bluuebunny/crossref_metadata_2025 huggingface dataset:
Investigation of the Circular Transcriptome in Alzheimer’s Disease Brain
Authors: Gao Yulan , Xu Si-Mei , Cheng Yuning , Takenaka Konii , Lindner Grace , Janitz Michael
Published: July 2024

Circular RNAs (circRNAs) are a subclass of non-coding RNAs which have demonstrated potential as biomarkers for Alzheimer’s disease (AD). In this study, we conducted a comprehensive exploration of the circRNA transcriptome within AD brain tissues. Specifically, we assessed circRNA expression patterns in the dorsolateral prefrontal cortex collected from nine AD-afflicted individuals and eight healthy controls. Utilising two circRNA detection tools, CIRI2 and CIRCexplorer2, we detected thousands of circRNAs and performed a differential expression analysis. CircRNAs which exhibited statistically significantly differential expression were identified as AD-specific differentially expressed circRNAs. Notably, our investigation revealed 120 circRNAs with significant upregulation and 1325 circRNAs displaying significant downregulation in AD brains when compared to healthy brain tissue. Additionally, we explored the expression profiles of the linear RNA counterparts corresponding to differentially expressed circRNAs in AD-afflicted brains and discovered that the linear RNA counterparts exhibited no significant changes in the levels of expression. We used CRAFT tool to predict that circUBE4B had potential to target miRNA named as hsa-miR-325-5p, ultimately regulated CD44 gene. This study provides a comprehensive overview of differentially expressed circRNAs in the context of AD brains, underscoring their potential as molecular biomarkers for AD. These findings significantly enhance our comprehension of AD’s underlying pathophysiological mechanisms, offering promising avenues for future diagnostic and therapeutic developments.
RCM based optimization of maintenance strategies for marine diesel engine using genetic algorithms
Authors: Tripathi Ankush , Hari Prasad M.
Published: July 2024

In the modern world the availability of the machinery for any industry is of utmost importance. It is the right maintenance at right time which keeps these machineries available for their jobs. The primary goal of maintenance is to avoid or mitigate consequences of failure of equipment. There are various types of maintenance schemes available such as breakdown maintenance, preventive maintenance, condition based maintenance etc. Out of all these schemes Reliability Centred Maintenance (RCM) is most recent one and the application of which will enhance the productivity and availability. RCM ensures better system uptime along with understanding of risk involved. RCM has been used in various industries, however, it is very less explored and utilized in marine operations.Hence in the present study maintenance schemes of a marine diesel engine has been considered for optimization using RCM.Failure Modes and Effects Analysis and Fault Tree Analysis (FTA)are some of the basic steps involved in RCM. Due to the scarcity of reliability data particularly in the marine environment some of the components data had to be estimated based on the operating experience. As FTA is based on binary state perspective, assuming the system exist in either functioning or failed state, some of the components (whose performance varies with time and degrades) cannot be modeled using FTA. Hence, in this paper reliability modeling of performance degraded components is dealt with Markov models and the required data is evaluated from condition monitoring techniques. After obtaining the availability of the marine diesel engine, based on the importance ranking, critical components have been obtained for optimizing the maintenance schedules. In this paper genetic algorithm approach has been used for optimization. The results obtained have been compared and new maintenance scheme has been proposed.
The Banach Fixed Point Theorem: selected topics from its hundred-year history
Authors: Jachymski Jacek , Jóźwik Izabela , Terepeta Małgorzata
Published: July 2024

On June 24, 1920 Stefan Banach presented his doctoral dissertation titled O operacjach na zbiorach abstrakcyjnych i ich zastosowaniach do równañ całkowych (On operations on abstract sets and their applications to integral equations) to the Philosophy Faculty of Jan Kazimierz University in Lvov. He passed his PhD examinations in mathematics, physics and philosophy, and in January 1921 he became a doctor. A year later, he published the results of his doctorate in Fundamenta Mathematicae. Among them there was the theorem known today as the Banach Fixed Point Theorem or the Banach Contraction Principle. It is one of the most famous theorems in mathematics, one of many under the name of Banach. It concerns certain mappings (called contractions) of a complete metric space into itself and it gives the conditions sufficient for the existence and uniqueness of a fixed point of such mapping. In 2022 we had a centenary of publishing this theorem. In the paper, we want to present its most important modifications and generalizations, several contractive conditions, the converse theorems and some applications. It is not possible to provide complete information about what has been written during the last hundred years about the Banach Fixed Point Theorem and we are just trying to touch on some breakthrough moments in the development of the metric fixed point theory. The main purpose of this article is to organize the knowledge on this subject and to elaborate a broad bibliography which all interested persons can refer to.
Production or transmission investments? A comparative analysis
Authors: de Paz Mario Blazquez
Published: July 2024

The European electricity market is moving towards an integration process, and to facilitate that integration and the flow of electricity in that market, the European Transmission System Operator proposes different investments in transmission and production capacities. I develop a model of imperfect competition to study those investments, and I identify the economic forces that determine the equilibrium price and the flow of electricity: The size and the competitive effects. I prove formally when those forces operate simultaneously or independently, and how they determine consumers’ surplus and suppliers’ profits. I prove that an investment in transmission capacity outperforms an investment in production capacity by maximizing consumers’ welfare, but the performance in terms of suppliers’ profits is ambiguous.
Late Cretaceous marine flooding and installation of a mangrove swamp environment in the Prebetic (Betic External Zones, SE Spain)
Authors: Reolid Matías , Sánchez-Gómez Mario , Laita Elisa , Sanz David
Published: July 2024

The Cenomanian (Upper Cretaceous) sedimentary rocks of the External Prebetic (Betic Cordillera) in the Sierra de Montearagón-Carcelén (SE Spain) record the transgression and flooding of continental deposits and the subsequent development of an inner shallow carbonate platform. The transgressive surface is densely colonized by infaunal trace-makers of the Glossifungites ichnofacies (Gastrochaenolites and Glossifungites), which indicate sediment starvation and erosion as well as colonization of a firmground. The first deposits were a thick calcarenite bar (2 to 11 m) with large-scale cross-bedding pointing to a high-energy environment in a shallow carbonate platform. The record of the Rosselia ichnofacies (Rosselia and Ophiomorpha) confirms a loose sandy bottom under high-energy conditions. The overlaying stratigraphic succession is characterized by subtidal laminated marly limestones and intertidal limestones with rhizoliths interpreted as a mangrove swamp environment. These facies are organized in shallowing-upwards sedimentary sequences. An episodic high-energy event is represented by bivalve-rich limestones representing shell lags of disarticulated valves. This facies could be related to a climatic perturbation evidenced by a negative excursion of δ13C and δ18O. The successive shallowing-upwards sedimentary sequences persisted thanks to subsidence related to the tectonically controlled depocenters located in the south of the Sierra de Montearagón-Carcelén. The differential subsidence, evidenced by the increasing thickness towards the south of the sector under study, suggests the activity of listric faults that controlled the depocenters. This is the first report of the Cenomanian transgression in this sector of the External Prebetic and the first record of the very extensive mangrove swamp that developed close to the land that emerged.
Using the classic trolley problem to teach AI students and researchers about their role as moral agents, and why they should be subject to moral scrutiny
Authors: Young Garry
Published: July 2024

This commentary proposes a means of teaching students – particularly computer science students – about their role as moral agents, who, on account of this role, are necessarily subject to moral scrutiny. It utilizes the classic Trolley Problem; but instead of focusing on the morality of the decision the bystander makes, it focuses, initially, on the role of the bystander as an agent of action, capable of effecting change and then, more importantly, as a moral agent whose action capabilities are subject to moral scrutiny. I believe that using the Trolley Problem in this way provides those tasked with teaching ethics to computer science students (but also others) a practical means of drawing attention not simply to whatever guidelines (e.g., code of ethics) have been produced in relation to AI and IT research, but to the fact that students and researchers alike are moral agents, however reluctant they may be to embrace this fact in the context of their studies and/or research.
A novel method for measuring center-axis velocity of unmanned aerial vehicles through synthetic motion blur images
Authors: Zhan Quanxi , Zhou Yanmin , Zhang Junrui , Sun Chenyang , Shen Runjie , He Bin
Published: July 2024

Accurate velocity measurement of unmanned aerial vehicles (UAVs) is essential in various applications. Traditional vision-based methods rely heavily on visual features, which are often inadequate in low-light or feature-sparse environments. This study presents a novel approach to measure the axial velocity of UAVs using motion blur images captured by a UAV-mounted monocular camera. We introduce a motion blur model that synthesizes imaging from neighboring frames to enhance motion blur visibility. The synthesized blur frames are transformed into spectrograms using the Fast Fourier Transform (FFT) technique. We then apply a binarization process and the Radon transform to extract light-dark stripe spacing, which represents the motion blur length. This length is used to establish a model correlating motion blur with axial velocity, allowing precise velocity calculation. Field tests in a hydropower station penstock demonstrated an average velocity error of 0.048 m/s compared to ultra-wideband (UWB) measurements. The root-mean-square error was 0.025, with an average computational time of 42.3 ms and CPU load of 17%. These results confirm the stability and accuracy of our velocity estimation algorithm in challenging environments.
Maximizing intrusion detection efficiency for IoT networks using extreme learning machine
Authors: Altamimi Shahad , Abu Al-Haija Qasem
Published: July 2024

Intrusion Detection Systems (IDSs) are crucial for safeguarding modern IoT communication networks against cyberattacks. IDSs must exhibit exceptional performance, low false positive rates, and significant flexibility in constructing attack patterns to efficiently identify and neutralize these attacks. This research paper discusses the use of an Extreme Learning Machine (ELM) as a new technique to enhance the performance of IDSs. The study utilizes two standard IDS-based IoT network datasets: NSL-KDD 2009 via Distilled-Kitsune 2021. Both datasets are used to assess the effectiveness of ELM in a conventional supervised learning setting. The study investigates the capacity of the ELM algorithm to handle high-dimensional and unbalanced data, indicating the potential to enhance IDS accuracy and efficiency. The research also examines the setup of ELM for both NSL_KDD and Kitsune using Python and Google COLAB to do binary and multi-class classification. The experimental evaluation revealed the proficient performance of the proposed ELM-based IDS among other implemented supervised learning-based IDSs and other state-of-the-art models in the same study area.
The evolution of the multidisciplinary tumor board in orthopedic oncology: from its historical roots to its future potential
Authors: Goker Barlas , Shea Mary , Zhang Ranxin , Wang Jichuan , Ferrena Alexander , Chae Sung-Suk , Borjihan Hasibagan , Yang Rui , Hoang Bang H. , Geller David S. , Thornhill Beverly A. , Haramati Nogah , Lu Chuanyong , Laurini Javier A. , Villanueva-Siles Esperanza , Mardakhaev Edward
Published: July 2024

Purpose

The purpose of this review is to summarize the impact of the multidisciplinary tumor board as a tool or mechanism for orthopedic oncology care, to highlight its evolution and changing role over time, to assess its strengths and weaknesses, and to report our institutional experience as an NCI-Designated Comprehensive Cancer Center.

Methods

We reviewed the relevant literature about multidisciplinary tumor boards in orthopedic oncology, and summarized the articles to provide a summary of the topic. Additionally, we retrospectively reviewed our electronic medical records to analyze the distribution, characteristics, and numbers of the cases that were discussed.

Results

Our retrospective institutional review revealed a total of 1178 individual patients discussed between August 2018 and August 2023. There was an even distribution of patients by sex, with 549 female (50.2%) patients and 544 male (49.8%). Diagnoses peaked in the second and sixth decades of life (189 and 175 patients, respectively). The majority of patients were discussed once (55%) or twice (21%). The most common neoplastic diagnosis that was presented in these meetings was giant cell tumor of bone (n = 51). Osteosarcoma (n = 41) was the most common diagnosis among the primary malignant bone tumors, and liposarcomas (n = 41) were the most frequently discussed soft tissue sarcoma histology.

Conclusion

Tumor boards have played a central role in cancer care for almost a century. Our experience at an NCI-designated comprehensive cancer center has yielded a review of over a thousand individual cases in only a 5-year span of time.
Moral and formal model-based control strategy for autonomous vehicles at traffic-light-free intersections
Authors: Zhou Teng , Zhao Yongsheng , Lin Zhizhe , Zhou Jinglin , Li Huan , Wang Fei
Published: July 2024

Making an effective traffic strategy is a challenging problem that involves efficiency and safety, where traffic lights play an important role. Especially in cases without traffic lights, creating traffic strategies benefits significantly more complex and challenging. This complexity underscores the importance of research on autonomous vehicles, which has been trained widespread attention in recent years. In order to avoid these potential crises, the designed traffic strategy at traffic light-free intersections must be effective and reliable, ensuring the basic processes work properly. In this paper, we propose a novel method to formally model the traffic strategy for vehicles to make sure they safely and orderly pass through traffic light-free intersections. We use the state space analysis method to analyze the vehicle traffic model to ensure the decision made at each step is correct. By using Petri net, our proposed model achieves excellent analytical capabilities for asynchronous or highly concurrent systems than simpler Unified Modeling Language (UML) systems, as well as the ability to dynamically analyze system security and reliability.
Past and Future Trends in Clear‐Air Turbulence Over the Northern Hemisphere
Authors: Foudad Mohamed , Sanchez‐Gomez Emilia , Jaravel Thomas , Rochoux Mélanie C. , Terray Laurent
Published: July 2024

Clear‐Air Turbulence (CAT) is associated with wind shear in the vicinity of jet streams in upper atmospheric levels. This turbulence occurs in cloudless regions and causes most weather‐related aircraft accidents. Recent studies have shown that in response to climate change, CAT could significantly increase over certain regions as a consequence of strengthening of jet streams. In this study we use several atmospheric reanalyses and coupled model experiments database to evaluate CAT recent and future changes in the Northern Hemisphere. Several CAT diagnostics are computed to assess the sensitivity of the results to different turbulence representations. A significant positive trend in CAT frequency is found in the reanalyses in different Northern Hemisphere regions over the period 1980–2021. The signal‐to‐noise analysis shows that over North Africa, East Asia and Middle East the increase of CAT occurrence in the last decades is likely attributed to the response to anthropogenic forcing. In contrast, over the North Atlantic and North Pacific the response to external forcing is not detectable due to a weak signal to noise ratio related to large internal variability. Future climate projections show that over several Northern Hemisphere regions, CAT is projected to increase with a high model agreement and independently of the CAT diagnostic used. The largest increase in CAT is projected to occur over East Asia. In the North Atlantic, large uncertainty remains due to lack of model agreement and different results between the various CAT diagnostics.
Warming Tropical Indian Ocean Wets the Tibetan Plateau
Authors: Zhou Aoqi , Yuan Chaoxia , Luo Jing‐Jia , Yamagata Toshio
Published: July 2024

Accurate detection and attribution of past climate change are crucial for projecting future climate change and formulating proper policies. In this study, we show that the warming of the tropical Indian Ocean contributes to the observed wetting trend in the Tibetan plateau. The warming tropical Indian Ocean can lead to more precipitation around the Arabian Sea. The associated diabatic heating triggers the cyclonic atmospheric response in the lower troposphere over the Arabian Sea and eastern Africa. It also causes the enhancement and westward extension of the western North Pacific subtropical high. The in‐between airflow transports more moisture northward to the plateau, leading to the increased precipitation over the plateau. These large‐scale circulation patterns can be detected from the long‐term trends based on the observations and the large‐ensemble historical simulations. They can also be simulated by an atmospheric general circulation model forced by the observed warming merely in the tropical Indian Ocean.
Detection and Energy Dissipation of ULF Waves in the Polar Ionosphere: A Case Study Using the EISCAT Radar
Authors: van Hazendonk C. M. , Baddeley L. , Laundal K. M. , Chau J. L.
Published: July 2024

Ultra‐low frequency (ULF) waves transfer energy and momentum into the ionosphere‐thermosphere system. To quantify this energy, this paper first presents a new method to quantitatively detect ULF waves in Incoherent Scatter Radar (ISR) data based on 2D fast‐Fourier transforms and subsequent reconstruction of the wave. In parallel with other data sets, including optical, magnetometer, satellite, and models, we present the first full ionospheric energy dissipation rates for a ULF wave, split into electromagnetic (EM) and kinetic fluxes. The EM energy deposition is calculated from the use of the Poynting theorem, looking at Joule and frictional heating rates, where both rates show the same order of magnitude (1.24 × 1013 and 7.3 × 1012 J) respectively when integrated over the wave lifetime of 2 hr 15 min and an area of 4° magnetic latitude × 74° magnetic longitude. However, contrary to the common assumption that the EM flux is dominant, we determined the kinetic flux, to be almost equal in magnitude (8.7 × 1012 J). This indicates that previous papers might have underestimated the total energy dissipation by ULF waves. Compared to the substorm energy budget, we find that locally, the ULF wave event studied here makes up approximately 10% of a typical substorm cycle budget.
Quasi‐Diurnal Lunar Tide O1 in Ionospheric Total Electron Content at Solar Minimum
Authors: Hocke Klemens , Wang Wenyue , Cahyadi Mokhamad Nur , Ma Guanyi
Published: July 2024

For the first time, characteristics of the geographical and seasonal distribution of the quasi‐diurnal lunar O1 tide were derived from a time series of ionospheric total electron content (TEC) maps provided by International Global Navigation Satellite System Service (IGS). The data analysis is focused on solar minimum in 2008 and 2009 where disturbing influences of geomagnetic and solar activity were minimal. We found that the magnitude of the O1 tide is as strong as the “dominant” semidiurnal lunar M2 tide. Relative amplitudes of 10% and larger are observed in some regions for the O1 component in TEC. The O1 component is particularly strong in northern hemispheric winter over the west coast of South America. There, two maxima occur which are northward and southward of the magnetic equator in the Equatorial Ionization Anomaly (EIA) crest regions. Following Yamazaki et al. (2017, https://doi.org/10.1002/2017ja024601), it might be assumed that a longitudinal anomaly of ionospheric conductivities in the Peruvian sector leads to a stronger modulation of the equatorial electrojet by the lunar tides. Electrodynamic lifting of plasma and transport to the EIA crests may explain the variations of the O1 component in TEC. Contrary to many studies, we find the O1 component (period 25.82 hr) more important than the M1 component (period 24.84 hr, a lunar day). We show that the geographical distribution of the O1 component is totally different from that of the M1 component which is smaller. The seasonal variation of O1 shows maximal amplitudes in northern hemispheric winter and minimal amplitudes in southern hemispheric winter.
Modeling GIC in the Southern South Island of Aotearoa New Zealand Using Magnetotelluric Data
Authors: Pratscher K. M. , Ingham M. , Mac Manus D. H. , Kruglyakov M. , Heise W. , Rodger C. J. , Divett T. , Bertrand E. , Dalzell M. , Brundell J.
Published: July 2024

Magnetotelluric (MT) impedances from 62 sites in southern South Island of Aotearoa New Zealand have been used to model geomagnetically induced currents (GIC) in four transformers during two solar storms. Induced electric fields during the storms are calculated from the MT impedances using the magnetic fields measured at the Eyrewell (EYR) geomagnetic observatory, approximately 200 km north of the study area. Calculated GIC during the sudden storm commencements (SSC) give a generally good match to GIC measured by the network operator, Transpower New Zealand. Long period GIC (periods longer than about 10,000 s) are less well modeled. Calculations based on thin‐sheet modeling, which has restrictions on the shortest period of variation which can be modeled, perform less well for the GIC associated with SSC, but are equally good, if not better, at modeling longer period GIC. Consistent underestimation of large GIC at one transformer (HWBT4) near Dunedin are likely to be the result of uncertainty in the assumed values of line, transformer, and earthing resistances. The assumption of a spatially uniform magnetic field across the study area, which is implied by use of the magnetic field measured at EYR as a basis for calculation, may also lead to incorrect calculation of GIC. For one storm use of magnetic field data from a magnetometer within the study area leads to much improved modeling of the observed GIC. This study compares modeled and measured GIC using specifically measured MT impedance data.
Validating genetic variants in innate immunity linked to infectious events in acute myeloid leukemia post-induction chemotherapy
Authors: Schnetzke Ulf , Fischer Mike , Röllig Christoph , Scherag André , Altmann Heidi , Stölzel Friedrich , Alakel Nael , Bornhäuser Martin , Hochhaus Andreas , Scholl Sebastian
Published: July 2024

Infectious events, such as sepsis and invasive fungal disease (IFD), pose significant risks in patients with acute myeloid leukemia (AML). Previous studies, including our own, have suggested a potential role of single nucleotide polymorphisms (SNPs) within the innate immune system in influencing individual infection susceptibility. However, many of these associations lack validation in independent cohorts. This study sought to validate the impact of 11 candidate SNPs across 6 genes (TLR2, TLR4, Dectin-1, DC-SIGN, PTX3, L-Ficolin) in an independent cohort of patients. Two cohorts with newly diagnosed AML patients receiving intensive induction chemotherapy were analyzed: a stratification cohort comprising 186 patients and a validation cohort consisting of 138 patients. Multiple SNPs in each cohort were found to be associated to infectious complications, notably the DC-SIGN SNP rs4804800 demonstrated a significant association with sepsis in both cohorts. SNPs within the PTX3 and Dectin-1 genes were linked to IFD development in one cohort each. This study represents the first validation study of candidate genes associated with infectious events in AML patients after intensive induction chemotherapy. Identifying genetic predispositions to infections could significantly impact the management of antimicrobial prophylaxis and treatment in AML patients.
Flavor-switchable scaffold for cultured meat with enhanced aromatic properties
Authors: Lee Milae , Choi Woojin , Lee Jeong Min , Lee Seung Tae , Koh Won-Gun , Hong Jinkee
Published: July 2024

Cultured meat is emerging as a new type of food that can provide animal protein in a sustainable way. Many previous studies employed various types of scaffolds to develop cultured meat with similar properties to slaughtered meat. However, important properties such as flavor were not discussed, even though they determine the quality of food. Flavor characteristics vary dramatically depending on the amount and types of amino acids and sugars that produce volatile compounds through the Maillard reaction upon cooking. In this study, a flavor-switchable scaffold is developed to release meaty flavor compounds only upon cooking temperature mimicking the Maillard reaction of slaughtered meat. By introducing a switchable flavor compound (SFC) into a gelatin-based hydrogel, we fabricate a functional scaffold that can enhance the aromatic properties of cultured meat. The temperature-responsive SFC stably remains in the scaffold during the cell culture period and can be released at the cooking temperature. Surprisingly, cultured meat fabricated with this flavor-switchable scaffold exhibits a flavor pattern similar to that of beef. This research suggests a strategy to develop cultured meat with enhanced sensorial characteristics by developing a functional scaffold which can mimic the natural cooking flavors of conventional meat.
Stimulus type shapes the topology of cellular functional networks in mouse visual cortex
Authors: Tang Disheng , Zylberberg Joel , Jia Xiaoxuan , Choi Hannah
Published: July 2024

On the timescale of sensory processing, neuronal networks have relatively fixed anatomical connectivity, while functional interactions between neurons can vary depending on the ongoing activity of the neurons within the network. We thus hypothesized that different types of stimuli could lead those networks to display stimulus-dependent functional connectivity patterns. To test this hypothesis, we analyzed single-cell resolution electrophysiological data from the Allen Institute, with simultaneous recordings of stimulus-evoked activity from neurons across 6 different regions of mouse visual cortex. Comparing the functional connectivity patterns during different stimulus types, we made several nontrivial observations: (1) while the frequencies of different functional motifs were preserved across stimuli, the identities of the neurons within those motifs changed; (2) the degree to which functional modules are contained within a single brain region increases with stimulus complexity. Altogether, our work reveals unexpected stimulus-dependence to the way groups of neurons interact to process incoming sensory information.
Estimation of joint torque in dynamic activities using wearable A-mode ultrasound
Authors: Jin Yichu , Alvarez Jonathan T. , Suitor Elizabeth L. , Swaminathan Krithika , Chin Andrew , Civici Umut S. , Nuckols Richard W. , Howe Robert D. , Walsh Conor J.
Published: July 2024

The human body constantly experiences mechanical loading. However, quantifying internal loads within the musculoskeletal system remains challenging, especially during unconstrained dynamic activities. Conventional measures are constrained to laboratory settings, and existing wearable approaches lack muscle specificity or validation during dynamic movement. Here, we present a strategy for estimating corresponding joint torque from muscles with different architectures during various dynamic activities using wearable A-mode ultrasound. We first introduce a method to track changes in muscle thickness using single-element ultrasonic transducers. We then estimate elbow and knee torque with errors less than 7.6% and coefficients of determination (R2) greater than 0.92 during controlled isokinetic contractions. Finally, we demonstrate wearable joint torque estimation during dynamic real-world tasks, including weightlifting, cycling, and both treadmill and outdoor locomotion. The capability to assess joint torque during unconstrained real-world activities can provide new insights into muscle function and movement biomechanics, with potential applications in injury prevention and rehabilitation.
Self-powered triboelectric-responsive microneedles with controllable release of optogenetically engineered extracellular vesicles for intervertebral disc degeneration repair
Authors: Zhang Weifeng , Qin Xuan , Li Gaocai , Zhou Xingyu , Li Hongyang , Wu Di , Song Yu , Zhao Kangcheng , Wang Kun , Feng Xiaobo , Tan Lei , Wang Bingjin , Sun Xuhui , Wen Zhen , Yang Cao
Published: July 2024

Excessive exercise is an etiological factor of intervertebral disc degeneration (IVDD). Engineered extracellular vesicles (EVs) exhibit excellent therapeutic potential for disease-modifying treatments. Herein, we fabricate an exercise self-powered triboelectric-responsive microneedle (MN) assay with the sustainable release of optogenetically engineered EVs for IVDD repair. Mechanically, exercise promotes cytosolic DNA sensing-mediated inflammatory activation in senescent nucleus pulposus (NP) cells (the master cell population for IVD homeostasis maintenance), which accelerates IVDD. TREX1 serves as a crucial nuclease, and disassembly of TRAM1-TREX1 complex disrupts the subcellular localization of TREX1, triggering TREX1-dependent genomic DNA damage during NP cell senescence. Optogenetically engineered EVs deliver TRAM1 protein into senescent NP cells, which effectively reconstructs the elimination function of TREX1. Triboelectric nanogenerator (TENG) harvests mechanical energy and triggers the controllable release of engineered EVs. Notably, an optogenetically engineered EV-based targeting treatment strategy is used for the treatment of IVDD, showing promising clinical potential for the treatment of degeneration-associated disorders.
Neutrophil extracellular traps promote immunopathogenesis of virus-induced COPD exacerbations
Authors: Katsoulis Orestis , Toussaint Marie , Jackson Millie M. , Mallia Patrick , Footitt Joseph , Mincham Kyle T. , Meyer Garance F. M. , Kebadze Tata , Gilmour Amy , Long Merete , Aswani Andrew D. , Snelgrove Robert J. , Johnston Sebastian L. , Chalmers James D. , Singanayagam Aran
Published: July 2024

Respiratory viruses are a major trigger of exacerbations in chronic obstructive pulmonary disease (COPD). Airway neutrophilia is a hallmark feature of stable and exacerbated COPD but roles played by neutrophil extracellular traps (NETS) in driving disease pathogenesis are unclear. Here, using human studies of experimentally-induced and naturally-occurring exacerbations we identify that rhinovirus infection induces airway NET formation which is amplified in COPD and correlates with magnitude of inflammation and clinical exacerbation severity. We show that inhibiting NETosis protects mice from immunopathology in a model of virus-exacerbated COPD. NETs drive inflammation during exacerbations through release of double stranded DNA (dsDNA) and administration of DNAse in mice has similar protective effects. Thus, NETosis, through release of dsDNA, has a functional role in the pathogenesis of COPD exacerbations. These studies open up the potential for therapeutic targeting of NETs or dsDNA as a strategy for treating virus-exacerbated COPD.
PKM2 aggregation drives metabolism reprograming during aging process
Authors: Bie Juntao , Li Ridong , Li Yutong , Song Chen , Chen Zhaoming , Zhang Tianzhuo , Tang Zhiheng , Su Li , Zhu Liangyi , Wang Jiaxin , Wan You , Chen Jun , Liu Xiaoyun , Li Tingting , Luo Jianyuan
Published: July 2024

While protein aggregation’s association with aging and age-related diseases is well-established, the specific proteins involved and whether dissolving them could alleviate aging remain unclear. Our research addresses this gap by uncovering the role of PKM2 aggregates in aging. We find that PKM2 forms aggregates in senescent cells and organs from aged mice, impairing its enzymatic activity and glycolytic flux, thereby driving cells into senescence. Through a rigorous two-step small molecule library screening, we identify two compounds, K35 and its analog K27, capable of dissolving PKM2 aggregates and alleviating senescence. Further experiments show that treatment with K35 and K27 not only alleviate aging-associated signatures but also extend the lifespan of naturally and prematurely aged mice. These findings provide compelling evidence for the involvement of PKM2 aggregates in inducing cellular senescence and aging phenotypes, and suggest that targeting these aggregates could be a promising strategy for anti-aging drug discovery.
EMBER creates a unified space for independent breast cancer transcriptomic datasets enabling precision oncology
Authors: Ronchi Carlos , Haider Syed , Brisken Cathrin
Published: July 2024

Transcriptomics has revolutionized biomedical research and refined breast cancer subtyping and diagnostics. However, wider use in clinical practice is hampered for a number of reasons including the application of transcriptomic signatures as single sample predictors. Here, we present an embedding approach called EMBER that creates a unified space of 11,000 breast cancer transcriptomes and predicts phenotypes of transcriptomic profiles on a single sample basis. EMBER accurately captures the five molecular subtypes. Key biological pathways, such as estrogen receptor signaling, cell proliferation, DNA repair, and epithelial-mesenchymal transition determine sample position in the space. We validate EMBER in four independent patient cohorts and show with samples from the window trial, POETIC, that it captures clinical responses to endocrine therapy and identifies increased androgen receptor signaling and decreased TGFβ signaling as potential mechanisms underlying intrinsic therapy resistance. Of direct clinical importance, we show that the EMBER-based estrogen receptor (ER) signaling score is superior to the immunohistochemistry (IHC) based ER index used in current clinical practice to select patients for endocrine therapy. As such, EMBER provides a calibration and reference tool that paves the way for using RNA-seq as a standard diagnostic and predictive tool for ER+ breast cancer.
The miniature genome of broad mite, Polyphagotarsonemus latus (Tarsonemidae: Acari)
Authors: Mohan Muthugounder , Augustine Neenu , Selvamani Selva Babu , P. J. Aneesha , Selvapandian Upasna , Pathak Jyoti , Gracy R. Gandhi , Thiruvengadam Venkatesan , S. N. Sushil
Published: July 2024

The broad mite, Polyphagotarsonemus latus (Tarsonemidae: Acari) is a highly polyphagous species that damage plant species spread across 57 different families. This pest has developed high levels of resistance to some commonly used acaricides. In the present investigation, we deciphered the genome information of P. latus by PacBio HiFi sequencing. P. latus is the third smallest arthropod genome sequenced so far with a size of 49.1 Mb. The entire genome was assembled into two contigs. A set of 9,286 protein-coding genes were annotated. Its compact genome size could be credited with multiple features such as very low repeat content (5.1%) due to the lack of proliferation of transposable elements, high gene density (189.1/Mb), more intronless genes (20.3%) and low microsatellite density (0.63%).
Integration of ten years of daily weather, traffic, and air pollution data from Norway’s six largest cities
Authors: Cao Cong
Published: July 2024

This study integrates ten years of daily weather, traffic, and air pollution data across the six largest Norwegian cities, utilizing data from the Norwegian Public Roads Administration, the Norwegian Institute of Air Research, and the Norwegian Meteorological Institute. The compilation of this dataset involved detailed selection and verification of monitoring stations to ensure consistency and accuracy. Initial data collection focused on the top ten most populous cities in Norway, with the subsequent examination of traffic and air pollution monitoring sites. Weather variables were then matched to the selected sites, resulting in a comprehensive dataset from 2009 to 2018. The resulting dataset encompasses extensive information, including harmful pollutants such as Nitric oxide (NO), Nitrogen dioxide (NO2), Nitrogen oxides (NOx), Particulate Matter less than 2.5 micrometers in diameter (PM2.5), and Particulate Matter less than 10 micrometers in diameter (PM10). The dataset’s potential for further analysis and its utility in informing policy decisions underscore its significance. This integrated dataset is a valuable resource for researchers and policymakers alike, facilitating comprehensive studies on the intersection of weather, traffic, and air pollution in urban environments.
Using artificial agents to nudge outgroup altruism and reduce ingroup favoritism in human-agent interaction
Authors: Igwe Kevin , Durrheim Kevin
Published: July 2024

Ingroup favoritism and intergroup discrimination can be mutually reinforcing during social interaction, threatening intergroup cooperation and the sustainability of societies. In two studies (N = 880), we investigated whether promoting prosocial outgroup altruism would weaken the ingroup favoritism cycle of influence. Using novel methods of human-agent interaction via a computer-mediated experimental platform, we introduced outgroup altruism by (i) nonadaptive artificial agents with preprogrammed outgroup altruistic behavior (Study 1; N = 400) and (ii) adaptive artificial agents whose altruistic behavior was informed by the prediction of a machine learning algorithm (Study 2; N = 480). A rating task ensured that the observed behavior did not result from the participant’s awareness of the artificial agents. In Study 1, nonadaptive agents prompted ingroup members to withhold cooperation from ingroup agents and reinforced ingroup favoritism among humans. In Study 2, adaptive agents were able to weaken ingroup favoritism over time by maintaining a good reputation with both the ingroup and outgroup members, who perceived agents as being fairer than humans and rated agents as more human than humans. We conclude that a good reputation of the individual exhibiting outgroup altruism is necessary to weaken ingroup favoritism and improve intergroup cooperation. Thus, reputation is important for designing nudge agents.
Factors of acute respiratory infection among under-five children across sub-Saharan African countries using machine learning approaches
Authors: Fenta Haile Mekonnen , Zewotir Temesgen T. , Naidoo Saloshni , Naidoo Rajen N. , Mwambi Henry
Published: July 2024

Symptoms of Acute Respiratory infections (ARIs) among under-five children are a global health challenge. We aimed to train and evaluate ten machine learning (ML) classification approaches in predicting symptoms of ARIs reported by mothers among children younger than 5 years in sub-Saharan African (sSA) countries. We used the most recent (2012–2022) nationally representative Demographic and Health Surveys data of 33 sSA countries. The air pollution covariates such as global annual surface particulate matter (PM 2.5) and the nitrogen dioxide available in the form of raster images were obtained from the National Aeronautics and Space Administration (NASA). The MLA was used for predicting the symptoms of ARIs among under-five children. We randomly split the dataset into two, 80% was used to train the model, and the remaining 20% was used to test the trained model. Model performance was evaluated using sensitivity, specificity, accuracy, and the area under the receiver operating characteristic curve. A total of 327,507 under-five children were included in the study. About 7.10, 4.19, 20.61, and 21.02% of children reported symptoms of ARI, Severe ARI, cough, and fever in the 2 weeks preceding the survey years respectively. The prevalence of ARI was highest in Mozambique (15.3%), Uganda (15.05%), Togo (14.27%), and Namibia (13.65%,), whereas Uganda (40.10%), Burundi (38.18%), Zimbabwe (36.95%), and Namibia (31.2%) had the highest prevalence of cough. The results of the random forest plot revealed that spatial locations (longitude, latitude), particulate matter, land surface temperature, nitrogen dioxide, and the number of cattle in the houses are the most important features in predicting the diagnosis of symptoms of ARIs among under-five children in sSA. The RF algorithm was selected as the best ML model (AUC = 0.77, Accuracy = 0.72) to predict the symptoms of ARIs among children under five. The MLA performed well in predicting the symptoms of ARIs and associated predictors among under-five children across the sSA countries. Random forest MLA was identified as the best classifier to be employed for the prediction of the symptoms of ARI among under-five children.
Noninvasive, label-free image approaches to predict multimodal molecular markers in pluripotency assessment
Authors: Akiyoshi Ryutaro , Hase Takeshi , Sathiyananthavel Mayuri , Ghosh Samik , Kitano Hiroaki , Yachie Ayako
Published: July 2024

Manufacturing regenerative medicine requires continuous monitoring of pluripotent cell culture and quality assessment while eliminating cell destruction and contaminants. In this study, we employed a novel method to monitor the pluripotency of stem cells through image analysis, avoiding the traditionally used invasive procedures. This approach employs machine learning algorithms to analyze stem cell images to predict the expression of pluripotency markers, such as OCT4 and NANOG, without physically interacting with or harming cells. We cultured induced pluripotent stem cells under various conditions to induce different pluripotent states and imaged the cells using bright-field microscopy. Pluripotency states of induced pluripotent stem cells were assessed using invasive methods, including qPCR, immunostaining, flow cytometry, and RNA sequencing. Unsupervised and semi-supervised learning models were applied to evaluate the results and accurately predict the pluripotency of the cells using only image analysis. Our approach directly links images to invasive assessment results, making the analysis of cell labeling and annotation of cells in images by experts dispensable. This core achievement not only contributes for safer and more reliable stem cell research but also opens new avenues for real-time monitoring and quality control in regenerative medicine manufacturing. Our research fills an important gap in the field by providing a viable, noninvasive alternative to traditional invasive methods for assessing pluripotency. This innovation is expected to make a significant contribution to improving regenerative medicine manufacturing because it will enable a more detailed and feasible understanding of cellular status during the manufacturing process.
Differential responses to thrombospondin-1 and PDGF-BB in smooth muscle cells from atherosclerotic coronary arteries and internal thoracic arteries
Authors: Pathak Alokkumar S. , Stouffer George A.
Published: July 2024

Atherosclerosis is rare in internal thoracic arteries (ITA) even in patients with severe atherosclerotic coronary artery (ACA) disease. To explore cellular differences, ITA SMC from 3 distinct donors and ACA SMC from 3 distinct donors were grown to sub-confluence and growth arrested for 48 h. Proliferation and thrombospondin-1 (TSP1) production were determined using standard techniques. ITA SMC were larger, grew more slowly and survived more passages than ACA SMC. ACA SMC had a more pronounced proliferative response to 10% serum than ITA SMC. Both ACA SMC and ITA SMC proliferated in response to exogenous TSP1 (12.5 µg/ml and 25 µg/ml) and platelet derived growth factor-BB (PDGF-BB; 20 ng/ml) but TSP1- and PDGF-BB-induced proliferation were partially inhibited by anti-TSP1 antibody A4.1, microRNA-21(miR-21)-3p inhibitors and miR-21-5p inhibitors in each of the 3 ACA SMC lines, but not in any of the ITA SMC lines. PDGF-BB stimulated TSP1 production in ACA SMC but not in ITA SMC but there was no increase in TSP1 levels in conditioned media in either SMC type. In summary, there are significant differences in morphology, proliferative capacity and in responses to TSP1 and PDGF-BB in SMC derived from ITA compared to SMC derived from ACA.
The prevalence, risk factors, and outcomes of acute pulmonary embolism complicating sepsis and septic shock: a national inpatient sample analysis
Authors: Hasegawa Daisuke , Sato Ryota , Lee Young Im , Wang Hong Yu , Nishida Kazuki , Steiger David
Published: July 2024

The study aimed to evaluate the prevalence, risk factors, and clinical outcomes of pulmonary embolism in patients diagnosed with sepsis with and without shock. The National Inpatient Sample was used to identify adults with sepsis with and without shock between 2017 and 2019. The prevalence of acute pulmonary embolism and the association of acute pulmonary embolism with in-hospital mortality, hospital length of stay for survivors, and overall costs of hospitalization were evaluated. Multivariable logistic and linear regression analyses, adjusted for various parameters, were used to explore these associations. Of the estimated 5,019,369 sepsis hospitalizations, 1.2% of patients with sepsis without shock and 2.3% of patients with septic shock developed pulmonary embolism. The odds ratio for in-hospital mortality was 1.94 (95% confidence interval (CI) 1.85–2.03, p < 0.001). The coefficient for hospital length of stay was 3.24 (95% CI 3.03–3.45, p < 0.001). The coefficient for total costs was 46,513 (95% CI 43,079–49,947, p < 0.001). The prevalence of pulmonary embolism in patients diagnosed with sepsis with and without shock was 1.2 and 2.3%, respectively. Acute pulmonary embolism was associated with higher in-hospital mortality, longer hospital length of stay for survivors, and higher overall costs of hospitalization.