bluuebunny/crossref_metadata_2025 huggingface dataset:
Undiagnosed Long COVID-19 in China Among Non-vaccinated Individuals: Identifying Persistent Symptoms and Impacts on Patients' Health-Related Quality of Life
Authors: Zhang Lin , Lei Jie , Zhang Jintao , Yin Longlong , Chen Yanjiao , Xi Yan , Moreira Joaquim Paulo
Published: November 2022

Is Long COVID-19 under-diagnosed? The definition of this new condition has received many contributions, and it is still under development as a great variety of symptoms have been associated to it. This study explores the possibility that there are non-diagnosed cases among individuals who have been infected by SARS-CoV-2 and have not been vaccinated. The long-term symptoms identified among a sample 255 individuals have been associated to Long COVID-19 by recent literature. The study relates these symptoms to risk factors and health-related quality of life (HRQoL) negative impacts. The individuals were screened 1 year after discharge to explore its potential relation to Long COVID-19. Patients diagnosed with COVID-19 and discharged from designated hospitals in a Chinese province between January and April 2020 were included in this study. They received computed tomography (CT) scans one month after discharge. One year after discharge, patients were invited to physical examination and interviewed with questionnaire on health-related quality of life (HRQoL) and post-COVID-19 symptoms. Tobit regression and Logistic regression were applied to evaluate the risk factors for health utility value and pain/discomfort and anxiety/depression. One year after discharge, 39.61% patients complained of several of the symptoms associated to Long COVID-19. More than half had abnormal chest CT. Previous studies focused on the post-COVID-19 symptoms and chest CT findings of patients, but few studies have assessed the COVID-19-associated risk factors for health-related quality of life.
A Value-centered Exploration of Data Privacy and Personalized Privacy Assistants
Authors: Carter Sarah E.
Published: November 2022

In the current post-GDPR landscape, privacy notices have become ever more prevalent on our phones and online. However, these notices are not well suited to their purpose of helping users make informed decisions. I suggest that instead of utilizing notice to elicit informed consent, we could repurpose privacy notices to create the space for more meaningful, value-centered user decisions. Value-centered privacy decisions, or those that accurately reflect who we are and what we value, encapsulate the intuitive role of personal values in data privacy decisions. To explore how we could design for such decisions, I utilize Suzy Killmister’s Four-Dimensional Theory of Autonomy (4DT) to operationalize value-centered privacy decisions. I then utilize 4DT to help design a system—called a value-centered privacy assistant (VcPA)—that could help create the space for value-centered data privacy decisions using privacy notices. Using this 4DT lens, I further assess the degree that an existing technology, personalized privacy assistants (PPAs), use notices in a manner that allows for value-centered decision-making. I lastly utilize insights from the PPA assessment to inform the design of a VcPA, concluding that a VcPA could utilize notices to assist users in value-centered app selection and in other data privacy decisions.
Predicting cyclone landfall using mutual information and dilated recurrent neural network
Authors: Mukherjee Abhijit , Mitra Pabitra
Published: November 2022

Cyclones are a severe storm system with a defined center, occurring in the tropical regions. Upon landfall, it causes massive damage to both lives and the economy. With the increase in frequency and intensity of tropical cyclones occurring over the years and growing coastal settlements, the study of cyclone landfall remains of paramount importance for disaster control and mitigation. Cyclones experience rapid changes, with various environmental factors modulating the trajectory and intensity. Thus predicting cyclone landfall demands a highly precise technique coupled with knowledge of environmental parameters. With the complexity and nonlinearity of the cyclone track data, determining parameters conducive for the landfall prediction of a cyclone remains crucial for precision and knowledge of the storm system. While numerous methods have been employed for detecting causal interactions among weather systems like Granger Causality and Transfer Entropy, each comes with its limitation and computational overhead. In this work, we investigate the where and when of a cyclone landfall by studying the influencing factors regulating the location and time of a cyclone landfall over the North Indian Ocean with mutual information (MI). We utilize dilated recurrent neural network with gated recurrent unit cells coupled with feature selection via MI criterion for predicting the cyclone landfall location and intensity between 12 and 36 training hours. The model efficacy is validated further on the landfall data of a recent devastating storm—Fani.
Judging reliability at wine and water competitions
Authors: Berg Elena C. , Mascha Michael , Capehart Kevin W.
Published: November 2022

Studies suggest the inter-rater reliability of judges at wine competitions is higher than what would be expected by random chance, but lower than what is observed when experts in other fields make judgments specific to their expertise. To further contextualize the (un-) reliability of wine judging while also extending the study of fine water, we examine the inter-rater reliability of judges at an annual international competition for bottled waters. We find that the inter-rater reliability of water judging is generally better than chance and, at best, about the same as the inter-rater reliability of wine judging at some wine competitions. These results suggest that perceptible differences between fine waters exist but are less pronounced than those between fine wines and, also, that aesthetic standards with respect to fine waters exist but are currently less established than those for fine wines.
Working musically with care-experienced children and their families in the early years
Authors: David Humphrey Ryan
Published: November 2022

Living within state care can have detrimental effects on children’s development, as substantial research has proposed. Recognising how music-making may support children’s social, emotional and personal development, many cultural organisations have begun developing music projects that work specifically with care-experienced children. Although evaluation has detailed the various benefits these projects may have, there has been little research into the approaches employed by the facilitators who deliver these projects. With this in mind, this article examines a community music project that focused on foster family music-making. It explores the facilitators’ social pedagogical approach to music-making and the benefits participants report they have gained from the project, both to themselves and the children in their care.
Public and private protected areas can work together to facilitate the long-term persistence of mammals
Authors: Ivanova Ielyzaveta M , Cook Carly N
Published: November 2022

The conservation performance of protected areas (PAs) is typically measured according to whether species are likely to be present within PAs. However, to attain the goal of long-term conservation it is important to consider the performance of PAs in terms of their ability to support the persistence of the species they contain. We used the concept of minimum viable population (MVP) size to examine the potential for PAs within a large national PA network to support mammal species over the long term. By developing habitat models for each species and estimating the area required to support the MVP size for each species, we identified whether each PA had sufficient habitat to meet the species’ requirements. We found that as a whole the PA network is able to support at least one viable population for all species studied. However, the extent of protection offered to species by the PA network varies considerably, with many PAs not able to support viable populations of individual species on their own. By understanding the capacity of PAs to provide long-term protection to species, our findings can guide strategies to increase the resilience of PA networks as a whole, including by improving habitat quality within and connectivity between PAs.
Development and complications of nutritional deficiencies after bariatric surgery
Authors: Steenackers Nele , Van der Schueren Bart , Augustijns Patrick , Vanuytsel Tim , Matthys Christophe
Published: November 2022

The clinical effectiveness of bariatric surgery has encouraged the use of bariatric procedures for the treatment of morbid obesity and its comorbidities, with sleeve gastrectomy and Roux-en-Y gastric bypass being the most common procedures. Notwithstanding its success, bariatric procedures are recognised to predispose the development of nutritional deficiencies. A framework is proposed that provides clarity regarding the immediate role of diet, the gastrointestinal tract and the medical state of the patient in the development of nutritional deficiencies after bariatric surgery, while highlighting different enabling resources that may contribute. Untreated, these nutritional deficiencies can progress in the short term into haematological, muscular and neurological complications and in the long term into skeletal complications. In this review, we explore the development of nutritional deficiencies after bariatric surgery through a newly developed conceptual framework. An in-depth understanding will enable the optimisation of the post-operative follow-up, including detecting clinical signs of complications, screening for laboratory abnormalities and treating nutritional deficiencies.
Seismic Anisotropy Tomography and Mantle Dynamics of Central‐Eastern USA
Authors: Liang Xuran , Zhao Dapeng , Hua Yuanyuan , Xu Yi‐Gang
Published: November 2022

We present high‐resolution 3‐D tomographic models of isotropic P‐wave velocity (Vp), azimuthal anisotropy, and radial anisotropy down to 1,300 km depth beneath the central and eastern United States (CEUS), which are obtained by inverting a great number of local and teleseismic data and making a whole‐mantle correction to teleseismic travel‐time data recorded by the USArray. Trade‐offs between azimuthal and radial anisotropies occur due to the correlation between the azimuthal and incidence angles of seismic rays, but the use of uniform and crisscrossing rays can reduce the trade‐off effect. Our tomographic images reveal the North American Craton with layered anisotropy and strong anisotropies in the lower mantle related to the deeply subducted Farallon slab and passage of the Bermuda hotspot. In the upper mantle, low‐velocity anomalies with significant seismic anisotropy are revealed beneath three intraplate seismic zones in New Madrid, East Tennessee, and South Carolina, suggesting that hot and wet mantle upwelling occurs under the seismic zones, and the related fluids affect the earthquake generation. The most important dynamic processes in the mantle beneath the CEUS are the deep subduction of the Farallon plate and the passage of the Bermuda hotspot, which have caused strong structural heterogeneities, seismic anisotropy, as well as thermal anomalies and fluids that contributed to the formation of intraplate seismic zones in the CEUS.
Biological drivers of clinical phenotype in myelofibrosis
Authors: Mascarenhas John , Gleitz Hélène F. E. , Chifotides Helen T. , Harrison Claire N. , Verstovsek Srdan , Vannucchi Alessandro Maria , Rampal Raajit K. , Kiladjian Jean-Jacques , Vainchenker William , Hoffman Ronald , Schneider Rebekka K. , List Alan F.
Published: November 2022

Myelofibrosis (MF) is a myeloproliferative disorder that exhibits considerable biological and clinical heterogeneity. At the two ends of the disease spectrum are the myelodepletive or cytopenic phenotype and the myeloproliferative phenotype. The cytopenic phenotype has a high prevalence in primary MF (PMF) and is characterized by low blood counts. The myeloproliferative phenotype is typically associated with secondary MF (SMF), mild anemia, minimal need for transfusion support, and normal to mild thrombocytopenia. Differences in somatic driver mutations and allelic burden, as well as the acquisition of non-driver mutations further influences these phenotypic differences, prognosis, and response to therapies such as JAK2 inhibitors. The outcome of patients with the cytopenic phenotype are comparatively worse and frequently pose a challenge to treat given the inherent exacerbation of cytopenias. Recent data indicate that an innate immune deregulated state that hinges on the myddosome-IRAK-NFκB axis favors the cytopenic myelofibrosis phenotype and offers opportunity for novel treatment approaches. We will review the biological and clinical features of the MF disease spectrum and associated treatment considerations.
Enhancement of THz generation in LiNbO3 waveguides via multi-bounce velocity matching
Authors: Dastrup Blake S. , Sung Eric R. , Wulf Frank , Saraceno Clara , Nelson Keith A.
Published: November 2022

To realize the full promise of terahertz polaritonics (waveguide-based terahertz field generation, interaction, and readout) as a viable spectroscopy platform, much stronger terahertz fields are needed to enable nonlinear and even robust linear terahertz measurements. We use a novel geometric approach in which the optical pump is totally internally reflected to increase the distance over which optical rectification occurs. Velocity matching is achieved by tuning the angle of internal reflection. By doing this, we are able to enhance terahertz spectral amplitude by over 10x compared to conventional single-pass terahertz generation. An analysis of the depletion mechanisms reveals that 3-photon absorption and divergence of the pump beam are the primary limiters of further enhancement. This level of enhancement is promising for enabling routine spectroscopic measurements in an integrated fashion and is made more encouraging by the prospect of further enhancement by using longer pump wavelengths.
BSP implementation of the 2017 classification of periodontal diseases: a practice retrospective
Authors: Claydon Nicholas , Thomas Dave W. , Adams Robert J. , West Nicola , Hodge Shaun
Published: November 2022

Introduction The new world classification of periodontal diseases and conditions was developed in 2017. The British Society of Periodontology and Implant Dentistry (BSP) implemented the classification in a series of papers published in the British Dental Journal in January 2019.

Aims and objectives This study aimed to investigate if the BSP implementation was workable in general dental practice and to reveal if any lessons were learnt from its regular use two years following its release.

Materials and methods This was a cross-sectional, retrospective, non-intervention analysis of a patient population (n = 891) drawn from a complete list of a private dental surgeon. Diagnostic and demographic data were drawn from the patient records, collated and analysed using SPSS Statistics v26.

Results Diagnoses derived from the new classification were identified for 92% of subjects, indicating a high level of implementation. In total, 20.9% of subjects were diagnosed with periodontitis, and of these, 57% were unstable, 39% stable and 4% in remission. The mean bleeding on probing score across the cohort was 7.7%. Moreover, 76% of the non-periodontitis patients were diagnosed with 'clinical gingival health', 23% with localised gingivitis and 1% with generalised gingivitis.

Conclusion The new classification has been found to be readily implemented in a general practice setting. Use of the new classification allows for close monitoring of periodontal status, and as a result, close monitoring of the effectiveness of pathways of care.
Additional consensus recommendations for conducting complex innovative trials of oncology agents: a post-pandemic perspective
Authors: Blagden Sarah P. , Yu Ly-Mee , Ellis Stephanie , Hughes Helen , Shaaban Abeer , Fennelly-Barnwell Jonathan , Lythgoe Mark P. , Cooper Alison M. , Maignen Francois M. , Buckland Sean W. , Kearns Pamela R. , Brown Louise C. ,   Experimental Cancer Medicine Centres (ECMC) CID trials working group
Published: November 2022

In our 2020 consensus paper, we devised ten recommendations for conducting Complex Innovative Design (CID) trials to evaluate cancer drugs. Within weeks of its publication, the UK was hit by the first wave of the SARS-CoV-2 pandemic. Large CID trials were prioritised to compare the efficacy of new and repurposed COVID-19 treatments and inform regulatory decisions. The unusual circumstances of the pandemic meant studies such as RECOVERY were opened almost immediately and recruited record numbers of participants. However, trial teams were required to make concessions and adaptations to these studies to ensure recruitment was rapid and broad. As these are relevant to cancer trials that enrol patients with similar risk factors, we have added three new recommendations to our original ten: employing pragmatism such as using focused information sheets and collection of only the most relevant data; minimising negative environmental impacts with paperless systems; and using direct-to-patient communication methods to improve uptake. These recommendations can be applied to all oncology CID trials to improve their inclusivity, uptake and efficiency. Above all, the success of CID studies during the COVID-19 pandemic underscores their efficacy as tools for rapid treatment evaluation.
Disentangling the aetiological pathways between body mass index and site-specific cancer risk using tissue-partitioned Mendelian randomisation
Authors: Leyden Genevieve M. , Greenwood Michael P. , Gaborieau Valérie , Han Younghun , Amos Christopher I. , Brennan Paul , Murphy David , Davey Smith George , Richardson Tom G.
Published: November 2022

Background

Body mass index (BMI) is known to influence the risk of various site-specific cancers, however, dissecting which subcomponents of this heterogenous risk factor are predominantly responsible for driving disease effects has proven difficult to establish. We have leveraged tissue-specific gene expression to separate the effects of distinct phenotypes underlying BMI on the risk of seven site-specific cancers.

Methods

SNP-exposure estimates were weighted in a multivariable Mendelian randomisation analysis by their evidence for colocalization with subcutaneous adipose- and brain-tissue-derived gene expression using a recently developed methodology.

Results

Our results provide evidence that brain-tissue-derived BMI variants are predominantly responsible for driving the genetically predicted effect of BMI on lung cancer (OR: 1.17; 95% CI: 1.01–1.36; P = 0.03). Similar findings were identified when analysing cigarettes per day as an outcome (Beta = 0.44; 95% CI: 0.26–0.61; P = 1.62 × 10−6), highlighting a possible shared aetiology or mediator effect between brain-tissue BMI, smoking and lung cancer. Our results additionally suggest that adipose-tissue-derived BMI variants may predominantly drive the effect of BMI and increased risk for endometrial cancer (OR: 1.71; 95% CI: 1.07–2.74; P = 0.02), highlighting a putatively important role in the aetiology of endometrial cancer.

Conclusions

The study provides valuable insight into the divergent underlying pathways between BMI and the risk of site-specific cancers.
Proof-of-principle studies on a strategy to enhance nucleotide imbalance specifically in cancer cells
Authors: Alkasalias Twana , Zhang Juan , Madapura Harsha , Dalarun Basile , Reina Oscar Bedoya , Lewensohn Rolf , Viktorsson Kristina , Salihi Abbas , Darekar Suhas , Laín Sonia
Published: November 2022

Highly specific and potent inhibitors of dihydroorotate dehydrogenase (DHODH), an essential enzyme of the de novo pyrimidine ribonucleotide synthesis pathway, are in clinical trials for autoimmune diseases, viral infections and cancer. However, because DHODH inhibitors (DHODHi) are immunosuppressants they may reduce the anticancer activity of the immune system. Therefore, there may be a need to improve the therapeutic index of DHODHi in cancer patients. The aim of this study was to find strategies to protect activated T cells from DHODHi and to identify cancer types hypersensitive to these inhibitors. First, we observed that like uridine supplementation, adding cytidine to the culture medium protects T cells from DHODH blockage. Next, we identified tumor types with altered expression of pyrimidine ribonucleotide synthesis enzymes. In this regard, we detected that the expression of cytidine deaminase (CDA), which converts cytidine into uridine, is low in an important proportion of cancer cell lines and consistently low in neuroblastoma samples and in cell lines from neuroblastoma and small cell lung carcinoma. This suggested that in the presence of a DHODHi, an excess of cytidine would be deleterious for low CDA expressing cancer cell lines. We show that this was the case (as could be seen almost immediately after treatment) when cells were cultured with fetal bovine serum but, was significantly less evident when cultures contained human serum. One interesting feature of CDA is that aside from acting intracellularly, it is also present in human plasma/serum. Altogether, experiments using recombinant CDA, human serum, pharmacologic inhibition of CDA and T cell/cancer cell co-cultures suggest that the therapeutic index of DHODHi could be improved by selecting patients with low-CDA expressing cancers in combination with strategies to increase cytidine or the cytidine/uridine ratio in the extracellular environment. Collectively, this proof-of-principle study warrants the discovery of agents to deplete extracellular CDA.
Growth of nonexudative macular neovascularization in age-related macular degeneration: an indicator of biological lesion activity
Authors: Wang Yusong , Sun Junran , Wu Jiali , Jia Huixun , Feng Jingyang , Chen Jieqiong , Yan Quan , Huang Peirong , Wang Fenghua , Bo Qiyu , Sun Xiaodong
Published: November 2022

Purpose

To investigate the growth of nonexudative macular neovascularization (MNV) in age-related macular degeneration (AMD) using swept-source optical coherence tomography angiography (SS-OCTA).

Methods

Patients with treatment-naïve nonexudative AMD in one eye and exudative AMD in the fellow eye who underwent SS-OCTA imaging for at least 12 months were retrospectively reviewed. The MNV area measurement was quantified in eyes with treatment-naïve nonexudative MNV using ImageJ for analysing the correlation between MNV growth and the onset of exudation, as well as evaluating the consistency of the MNV growth rate during the subclinical and exudative stages. Kaplan-Meier survival analysis and logistic regression analyses were used.

Results

In total, 45 eyes with treatment-naïve nonexudative AMD from 45 patients were enrolled. Treatment-naïve nonexudative MNV was identified in 21 eyes (46.67%) at baseline. The development of exudative findings was noted in eight eyes (17.78%), including six eyes with previously noted nonexudative MNV. Eyes with growing MNV (increase in area ≥50% within 12 months) had an increased risk of exudation and developed exudation earlier than eyes with stable MNV (13.60 [6.43–20.77] months versus 31.11 [26.61–35.62] months, P < 0.0001, Log-rank test). Consistent growth pattern of MNV lesions was further identified in eyes with growing MNV during anti-VEGF treatment.

Conclusion

SS-OCTA allows to qualitatively and quantitatively evaluate nonexudative MNV in AMD patients. Growing MNV involved higher probabilities and a faster onset of exudation compared to stable MNV. Identifying the growth of MNV on OCTA might be helpful for establishing treatment strategies and follow-up planning.
Motor cortex excitability is reduced during freezing of upper limb movement in Parkinson’s disease
Authors: Topka Marlene , Schneider Marlieke , Zrenner Christoph , Belardinelli Paolo , Ziemann Ulf , Weiss Daniel
Published: November 2022

Whilst involvement of the motor cortex in the phenomenon of freezing in Parkinson’s disease has been previously suggested, few empiric studies have been conducted to date. We investigated motor cortex (M1) excitability in eleven right-handed Parkinson’s disease patients (aged 69.7 ± 9.6 years, disease duration 11.2 ± 3.9 years, akinesia-rigidity type) with verified gait freezing using a single-pulse transcranial magnetic stimulation (TMS) repetitive finger tapping paradigm. We delivered single TMS pulses at 120% of the active motor threshold at the ‘ascending (contraction)’ and ‘descending (relaxation)’ slope of the tap cycle during i) regular tapping, ii) the transition period of the three taps prior to a freeze and iii) during freezing of upper limb movement. M1 excitability was modulated along the tap cycle with greater motor evoked potentials (MEPs) during ‘ascending’ than ‘descending’. Furthermore, MEPs during the ‘ascending’ phase of regular tapping, but not during the transition period, were greater compared to the MEPs recorded throughout a freeze. Neither force nor EMG activity 10–110 s before the stimulus predicted MEP size. This piloting study suggests that M1 excitability is reduced during freezing and the transition period preceding a freeze. This supports that M1 excitability is critical to freezing in Parkinson’s disease.
Detecting Parkinson’s disease and its cognitive phenotypes via automated semantic analyses of action stories
Authors: García Adolfo M. , Escobar-Grisales Daniel , Vásquez Correa Juan Camilo , Bocanegra Yamile , Moreno Leonardo , Carmona Jairo , Orozco-Arroyave Juan Rafael
Published: November 2022

Action-concept outcomes are useful targets to identify Parkinson’s disease (PD) patients and differentiate between those with and without mild cognitive impairment (PD-MCI, PD-nMCI). Yet, most approaches employ burdensome examiner-dependent tasks, limiting their utility. We introduce a framework capturing action-concept markers automatically in natural speech. Patients from both subgroups and controls retold an action-laden and a non-action-laden text (AT, nAT). In each retelling, we weighed action and non-action concepts through our automated Proximity-to-Reference-Semantic-Field (P-RSF) metric, for analysis via ANCOVAs (controlling for cognitive dysfunction) and support vector machines. Patients were differentiated from controls based on AT (but not nAT) P-RSF scores. The same occurred in PD-nMCI patients. Conversely, PD-MCI patients exhibited reduced P-RSF scores for both texts. Direct discrimination between patient subgroups was not systematic, but it yielded best outcomes via AT scores. Our approach outperformed classifiers based on corpus-derived embeddings. This framework opens scalable avenues to support PD diagnosis and phenotyping.
Functional analysis of structural variants in single cells using Strand-seq
Authors: Jeong Hyobin , Grimes Karen , Rauwolf Kerstin K. , Bruch Peter-Martin , Rausch Tobias , Hasenfeld Patrick , Benito Eva , Roider Tobias , Sabarinathan Radhakrishnan , Porubsky David , Herbst Sophie A. , Erarslan-Uysal Büşra , Jann Johann-Christoph , Marschall Tobias , Nowak Daniel , Bourquin Jean-Pierre , Kulozik Andreas E. , Dietrich Sascha , Bornhauser Beat , Sanders Ashley D. , Korbel Jan O.
Published: November 2022

Somatic structural variants (SVs) are widespread in cancer, but their impact on disease evolution is understudied due to a lack of methods to directly characterize their functional consequences. We present a computational method, scNOVA, which uses Strand-seq to perform haplotype-aware integration of SV discovery and molecular phenotyping in single cells by using nucleosome occupancy to infer gene expression as a readout. Application to leukemias and cell lines identifies local effects of copy-balanced rearrangements on gene deregulation, and consequences of SVs on aberrant signaling pathways in subclones. We discovered distinct SV subclones with dysregulated Wnt signaling in a chronic lymphocytic leukemia patient. We further uncovered the consequences of subclonal chromothripsis in T cell acute lymphoblastic leukemia, which revealed c-Myb activation, enrichment of a primitive cell state and informed successful targeting of the subclone in cell culture, using a Notch inhibitor. By directly linking SVs to their functional effects, scNOVA enables systematic single-cell multiomic studies of structural variation in heterogeneous cell populations.
Year-round trace gas measurements in the central Arctic during the MOSAiC expedition
Authors: Angot Hélène , Blomquist Byron , Howard Dean , Archer Stephen , Bariteau Ludovic , Beck Ivo , Boyer Matthew , Crotwell Molly , Helmig Detlev , Hueber Jacques , Jacobi Hans-Werner , Jokinen Tuija , Kulmala Markku , Lan Xin , Laurila Tiia , Madronich Monica , Neff Donald , Petäjä Tuukka , Posman Kevin , Quéléver Lauriane , Shupe Matthew D. , Vimont Isaac , Schmale Julia
Published: November 2022

Despite the key role of the Arctic in the global Earth system, year-round in-situ atmospheric composition observations within the Arctic are sparse and mostly rely on measurements at ground-based coastal stations. Measurements of a suite of in-situ trace gases were performed in the central Arctic during the Multidisciplinary drifting Observatory for the Study of Arctic Climate (MOSAiC) expedition. These observations give a comprehensive picture of year-round near-surface atmospheric abundances of key greenhouse and trace gases, i.e., carbon dioxide, methane, nitrous oxide, ozone, carbon monoxide, dimethylsulfide, sulfur dioxide, elemental mercury, and selected volatile organic compounds (VOCs). Redundancy in certain measurements supported continuity and permitted cross-evaluation and validation of the data. This paper gives an overview of the trace gas measurements conducted during MOSAiC and highlights the high quality of the monitoring activities. In addition, in the case of redundant measurements, merged datasets are provided and recommended for further use by the scientific community.
TractoInferno - A large-scale, open-source, multi-site database for machine learning dMRI tractography
Authors: Poulin Philippe , Theaud Guillaume , Rheault Francois , St-Onge Etienne , Bore Arnaud , Renauld Emmanuelle , de Beaumont Louis , Guay Samuel , Jodoin Pierre-Marc , Descoteaux Maxime
Published: November 2022

TractoInferno is the world’s largest open-source multi-site tractography database, including both research- and clinical-like human acquisitions, aimed specifically at machine learning tractography approaches and related ML algorithms. It provides 284 samples acquired from 3 T scanners across 6 different sites. Available data includes T1-weighted images, single-shell diffusion MRI (dMRI) acquisitions, spherical harmonics fitted to the dMRI signal, fiber ODFs, and reference streamlines for 30 delineated bundles generated using 4 tractography algorithms, as well as masks needed to run tractography algorithms. Manual quality control was additionally performed at multiple steps of the pipeline. We showcase TractoInferno by benchmarking the learn2track algorithm and 5 variations of the same recurrent neural network architecture. Creating the TractoInferno database required approximately 20,000 CPU-hours of processing power, 200 man-hours of manual QC, 3,000 GPU-hours of training baseline models, and 4 Tb of storage, to produce a final database of 350 Gb. By providing a standardized training dataset and evaluation protocol, TractoInferno is an excellent tool to address common issues in machine learning tractography.
Biochemical characterization of Dimocarpus longan polyphenol oxidase provides insights into its catalytic efficiency
Authors: Ruckthong Leela , Pretzler Matthias , Kampatsikas Ioannis , Rompel Annette
Published: November 2022

The “dragon-eye” fruits produced by the tropical longan tree are rich in nutrients and antioxidants. They suffer from post-harvest enzymatic browning, a process for which mainly the polyphenol oxidase (PPO) family of enzymes is responsible. In this study, two cDNAs encoding the PPO have been cloned from leaves of Dimocarpus longan (Dl), heterologously expressed in Escherichia coli and purified by affinity chromatography. The prepro-DlPPO1 contains two signal peptides at its N-terminal end that facilitate transportation of the protein into the chloroplast stroma and to the thylakoid lumen. Removal of the two signal peptides from prepro-DlPPO1 yields pro-DlPPO1. The prepro-DlPPO1 exhibited higher thermal tolerance than pro-DlPPO1 (unfolding at 65 °C vs. 40 °C), suggesting that the signal peptide may stabilize the fold of DlPPO1. DlPPO1 can be classified as a tyrosinase because it accepts both monophenolic and diphenolic substrates. The pro-DlPPO1 exhibited the highest specificity towards the natural diphenol (–)-epicatechin (kcat/KM of 800 ± 120 s−1 mM−1), which is higher than for 4-methylcatechol (590 ± 99 s−1 mM−1), pyrogallol (70 ± 9.7 s−1 mM−1) and caffeic acid (4.3 ± 0.72 s−1 mM−1). The kinetic efficiencies of prepro-DlPPO1 are 23, 36, 1.7 and 4.7-fold lower, respectively, than those observed with pro-DlPPO1 for the four aforementioned diphenolic substrates. Additionally, docking studies showed that (–)-epicatechin has a lower binding energy than any other investigated substrate. Both kinetic and in-silico studies strongly suggest that (–)-epicatechin is a good substrate of DlPPO1 and ascertain the affinity of PPOs towards specific flavonoid compounds.
Slowing down x-ray photons in a vibrating recoilless resonant absorber
Authors: Khairulin I. R. , Radeonychev Y. V. , Kocharovskaya Olga
Published: November 2022

Recently, an observation of acoustically induced transparency (AIT) of a stainless-steel foil for resonant 14.4-keV photons from a radioactive 57Co Mössbauer source due to collective uniform oscillations of atomic nuclei was reported [Phys Rev Lett 124,163602, 2020]. In this paper, we propose to use the steep resonant dispersion of the absorber within the AIT spectral window to dramatically reduce a propagation velocity of γ-ray and x-ray photons. In particular, we show that a significant fraction (more than 40%) of a 97-ns γ-ray single-photon wave packet from a 57Co radioactive source can be slowed down up to 3 m/s and delayed by 144 ns in a 57Fe-enriched stainless-steel foil at room temperature. We also show that a similarly significant slowing down up to 24 m/s and a delay by 42 ns can be achieved for more than 70% of the 100-ns 14.4-keV x-ray single-photon pulse from a synchrotron Mössbauer source available at European Synchrotron Radiation Facility (ESRF) and Spring-8 facility. The propagation velocity can be widely controlled by changing the absorber vibration frequency. Achieving the propagation velocity on the order of 1–50 m/s would set a record in the hard x-ray range, comparable to what was obtained in the optical range.
Tobacco use and risk of COVID-19 infection in the Finnish general population
Authors: Peña Sebastián , Ilmarinen Katja , Kestilä Laura , Parikka Suvi , Kärkkäinen Sanna , Caspersen Ida Henriette , Shaaban Ahmed Nabil , Magnus Per , Galanti Maria Rosaria , Karvonen Sakari
Published: November 2022

Empirical evidence, primarily based on hospital-based or voluntary samples, suggests that current smokers have a lower risk of COVID-19 infection than never smokers. In this study, we used nationally representative data to examine the association between tobacco use and the risk of having a confirmed COVID-19 case. We explored several forms of tobacco use, contributing to separate the role of nicotine from smoking. We used data from 44,199 participants from three pooled national health surveys in Finland (FinSote 2018–2020). The primary outcome was a confirmed COVID-19 case. We examined current smoking, moist smokeless tobacco (snus), e-cigarettes with and without nicotine and nicotine replacement therapy products. Current daily smokers had a relative risk of 1.12 of a confirmed COVID-19 case (95% CI 0.65; 1.94) in fully adjusted models compared with never smokers. Current snus use was associated with a 68% higher risk of a confirmed COVID-19 case (RR 1.68, 95% CI 1.02; 2.75) than never users. We did not find conclusive evidence of associations between e-cigarettes with and without nicotine and nicotine replacement therapy products and the risk of confirmed COVID-19 cases. Our findings suggest that nicotine might not have a protective role in the risk of COVID-19 as previously hypothesized.
The mu opioid receptor and the orphan receptor GPR151 contribute to social reward in the habenula
Authors: Allain Florence , Carter Michelle , Dumas Sylvie , Darcq Emmanuel , Kieffer Brigitte L.
Published: November 2022

The mu opioid receptor (MOR) and the orphan GPR151 receptor are inhibitory G protein coupled receptors that are enriched in the habenula, a small brain region involved in aversion processing, addiction and mood disorders. While MOR expression in the brain is widespread, GPR151 expression is restricted to the habenula. In a previous report, we created conditional ChrnB4-Cre × Oprm1fl/fl (so-called B4MOR) mice, where MORs are deleted specifically in Chrnb4-positive neurons restricted to the habenula, and shown a role for these receptors in naloxone aversion. Here we characterized the implication of habenular MORs in social behaviors. B4MOR−/− mice and B4MOR+/+ mice were compared in several social behavior measures, including the chronic social stress defeat (CSDS) paradigm, the social preference (SP) test and social conditioned place preference (sCPP). In the CSDS, B4MOR−/− mice showed lower preference for the social target (unfamiliar mouse of a different strain) at baseline, providing a first indication of deficient social interactions in mice lacking habenular MORs. In the SP test, B4MOR−/− mice further showed reduced sociability for an unfamiliar conspecific mouse. In the sCPP, B4MOR−/− mice also showed impaired place preference for their previous familiar littermates after social isolation. We next created and tested Gpr151−/− mice in the SP test, and also found reduced social preference compared to Gpr151+/+ mice. Altogether our results support the underexplored notion that the habenula regulates social behaviors. Also, our data suggest that the inhibitory habenular MOR and GPR151 receptors normally promote social reward, possibly by dampening the aversive habenula activity.
The adaptive significance of human scleral brightness: an experimental study
Authors: Wacewicz Slawomir , Perea-García Juan Olvido , Lewandowski Zdzisław , Danel Dariusz P.
Published: November 2022

Homogeneously depigmented sclerae have long been proposed to be uniquely human—an adaptation to enable cooperative behaviour by facilitating interpersonal coordination through gaze following. However, recent evidence has shown that deeply pigmented sclerae also afford gaze following if surrounding a bright iris. Furthermore, while current scleral depigmentation is clearly adaptive in modern humans, it is less clear how the evolutionarily intermediate stages of scleral pigmentation may have been adaptive. In sum, it is unclear why scleral depigmentation became the norm in humans, while not so in sister species like chimpanzees, or why some extant species display intermediate degrees of pigmentation (as our ancestors presumably did at some point). We created realistic facial images of 20 individually distinct hominins with diverse facial morphologies, each face in the (i) humanlike bright sclera and (ii) generalised apelike dark sclera version. Participants in two online studies rated the bright-sclera hominins as younger, healthier, more attractive and trustworthy, but less aggressive than the dark-sclera hominins. Our results support the idea that the appearance of more depigmented sclerae promoted perceived traits that fostered trust, increasing fitness for those individuals and resulting in depigmentation as a fixed trait in extant humans.
Preparation of a cellulose acetate membrane using cigarette butt recycling and investigation of its efficiency in removing heavy metals from aqueous solution
Authors: Torkashvand Javad , Saeedi-Jurkuyeh Alireza , Rezaei Kalantary Roshanak , Gholami Mitra , Esrafili Ali , Yousefi Mahmood , Farzadkia Mahdi
Published: November 2022

This study investigated the recycling of freshly-smoked cigarette butts (FCBs) and unsmoked cigarette filters (UCFs) into a cellulose acetate (CA) membrane. The both samples were prepared by means of a combination of seven cigarette brands, and the phase inversion method was used to recycle each sample into a membrane using N-methyl-2-pyrrolidone. The efficiency of the prepared membranes for the removal of chromium, cadmium, and lead from an aqueous solution in a forward osmosis reactor was investigated. The results showed that the both membranes had a smooth surface and macrovoids. The flux of the prepared membranes from the UCFs and FCBs recycling were 14.8 and 13.2 LMH, respectively. The porosity and reverse salt of the UCFs membrane were 61% and 3.5 gMH, while those for FCBs membrane were 58% and 3.9 gMH. The observed metal removal efficiency of the both membranes was in the range of 85 to 90%. However, increasing the concentration of metals up to five times caused a slight decrease in the removal efficiency (less than 5%).
In vitro model of predicting metastatic ability using tumor derived extracellular vesicles; beyond seed soil hypothesis
Authors: Bhadresha Kinjal , Upadhyay Vinal , Brahmbhatt Jpan , Mughal Muhammad Jameel , Jain Nayan , Rawal Rakesh
Published: November 2022

Lung cancer progression is often driven by metastasis, which has resulted in a considerable increase in lung cancer-related deaths. Cell-derived extracellular vesicles (EVs), particularly exosomes, serve key roles in cellular signal transmission via microenvironment, however, their biological relevance in cancer development and metastasis still needs to be clear. Here, we demonstrate that extracellular vesicles (EVs) derived from lung cancer bone metastatic patients exhibited a great capacity to promote the progression of lung cancer cells. We carried out a comprehensive meta-analysis to identify the gene expression profile of bone metastases using publicly available microarray datasets. Furthermore, mRNA expression of six identified genes was quantified by real time PCR in lung cancer with and without bone metastasis and healthy individual derived EVs. In addition, we utilized a very novel approach by to study how lung cancer cells uptake EVs by co-culturing EVs with lung cells. We observed that EVs obtained from bone metastases patients were efficiently ingested by lung cancer cells. Morevore, integration and uptake of these EVs lead to increased lung cancer cell proliferation, migration, invasion, and sphere formation. We discovered that EV uptake increase the expression of SPP1, CD44, and POSTN genes in lung cancer cells. The data obtained from this study, support to the possibility that circulating EVs play a significant role in the formation of the pre-metastatic niche, eventually leading to metastasis.
Nuclear factor (erythroid-derived 2)-like 2 counter-regulates thymosin beta-4 expression and primary cilium formation for HeLa cervical cancer cell survival
Authors: Lee Jae-Wook , Thuy Pham Xuan , Koo Ja Hyun , Moon Eun-Yi
Published: November 2022

We investigated the function of thymosin beta-4 (TB4) expression and primary cilium (PC) formation via the underlying Nrf2-dependent mechanism for cervical cancer cell (CC) survival under conditions of serum deprivation (SD). TB4 silencing was achieved using RNA interference. The percentage of PC formation was analyzed by immunofluorescence staining. Nrf2 expression was modified by the preparation of stable Nrf2-knockdown cells with shNrf2 and the overexpression of Nrf2 with pcDNA-Nrf2 plasmids. Gene expression was measured using reverse-transcription PCR, Gaussia luciferase assay, and western blotting. Cell viability was assessed using the MTT assay or CellTiter Glo assay. Reactive oxygen species (ROS) were detected with flow cytometry. CCs incubated in SD without fetal bovine serum remained viable, and SD increased PC formation and TB4 transcription. CC viability was further decreased by treatment with ciliobrevin A to inhibit PC formation or TB4-siRNA. SD increased ROS, including H2O2. N-acetylcysteine inhibited ROS production following H2O2 treatment or SD, which also decreased PC formation and TB4 transcription. Meanwhile, H2O2 increased PC formation, which was attenuated in response to TB4 siRNA. Treatment with H2O2 increased Nrf2 expression, antioxidant responsive element (ARE) activity, and PC formation, which were inhibited by the Nrf2 inhibitor clobestasol propionate. Nrf2 knockdown via expression of Tet-On shNrf2 enhanced ROS production, leading to increased PC formation and decreased TB4 expression; these effects were counteracted by Nrf2 overexpression. Our data demonstrate that Nrf2 counter-regulates TB4 expression and PC formation for CC survival under conditions of SD, suggesting cervical CC survival could be upregulated by PC formation via Nrf2 activation and TB4 expression.
Whole genome DNA and RNA sequencing of whole blood elucidates the genetic architecture of gene expression underlying a wide range of diseases
Authors: Liu Chunyu , Joehanes Roby , Ma Jiantao , Wang Yuxuan , Sun Xianbang , Keshawarz Amena , Sooda Meera , Huan Tianxiao , Hwang Shih-Jen , Bui Helena , Tejada Brandon , Munson Peter J. , Demirkale Cumhur Y. , Heard-Costa Nancy L. , Pitsillides Achilleas N. , Peloso Gina M. , Feolo Michael , Sharopova Nataliya , Vasan Ramachandran S. , Levy Daniel
Published: November 2022

To create a scientific resource of expression quantitative trail loci (eQTL), we conducted a genome-wide association study (GWAS) using genotypes obtained from whole genome sequencing (WGS) of DNA and gene expression levels from RNA sequencing (RNA-seq) of whole blood in 2622 participants in Framingham Heart Study. We identified 6,778,286 cis-eQTL variant-gene transcript (eGene) pairs at p < 5 × 10–8 (2,855,111 unique cis-eQTL variants and 15,982 unique eGenes) and 1,469,754 trans-eQTL variant-eGene pairs at p < 1e−12 (526,056 unique trans-eQTL variants and 7233 unique eGenes). In addition, 442,379 cis-eQTL variants were associated with expression of 1518 long non-protein coding RNAs (lncRNAs). Gene Ontology (GO) analyses revealed that the top GO terms for cis-eGenes are enriched for immune functions (FDR < 0.05). The cis-eQTL variants are enriched for SNPs reported to be associated with 815 traits in prior GWAS, including cardiovascular disease risk factors. As proof of concept, we used this eQTL resource in conjunction with genetic variants from public GWAS databases in causal inference testing (e.g., COVID-19 severity). After Bonferroni correction, Mendelian randomization analyses identified putative causal associations of 60 eGenes with systolic blood pressure, 13 genes with coronary artery disease, and seven genes with COVID-19 severity. This study created a comprehensive eQTL resource via BioData Catalyst that will be made available to the scientific community. This will advance understanding of the genetic architecture of gene expression underlying a wide range of diseases.