bluuebunny/crossref_metadata_2025 huggingface dataset:
Time‐Domain Reflectometry Measurements and Modeling of Firn Meltwater Infiltration at DYE‐2, Greenland
Authors: Samimi S. , Marshall S. J. , Vandecrux B. , MacFerrin M.
Published: September 2021

Surface meltwater can be retained in an ice sheet if it infiltrates the firn and refreezes. This is an important mass balance process for the Greenland Ice Sheet, reducing meltwater runoff and associated sea‐level rise. The processes of meltwater infiltration and refreezing are not fully understood, however, and remain difficult to monitor remotely. We deployed vertical arrays of thermistors and time‐domain reflectometry (TDR) probes to 4‐m depth in the firn to continuously monitor meltwater infiltration and refreezing processes at DYE‐2, Greenland. The observations provide a detailed picture of the coupled thermal and hydrological evolution of the firn through the 2016 melt season, including estimates of firn water content. The thaw and wetting fronts reached a maximum depth of 1.8 m, with meltwater infiltration concentrated in four main pulses of melting and subsurface warming that reached progressively deeper into the firn. The observations were used to constrain a coupled model of firn thermodynamics and hydrology, which was then run over the period 1950–2020, driven by meteorological forcing from GC‐Net station data and ERA5 climate reanalyses. Model results suggest that decadal‐scale firn evolution at DYE‐2 is strongly influenced by extreme melt seasons such as those of 1968, 2012, and 2019, when meltwater infiltration reached depths of 6–7 m. Extreme melt years drive increases in firn temperature, ice content, and density, reducing firn meltwater retention capacity. Such processes are likely to govern future meltwater retention as the percolation zone extends to higher elevations in Greenland in the coming decades.
Active Faulting and Deep‐Seated Gravitational Slope Deformation in Carbonate Rocks (Central Apennines, Italy): A New “Close‐Up” View
Authors: Del Rio Luca , Moro Marco , Fondriest Michele , Saroli Michele , Gori Stefano , Falcucci Emanuela , Cavallo Andrea , Doumaz Fawzi , Di Toro Giulio
Published: September 2021

Active faulting and deep‐seated gravitational slope deformation (DGSD) are common geological hazards in mountain belts worldwide. In the Italian central Apennines, kilometer‐thick carbonate sedimentary sequences are cut by major active normal faults that shape the landscape, generating intermontane basins. Geomorphological observations suggest that the DGSDs are commonly located in fault footwalls. We selected five mountain slopes affected by DGSD and exposing the footwall of active seismogenic normal faults exhumed from 2 to 0.5 km depth. Field structural analysis of the slopes shows that DGSDs exploit preexisting surfaces formed both at depth and near the ground surface by tectonic faulting and, locally, by gravitational collapse. Furthermore, the exposure of sharp scarps along mountain slopes in the central Apennines can be enhanced either by surface seismic rupturing or gravitational movements (e.g., DGSD) or by a combination of the two. At the microscale, DGSDs accommodate deformation mechanisms similar to those associated with tectonic faulting. The widespread compaction of micro‐grains (e.g., clast indentation), observed in the matrix of both normal faults and DGSD slip zones, is consistent with clast fragmentation, fluid‐infiltration, and congruent pressure‐solution active at low ambient temperatures (<60°C) and lithostatic pressures (<80 MPa). Although clast comminution is more intense in the slip zones of normal faults because of the larger displacement accommodated, we are not able to find microstructural markers that allow us to uniquely distinguish faults from DGSDs.
Microglial-expressed genetic risk variants, cognitive function and brain volume in patients with schizophrenia and healthy controls
Authors: Corley Emma , Holleran Laurena , Fahey Laura , Corvin Aiden , Morris Derek W. , Donohoe Gary
Published: September 2021

Changes in immune function are associated with variance in cognitive functioning in schizophrenia. Given that microglia are the primary innate immune cells in the brain, we examined whether schizophrenia risk-associated microglial genes (measured via polygenic score analysis) explained variation in cognition in patients with schizophrenia and controls (n = 1,238) and tested whether grey matter mediated this association. We further sought to replicate these associations in an independent sample of UK Biobank participants (n = 134,827). We then compared the strength of these microglial associations to that of neuronal and astroglial (i.e., other brain-expressed genes) polygenic scores, and used MAGMA to test for enrichment of these gene-sets with schizophrenia risk. Increased microglial schizophrenia polygenic risk was associated with significantly lower performance across several measures of cognitive functioning in both samples; associations which were then found to be mediated via total grey matter volume in the UK Biobank. Unlike neuronal genes which did show evidence of enrichment, the microglial gene-set was not significantly enriched for schizophrenia, suggesting that the relevance of microglia may be for neurodevelopmental processes related more generally to cognition. Further, the microglial polygenic score was associated with performance on a range of cognitive measures in a manner comparable to the neuronal schizophrenia polygenic score, with fewer cognitive associations observed for the astroglial score. In conclusion, our study supports the growing evidence of the importance of immune processes to understanding cognition and brain structure in both patients and in the healthy population.
Inhibition of Notch activity promotes pancreatic cytokeratin 5-positive cell differentiation to beta cells and improves glucose homeostasis following acute pancreatitis
Authors: Zhang Xiaoyi , Tao Jing , Yu Jia , Hu Ning , Zhang Xuanzhe , Wang Guirong , Feng Jiarui , Xiong Xingcheng , Li Man , Chai Dongqi , Li Hanjun , Rong Yuping , Tang Zhigang , Wang Weixing , Peng Zhiyong , Shi Qiao
Published: September 2021

Some individuals develop prediabetes and/or diabetes following acute pancreatitis (AP). AP-induced beta-cell injury and the limited regenerative capacity of beta cells might account for pancreatic endocrine insufficiency. Previously, we found that only a few pancreatic cytokeratin 5 positive (Krt5+) cells differentiated into beta cells in the murine AP model, which was insufficient to maintain glucose homeostasis. Notch signaling determines pancreatic progenitor differentiation in pancreas development. This study aimed to examine whether Notch signaling inhibition could promote pancreatic Krt5+ cell differentiation into beta cells and improve glucose homeostasis following AP. Pancreatic tissues from patients with acute necrotizing pancreatitis (ANP) were used to evaluate beta-cell injury, Krt5+ cell activation and differentiation, and Notch activity. The murine AP model was induced by cerulein, and the effect of Notch inhibition on Krt5+ cell differentiation was evaluated both in vivo and in vitro. The results demonstrated beta-cell loss in ANP patients and AP mice. Krt5+ cells were activated in ANP pancreases along with persistently elevated Notch activity, which resulted in the formation of massive duct-like structures. AP mice that received Notch inhibitor showed that impaired glucose tolerance was reversed 7 and 15 days following AP, and increased numbers of newborn small islets due to increased differentiation of Krt5+ cells to beta cells to some extent. In addition, Krt5+ cells isolated from AP mice showed increased differentiation to beta cells by Notch inhibition. Collectively, these findings suggest that beta-cell loss contributes to pancreatic endocrine insufficiency following AP, and inhibition of Notch activity promotes pancreatic Krt5+ cell differentiation to beta cells and improves glucose homeostasis. The findings from this study may shed light on the potential treatment of prediabetes/diabetes following AP.
Genome-wide sequencing-based identification of methylation quantitative trait loci and their role in schizophrenia risk
Authors: Perzel Mandell Kira A. , Eagles Nicholas J. , Wilton Richard , Price Amanda J. , Semick Stephen A. , Collado-Torres Leonardo , Ulrich William S. , Tao Ran , Han Shizhong , Szalay Alexander S. , Hyde Thomas M. , Kleinman Joel E. , Weinberger Daniel R. , Jaffe Andrew E.
Published: September 2021

DNA methylation (DNAm) is an epigenetic regulator of gene expression and a hallmark of gene-environment interaction. Using whole-genome bisulfite sequencing, we have surveyed DNAm in 344 samples of human postmortem brain tissue from neurotypical subjects and individuals with schizophrenia. We identify genetic influence on local methylation levels throughout the genome, both at CpG sites and CpH sites, with 86% of SNPs and 55% of CpGs being part of methylation quantitative trait loci (meQTLs). These associations can further be clustered into regions that are differentially methylated by a given SNP, highlighting the genes and regions with which these loci are epigenetically associated. These findings can be used to better characterize schizophrenia GWAS-identified variants as epigenetic risk variants. Regions differentially methylated by schizophrenia risk-SNPs explain much of the heritability associated with risk loci, despite covering only a fraction of the genomic space. We provide a comprehensive, single base resolution view of association between genetic variation and genomic methylation, and implicate schizophrenia GWAS-associated variants as influencing the epigenetic plasticity of the brain.
Peroxisome inspired hybrid enzyme nanogels for chemodynamic and photodynamic therapy
Authors: Qin Xing , Wu Chu , Niu Dechao , Qin Limei , Wang Xia , Wang Qigang , Li Yongsheng
Published: September 2021

Peroxisome, a special cytoplasmic organelle, possesses one or more kinds of oxidases for hydrogen peroxide (H2O2) production and catalase for H2O2 degradation, which serves as an intracellular H2O2 regulator to degrade toxic peroxides to water. Inspired by this biochemical pathway, we demonstrate the reactive oxygen species (ROS) induced tumor therapy by integrating lactate oxidase (LOx) and catalase (CAT) into Fe3O4 nanoparticle/indocyanine green (ICG) co-loaded hybrid nanogels (designated as FIGs-LC). Based on the O2 redistribution and H2O2 activation by cascading LOx and CAT catalytic metabolic regulation, hydroxyl radical (·OH) and singlet oxygen (1O2) production can be modulated for glutathione (GSH)-activated chemodynamic therapy (CDT) and NIR-triggered photodynamic therapy (PDT), by manipulating the ratio of LOx and CAT to catalyze endogenous lactate to produce H2O2 and further cascade decomposing H2O2 into O2. The regulation reactions of FIGs-LC significantly elevate the intracellular ROS level and cause fatal damage to cancer cells inducing the effective inhibition of tumor growth. Such enzyme complex loaded hybrid nanogel present potential for biomedical ROS regulation, especially for the tumors with different redox state, size, and subcutaneous depth.
Synthetic exploration of sulfinyl radicals using sulfinyl sulfones
Authors: Wang Zikun , Zhang Zhansong , Zhao Wanjun , Sivaguru Paramasivam , Zanoni Giuseppe , Wang Yingying , Anderson Edward A. , Bi Xihe
Published: September 2021

Sulfinyl radicals – one of the fundamental classes of S-centered radicals – have eluded synthetic application in organic chemistry for over 60 years, despite their potential to assemble valuable sulfoxide compounds. Here we report the successful generation and use of sulfinyl radicals in a dual radical addition/radical coupling with unsaturated hydrocarbons, where readily-accessed sulfinyl sulfones serve as the sulfinyl radical precursor. The strategy provides an entry to a variety of previously inaccessible linear and cyclic disulfurized adducts in a single step, and demonstrates tolerance to an extensive range of hydrocarbons and functional groups. Experimental and theoretical mechanistic investigations suggest that these reactions proceed through sequential sulfonyl and sulfinyl radical addition.
A comprehensive map of alternative polyadenylation in African American and European American lung cancer patients
Authors: Zingone Adriana , Sinha Sanju , Ante Michael , Nguyen Cu , Daujotyte Dalia , Bowman Elise D. , Sinha Neelam , Mitchell Khadijah A. , Chen Qingrong , Yan Chunhua , Loher Phillipe , Meerzaman Daoud , Ruppin Eytan , Ryan Bríd M.
Published: September 2021

Deciphering the post-transcriptional mechanisms (PTM) regulating gene expression is critical to understand the dynamics underlying transcriptomic regulation in cancer. Alternative polyadenylation (APA)—regulation of mRNA 3′UTR length by alternating poly(A) site usage—is a key PTM mechanism whose comprehensive analysis in cancer remains an important open challenge. Here we use a method and analysis pipeline that sequences 3′end-enriched RNA directly to overcome the saturation limitation of traditional 5′–3′ based sequencing. We comprehensively map the APA landscape in lung cancer in a cohort of 98 tumor/non-involved tissues derived from European American and African American patients. We identify a global shortening of 3′UTR transcripts in lung cancer, with notable functional implications on the expression of both coding and noncoding genes. We find that APA of non-coding RNA transcripts (long non-coding RNAs and microRNAs) is a recurrent event in lung cancer and discover that the selection of alternative polyA sites is a form of non-coding RNA expression control. Our results indicate that mRNA transcripts from EAs are two times more likely than AAs to undergo APA in lung cancer. Taken together, our findings comprehensively map and identify the important functional role of alternative polyadenylation in determining transcriptomic heterogeneity in lung cancer.
Analyses of child cardiometabolic phenotype following assisted reproductive technologies using a pragmatic trial emulation approach
Authors: Huang Jonathan Yinhao , Cai Shirong , Huang Zhongwei , Tint Mya Thway , Yuan Wen Lun , Aris Izzuddin M. , Godfrey Keith M. , Karnani Neerja , Lee Yung Seng , Chan Jerry Kok Yen , Chong Yap Seng , Eriksson Johan Gunnar , Chan Shiao-Yng
Published: September 2021

Assisted reproductive technologies (ART) are increasingly used, however little is known about the long-term health of ART-conceived offspring. Weak selection of comparison groups and poorly characterized mechanisms impede current understanding. In a prospective cohort (Growing Up in Singapore Towards healthy Outcomes; GUSTO; Clinical Trials ID: NCT01174875) including 83 ART-conceived and 1095 spontaneously-conceived singletons, we estimate effects of ART on anthropometry, blood pressure, serum metabolic biomarkers, and cord tissue DNA methylation by emulating a pragmatic trial supported by machine learning-based estimators. We find ART-conceived children to be shorter (−0.5 SD [95% CI: −0.7, −0.2]), lighter (−0.6 SD [−0.9, −0.3]) and have lower skinfold thicknesses (e.g. −14% [−24%, −3%] suprailiac), and blood pressure (−3 mmHg [−6, −0.5] systolic) at 6-6.5 years, with no strong differences in metabolic biomarkers. Differences are not explained by parental anthropometry or comorbidities, polygenic risk score, breastfeeding, or illnesses. Our simulations demonstrate ART is strongly associated with lower NECAB3 DNA methylation, with negative control analyses suggesting these estimates are unbiased. However, methylation changes do not appear to mediate observed differences in child phenotype.
Field-free topological behavior in the magnetic domain wall of ferrimagnetic GdFeCo
Authors: Li Zhuolin , Su Jian , Lin Shi-Zeng , Liu Dan , Gao Yang , Wang Shouguo , Wei Hongxiang , Zhao Tongyun , Zhang Ying , Cai Jianwang , Shen Baogen
Published: September 2021

Exploring and controlling topological textures such as merons and skyrmions has attracted enormous interests from the perspective of fundamental research and spintronic applications. It has been predicted theoretically and proved experimentally that the lattice form of topological meron-skyrmion transformation can be realized with the requirement of external magnetic fields in chiral ferromagnets. However, such topological transition behavior has yet to be verified in other materials. Here, we report real-space observation of magnetic topology transformation between meron pairs and skyrmions in the localized domain wall of ferrimagnetic GdFeCo films without the need of magnetic fields. The topological transformation in the domain wall of ferrimagnet is introduced by temperature-induced spin reorientation transition (SRT) and the underlying mechanism is revealed by micromagnetic simulations. The convenient electric-controlling topology transformation and driving motion along the confined domain wall is further anticipated, which will enable advanced application in magnetic devices.
Generation of a more efficient prime editor 2 by addition of the Rad51 DNA-binding domain
Authors: Song Myungjae , Lim Jung Min , Min Seonwoo , Oh Jeong-Seok , Kim Dong Young , Woo Jae-Sung , Nishimasu Hiroshi , Cho Sung-Rae , Yoon Sungroh , Kim Hyongbum Henry
Published: September 2021

Although prime editing is a promising genome editing method, the efficiency of prime editor 2 (PE2) is often insufficient. Here we generate a more efficient variant of PE2, named hyPE2, by adding the Rad51 DNA-binding domain. When tested at endogenous sites, hyPE2 shows a median of 1.5- or 1.4- fold (range, 0.99- to 2.6-fold) higher efficiencies than PE2; furthermore, at sites where PE2-induced prime editing is very inefficient (efficiency < 1%), hyPE2 enables prime editing with efficiencies ranging from 1.1% to 2.9% at up to 34% of target sequences, potentially facilitating prime editing applications.
A blueprint of the topology and mechanics of the human ovary for next-generation bioengineering and diagnosis
Authors: Ouni Emna , Peaucelle Alexis , Haas Kalina T. , Van Kerk Olivier , Dolmans Marie-Madeleine , Tuuri Timo , Otala Marjut , Amorim Christiani A.
Published: September 2021

Although the first dissection of the human ovary dates back to the 17th century, the biophysical characteristics of the ovarian cell microenvironment are still poorly understood. However, this information is vital to deciphering cellular processes such as proliferation, morphology and differentiation, as well as pathologies like tumor progression, as demonstrated in other biological tissues. Here, we provide the first readout of human ovarian fiber morphology, interstitial and perifollicular fiber orientation, pore geometry, topography and surface roughness, and elastic and viscoelastic properties. By determining differences between healthy prepubertal, reproductive-age, and menopausal ovarian tissue, we unravel and elucidate a unique biophysical phenotype of reproductive-age tissue, bridging biophysics and female fertility. While these data enable to design of more biomimetic scaffolds for the tissue-engineered ovary, our analysis pipeline is applicable for the characterization of other organs in physiological or pathological states to reveal their biophysical markers or design their bioinspired analogs.
Berberine is an insulin secretagogue targeting the KCNH6 potassium channel
Authors: Zhao Miao-Miao , Lu Jing , Li Sen , Wang Hao , Cao Xi , Li Qi , Shi Ting-Ting , Matsunaga Kohichi , Chen Chen , Huang Haixia , Izumi Tetsuro , Yang Jin-Kui
Published: September 2021

Coptis chinensisis an ancient Chinese herb treating diabetes in China for thousands of years. However, its underlying mechanism remains poorly understood. Here, we report the effects of its main active component, berberine (BBR), on stimulating insulin secretion. In mice with hyperglycemia induced by a high-fat diet, BBR significantly increases insulin secretion and reduced blood glucose levels. However, in mice with hyperglycemia induced by global or pancreatic islet β-cell-specificKcnh6knockout, BBR does not exert beneficial effects. BBR directly binds KCNH6 potassium channels, significantly accelerates channel closure, and subsequently reduces KCNH6 currents. Consequently, blocking KCNH6 currents prolongs high glucose-dependent cell membrane depolarization and increases insulin secretion. Finally, to assess the effect of BBR on insulin secretion in humans, a randomized, double-blind, placebo-controlled, two-period crossover, single-dose, phase 1 clinical trial (NCT03972215) including 15 healthy men receiving a 160-min hyperglycemic clamp experiment is performed. The pre-specified primary outcomes are assessment of the differences of serum insulin and C-peptide levels between BBR and placebo treatment groups during the hyperglycemic clamp study. BBR significantly promotes insulin secretion under hyperglycemic state comparing with placebo treatment, while does not affect basal insulin secretion in humans. All subjects tolerate BBR well, and we observe no side effects in the 14-day follow up period. In this study, we identify BBR as a glucose-dependent insulin secretagogue for treating diabetes without causing hypoglycemia that targets KCNH6 channels.
Periodontitis associates with species-specific gene expression of the oral microbiota
Authors: Belstrøm Daniel , Constancias Florentin , Drautz-Moses Daniela I. , Schuster Stephan C. , Veleba Mark , Mahé Frédéric , Givskov Michael
Published: September 2021

The purpose of the present investigation was to characterize species-specific bacterial activity of the oral microbiota in periodontitis. We tested the hypotheses that chronic inflammation, i.e., periodontitis, associates with bacterial gene expression of the oral microbiota. Oral microbial samples were collected from three oral sites—subgingival plaque, tongue, and saliva from patients with periodontitis and healthy controls. Paired metagenomics and metatranscriptomics were used to perform concomitant characterization of taxonomic composition and to determine species-specific bacterial activity as expressed by the ratio of specific messenger RNA reads to their corresponding genomic DNA reads. Here, we show the association of periodontitis with bacterial gene expression of the oral microbiota. While oral site was the main determinant of taxonomic composition as well as bacterial gene expression, periodontitis was significantly associated with a reduction of carbohydrate metabolism of the oral microbiota at three oral sites (subgingival plaque, tongue, and saliva). Data from the present study revealed the association of periodontitis with bacterial gene expression of the oral microbiota. Conditions of periodontitis was associated with bacterial activity of local subgingival plaque, but also on tongue and the salivary microbiota. Collectively, data suggest that periodontitis associates with impaired carbohydrate metabolism of the oral microbiota. Future longitudinal and interventional studies are warranted to evaluate the potential pathogenic role of impaired bacterial carbohydrate metabolism not only in periodontitis but also in other diseases with low-grade inflammation, such as type 2 diabetes mellitus.
Comparison of the tumor immune microenvironment of primary hormone receptor-negative HER2-positive and triple negative breast cancer
Authors: Vos Hanne , Lambein Kathleen , Richard François , Mariën Bram , Nevelsteen Ines , Punie Kevin , Wildiers Hans , Berben Lieze , Laenen Annouschka , Floris Giuseppe , Desmedt Christine , Smeets Ann
Published: September 2021

The vast majority of studies investigating immune checkpoint inhibition (ICI) in patients with breast cancer have focused on triple-negative breast cancer (TNBC). In this study, we compared the tumor immune microenvironment (TIME) between TNBC and hormone receptor-negative HER2-positive breast cancer based on a selection of immune markers at the protein level in an institutional retrospective series. Additionally, we performed a similar comparison using publicly available transcriptomics data. Altogether, the results show a comparable TIME in both groups, with possible implications for the use of ICI in patients with hormone receptor-negative HER2-positive breast tumors.
High CYP27A1 expression is a biomarker of favorable prognosis in premenopausal patients with estrogen receptor positive primary breast cancer
Authors: Inasu Maria , Bendahl Pär-Ola , Fernö Mårten , Malmström Per , Borgquist Signe , Kimbung Siker
Published: September 2021

27-hydroxycholesterol (27HC), synthesized from cholesterol by the enzyme CYP27A1, differentially impacts estrogen receptor positive (ER+) breast cancer (BC) cell growth depending on estrogen levels. This study examined the association between CYP27A1 expression and prognosis in a cohort of 193 premenopausal patients with lymph node-negative primary BC with limited exposure to adjuvant systemic cancer treatments. In multivariable analyses among patients with ER+ tumors, high CYP27A1 protein and mRNA expressions were associated with four- and eight-fold reductions in the incidence of distant recurrence-free survival events: HRadj = 0.26, 95% CI = 0.07–0.93 and HRadj = 0.13, 95% CI = 0.03–0.60, respectively. In vitro studies revealed that 27HC treatment potently inhibited ER+ BC cell proliferation under lipid-depleted conditions regardless of estradiol levels, transcriptionally mediated through the downregulation of ER signaling with a concomitant upregulation of cholesterol export. Importantly, if validated, these results may have implications for adjuvant treatment decisions in premenopausal patients, especially when de-escalation of therapy is being considered.
Quantum efficiency, purity and stability of a tunable, narrowband microwave single-photon source
Authors: Lu Yong , Bengtsson Andreas , Burnett Jonathan J. , Suri Baladitya , Sathyamoorthy Sankar Raman , Nilsson Hampus Renberg , Scigliuzzo Marco , Bylander Jonas , Johansson Göran , Delsing Per
Published: September 2021

We demonstrate an on-demand source of microwave single photons with 71–99% intrinsic quantum efficiency. The source is narrowband (300 kHz) and tuneable over a 600 MHz range around 5.2 GHz. Such a device is an important element in numerous quantum technologies and applications. The device consists of a superconducting transmon qubit coupled to the open end of a transmission line. A π-pulse excites the qubit, which subsequently rapidly emits a single photon into the transmission line. A cancellation pulse then suppresses the reflected π-pulse by 33.5 dB, resulting in 0.005 photons leaking into the photon emission channel. We verify strong antibunching of the emitted photon field and determine its Wigner function. Non-radiative decay and 1/f flux noise both affect the quantum efficiency. We also study the device stability over time and identify uncorrelated discrete jumps of the pure dephasing rate at different qubit frequencies on a time scale of hours, which we attribute to independent two-level system defects in the device dielectrics, dispersively coupled to the qubit. Our single-photon source with only one input port is more compact and scalable compared to standard implementations.
Lake Ohrid’s tephrochronological dataset reveals 1.36 Ma of Mediterranean explosive volcanic activity
Authors: Leicher Niklas , Giaccio Biagio , Zanchetta Giovanni , Sulpizio Roberto , Albert Paul G. , Tomlinson Emma L. , Lagos Markus , Francke Alexander , Wagner Bernd
Published: September 2021

Tephrochronology relies on the availability of the stratigraphical, geochemical and geochronological datasets of volcanic deposits, three preconditions which are both often only fragmentary accessible. This study presents the tephrochronological dataset from the Lake Ohrid (Balkans) sediment succession continuously reaching back to 1.36 Ma. 57 tephra layers were investigated for their morphological appearance, geochemical fingerprint, and (chrono-)stratigraphic position. Glass fragments of tephra layers were analyzed for their major element composition using Energy-Dispersive-Spectroscopy and Wavelength-Dispersive Spectroscopy and for their trace element composition by Laser Ablation-Inductively Coupled Plasma-Mass Spectrometry. Radiometric dated equivalents of 16 tephra layers and orbital tuning of geochemical proxy data provided the basis for the age-depth model of the Lake Ohrid sediment succession. The age-depth model, in turn, provides ages for unknown or undated tephra layers. This dataset forms the basis for a regional stratigraphic framework and provides insights into the central Mediterranean explosive volcanic activity during the last 1.36 Ma.
Cydrasil 3, a curated 16S rRNA gene reference package and web app for cyanobacterial phylogenetic placement
Authors: Roush Daniel , Giraldo-Silva Ana , Garcia-Pichel Ferran
Published: September 2021

Cyanobacteria are a widespread and important bacterial phylum, responsible for a significant portion of global carbon and nitrogen fixation. Unfortunately, reliable and accurate automated classification of cyanobacterial 16S rRNA gene sequences is muddled by conflicting systematic frameworks, inconsistent taxonomic definitions (including the phylum itself), and database errors. To address this, we introduce Cydrasil 3 (https://www.cydrasil.org), a curated 16S rRNA gene reference package, database, and web application designed to provide a full phylogenetic perspective for cyanobacterial systematics and routine identification. Cydrasil 3 contains over 1300 manually curated sequences longer than 1100 base pairs and can be used for phylogenetic placement or as a reference sequence set for de novo phylogenetic reconstructions. The web application (utilizing PaPaRA and EPA-ng) can place thousands of sequences into the reference tree and has detailed instructions on how to analyze results. While the Cydrasil web application offers no taxonomic assignments, it instead provides phylogenetic placement, as well as a searchable database with curation notes and metadata, and a mechanism for community feedback.
A database of travel-related behaviors and attitudes before, during, and after COVID-19 in the United States
Authors: Chauhan Rishabh Singh , Bhagat-Conway Matthew Wigginton , Capasso da Silva Denise , Salon Deborah , Shamshiripour Ali , Rahimi Ehsan , Khoeini Sara , Mohammadian Abolfazl , Derrible Sybil , Pendyala Ram
Published: September 2021

The COVID-19 pandemic has impacted billions of people around the world. To capture some of these impacts in the United States, we are conducting a nationwide longitudinal survey collecting information about activity and travel-related behaviors and attitudes before, during, and after the COVID-19 pandemic. The survey questions cover a wide range of topics including commuting, daily travel, air travel, working from home, online learning, shopping, and risk perception, along with attitudinal, socioeconomic, and demographic information. The survey is deployed over multiple waves to the same respondents to monitor how behaviors and attitudes evolve over time. Version 1.0 of the survey contains 8,723 responses that are publicly available. This article details the methodology adopted for the collection, cleaning, and processing of the data. In addition, the data are weighted to be representative of national and regional demographics. This survey dataset can aid researchers, policymakers, businesses, and government agencies in understanding both the extent of behavioral shifts and the likelihood that changes in behaviors will persist after COVID-19.
Similarity of gaze patterns across physical and virtual versions of an installation artwork
Authors: Gulhan Doga , Durant Szonya , Zanker Johannes M.
Published: September 2021

An experiment was conducted to compare museum visitors’ gaze patterns using mobile eye-trackers, whilst they were engaging with a physical and a virtual reality (VR) installation of Piet Mondrian’s Neo-plasticist room design. Visitors’ eye movements produced approximately 25,000 fixations and were analysed using linear mixed-effects models. Absolute and area-normalized dwell time analyses yielded mostly non-significant main effects of the environment, indicating similarity of visual exploration patterns between physical and VR settings. One major difference observed was the decrease of average fixation duration in VR, where visitors tended to more rapidly switch focus in this environment with shorter bursts of attentional focus. The experiment demonstrated the ability to compare gaze data between physical and virtual environments as a proxy to measure the similarity of aesthetic experience. Similarity of viewing patterns along with questionnaire results suggested that virtual galleries can be treated as ecologically valid environments that are parallel to physical art galleries.
Protein disulphide isomerase (PDI) is protective against amyotrophic lateral sclerosis (ALS)-related mutant Fused in Sarcoma (FUS) in in vitro models
Authors: Parakh S. , Perri E. R. , Vidal M. , Sultana J. , Shadfar S. , Mehta P. , Konopka A. , Thomas C. J. , Spencer D. M. , Atkin J. D.
Published: September 2021

Mutations in Fused in Sarcoma (FUS) are present in familial and sporadic cases of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). FUS is localised in the nucleus where it has important functions in DNA repair. However, in ALS/FTD, mutant FUS mislocalises from the nucleus to the cytoplasm where it forms inclusions, a key pathological hallmark of neurodegeneration. Mutant FUS also inhibits protein import into the nucleus, resulting in defects in nucleocytoplasmic transport. Fragmentation of the neuronal Golgi apparatus, induction of endoplasmic reticulum (ER) stress, and inhibition of ER-Golgi trafficking are also associated with mutant FUS misfolding in ALS. Protein disulphide isomerase (PDI) is an ER chaperone previously shown to be protective against misfolding associated with mutant superoxide dismutase 1 (SOD1) and TAR DNA-binding protein-43 (TDP-43) in cellular and zebrafish models. However, a protective role against mutant FUS in ALS has not been previously described. In this study, we demonstrate that PDI is protective against mutant FUS. In neuronal cell line and primary cultures, PDI restores defects in nuclear import, prevents the formation of mutant FUS inclusions, inhibits Golgi fragmentation, ER stress, ER-Golgi transport defects, and apoptosis. These findings imply that PDI is a new therapeutic target in FUS-associated ALS.
The impact of anthropogenic noise on individual identification via female song in Black-capped chickadees (Poecile atricapillus)
Authors: Montenegro Carolina , Service William D. , Scully Erin N. , Mischler Shannon K. , Sahu Prateek K. , Benowicz Thomas J. , Fox Katelyn V. R. , Sturdy Christopher B.
Published: September 2021

When anthropogenic noise occurs simultaneously with an acoustic signal or cue, it can be difficult for an animal to interpret the information encoded within vocalizations. However, limited research has focused on how anthropogenic noise affects the identification of acoustic communication signals. In songbirds, research has also shown that black-capped chickadees (Poecile atricapillus) will shift the pitch and change the frequency at which they sing in the presence of anthropogenic, and experimental noise. Black-capped chickadees produce several vocalizations; their fee-bee song is used for mate attraction and territorial defence, and contains information about dominance hierarchy and native geographic location. Previously, we demonstrated that black-capped chickadees can discriminate between individual female chickadees via their fee-bee songs. Here we used an operant discrimination go/no-go paradigm to discern whether the ability to discriminate between individual female chickadees by their song would be impacted by differing levels of anthropogenic noise. Following discrimination training, two levels of anthropogenic noise (low: 40 dB SPL; high: 75 dB SPL) were played with stimuli to determine how anthropogenic noise would impact discrimination. Results showed that even with low-level noise (40 dB SPL) performance decreased and high-level (75 dB SPL) noise was increasingly detrimental to discrimination. We learned that perception of fee-bee songs does change in the presence of anthropogenic noise such that birds take significantly longer to learn to discriminate between females, but birds were able to generalize responding after learning the discrimination. These results add to the growing literature underscoring the impact of human-made noise on avian wildlife, specifically the impact on perception of auditory signals.
Drastic change of magnetic anisotropy in Fe3GeTe2 and Fe4GeTe2 monolayers under electric field studied by density functional theory
Authors: Kim Dongwook , Lee Changhoon , Jang Bo Gyu , Kim Kyoo , Shim Ji Hoon
Published: September 2021

Magnetic anisotropy energy (MAE) is one of the most important properties in two-dimensional magnetism since the magnetization in two dimension is vulnerable to the spin rotational fluctuations. Using density functional theory calculation, we show that perpendicular electric field dramatically enhances the in-plane and out-of-plane magnetic anisotropies in Fe3GeTe2 and Fe4GeTe2 monolayers, respectively, allowing the change of easy axis in both systems. The changes of the MAE under the electric field are understood as the result of charge redistribution inside the layer, which is available due to the three-dimensional (3D) network of Fe atoms in the monolayers. As a result, we suggest that due to the unique structure of FenGeTe2 compounds composed by peculiar 3D networks of metal atoms, the MAE can be dramatically changed by the external perpendicular electric field.
5G-enabled contactless multi-user presence and activity detection for independent assisted living
Authors: Ashleibta Aboajeila Milad , Taha Ahmad , Khan Muhammad Aurangzeb , Taylor William , Tahir Ahsen , Zoha Ahmed , Abbasi Qammer H. , Imran Muhammad Ali
Published: September 2021

Wireless sensing is the state-of-the-art technique for next generation health activity monitoring. Smart homes and healthcare centres have a demand for multi-subject health activity monitoring to cater for future requirements. 5G-sensing coupled with deep learning models has enabled smart health monitoring systems, which have the potential to classify multiple activities based on variations in channel state information (CSI) of wireless signals. Proposed is the first 5G-enabled system operating at 3.75 GHz for multi-subject, in-home health activity monitoring, to the best of the authors’ knowledge. Classified are activities of daily life performed by up to 4 subjects, in 16 categories. The proposed system combines subject count and activities performed in different classes together, resulting in simultaneous identification of occupancy count and activities performed. The CSI amplitudes obtained from 51 subcarriers of the wireless signal are processed and combined to capture variations due to simultaneous multi-subject movements. A deep learning convolutional neural network is engineered and trained on the CSI data to differentiate multi-subject activities. The proposed system provides a high average accuracy of 91.25% for single subject movements and an overall high multi-class accuracy of 83% for 4 subjects and 16 classification categories. The proposed system can potentially fulfill the needs of future in-home health activity monitoring and is a viable alternative for monitoring public health and well being.
A new long-term sampling approach to viruses on surfaces
Authors: Sommer Julia , Bobal Martin , Bromberger Birgit , Mester Patrick-Julian , Rossmanith Peter
Published: September 2021

The importance of virus disease outbreaks and its prevention is of growing public concern but our understanding of virus transmission routes is limited by adequate sampling strategies. While conventional swabbing methods provide merely a microbial snapshot, an ideal sampling strategy would allow reliable collection of viral genomic data over longer time periods. This study has evaluated a new, paper-based sticker approach for collection of reliable viral genomic data over longer time periods up to 14 days and after implementation of different hygiene measures. In contrast to swabbing methods, which sample viral load present on a surface at a given time, the paper-based stickers are attached to the surface area of interest and collect viruses that would have otherwise been transferred onto that surface. The major advantage of one-side adhesive stickers is that they are permanently attachable to a variety of surfaces. Initial results demonstrate that stickers permit stable recovery characteristics, even at low virus titers. Stickers also allow reliable virus detection after implementation of routine hygiene measures and over longer periods up to 14 days. Overall, results for this new sticker approach for virus genomic data collection are encouraging, but further studies are required to confirm anticipated benefits over a range of virus types.
Asymmetrical activation and asymmetrical weakness as two different mechanisms of adolescent idiopathic scoliosis
Authors: Park Yulhyun , Ko Jin Young , Jang Joon Young , Lee Seungeun , Beom Jaewon , Ryu Ju Seok
Published: September 2021

There have been many studies on adolescent idiopathic scoliosis related abnormal muscle contractions of the spine. However, previous studies using surface electromyography to investigate paraspinal muscle asymmetry are controversial, lacking in clarity of results, and hindered by methodological limitations. The purpose of this study was to investigate the relationship between imbalance factors including surface electromyography activity according to the scoliosis curve type and leg length discrepancy and adolescent idiopathic scoliosis curve types. Seventy-nine patients with scoliosis were prospectively enrolled and were divided into five types: single thoracic, thoracolumbar, lumbar, double thoracic, and double major. Cobb angle and structural variables were measured. Surface electromyography examinations were conducted at the 7th, 12th thoracic erector spinae, 3rd lumbar erector spinae, and multifidus muscles during the superman position keeping prone spinal extension to lift the arms and legs off the floor. Whole spine radiographs were obtained to measure the Cobb angle, coronal imbalance, pelvic height and angle, and femoral head height. In the double major, thoracolumbar, and lumbar types, the mean root mean squared (RMS) EMG amplitudes were significantly higher on the convex side than the concave side (P < 0.005). In the DM type, the mean RMS EMG amplitudes of EST7 and ESL3 where the apex was located were significantly higher at the convex side than those of the concave side (P < 0.005, effect size (Cohen’s d) for EST7/ESL3: 0.517/0.573). The TL and L types showed a similar pattern. The mean RMS EMG amplitudes of the EST12 concave side and MuL3 and ESL3 concave sides were significantly lower than those of the convex side in the TL and L types, respectively (P < 0.008, effect size (Cohen’s d) for EST12/MuL3/ESL3: 0.960/0.264/0.448). Conversely, there were no significant differences in the single thoracic and double thoracic types. All structural variables (coronal imbalance, pelvic height and angle, and femur head height) were higher in the lumbar type, but only coronal imbalance was significantly different (P < 0.05). Different patterns of asymmetry of paraspinal muscles and structural variables were described based on the curvature of the spine. L type showed that EMG activity was asymmetric in the paraspinalis muscles where the apex was located and that structural asymmetry, such as coronal imbalance was significantly greater than other types. DM type showed similar paraspinalis asymmetry pattern to the ST type but there was no structural asymmetry in DM and ST types. TL type has the features of both thoracic and lumbar origins. Understanding these could contribute to the management in correcting scoliosis.
Flight performance and the factors affecting the flight behaviour of Philaenus spumarius the main vector of Xylella fastidiosa in Europe
Authors: Lago Clara , Garzo Elisa , Moreno Aránzazu , Barrios Laura , Martí-Campoy Antonio , Rodríguez-Ballester Francisco , Fereres Alberto
Published: September 2021

The recent emergence of Xylella fastidiosa in Europe is a major threat to agriculture, including olive, almond and grape. Philaenus spumarius is the predominant vector of X. fastidiosa in Europe. Understanding vector movement is critical for developing effective control measures against bacterial spread. In this study, our goal was to set up a flight-mill protocol to assess P. spumarius flight potential and to analyse how different variables may affect its flight behaviour. We found that P. spumarius was able to fly ≈ 500 m in 30 min with a maximum single flight of 5.5 km in 5.4 h. Based on the observations, the flight potential of the females was higher in spring and autumn than in summer, and that of the males was highest in autumn. Moreover, we found that P. spumarius had a higher flight potential during the morning and the night than during the afternoon. Our results revealed that P. spumarius is likely to disperse much further than the established sizes of the infected and buffer zones designated by the EU. This knowledge on the flight potential of P. spumarius will be critical for improving management actions against P. spumarius and the spread of X. fastidiosa in Europe.
Factors influencing surgical outcomes in orbital trapdoor fracture
Authors: Chen Yi-Hua , Tsai Yueh-Ju , Tzeng I-Shiang
Published: September 2021

This study is aimed to determine the appropriate timing of performing surgical reduction on trapdoor fractures for bringing out better visual outcomes and the factors influencing surgical outcomes in this special subgroup of fracture victims. Data for 72 patients of orbital trapdoor fracture were analyzed retrospectively. Post-operative diplopia is the main posttreatment outcome of orbital bone fracture reduction. The receiver-operating characteristic (ROC) analysis indicated the cut-off point of surgical reduction timing at day 10 post-fracture. The rate of postoperative diplopia showed a significant difference between patients who underwent surgical reduction within 10 days and those who did after 10 days of injury (5.3% vs. 38.2%). Multivariate analysis revealed that preoperative infra-duction limitation (p = 0.02), muscle incarceration (p = 0.01), duration from injury to surgical reduction (p = 0.004), and postoperative supra-duction limitation (p = 0.004) were independent factors for poor surgical outcomes. In younger patients with head injury, the diagnosis of orbital trapdoor fracture should be kept in mind. Timely recognition and surgical reduction, especially within 10 days, can result in better visual outcomes without the occurrence of postoperative diplopia.
Rising Canadian and falling Swedish radon gas exposure as a consequence of 20th to 21st century residential build practices
Authors: Khan Selim M. , Pearson Dustin D. , Rönnqvist Tryggve , Nielsen Markus E. , Taron Joshua M. , Goodarzi Aaron A.
Published: September 2021

Radioactive radon gas inhalation is a major cause of lung cancer worldwide and is a consequence of the built environment. The average radon level of properties built in a given period (their ‘innate radon risk’) varies over time and by region, although the underlying reasons for these differences are unclear. To investigate this, we analyzed long term radon tests and buildings from 25,489 Canadian to 38,596 Swedish residential properties constructed after 1945. While Canadian and Swedish properties built from 1970 to 1980s are comparable (96–103 Bq/m3), innate radon risks subsequently diverge, rising in Canada and falling in Sweden such that Canadian houses built in the 2010–2020s have 467% greater radon (131 Bq/m3) versus Swedish equivalents (28 Bq/m3). These trends are consistent across distinct building types, and regional subdivisions. The introduction of energy efficiency measures (such as heat recovery ventilation) within each nation’s build codes are independent of radon fluctuations over time. Deep learning-based models forecast that (without intervention) the average Canadian residential radon level will increase to 176 Bq/m3 by 2050. Provisions in the 2010 Canada Build Code have not significantly reduced innate radon risks, highlighting the urgency of novel code interventions to achieve systemic radon reduction and cancer prevention in Canada.