) and poor blood–brain barrier drug penetration. Therapies capable of effectively targeting the TIC population are in high demand. Here, we synthesize spherical diketopyrrolopyrrole-based Conjugated Polymer Nanoparticles (CPNs) with an average diameter of 109 nm. CPNs were designed to include fluorescein-conjugated Hyaluronic Acid (HA), a ligand for the CD44 receptor present on one population of TICs. We demonstrate blood–brain barrier permeability of this system and concentration and cell cycle phase-dependent selective uptake of HA-CPNs in CD44 positive GBM-patient derived cultures. Interestingly, we found that uptake alone regulated the levels and signaling activity of the CD44 receptor, decreasing stemness, invasive properties and proliferation of the CD44-TIC populations in vitro and in a patient-derived xenograft zebrafish model. This work proposes a novel, CPN- based, and surface moiety-driven selective way of targeting of TIC populations in brain cancer.
Statistical evaluation of proxies for estimating the rainfall erosivity factor
Authors: Ma Xiaoqing , Zheng Mingguo
Published: July 2022

Considering the high-temporal-resolution rainfall data requirements for calculating the Rainfall Erosivity factor (that is, the R-factor), studies have developed a large number of proxies for the R-factor (PR). This study aims to evaluate 15 widely used proxies, which were developed in various countries using daily, monthly, or yearly rainfall data, in terms of correlation and statistical equality with the R-factor by using the 6-min pluviographic data from 28 stations in Australia. Meng’s test was applied to rank the correlations. Although the Meng’s test indicated that the correlation between Rainfall Erosivity (R) and Rainfall Erosivity calculated by the proxy model (PR) generally increased with a finer time resolution of the rainfall data (in the order of year, month, and day), the 15 PRs under examination were all highly correlated with R (r > 0.62, p < 0.004), implying that all of them can be reasonably used as an R predictor. A direct estimation of the R-factor using PRs produced a mean relative error (MRE), root mean square error (RMSE), and Nash–Sutcliffe efficiency coefficient (NSE) with a mean of 50.0%, 1392 MJ mm ha−1 h−1 a−1, and 0.17, respectively. The linear calibrations improved the accuracy of the estimation and produced an MRE, RMSE, and NSE with a mean of 36.0%, 887 MJ mm ha−1 h−1 a−1, and 0.70, respectively. Finally, suitable proxies for instances where only daily, monthly, or yearly rainfall data are available were recommended.
Plasmonic hot spots reveal local conformational transitions induced by DNA double-strand breaks
Authors: Seweryn Sara , Skirlińska-Nosek Katarzyna , Wilkosz Natalia , Sofińska Kamila , Perez-Guaita David , Oćwieja Magdalena , Barbasz Jakub , Szymoński Marek , Lipiec Ewelina
Published: July 2022

DNA double-strand breaks (DSBs) are typical DNA lesions that can lead to cell death, translocations, and cancer-driving mutations. The repair process of DSBs is crucial to the maintenance of genomic integrity in all forms of life. However, the limitations of sensitivity and special resolution of analytical techniques make it difficult to investigate the local effects of chemotherapeutic drugs on DNA molecular structure. In this work, we exposed DNA to the anticancer antibiotic bleomycin (BLM), a damaging factor known to induce DSBs. We applied a multimodal approach combining (i) atomic force microscopy (AFM) for direct visualization of DSBs, (ii) surface-enhanced Raman spectroscopy (SERS) to monitor local conformational transitions induced by DSBs, and (iii) multivariate statistical analysis to correlate the AFM and SERS results. On the basis of SERS results, we identified that bands at 1050 cm−1 and 730 cm−1 associated with backbone and nucleobase vibrations shifted and changed their intensities, indicating conformational modifications and strand ruptures. Based on averaged SERS spectra, the PLS regressions for the number of DSBs caused by corresponding molar concentrations of bleomycin were calculated. The strong correlation (R2 = 0.92 for LV = 2) between the predicted and observed number of DSBs indicates, that the model can not only predict the number of DSBs from the spectra but also detect the spectroscopic markers of DNA damage and the associated conformational changes.
Time resolved in-situ multi-contrast X-ray imaging of melting in metals
Authors: Massimi Lorenzo , Clark Samuel J. , Marussi Sebastian , Doherty Adam , Shah Saurabh M. , Schulz Joachim , Marathe Shashidhara , Rau Christoph , Endrizzi Marco , Lee Peter D. , Olivo Alessandro
Published: July 2022

In this work, the application of a time resolved multi-contrast beam tracking technique to the investigation of the melting and solidification process in metals is presented. The use of such a technique allows retrieval of three contrast channels, transmission, refraction and dark-field, with millisecond time resolution. We investigated different melting conditions to characterize, at a proof-of-concept level, the features visible in each of the contrast channels. We found that the phase contrast channel provides a superior visibility of the density variations, allowing the liquid metal pool to be clearly distinguished. Refraction and dark-field were found to highlight surface roughness formed during solidification. This work demonstrates that the availability of the additional contrast channels provided by multi-contrast X-ray imaging delivers additional information, also when imaging high atomic number specimens with a significant absorption.
Research on instability characteristics and precursory effect of coal-rock parting-coal structures
Authors: Liu Yang , Wang Jian-Hua , Lu Cai-Ping , Wang Chao , Xie Hua-Dong , Yan Xian-Yang
Published: July 2022

The slip and instability mechanisms of coal-rock parting-coal structures under uniaxial loading conditions were investigated using experiments and case verification. The slip and the corresponding precursors were described by monitoring the displacement, strain, and acoustic emissions (AEs) of coal and rock parting blocks during testing, and the experimental results were verified by analyzing the microseismic (MS) effects during the working face advancing in a coal seam bifurcation area. The main conclusions were as follows: (1) each slip of the discontinuities sandwiched between coal and rock parting produced shear and tensile cracks, but the shear cracks was dominant; (2) for the instability mode that was characterized by low peak stress, high energy release, and a stablebvalue of AE, each slip corresponds to a peak frequency of AE, which can reveal the final instability mode; (3) the sudden drop in the fault total area of AE can be regarded as a precursor for the warning fracture or slip instability of a discontinuity; and (4) the MS events in the coal seam bifurcation area were mainly characterized by a wide frequency and high amplitude, especially near the coal bifurcation line, where there were obvious characteristics of low-frequency shear fracture for the MS events. This study is relevant for the early warning of coal-rock dynamic disasters triggered by the slip, fracture, and instability of coal-rock parting compound structures in coal mines.
Relaxation anisotropy of quantitative MRI parameters in biological tissues
Authors: Hänninen Nina Elina , Liimatainen Timo , Hanni Matti , Gröhn Olli , Nieminen Miika Tapio , Nissi Mikko Johannes
Published: July 2022

Quantitative MR relaxation parameters vary in the sensitivity to the orientation of the tissue in the magnetic field. In this study, the orientation dependence of multiple relaxation parameters was assessed in various tissues. Ex vivo samples of each tissue type were prepared either from bovine knee (tendon, cartilage) or mouse (brain, spinal cord, heart, kidney), and imaged at 9.4 T MRI with T1, T2, continuous wave (CW-) T1ρ, adiabatic T1ρ and T2ρ, and Relaxation along fictitious field (RAFF2-4) sequences at five different orientations with respect to the main magnetic field. Relaxation anisotropy of the measured parameters was quantified and compared. The highly ordered collagenous tissues, i.e. cartilage and tendon, presented the highest relaxation anisotropy for T2, CW-T1ρ with spin-lock power < 1 kHz, Ad-T2ρ and RAFF2-4. Maximally anisotropy was 75% in cartilage and 30% in tendon. T1 and adiabatic T1ρ did not exhibit observable anisotropy. In the other measured tissue types, anisotropy was overall less than 10% for all the parameters. The results confirm that highly ordered collagenous tissues have properties that induce very clearly observable relaxation anisotropy, whereas in other tissues the effect is not as prominent. Quantitative comparison of anisotropy of different relaxation parameters highlights the importance of sequence choice and design in MR imaging.
Spatial and temporal patterns of agrometeorological indicators in maize producing provinces of South Africa
Authors: Simanjuntak Christian , Gaiser Thomas , Ahrends Hella Ellen , Srivastava Amit Kumar
Published: July 2022

Climate change impacts on maize production in South Africa, i.e., interannual yield variabilities, are still not well understood. This study is based on a recently released reanalysis of climate observations (AgERA5), i.e., temperature, precipitation, solar radiation, and wind speed data. The study assesses climate change effects by quantifying the trend of agrometeorological indicators, their correlation with maize yield, and analyzing their spatiotemporal patterns using Empirical Orthogonal Function. Thereby, the main agrometeorological factors that affected yield variability for the last 31 years (1990/91–2020/21 growing season) in major maize production provinces, namely Free State, KwaZulu-Natal, Mpumalanga, and North West are identified. Results show that there was a significant positive trend in temperature that averages 0.03–0.04 °C per year and 0.02–0.04 °C per growing season. There was a decreasing trend in precipitation in Free State with 0.01 mm per year. Solar radiation did not show a significant trend. Wind speed in Free State increased at a rate of 0.01 ms−1per growing season. Yield variabilities in Free State, Mpumalanga, and North West show a significant positive correlation (r > 0.43) with agrometeorological variables. Yield in KwaZulu-Natal is not influenced by climate factors. The leading mode (50–80% of total variance) of each agrometeorological variable indicates spatially homogenous pattern across the regions. The dipole patterns of the second and the third mode suggest the variabilities of agrometeorological indicators are linked to South Indian high pressure and the warm Agulhas current. The corresponding principal components were mainly associated with strong climate anomalies which are identified as El Niño and La Niña events.
Reliability and validity of the Roche PD Mobile Application for remote monitoring of early Parkinson’s disease
Authors: Lipsmeier Florian , Taylor Kirsten I. , Postuma Ronald B. , Volkova-Volkmar Ekaterina , Kilchenmann Timothy , Mollenhauer Brit , Bamdadian Atieh , Popp Werner L. , Cheng Wei-Yi , Zhang Yan-Ping , Wolf Detlef , Schjodt-Eriksen Jens , Boulay Anne , Svoboda Hanno , Zago Wagner , Pagano Gennaro , Lindemann Michael
Published: July 2022

Digital health technologies enable remote and therefore frequent measurement of motor signs, potentially providing reliable and valid estimates of motor sign severity and progression in Parkinson’s disease (PD). The Roche PD Mobile Application v2 was developed to measure bradykinesia, bradyphrenia and speech, tremor, gait and balance. It comprises 10 smartphone active tests (with ½ tests administered daily), as well as daily passive monitoring via a smartphone and smartwatch. It was studied in 316 early-stage PD participants who performed daily active tests at home then carried a smartphone and wore a smartwatch throughout the day for passive monitoring (study NCT03100149). Here, we report baseline data. Adherence was excellent (96.29%). All pre-specified sensor features exhibited good-to-excellent test–retest reliability (median intraclass correlation coefficient = 0.9), and correlated with corresponding Movement Disorder Society–Unified Parkinson's Disease Rating Scale items (rho: 0.12–0.71). These findings demonstrate the preliminary reliability and validity of remote at-home quantification of motor sign severity with the Roche PD Mobile Application v2 in individuals with early PD.
Immigrant background and socioeconomic status are associated with severe COVID-19 requiring intensive care
Authors: Nordberg Per , Jonsson Martin , Hollenberg Jacob , Ringh Mattias , Kiiski Berggren Ritva , Hofmann Robin , Svensson Per
Published: July 2022

To determine whether immigrant background and socioeconomic status were associated with increased risk to develop severe Coronavirus disease 2019 (COVID-19) requiring mechanical ventilation at the intensive care unit and to study their effects on 90-day mortality. Nationwide case–control study with personal-level data from the Swedish Intensive Care register linked with socioeconomic data from Statistics Sweden and comorbidity data from the national patient register. For each case of COVID-19 treated with mechanical ventilation at the intensive care unit (outcome), 10 population controls were matched for age, sex and area of residence. Logistic and Cox regression were used to study the association between the exposure (immigrant background, income and educational level) and 90-day mortality. In total, 4 921 cases and 49 210 controls were matched. In the adjusted model, the risk of severe COVID-19 was highest in individuals born in Asia (Odds ratio [OR] = 2.44, 95% confidence interval [CI] = 2.20–2.69), South America (OR = 2.34, 95% CI = 1.82–2.98) and Africa (OR = 2.11, 95% CI = 1.76–2.50). Post-secondary education was associated with a lower risk of severe COVID-19 (OR = 0.75, CI = 0.69–0.82) as was the highest (vs. lowest) income quintile (OR = 0.87, CI = 0.77–0.97). In the fully adjusted Cox-regression analysis birth region of Africa (OR 1.38, CI = 1.03–1.86) and high income (OR 0.75, CI 0.63–0.89) were associated with 90-day mortality. Immigrant background, educational level and income were independently associated with acquiring severe COVID-19 with need for mechanical ventilation.
Electron–phonon coupling in copper intercalated Bi$$_{2}$$Se$$_{3}$$
Authors: Wiesner Maciej , Koski Kristie , Laitinen Antti , Manninen Juuso , Zyuzin Alexander A. , Hakonen Pertti
Published: July 2022

We report charge and heat transport studies in copper-intercalated topological insulator Bi$$_2$$

2

Se$$_3$$

3

hybrid devices. Measured conductivity shows impact of quantum corrections, electron–electron and electron–phonon interactions. Our shot noise measurements reveal that heat flux displays a crossover between $$T^2$$

T
2

and $$T^4$$

T
4

with the increase of temperature. The results might be explained by a model of inelastic electron scattering on disorder, increasing the role of transverse acoustic phonons in the electron–phonon coupling process.
Sound localization in web-based 3D environments
Authors: Rajguru Chinmay , Brianza Giada , Memoli Gianluca
Published: July 2022

Sound delivery is a key aspect of immersivity in virtual and augmented reality (VR/AR), with studies hinting at a correlation between users’ ability to locate sounds around them and the ‘feeling of being there’. This is particularly true for WebVR, a method of delivering immersive experiences through a local web browser that has recently captured attention in multiple industries. In WebVR, audio is the main spatial cue. Designers need to select the correct number of sound sources so that users perceive the location of incoming sound correctly. Information on how users localize sound is essential. Sound localization experiments, so far, have been run only in empty spaces or closed rooms, without clear indications for designers in WebVR. Thus, in this study, we investigate sound localization directly through WebVR. To do so, we designed a traditional empty room for training and a city-like virtual environment for testing purposes. In our paper, we also discuss key design parameters, differences in perception for vertical and horizontal directions, the impact of training, and the role of changing virtual environments. In addition, we introduce and test a new sound cue along with the traditional pink noise sound to measure and explore the impact of different sound cues in different environments. The results demonstrate the potential of exploring sound localization using WebVR, and our study will support the development of virtual experiences in human-computer interaction that may be able to reach a large number of participants using a local web browser.
Mechanical properties and failure modes of CRCB specimen under impact loading
Authors: Liu Wenjie , Yang Ke , Dou Litong , Wei Zhen , Chi Xiaolou , Xu Rijie
Published: July 2022

To explore the dynamic mechanical characteristics of CRCB specimens, a separated Hopkinson pressure bar (SHPB) test device combined with ultra-high-speed camera system was used to carry out the impact compression test on CRCB specimens. The stress wave propagation, dynamic stress–strain relationship, dynamic evolution of cracks, energy dissipation law and failure characteristics of the coal–rock combined body in the case of stress waves entering coal from rock were compared and analyzed. The influence of the difference between the rock and the incident bar on the propagation of stress wave gradually weakens with the increase of the impact velocity. The strength stress and peak strain of the CRCB specimens have obvious strain-rate effects. Besides, with increased impact velocity, the incident energy increases linearly, the reflected energy proportion decreases linearly and the absorbed energy proportion change approximately as a power function. Under the same stress wave, as the strength of the rock increases, the failure degree of coal gradually increases, the broken particles gradually transition from massive to powder and the rock mode changes from splitting failure to shear failure. As a result, the average particle size of broken coal blocks decreases, and the fractal dimension of CRCB specimens increases gradually. The research results provide basic research for the control of surrounding rock of roadway under dynamic pressure.
Periodical assessment of four horns of knee meniscus using MR T2 mapping imaging in volunteers before and after amateur marathons
Authors: Zhang Xuesong , Li Jujia , Ren Congcong , Zhang Ping , Zeng Yan , Zhang Ranxu , Wang Ming , Zhou Xiaoyue , Zhao Jian
Published: July 2022

To observe the changes and recovery of T2 values of menisci in amateur marathon participants at different times, and to examine the effect of marathon exercise on meniscal microstructure. Twelve healthy marathon volunteers were recruited continuously, including 5 males and 7 females, with mean (± SD) age of 27.5 ± 5.2 years. The body mass indices (BMIs) ranged from 17.6 to 27.2 kg/m2, with a mean of 21.9 ± 2.5 kg/m2. The 24 knee joints were scanned using a 3 T MR scanner at 1 week before the event, and at 12 h and 2 months after the event. T2 values of the anterior horn of the medial meniscus (MMAH), posterior horn of the medial meniscus (MMPH), anterior horn of the lateral meniscus (LMAH), and posterior horn of the lateral meniscus (LMPH) were measured by drawing the regions of interest (ROIs) on the T2 map images. Wilcoxon sign rank test was used to compare the T2 values between 1 week before and 12 h after the event, and between 1 week before and 2 months after the event in each anatomical region, respectively. The T2 values of the menisci at 12 h after the event were significantly higher (P < 0.05) than those at 1 week before the event. No statistically significant differences in the T2 values of the menisci were found between 2 months after and 1 week before the event (P > 0.05). The T2 values of MMAH, MMPH, LMAH, and LMPH showed a trend of "increasing first and then decreasing" over time, suggesting that the T2 values may reflect meniscal microstructure in amateur marathon runner.