bluuebunny/crossref_metadata_2025 huggingface dataset:
Generalizing Simultaneously to Support Smooth Zooming: Case Study of Merging Area Objects
Authors: Peng Dongliang , Meijers Martijn , van Oosterom Peter
Published: May 2023

When users zoom in or out on a digital map, the map should change correspondingly to present geographical information at proper levels. A way to help map users better keep track of their interested objects is to change the map smoothly instead of discretely switching between several levels of detail. This paper focuses on the problem of providing smooth merging of area objects. We propose to merge multiple areas simultaneously to share their animation durations. In this way, each merging operation can be prolonged, and it is visually smoother. We present a greedy algorithm to decide which areas should be merged at each step. The merging process is pre-computed and is recorded into a space-scale cube (SSC). When a user accesses our web map, the SSC is sent to the client side so that the map can be generated by slicing the SSC in the graphics processing unit (GPU). We also explain how to snap the zooming to valid states so that the zooming will not stop halfway of the merging operations. Our case study shows that it is visually smoother to merge simultaneously than to sequentially merge each pair of areas.
Psychotropic medication use and future unexplained and injurious falls and fracture amongst community-dwelling older people: data from TILDA
Authors: Gallagher Eleanor , Mehmood Mustafa , Lavan Amanda , Kenny Rose Anne , Briggs Robert
Published: May 2023

Purpose

Psychotropic medications (antidepressants, anticholinergics, benzodiazepines, ‘Z’-drugs and antipsychotics) are frequently identified as Falls Risk Increasing Drugs. The aim of this study is to clarify the association of psychotropic medication use with future falls/fracture amongst community-dwelling older people.

Methods

Participants ≥ 65 years from TILDA were included and followed from Waves 1 to 5 (8-year follow-up). Incidence of falls (total falls/unexplained/injurious) and fracture was by self-report; unexplained falls were falls not caused by a slip/trip, with no apparent cause. Poisson regression models reporting incidence rate ratios (IRR) assessed the association between medications and future falls/fracture, adjusted for relevant covariates.

Results

Of 2809 participants (mean age 73 years), 15% were taking ≥ 1 psychotropic medication. During follow-up, over half of participants fell, with 1/3 reporting injurious falls, over 1/5 reporting unexplained falls and almost 1/5 reporting fracture. Psychotropic medications were independently associated with falls [IRR 1.15 (95% CI 1.00–1.31)] and unexplained falls [IRR 1.46 (95% CI 1.20–1.78)]. Taking ≥ 2 psychotropic medications was further associated with future fracture (IRR 1.47 (95% CI 1.06–2.05)]. Antidepressants were independently associated with falls [IRR 1.20 (1.00–1.42)] and unexplained falls [IRR 2.12 (95% CI 1.69–2.65)]. Anticholinergics were associated with unexplained falls [IRR 1.53 (95% CI 1.14–2.05)]. ‘Z’-drug and benzodiazepine use were not associated with falls or fractures.

Conclusion

Psychotropic medications, particularly antidepressants and anticholinergic medications, are independently associated with falls and fractures. Regular review of ongoing need for these medications should therefore be central to the comprehensive geriatric assessment.
Recursive expectations approach in policymaking
Authors: Kobayashi Keiichiro
Published: May 2023

The primary contribution of modern economics to policy analysis may be the recognition of the crucial role of expectations in policy intervention. The essence of expectations is to think about others’ thinking. We argue that policymakers need recursive thinking, that is, the ability to think about thinking and review three policy episodes related to the lack of recursive thinking. We see that the disciplinary divide or the limited scope of recursive thinking on the side of policymakers can cause huge damage to social welfare in times of crisis. Finally, we consider two examples of future agendas in the recursive approach.
Brain Tumor Segmentation from 3D MRI Scans Using U-Net
Authors: Montaha Sidratul , Azam Sami , Rakibul Haque Rafid A. K. M. , Hasan Md. Zahid , Karim Asif
Published: May 2023

A fully automated system based on three-dimensional (3D) magnetic resonance imaging (MRI) scans for brain tumor segmentation could be a diagnostic aid to clinical specialists, as manual segmentation is challenging, arduous, tedious and error prone. Employing 3D convolutions requires large computational cost and memory capacity. This study proposes a fully automated approach using 2D U-net architecture on BraTS2020 dataset to extract tumor regions from healthy tissue. All the MRI sequences are experimented with the model to determine for which sequence optimal performance is achieved. After normalization and rescaling, using optimizer Adam with learning rate 0.001 on T1 MRI sequence, we get an accuracy of 99.41% and dice similarity coefficient (DSC) of 93%, demonstrating the effectiveness of our approach. The model is further trained with different hyper-parameters to assess the robustness and performance consistency.
Detection of Arrhythmia Heartbeats from ECG Signal Using Wavelet Transform-Based CNN Model
Authors: pandey Saroj Kumar , Shukla Anupam , Bhatia Surbhi , Gadekallu Thippa Reddy , Kumar Ankit , Mashat Arwa , Shah Mohd Asif , Janghel Rekh Ram
Published: May 2023

In India, over 25,000 people have died from cardiovascular annually over the past 4 years , and over 28,000 in the previous 3 years. Most of the deaths nowadays are mainly due to cardiovascular diseases (CVD). Arrhythmia is the leading cause of cardiovascular mortality. Arrhythmia is a condition in which the heartbeat is abnormally fast or slow. The current detection method for diseases is analyzing by the electrocardiogram (ECG), a medical monitoring technique that records heart activity. Since actuations in ECG signals are so slight that they cannot be seen by the human eye, the identification of cardiac arrhythmias is one of the most difficult undertakings. Unfortunately, it takes a lot of medical time and money to find professionals to examine a large amount of ECG data . As a result, machine learning-based methods have become increasingly prevalent for recognizing ECG features. In this work, we classify five different heartbeats using the MIT-BIH arrhythmia database . Wavelet self-adaptive thresholding methods are used to first denoise the ECG signal. Then, an efficient 12-layer deep 1D Convolutional Neural Network (CNN) is introduced for better features extraction, and finally, SoftMax and machine learning classifiers are applied to classify the heartbeats. The proposed method achieved an average accuracy of 99.40%, precision of 98.78%, recall of 98.78%, and F1 score of 98.74%, which clearly show that it outperforms with the exiting model . Architecture of proposed work is simple but effective in remote cardiac diagnosis paradigm that can be implemented on e-health devices.
Testing and evaluation of the structural performance of a 3D-printed polylactic acid aircraft wing rib
Authors: Dogea Ramona , Yan Xiu T. , Millar Richard
Published: May 2023

This paper presents an investigation of the structural performance of a 3D-printed Polylactic Acid (PLA) wing rib structure that is integrated with Internet of Things (IoT) sensory capabilities for application in an Industry 4.0 ecosystem. Both finite element analysis and experimental testing were employed to assess the strain distribution in the structure under various loading conditions and testing setups. The Taguchi approach was utilized to identify the physical factors and their interactions that have a significant impact on the strain distribution in the structure. The findings indicate that the bending load versus strain curve is highly influenced by the applied load position and wing rib cut-out locations, while the structural performance is also highly dependent on torsion. The incorporation of sensory locations with covers improved the component’s ability to withstand traction load and resulted in a 61% reduction in corresponding strain. The most significant factor during bending tests was identified as the applied load, along with the interactions between the load location and crosshead speed of the testing machine.
Digital economy and wage gap between high- and low-skilled workers
Authors: Yang Gongyan , Yao Shujie , Dong Xinran
Published: May 2023

This paper explores the impact of digital economy development on the wage gap between high- and low-skilled workers based on the China Family Panel Studies (CFPS) database in 2010–2020. The research results suggest that the higher the level of digital economy development, the larger the wage gap between high- and low-skilled workers. Some mediating mechanisms are identified and tested from the perspectives of the reaction of human labor to the development of digital economy: the labor misallocation and the mismatch between technologies and skills of workforce. The latter is represented by the response of workers to the risk of being replaced by machines, implying that high-skilled workers use the Internet to improve their abilities more than their low-skilled counterparts to cope with the substitution effect brought about by digital economic progress. The findings in this paper have important policy implications in the sense that governments at different levels should play an important role in assisting digital economy development in favor of the social disadvantaged groups, particularly the low-skilled workers in the labor market.
The Grammar of Time
Authors: Kreuzer Marcus
Published: May 2023

Kreuzer offers guidance to scholars looking to comparative historical analysis (CHA) for the tools to analyze macro-historical questions. Like history, CHA uses the past to formulate research questions, describe social transformations, and generate inductive insights. Like social science, CHA compares those patterns to explicate generalizable and testable theories. It operates in two different worlds—one constantly changing and full of cultural particularities and another static and full of orderly uniformities. CHA draws attention to the ontological constructions of these worlds; how scholars background historical and geographic particularities to create a social reality orderly enough for theorizing, while others foreground those particularities to re-complexify it to generate new inductive insights. CHA engages in ontological triage, dialogue between exploration and confirmation, and conversation in how to translate test results into genuine answers. This book is supplemented by online materials including introductory videos, diagnostic quizzes, advanced exercises, and annotated bibliographies.
Quantum Mechanics in Nanoscience and Engineering
Authors: Peskin Uri
Published: May 2023

Quantum Mechanics in Nanoscience and Engineering covers both elementary and advanced quantum mechanics within a coherent and self-contained framework. Undergraduate students of physics, chemistry and engineering will find comprehensive coverage of their introductory quantum mechanics courses, and graduate students will gain an understanding of additional tools and concepts necessary to describe real world phenomena. Each topic presented is first motivated by an experimental technique, phenomenon or concept derived directly from the realm of nanoscience and technology. The machinery of quantum mechanics is described and reinforced through the perspective of nanoscale phenomena, and in this manner practical and fundamental questions are raised and answered. The main text remains fluent and accessible by leaving technical details and mathematical proofs to guided exercises. Introductory readers may overlook these exercises, while rigorous students can benefit from reading the guidance or solving the exercises in full to strengthen and consolidate their understanding of the material.
Guidance on selecting a translational framework for intervention development: Optimizing interventions for impact
Authors: Guastaferro Kate , Pfammatter Angela F.
Published: May 2023

Intervention development frameworks offer the behavioral sciences a systematic and rigorous empirical process to guide the translation of basic science into practice in pursuit of desirable public health and clinical outcomes. The multiple frameworks that have emerged share a goal of optimization during intervention development and can increase the likelihood of arriving at an effective and disseminable intervention. Yet, the process of optimizing an intervention differs functionally and conceptually across frameworks, creating confusion and conflicting guidance on when and how to optimize. This paper seeks to facilitate the use of translational intervention development frameworks by providing a blueprint for selecting and using a framework by considering the process of optimization as conceptualized by each. First, we operationalize optimization and contextualize its role in intervention development. Next, we provide brief overviews of three translational intervention development frameworks (ORBIT, MRC, and MOST), identifying areas of overlap and divergence thereby aligning core concepts across the frameworks to improve translation. We offer considerations and concrete use cases for investigators seeking to identify and use a framework in their intervention development research. We push forward an agenda of a norm to use and specify frameworks in behavioral science to support a more rapid translational pipeline.
Refugia or reservoir? Feral goats and their role in the maintenance and circulation of benzimidazole-resistant gastrointestinal nematodes on shared pastures
Authors: Francis Emily Kate , Šlapeta Jan
Published: May 2023

Gastrointestinal nematodes threaten the productivity of grazing livestock and anthelmintic resistance has emerged globally. It is broadly understood that wild ruminants living in sympatry with livestock act as a positive source of refugia for anthelmintic-susceptible nematodes. However, they might also act as reservoirs of anthelmintic-resistant nematodes, contributing to the spread of anthelmintic resistance at a regional scale. Here, we sampled managed sheep and cattle together with feral goats within the same property in New South Wales, Australia. Internal transcribed spacer 2 (ITS-2) nemabiome metabarcoding identified 12 gastrointestinal nematodes (Cooperia oncophora, Cooperia punctata, Haemonchus contortus, Haemonchus placei, Nematodirus spathiger, Ostertagia ostertagi, Teladorsagia circumcincta, Oesophagostomum radiatum, Oesophagostomum venulosum, Trichostrongylus axei, Trichostrongylus colubriformis and Trichostrongylus rugatus). Isotype-1 β-tubulin metabarcoding targeting benzimidazole resistance polymorphisms identified 6 of these nematode species (C. oncophora, C. punctata, H. contortus, H. placei, O. ostertagi and T. circumcincta), with the remaining 3 genera unable to be identified to the species level (Nematodirus, Oesophagostomum, Trichostrongylus). Both ITS-2 and β-tubulin metabarcoding showed the presence of a cryptic species of T. circumcincta, known from domestic goats in France. Of the gastrointestinal nematodes detected via β-tubulin metabarcoding, H. contortus, T. circumcincta, Nematodirus and Trichostrongylus exhibited the presence of at least one resistance genotype. We found that generalist gastrointestinal nematodes in untreated feral goats had a similarly high frequency of the benzimidazole-resistant F200Y polymorphism as those nematodes in sheep and cattle. This suggests cross-transmission and maintenance of the resistant genotype within the wild ruminant population, affirming that wild ruminants should be considered potential reservoirs of anthelmintic resistance.
Neglected Tropical Diseases in Italy: introducing IN-NTD, the Italian network for NTDs
Authors: Casulli Adriano , Antinori Spinello , Bartoloni Alessandro , D'Amelio Stefano , Gabrielli Albis Francesco , Gazzoli Giovanni , Rinaldi Laura , Bruschi Fabrizio ,   IN-NTD network
Published: May 2023

The World Health Organization (WHO) defines neglected tropical diseases (NTDs) as a diverse group of primarily infectious diseases, which disproportionately affect poor and marginalized populations worldwide. In this context, NTDs are responsible for important morbidity and mortality and justify a global response. Moreover, NTDs are relatively neglected by research and development as well as by funding, if compared with the magnitude of the public health problem they represent. This happens even though, unlike other infectious diseases, they can be prevented, controlled and eliminated by targeted public health interventions. NTDs are mainly prevalent in communities from low-income countries in tropical and sub-tropical areas but are also present in upper–middle-income countries, including several in Europe. Here, we provide an update on the most relevant parasitic endemic or imported NTDs in Italy and illustrate the rationale for the establishment of the Italian network on NTDs, an alliance of scientific societies, institutes, foundations, universities and non-profit organizations united to fight NTDs.
Effectiveness of a text-messaging intervention on intuitive eating: a randomised controlled trial
Authors: Manana Batoul , El-Jor Claire , Abi Kharma Joelle , Zeeni Nadine
Published: May 2023

Intuitive eating (IE) is a concept based on mind–body integration of instinct, emotion and rational thought, to improve eating behaviours, physical and mental health. Several attempts were developed to teach IE principles including text-messaging interventions given that they are easy to implement and low cost.

Objective:

The present study aimed to assess the effectiveness of a 5-week text message-based IE intervention on IE, while correcting for perceived stress (PS) and self-compassion (SC).

Design:

A randomised controlled trial.

Setting:

Online, in Lebanon.

Participants:

Adults (n 195) were randomised into one of three groups: the active IE group receiving IE-related messages with a practice exercise, the passive IE group receiving only IE-related messages and the control group receiving general health-related tips. Ten messages were delivered over 5 weeks. Two follow-ups were made: directly post-intervention and 7 weeks later. Baseline data and follow-ups included demographics, nutrition-related variables and measures of IE, SC and PS.

Results:

Results indicated improvements in IE scores in the two intervention groups (P = 0·05), with the passive IE group showing the most improvement. Also, a significant improvement in SC (Λ = 0·88, F (2, 63) = 4·40, P = 0·01) and reduction in PS (Λ = 0·86, F (2, 63) = 5·21, P = 0·008) were observed in the active IE group.

Conclusion:

Text-messaging interventions might be efficient in enhancing IE. Results shed light on the need for further large-scale interventions that use visual aids and provide practical guidance to teach IE, while further characterising the relation between IE, SC and stress.
Je-Desto, Je-Umso: An Analysis of the German Comparative Correlative Construction
Authors: Meinunger André
Published: May 2023

This paper argues that German je-desto-sentences are regular verb-second structures. Unlike left-dislocation(-like) structures (such as wenn-dann-clauses or free relative clause constructions with case mis-match and resumption), je-desto-strings are normal, regular prefield structures. A proposal from the literature is developed further, accord-ing to which je-clauses, like relative clauses, belong structurally to the clausal constituent into which they are integrated. The head of these constituents remains in its canonical middle field position, whereas relative as well as je-clauses usually extrapose to the right. If the host constituent is moved to the prefield, the attributive clause is carried along with it, with the je-clause realized initially and the relative clause usually finally. However, relatives may also precede their head noun. Such an analysis highlights the common features of clause types that are otherwise treated as fundamentally distinct from one another, without denying the differences and postulating construction-specific verb-third realizations. In addition, various other realization options are discussed and dismissed as grammatical illusions.*
Characteristics and Formation Mechanism of the Cloud Vertical Structure Over the Southeastern Tibetan Plateau in Summer
Authors: Ma Jiali , Yao Xiuping , Yuan Cheng
Published: May 2023

Cloud vertical structure (CVS) has important influence on cloud radiative effect and atmospheric circulation, especially for the third pole of the world–the Tibetan Plateau (TP). However, the characteristics and formation mechanism of the CVS over the TP are not well understood. This study revealed the characteristics and formation mechanism of the CVS over the southeastern Tibetan Plateau (SETP) in summer using the radiosonde datasets and the ERA5 data sets during June–August from 2015 to 2021. Results show that SETP is cloudy for 71% of the summertime with 73% of the clouds single–layered and 27% multi–layered. Multi–layer cloud occurs more frequently over the eastern SETP. With the number of cloud layers increases, the vertical range of cloud increases but the layer thickness and the inter–layer distance decrease. Water vapor, ascent, circulation and vertical wind shear are important factors for CVS formation. Single–layer cloud tends to form when the strengthening of the water vapor and the ascent is most significant at 400 hPa. In comparison, a stronger South Asian High (SAH) brings more water vapor and stronger ascent to the upper level, helping form the upper cloud and favoring the two–layer cloud structure. Three–layer cloud is likely to form when the upper–level vertical wind shear strengthens and the ascent between the middle and low cloud layer weakens. This study deepens the scientific understanding of the characteristics and formation mechanism of the CVS over the TP, and provides scientific reference for modeling the cloud–climate feedback process over the plateau.
Role of Oceanic Internal Instability in the Generation of Low‐Frequency Variability in the Indian Ocean
Authors: Anjana S. , Chatterjee A. , Han W. , Prerna S. , Sajidh C. K.
Published: May 2023

Low‐frequency (Interannual and longer timescale) variability in sea surface temperature (SST) of the Indian Ocean plays a crucial role in affecting the regional climate. Using a high‐resolution global model simulation, we show that internal oceanic variability is an important cause of the observed low‐frequency variability in the subtropical‐midlatitude south Indian Ocean (SIO) between 20° and 40°S, a marked southward shift in the latitude band of active internal variability for the low‐frequency compared to earlier estimates based on coarser Indian Ocean regional models. Notably, we show that internal variability does not contribute to the observed low‐frequency variability in the Seychelles−Chagos thermocline ridge region. Energy budget analysis shows that baroclinic instability is the primary cause for the internal variability. The slowly growing baroclinic instabilities at low frequency and longer length scale favor Rossby waves' generation, propagating the SST and sea level anomaly signals westward.
Compositional Variability of 2.0‐Ga Lunar Basalts at the Chang'e‐5 Landing Site
Authors: Boschi Samuele , Wang Xiao‐Lei , Hui Hejiu , Yin Zongjun , Guan Yue , Hu Huan , Zhang Wenlan , Chen Jiayang , Li Weiqiang
Published: May 2023

China's Chang'e‐5 (CE‐5) mission successfully returned a total of 1.731 kg of lunar material from the north‐eastern Oceanus Procellarum region. Young (∼2.0 Ga) ages were reported from the CE‐5 basalts. However, there are controversies on whether they are low‐Ti or high‐Ti mare basalt type. Here, we report the results of a comprehensive petrographic, elemental, and Pb isotopic investigation on a 17.6 mg CE‐5 basalt clast (CE5C0000YJYX048). By combining high‐resolution X‐ray tomography of the clast and microbeam (scanning electron microscope SEM, electron probe microanalyzer EPMA) analyses of mineral grains peeled off the clast surface, we derived the bulk clast chemical composition with a very small sample consumption (i.e., <3 mg). The poikilitic clast has a bulk TiO2 content of 3.78 ± 1.01 wt%, which is representative of a low‐Ti basalt end‐member in the lunar mare basalts samples. Furthermore, the pyroxene in the studied clast is dominantly pigeonite, in contrast to other reported CE‐5 samples where augite is the dominant pyroxene mineralogy. Despite these compositional peculiarities, in situ secondary ion mass spectrometer dating yielded a Pb‐Pb age of 2,040 ± 22 Ma for the fragment, which is consistent with ages reported from other CE‐5. Based on the chemical and age data analyzed in this study, it can be concluded that the lunar basalts obtained from the CE‐5 mission originated from a low‐Ti mare basalt‐type source. The mineral composition of the mare basalt clast studied, which is dominated by pigeonite, fayalite, and anorthite, likely resulted from late‐stage magmatic crystallization when the magma was enriched in Fe.
Low‐Temperature Thermochronological Perspective on Geodynamic Evolution of the Cathaysia Block Since Early Mesozoic
Authors: Wu Jinghua , Li Huan , Danišík Martin , Yonezu Kotaro , Zheng Han , Li Zhihan
Published: May 2023

Mesozoic intrusive rocks are extensively outcropped in the Cathaysia Block (CB), indicating that they underwent significant exhumation after being formed. However, tectonothermal evolution of the CB during Mesozoic–Cenozoic times is still poorly constrained and associated geodynamic mechanisms driving the regional exhumation remain elusive. Toward this end, we present first zircon and apatite (U‐Th)/He data of eight Mesozoic granitic plutons distributed across the intracontinental CB. Our new dating results are integrated with a compilation of regional low‐temperature thermochronological data to determine the CB evolution in a tectonic and topographic evolution framework. Zircon and apatite (U‐Th)/He central ages of the eight granitoids range from 146 to 30 and 82 to 31 Ma, respectively, implying a long‐lasting exhumation of the intracontinental CB. Inverse thermal modeling of the thermochronological data for the eight plutons indicates that the intracontinental CB underwent three exhumation phases at 150–110, 110–85, and 66–38 Ma, of which the former two exhumation phases were prolonged and significant. A compilation of regional thermochronological data reveals a propagating locus of fast exhumation phase from the intracontinental CB to the seaward epicontinental CB over time. Combined with other geological evidence, we infer that primary exhumation events of the CB resulted from changing subduction processes of the Paleo‐Pacific Plate, which include slab break‐off and foundering in the Late Jurassic, progressive slab retreat in the Early Cretaceous, and normal subduction in the Late Cretaceous, with minor exhumation events presumably triggered by the Paleogene opening of the South China Sea Basin.
Mexico’s Biggest Earth Science Festival Draws Crowds
Authors: Basilio Humberto
Published: May 2023

More than 1,400 people attended TierraFest 2023, an annual event where children, teenagers, scientists, and activists share knowledge about Earth sciences and the environment in Mexico.
No Consistent Simulated Trends in the Atlantic Meridional Overturning Circulation for the Past 6,000 Years
Authors: Jiang Zhiyi , Brierley Chris M. , Bader Jürgen , Braconnot Pascale , Erb Michael , Hopcroft Peter O. , Jiang Dabang , Jungclaus Johann , Khon Vyacheslav , Lohmann Gerrit , Marti Olivier , Osman Matthew B. , Otto‐Bliesner Bette , Schneider Birgit , Shi Xiaoxu , Thornalley David J. R. , Tian Zhiping , Zhang Qiong
Published: May 2023

The Atlantic Meridional Overturning Circulation (AMOC) is a key feature of the North Atlantic with global ocean impacts. The AMOC's response to past changes in forcings during the Holocene provides important context for the coming centuries. Here, we investigate AMOC trends using an emerging set of transient simulations using multiple global climate models for the past 6,000 years. Although some models show changes, no consistent trend in overall AMOC strength during the mid‐to‐late Holocene emerges from the ensemble. We interpret this result to suggest no overall change in AMOC, which fits with our assessment of available proxy reconstructions. The decadal variability of the AMOC does not change in ensemble during the mid‐ and late‐Holocene. There are interesting AMOC changes seen in the early Holocene, but their nature depends a lot on which inputs are used to drive the experiment.
Interhemispheric Conjugacy of Multiple Transpolar Arcs
Authors: Thor S. , Kullen A. , Cai L. , Katrougkalou M. C. , Zhang Y.
Published: May 2023

Multiple transpolar arcs appearing simultaneously in the polar cap have gained much interest in recent years. By analyzing Defense Meteorological Satellite Program Special Sensor Ultraviolet Spectrographic Imagers data, we report for the first time, that less than half of the multiple arc events occur simultaneously in both hemispheres. In 60% of the cases, multiple arcs appear in only one hemisphere. There is a clear difference in interplanetary magnetic field (IMF) conditions for those two groups. Conjugate multiple arcs appear on average during stronger northward IMF and smaller IMF clock angles than non‐conjugate multiple arcs. Only non‐conjugate multiple arcs show a dependence on IMF BX. They form in the northern (southern) hemisphere during negative (positive) BX. An IMF BX induced interhemispheric asymmetry in the magnetospheric field line topology might explain why multiple arcs appear sometimes in only one hemisphere.
Efficient Scattering Loss of Energetic Electrons by Enhanced Higher‐Band ECH Waves Observed by Van Allen Probes
Authors: Yang Qiwu , Liu Si , Yang Hongming , Zhang Sai , Tang Jiawen , Xiao Fuliang , Zhou Qinghua , Gao Zhonglei , He Yihua , Deng Zhoukun , Li Ping
Published: May 2023

Electron cyclotron harmonic (ECH) waves, which are responsible for the diffuse aurora, are usually observed with the strongest intensity in the first band. Here, we present observations of enhanced higher‐band ECH with wave intensities above 10−3 mV2m−2 Hz−1 by Van Allen Probes. Fully thermal simulation results indicate that these waves can be locally excited by the observed electron distributions, and higher plasma density and lower magnetic strength are favorable for generating the enhanced higher‐band ECH. The pitch angle diffusion coefficient of the higher‐band ECH can exceed 10−5 s−1 inside the loss cone for energetic electrons (300 eV–∼15 keV), greater than the momentum diffusion coefficient by ∼100 times. It is suggested that the enhanced higher‐band ECH can also efficiently scatter these electrons into the loss cone and contribute to the diffuse aurora.
BLM helicase overexpressed in human gliomas contributes to diverse responses of human glioma cells to chemotherapy
Authors: Wojnicki Kamil , Kaczmarczyk Agnieszka , Wojtas Bartosz , Kaminska Bozena
Published: May 2023

Most of anti-tumour therapies eliminate neoplastic cells by introducing DNA damage which ultimately triggers cell death. These effects are counteracted by activated DNA repair pathways to sustain tumour proliferation capacity. RECQL helicases family, including BLM, participate in DNA damage and repair, and prevent the replication stress. Glioblastoma (GBM) is a common, malignant brain tumour that inevitably recurs despite surgical resection, radiotherapy, and chemotherapy with temozolomide (TMZ). Expression and functions of the BLM helicase in GBM therapy resistance have not been elucidated. We analysed expression and localisation of BLM in human gliomas and several glioma cell lines using TCGA datasets, immunostaining and Western blotting. BLM depleted human glioma cells were generated with CRISPR/Cas9 system. Effects of chemotherapeutics on cell proliferation, DNA damage and apoptosis were determined with flow cytometry, immunofluorescence, Western blotting and RNA sequencing. We found upregulated BLM mRNA levels in malignant gliomas, increased cytosolic localisation and poor survival of GBM patients with high BLM expression. BLM deficiency in LN18 and LN229 glioma cells resulted in profound transcriptomic alterations, reduced cell proliferation, and altered cell responses to chemotherapeutics. BLM-deficient glioma cells were resistant to the TMZ and PARP inhibitor treatment and underwent polyploidy or senescence depending on the TP53 activity. Our findings of high BLM expression in GBMs and its roles in responses to chemotherapeutics provide a rationale for targeting BLM helicase in brain tumours. BLM deficiency affects responses of glioma cells to chemotherapeutics targeting PARP1 dependent pathways.
Machine learning for diagnosis of myocardial infarction using cardiac troponin concentrations
Authors: Doudesis Dimitrios , Lee Kuan Ken , Boeddinghaus Jasper , Bularga Anda , Ferry Amy V. , Tuck Chris , Lowry Matthew T. H. , Lopez-Ayala Pedro , Nestelberger Thomas , Koechlin Luca , Bernabeu Miguel O. , Neubeck Lis , Anand Atul , Schulz Karen , Apple Fred S. , Parsonage William , Greenslade Jaimi H. , Cullen Louise , Pickering John W. , Than Martin P. , Gray Alasdair , Mueller Christian , Mills Nicholas L. ,   CoDE-ACS Investigators, Richards A. Mark , Pemberton Chris , Troughton Richard W. , Aldous Sally J. , Brown Anthony F. T. , Dalton Emily , Hammett Chris , Hawkins Tracey , O’Kane Shanen , Parke Kate , Ryan Kimberley , Schluter Jessica , Wild Karin , Wussler Desiree , Miró Òscar , Martin-Sanchez F. Javier , Keller Dagmar I. , Christ Michael , Buser Andreas , Giménez Maria Rubini , Barker Stephanie , Blades Jennifer , Chapman Andrew R. , Fujisawa Takeshi , Kimenai Dorien M. , Leung Jeremy , Li Ziwen , McDermott Michael , Newby David E. , Schulberg Stacey D. , Shah Anoop S. V. , Sorbie Andrew , Soutar Grace , Strachan Fiona E. , Taggart Caelan , Vicencio Daniel Perez , Wang Yiqing , Wereski Ryan , Williams Kelly , Weir Christopher J. , Berry Colin , Reid Alan , Maguire Donogh , Collinson Paul O. , Sandoval Yader , Smith Stephen W.
Published: May 2023

Although guidelines recommend fixed cardiac troponin thresholds for the diagnosis of myocardial infarction, troponin concentrations are influenced by age, sex, comorbidities and time from symptom onset. To improve diagnosis, we developed machine learning models that integrate cardiac troponin concentrations at presentation or on serial testing with clinical features and compute the Collaboration for the Diagnosis and Evaluation of Acute Coronary Syndrome (CoDE-ACS) score (0–100) that corresponds to an individual’s probability of myocardial infarction. The models were trained on data from 10,038 patients (48% women), and their performance was externally validated using data from 10,286 patients (35% women) from seven cohorts. CoDE-ACS had excellent discrimination for myocardial infarction (area under curve, 0.953; 95% confidence interval, 0.947–0.958), performed well across subgroups and identified more patients at presentation as low probability of having myocardial infarction than fixed cardiac troponin thresholds (61 versus 27%) with a similar negative predictive value and fewer as high probability of having myocardial infarction (10 versus 16%) with a greater positive predictive value. Patients identified as having a low probability of myocardial infarction had a lower rate of cardiac death than those with intermediate or high probability 30 days (0.1 versus 0.5 and 1.8%) and 1 year (0.3 versus 2.8 and 4.2%; P < 0.001 for both) from patient presentation. CoDE-ACS used as a clinical decision support system has the potential to reduce hospital admissions and have major benefits for patients and health care providers.
Cross-modality supervised image restoration enables nanoscale tracking of synaptic plasticity in living mice
Authors: Xu Yu Kang T. , Graves Austin R. , Coste Gabrielle I. , Huganir Richard L. , Bergles Dwight E. , Charles Adam S. , Sulam Jeremias
Published: May 2023

Learning is thought to involve changes in glutamate receptors at synapses, submicron structures that mediate communication between neurons in the central nervous system. Due to their small size and high density, synapses are difficult to resolve in vivo, limiting our ability to directly relate receptor dynamics to animal behavior. Here we developed a combination of computational and biological methods to overcome these challenges. First, we trained a deep-learning image-restoration algorithm that combines the advantages of ex vivo super-resolution and in vivo imaging modalities to overcome limitations specific to each optical system. When applied to in vivo images from transgenic mice expressing fluorescently labeled glutamate receptors, this restoration algorithm super-resolved synapses, enabling the tracking of behavior-associated synaptic plasticity with high spatial resolution. This method demonstrates the capabilities of image enhancement to learn from ex vivo data and imaging techniques to improve in vivo imaging resolution.
ARG1-expressing microglia show a distinct molecular signature and modulate postnatal development and function of the mouse brain
Authors: Stratoulias Vassilis , Ruiz Rocío , Kanatani Shigeaki , Osman Ahmed M. , Keane Lily , Armengol Jose A. , Rodríguez-Moreno Antonio , Murgoci Adriana-Natalia , García-Domínguez Irene , Alonso-Bellido Isabel , González Ibáñez Fernando , Picard Katherine , Vázquez-Cabrera Guillermo , Posada-Pérez Mercedes , Vernoux Nathalie , Tejera Dario , Grabert Kathleen , Cheray Mathilde , González-Rodríguez Patricia , Pérez-Villegas Eva M. , Martínez-Gallego Irene , Lastra-Romero Alejandro , Brodin David , Avila-Cariño Javier , Cao Yang , Airavaara Mikko , Uhlén Per , Heneka Michael T. , Tremblay Marie-Ève , Blomgren Klas , Venero Jose L. , Joseph Bertrand
Published: May 2023

Molecular diversity of microglia, the resident immune cells in the CNS, is reported. Whether microglial subsets characterized by the expression of specific proteins constitute subtypes with distinct functions has not been fully elucidated. Here we describe a microglial subtype expressing the enzyme arginase-1 (ARG1; that is, ARG1+ microglia) that is found predominantly in the basal forebrain and ventral striatum during early postnatal mouse development. ARG1+ microglia are enriched in phagocytic inclusions and exhibit a distinct molecular signature, including upregulation of genes such as Apoe, Clec7a, Igf1, Lgals3 and Mgl2, compared to ARG1– microglia. Microglial-specific knockdown of Arg1 results in deficient cholinergic innervation and impaired dendritic spine maturation in the hippocampus where cholinergic neurons project, which in turn results in impaired long-term potentiation and cognitive behavioral deficiencies in female mice. Our results expand on microglia diversity and provide insights into microglia subtype-specific functions.
Allele-aware chromosome-level genome assembly of the autohexaploid Diospyros kaki Thunb
Authors: Li Huawei , Sun Peng , Wang Yiru , Zhang Zhongren , Yang Jun , Suo Yujing , Han Weijuan , Diao Songfeng , Li Fangdong , Fu Jianmin
Published: May 2023

Artificially improving persimmon (Diospyros kakiThunb.), one of the most important fruit trees, remains challenging owing to the lack of reference genomes. In this study, we generated an allele-aware chromosome-level genome assembly for the autohexaploid persimmon ‘Xiaoguotianshi’ (Chinese-PCNA type) using PacBio CCS and Hi-C technology. The final assembly contained 4.52 Gb, with a contig N50 value of 5.28 Mb and scaffold N50 value of 44.01 Mb, of which 4.06 Gb (89.87%) of the assembly were anchored onto 90 chromosome-level pseudomolecules comprising 15 homologous groups with 6 allelic chromosomes in each. A total of 153,288 protein-coding genes were predicted, of which 98.60% were functionally annotated. Repetitive sequences accounted for 64.02% of the genome; and 110,480 rRNAs, 12,297 tRNAs, 1,483 miRNAs, and 3,510 snRNA genes were also identified. This genome assembly fills the knowledge gap in the autohexaploid persimmon genome, which is conducive in the study on the regulatory mechanisms underlying the major economically advantageous traits of persimmons and promoting breeding programs.
Multimodal perturbation analyses of cyclin-dependent kinases reveal a network of synthetic lethalities associated with cell-cycle regulation and transcriptional regulation
Authors: Ford Kyle , Munson Brenton P. , Fong Samson H. , Panwala Rebecca , Chu Wai Keung , Rainaldi Joseph , Plongthongkum Nongluk , Arunachalam Vinayagam , Kostrowicki Jarek , Meluzzi Dario , Kreisberg Jason F. , Jensen-Pergakes Kristen , VanArsdale Todd , Paul Thomas , Tamayo Pablo , Zhang Kun , Bienkowska Jadwiga , Mali Prashant , Ideker Trey
Published: May 2023

Cell-cycle control is accomplished by cyclin-dependent kinases (CDKs), motivating extensive research into CDK targeting small-molecule drugs as cancer therapeutics. Here we use combinatorial CRISPR/Cas9 perturbations to uncover an extensive network of functional interdependencies among CDKs and related factors, identifying 43 synthetic-lethal and 12 synergistic interactions. We dissect CDK perturbations using single-cell RNAseq, for which we develop a novel computational framework to precisely quantify cell-cycle effects and diverse cell states orchestrated by specific CDKs. While pairwise disruption of CDK4/6 is synthetic-lethal, only CDK6 is required for normal cell-cycle progression and transcriptional activation. Multiple CDKs (CDK1/7/9/12) are synthetic-lethal in combination with PRMT5, independent of cell-cycle control. In-depth analysis of mRNA expression and splicing patterns provides multiple lines of evidence that the CDK-PRMT5 dependency is due to aberrant transcriptional regulation resulting in premature termination. These inter-dependencies translate to drug–drug synergies, with therapeutic implications in cancer and other diseases.
Large variation in the movement of individual broiler chickens tracked in a commercial house using ultra-wideband backpacks
Authors: Baxter Mary , O’Connell Niamh E.
Published: May 2023

Our understanding of the movement patterns of individual broiler chickens in large flocks is extremely limited. Here we report the use of a Real Time Locating System to track individual broilers in a house of 28 000 birds. Broilers were fitted with backpacks containing ultra-wideband tags on day 21 (N = 8 broilers) or day 24 (N = 9 broilers), with tags recording positioning and distance data until Day 38. Tagged birds were penned overnight on Day 31 to avoid ‘thinning’. We found no clear evidence of broilers consistently creating similar sized “home ranges”. Some broilers spent most time < 10 m from where they were originally found while others visited at least 90% of the house in the period before thinning. While some broilers rapidly returned to the area they were collected from at thinning, the majority did not. Movement data suggested that broilers that restricted themselves to smaller areas of the house were not necessarily less active. Although there was an average reduction in movement with age, this was not linear and there was individual variation. There was also no clear association between movement patterns and broiler weight or gait score, suggesting a more complicated relationship between activity, ranging and some welfare measures.
Mechanical deformation of elastomer medical devices can enable microbial surface colonization
Authors: van den Berg Desmond , Asker Dalal , Awad Tarek S. , Lavielle Nicolas , Hatton Benjamin D.
Published: May 2023

Elastomers such as silicone are common in medical devices (catheters, prosthetic implants, endoscopes), but they remain prone to microbial colonization and biofilm infections. For the first time, our work shows that rates of microbial surface attachment to polydimethylsiloxane (PDMS) silicone can be significantly affected by mechanical deformation. For a section of bent commercial catheter tubing, bacteria (P. aeruginosa) show a strong preference for the ‘convex’ side compared to the ‘concave’ side, by a factor of 4.2. Further testing of cast PDMS materials in bending only showed a significant difference for samples that were manually wiped (damaged) beforehand (1.75 × 104 and 6.02 × 103 cells/mm2 on the convex and concave sides, respectively). We demonstrate that surface microcracks in elastomers are opened under tensile stress (convex bending) to become ‘activated’ as sites for microbial colonization. This work demonstrates that the high elastic limit of elastomers enables these microcracks to reversibly open and close, as ‘dynamic defects’. Commercial catheters have relatively high surface roughness inherent to manufacturing, but we show that even manual wiping of newly-cast PDMS is sufficient to generate surface microcracks. We consider the implication for medical devices that feature sustained, surgical, or cyclic deformation, in which localized tensile conditions may expose these surface defects to opportunistic microbes. As a result, our work showcases serious potential problems in the widespread usage and development of elastomers in medical devices.
Anticancer role of mango (Mangifera indica L.) peel and seed kernel extracts against 7,12- dimethylbenz[a]anthracene-induced mammary carcinogenesis in female rats
Authors: Shaban Nadia Z. , El-Rashidy Fatma H. , Adam Amany H. , Beltagy Doha M. , Ali Alaa E. , Abde-Alaziz Ahmed A. , Talaat Iman M.
Published: May 2023

Breast cancer is the second leading cause of cancer death among women. The present study is an effort to reveal the antiproliferative and antioxidant actions of mango seed kernel extract (KE), peel extract (PE), and their combination (KEPE) on mammary tumors induced by 7,12 dimethylbenz[a]anthracene (DMBA). Seven groups of adult female Sprague–Dawley rats were prepared, including C: (control), DMBA: (rats were administered with DMBA), (DMBA-KE), (DMBA-PE), and (DMBA-KEPE): rats were administered with DMBA and then treated with KE, PE, and (both KE and PE), respectively, (KE) and (PE): rats were administered with KE and PE, separately. The study focused on the assessment of markers of endocrine derangement [serum 17-β estradiol (E2)], apoptosis [caspase-3 and deoxyribonucleic acid fragmentation (DNAF)], and oxidative stress [lipid peroxidation and antioxidants (glutathione, glutathione-S-transferase, glutathione reductase, glutathione peroxidase, and superoxide dismutase)]. Histopathological examination and immunohistochemical expression of caspase-3 and estrogen receptor-α (ER-α) in mammary gland tissues (MGTs) were determined, as well as the characterization of mango extracts. The results showed that DMBA administration induced mammary tumors by increasing cell proliferation and evading apoptosis. In addition, DMBA administration caused oxidative stress by the production of reactive oxygen species, which increased lipid peroxidation and decreased cellular antioxidants, allowing cancer to progress. In contrast, treatment with DMBA-KE, DMBA-PE, or DMBA-KEPE diminished mammary tumors induced by DMBA, where they reduced oxidative stress via increased antioxidant parameters including reduced glutathione, superoxide dismutase, total glutathione peroxidase, glutathione reductase, and glutathione S-transferase. Also, different treatments decreased proliferation through the reduction of E2, and ER-α expression levels. However, these treatments increased the apoptosis of unwanted cells as they increased caspase-3 activity and DNAF. All these changes led to the prevention of breast injuries and the reduction of mammary tumors. This demonstrates that the contents of mango extracts, especially phenolics and flavonoids, have an important role in mammary tumor treatment through their potential antioxidant, antiproliferative, proapoptotic, and anti-estrogenic effects. KE and PE administration for 4 weeks had no adverse effects. Conclusion: Each of KE, PE, and KEPE has a therapeutic effect against DMBA-induced mammary tumors via induction of apoptosis and reduction of each of the OS, proliferation, and estrogenic effects. So, they can play an important role in the pharmacological tole.