bluuebunny/crossref_metadata_2025 huggingface dataset:
Dynamic causal modeling analysis reveals the modulation of motor cortex and integration in superior temporal gyrus during multisensory speech perception
Authors: Zou Ting , Li Liyuan , Huang Xinju , Deng Chijun , Wang Xuyang , Gao Qing , Chen Huafu , Li Rong
Published: March 2023

The processing of speech information from various sensory modalities is crucial for human communication. Both left posterior superior temporal gyrus (pSTG) and motor cortex importantly involve in the multisensory speech perception. However, the dynamic integration of primary sensory regions to pSTG and the motor cortex remain unclear. Here, we implemented a behavioral experiment of classical McGurk effect paradigm and acquired the task functional magnetic resonance imaging (fMRI) data during synchronized audiovisual syllabic perception from 63 normal adults. We conducted dynamic causal modeling (DCM) analysis to explore the cross-modal interactions among the left pSTG, left precentral gyrus (PrG), left middle superior temporal gyrus (mSTG), and left fusiform gyrus (FuG). Bayesian model selection favored a winning model that included modulations of connections to PrG (mSTG → PrG, FuG → PrG), from PrG (PrG → mSTG, PrG → FuG), and to pSTG (mSTG → pSTG, FuG → pSTG). Moreover, the coupling strength of the above connections correlated with behavioral McGurk susceptibility. In addition, significant differences were found in the coupling strength of these connections between strong and weak McGurk perceivers. Strong perceivers modulated less inhibitory visual influence, allowed less excitatory auditory information flowing into PrG, but integrated more audiovisual information in pSTG. Taken together, our findings show that the PrG and pSTG interact dynamically with primary cortices during audiovisual speech, and support the motor cortex plays a specifically functional role in modulating the gain and salience between auditory and visual modalities.
Key Targets and Molecular Mechanisms of the Fat-soluble Components of Ginseng for Lung Cancer Treatment
Authors: Gao Dongdong , Li Yingyue , Xiang Sen , Zhang Jing
Published: March 2023

Objective: To analyze the regulatory effects and key targets of the fat-soluble components of ginseng in lung cancer. Methods: Gas chromatography–mass spectrometry and the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform were used to analyze and identify the fat-soluble components of ginseng. Network pharmacology was used to analyze the therapeutic targets of the fat-soluble components of ginseng in lung cancer and screen key proteins. In vitro assays were conducted to verify the effects of the active fat-soluble components of ginseng on proliferation and apoptosis in lung cancer cells and to verify the regulation of key proteins. Results: Ten active fat-soluble components of ginseng were screened for follow-up. Network pharmacology showed 33 overlapping targets between the active fat-soluble components of ginseng and lung cancer, and functional enrichment of the targets showed involvement of response to nitrogen, hormone response, membrane raft, and positive regulation of external stimulus. Pathway enrichment analysis showed vascular endothelial growth factor (VEGF) signaling, adipocyte lipolysis regulation, chronic myelogenous leukemia, endocrine resistance, and NSCLC-related pathways. A protein-protein interaction network was constructed, and the top 10 targets were selected in accordance with their scores. Ultimately, five target genes (EGFR, KDR, MAPK3, PTPN11, and CTNNB1) were selected in combination with literature mining for subsequent experimental verification. Proliferation assays showed that the growth of lung cancer cells was significantly decreased in a concentration-dependent manner in the fat-soluble components of ginseng intervention group compared with controls. Flow cytometry showed that active fat-soluble components of ginseng promoted apoptosis in a concentration-dependent manner in lung cancer cells. Western blot and quantitative real-time PCR showed that levels of the five key proteins and mRNAs were significantly decreased in the intervention group; furthermore, histone protein and mRNA levels were significantly higher in the high-concentration intervention group compared with the low-concentration group. Conclusion: The active fat-soluble components of ginseng inhibited the growth of lung cancer cells and promoted apoptosis. The underlying regulatory mechanisms may be related to signaling pathways involving EGFR, KDR, MAPK3, PTPN11, and CTNNB1.
Human Amniotic Mesenchymal Stem Cells Alleviate aGVHD after allo-HSCT by Regulating Interactions between Gut Microbiota and Intestinal Immunity
Authors: Bu Xiaoyin , Wang Junhui , Yin Zhao , Pan Weifeng , Liu Liping , Jin Hua , Liu Qifa , Zheng Lei , Sun Haitao , Gao Ya , Ping Baohong
Published: March 2023

Acute graft-versus-host disease (aGVHD) after allogeneic hematopoietic stem cell transplantation poses one of the most vexing challenges. Gut microbiota dysbiosis can proceed aGVHD and mesenchymal stem cells (MSCs) have promising therapeutic potential for aGVHD. However, whether hAMSCs affect the gut microbiota during aGVHD mitigation remains unknown. Accordingly, we sought to define the effects and underlying mechanisms of human amniotic membrane-derived MSCs (hAMSCs) regulating the gut microbiota and intestinal immunity in aGVHD. By establishing humanized aGVHD mouse models and hAMSCs treatment, we found that hAMSCs significantly ameliorated aGVHD symptoms, reversed the immune imbalance of T cell subsets and cytokines, and restored intestinal barrier. Moreover, the diversity and composition of gut microbiota were improved upon treatment with hAMSCs. Spearman’s correlation analysis showed that there was a correlation between the gut microbiota and tight junction proteins, immune cells as well as cytokines. Our research suggested that hAMSCs alleviated aGVHD by promoting gut microbiota normalization and regulating the interactions between the gut microbiota and intestinal barrier, immunity.

Graphical Abstract
Nanospanlastics as a Novel Approach for Improving the Oral Delivery of Resveratrol in Lipopolysaccharide-Induced Endotoxicity in Mice
Authors: Younis Mostafa Mohamed , Fadel Noha Abd El-Fattah , Darwish Asmaa Badawy , Mohsen Amira Mohamed
Published: March 2023

Purpose

Resveratrol (RSV) is a natural polyphenolic compound that has numerous biological effects. Owing to its poor bioavailability, only trace concentrations of RSV could be found at the site of action. Therefore, the present study was aimed at developing RSV-loaded nanospanlastics to improve its oral delivery and therapeutic activity.

Methods

RSV-loaded nanospanlastics were prepared using the thin film hydration technique. The developed formulations were characterized via vesicular size (VS), polydispersity index (PDI), zeta potential (ZP) measurements, fourier transform infrared (FT-IR) spectroscopy analysis and transmission electron microscopy (TEM). In vitro release profile was carried out using dialysis bag diffusion technique. In vivo study was carried out using lipopolysaccharide (LPS)-induced endotoxicity model in mice to evaluate the formulations activity.

Results

The results revealed the successful development of RSV-loaded nanospanlastics which exhibited EE% ranging from 45 to 85%, particle sizes ranging from 260.5 to 794.3 nm; negatively charged zeta potential (≤ − 20 mV) and TEM revealed their spherical shape. An in vitro release study showed biphasic pattern with sustained release of drug up to 24 h. In vivo results showed the superiority of RSV-loaded nanospanlastics over conventional niosomes in attenuating serum levels of liver and kidney functions (aspartate transaminase (AST), alanine transaminase (ALT), and creatinine) in LPS-induced endotoxic mice. Furthermore, both of them suppressed the elevated oxidative stress and inflammatory markers (malondialdehyde (MDA), nitric oxide (NO), and interleukin-1beta (IL-1β)) estimated in the liver and kidney tissues. However, the nanospanlastics showed a prevalence effect over conventional niosomes in kidney measurements and the histopathological examinations.

Conclusions

These findings reveal the potential of nanospanlastics in improving the oral delivery and therapeutic efficacy of RSV.
Standards of NGS Data Sharing and Analysis in Ataxias: Recommendations by the NGS Working Group of the Ataxia Global Initiative
Authors: Beijer Danique , Fogel Brent L. , Beltran Sergi , Danzi Matt C. , Németh Andrea H. , Züchner Stephan , Synofzik Matthis ,   AGI Ataxia NGS genomics, platforms Working Group, Adarmes Astrid , Alhusaini Saud , Ashrafi Mahmoud Reza , Bataller Luis , Bertini Enrico , Boesch Sylvia , Buijsen Ronald , Cassou Emanuel , Chan Edwin , Damásio Joana , Donis Karina , Elert-Dobkowska Ewelina , Elsayed Liena , Espinos Carmen , Hanağasi Haşmet , Heidari Morteza , Nachbauer Wolfgang , Oliveira Jorge , Opal Puneet , Paisan-Ruiz Coro , Puccio Hélène , Saccà Francesco , Saraiva-Pereira Maria Luiza , Schmidt Thorsten , Schüle Rebecca , Stevanin Giovanni , Wilke Carlo , Yoon Grace , Zach Neta , Zanni Ginevra
Published: March 2023

The Ataxia Global Initiative (AGI) is a worldwide multi-stakeholder research platform to systematically enhance trial-readiness in degenerative ataxias. The next-generation sequencing (NGS) working group of the AGI aims to improve methods, platforms, and international standards for ataxia NGS analysis and data sharing, ultimately allowing to increase the number of genetically ataxia patients amenable for natural history and treatment trials. Despite extensive implementation of NGS for ataxia patients in clinical and research settings, the diagnostic gap remains sizeable, as approximately 50% of patients with hereditary ataxia remain genetically undiagnosed. One current shortcoming is the fragmentation of patients and NGS datasets on different analysis platforms and databases around the world. The AGI NGS working group in collaboration with the AGI associated research platforms—CAGC, GENESIS, and RD-Connect GPAP—provides clinicians and scientists access to user-friendly and adaptable interfaces to analyze genome-scale patient data. These platforms also foster collaboration within the ataxia community. These efforts and tools have led to the diagnosis of > 500 ataxia patients and the discovery of > 30 novel ataxia genes. Here, the AGI NGS working group presents their consensus recommendations for NGS data sharing initiatives in the ataxia field, focusing on harmonized NGS variant analysis and standardized clinical and metadata collection, combined with collaborative data and analysis tool sharing across platforms.
Multimodal biomedical image retrieval and indexing system using handcrafted with deep convolution neural network features
Authors: Mansour Romany F.
Published: March 2023

The advances in biomedical imaging equipment have produced a massive amount of medical images that are generated by the different modalities. Consequently, a huge volume of data has been produced and caused a complex and time-consuming retrieving process of the relevant cases. To resolve this issue, the Content-Based Biomedical Image Retrieval (CBMIR) system is applied to retrieve the related images from the earlier patients’ databases. However, the previous handcrafted features methods that applied the CBMIR model have shown poor performance in many multimodal databases. In this paper, we focus on designing CBMIR technique using Deep Learning (DL) models. We present a new Multimodal Biomedical Image Retrieval and Classification (M-BMIRC) technique for retrieving and classifying the biomedical images from huge databases. The proposed M-BMIRC model involves three dissimilar processes as following: feature extraction, similarity measurement, and classification. It uses an ensemble of handcrafted features from Zernike Moments (ZM) and deep features from Deep Convolutional Neural Networks (DCNN) for feature extraction process. Additionally, the Hausdorff Distance based similarity measure is employed to identify the resemblance between the queried image and the images that exist in the database. Moreover, the classification process gets executed on the retrieval images using the Probabilistic Neural Network (PNN) model, which allocates the class labels of the tested images. Finally, the experimental studies are conducted using two benchmark medical datasets and the results ensure the superior performance of the proposed model in terms of different measures include Average Precision Rate (APR), Average Recall Rate (ARR), F-score, accuracy, and Computation Time (CT).
Application of sensor data based predictive maintenance and artificial neural networks to enable Industry 4.0
Authors: Fordal Jon Martin , Schjølberg Per , Helgetun Hallvard , Skjermo Tor Øistein , Wang Yi , Wang Chen
Published: March 2023

Possessing an efficient production line relies heavily on the availability of the production equipment. Thus, to ensure that the required function for critical equipment is in compliance, and unplanned downtime is minimized, succeeding with the field of maintenance is essential for industrialists. With the emergence of advanced manufacturing processes, incorporating predictive maintenance capabilities is seen as a necessity. Another field of interest is how modern value chains can support the maintenance function in a company. Accessibility to data from processes, equipment and products have increased significantly with the introduction of sensors and Industry 4.0 technologies. However, how to gather and utilize these data for enabling improved decision making within maintenance and value chain is still a challenge. Thus, the aim of this paper is to investigate on how maintenance and value chain data can collectively be used to improve value chain performance through prediction. The research approach includes both theoretical testing and industrial testing. The paper presents a novel concept for a predictive maintenance platform, and an artificial neural network (ANN) model with sensor data input. Further, a case of a company that has chosen to apply the platform, with the implications and determinants of this decision, is also provided. Results show that the platform can be used as an entry-level solution to enable Industry 4.0 and sensor data based predictive maintenance.
Assessing cognitive impairment in an ethnically diverse cohort of oldest-old: the life after 90 study
Authors: Petrosyan Diana , Corrada Maria M. , Kawas Claudia H. , Demoz Asmeret , Ganzon Czarina , Popovich Oksana , Gaied Reham , Mungas Dan , Gilsanz Paola , Vieira Katharine E. , Whitmer Rachel A. , DeCarli Charles
Published: March 2023

Background

Though dementia rates vary by racial or ethnic groups, it is unknown if these disparities remain among those aged 90 or older.

Aims

To test this hypothesis, we used baseline clinical evaluation of 541 ethnically and racially diverse individuals participating in the LifeAfter90 Study to assess how associations between core demographic characteristics and measures of physical and cognitive performance differ across the racial/ethnic groups.

Methods

Participants in this study were long-term non-demented members of Kaiser Permanente Northern California. They were clinically evaluated and diagnosed with normal or impaired cognition (mild cognitive impairment and dementia) through an in-person comprehensive clinical assessment consisting of a detailed medical history, physical and neurological examination, functional, and cognitive tests.

Results

The average age at enrollment was 93.0 ± 2.6 years, 62.4% female and 34.2% non-Hispanic White. At initial evaluation 301 participants had normal cognition and 165 had mild cognitive impairment (MCI) and despite screening, 69 participants were determined to have dementia. Age, education, 3MS, FAQ and CDR scores were significantly associated with cognitive impairment (normal versus MCI and dementia), but not gender. There was a significant univariate association between race/ethnicity and cognitive impairment (p < 0.02) being highest among Black (57.4%) and lowest among Asian (32.7%) individuals. After adjustment for age, gender, and education, however, prevalence of cognitive impairment was not influenced by race or ethnicity.

Conclusion

Our results confirm the ability to reliably assess clinical diagnosis in a diverse sample of very old individuals.
Retinal sensitivity and gaze fixation evaluated by microperimetry in subjects with type 2 diabetes: two independent parameters that explore different neuronal circuits
Authors: Ortiz-Zuñiga A. M. , Rojano Toimil A. , Rahnama K. , Lainez E. , Raguer N. , Simó-Servat O. , Hernández C. , Simó R. , Ciudin A.
Published: March 2023

Background and aims

Retinal sensitivity (RS) and gaze fixation (GF) assessed by retinal microperimetry are useful and complementary tools for identifying mild cognitive impairment (MCI) in patients with type 2 diabetes (T2D). The hypothesis is that RS and GF examine different neural circuits: RS depends only on the visual pathway while GF reflects white matter complex connectivity networks. The aim of the study is to shed light to this issue by examining the relationship of these two parameters with visual evoked potentials (VEP), the current gold standard to examine the visual pathway.

Materials and methods

Consecutive T2D patients > 65 years were recruited from the outpatient clinic. Retinal microperimetry (MAIA 3rd generation) and visual evoked potentials (VEP) (Nicolet Viking ED). RS (dB), GF (BCEA63%, BCEA95%) (MAIA) and VEP (Latency P100ms, Amplitude75–100 uV) were analyzed.

Results

Thirty three patients (45% women, 72.1 ± 4.6 years) were included. VEP parameters significantly correlated with RS but not with GF.

Conclusions

These results confirm that RS but not GF depends on the visual pathway, reinforcing the concept that they are complementary diagnostic tools. Used together can further increase the value of microperimetry as screening test for identifying T2D population with cognitive impairment.
Compatibility and complementarity between institutional and post-Keynesian economics: a literature review with a particular focus on methodology
Authors: Fernández-Huerga Eduardo , Pardo Ana , Salvador Ana
Published: March 2023

The objective of this article is to carry out a review of the links between institutional and post-Keynesian economics, in order to raise the possible compatibility and even complementarity between the two branches of economic thought. To this end, we first review the question of compatibility from the perspective of institutional economics and then from the post-keynesian standpoint. Next, methodological issues are addressed by presenting the essential elements that characterize post-keynesian and institutional methodology (and internal debates in this regard) and then by describing the areas of compatibility between the two. The final section presents the main conclusions and summarizes the basic elements that could constitute a theoretical framework of synthesis between institutional and post-keynesian economics.
Laser beam heat treatment in large-scale additive manufacturing
Authors: Layher Michel , Eckhardt Lukas , Linke Daniel , Hopf Andreas , Bliedtner Jens
Published: March 2023

Large-scale additive manufacturing (LSAM) has been developing a huge potential to address certain tasks in industrial applications over the last years. Particularly granule extrusion technologies enable the processing of an enormous variety of materials but also introduce new challenges in printing large-scale parts. Compared to fused layer modelling and due to larger nozzle diameters as well as higher extrusion rates strand geometry and consequently, process-related voids are enlarged. A promising approach to improve part quality is the integration of carbon dioxide laser (CO2) radiation into the additive manufacturing process to weld deposited strands by increasing the interface temperature. Experiments are conducted for polymethyl methacrylate (PMMA) and styrene-acrylonitrile (SAN) which are very good absorbers of the wavelength 10.6 µm. Due to the locally defined heat treatment, merely certain areas of the strands are heated to a desired temperature. This leads to a more complete diffusion. At the same time, temperature gradients in the overall part are avoided. By means of a thermographic camera, the temperatures at the re-melting process of deposited strands can be precisely monitored. Therefore, the relation between laser intensity and resulting temperature can be transferred into a repeatable process window. The interaction between laser and deposited material leads to a wider contact area between stacked strands. While flexural strength is not significantly affected, compared to specimens manufactured without any heat treatment bending force is increased by 66% (PMMA) and 48% (SAN), respectively. In addition, voids between adjacent strands are reduced by up to 57%.
Integrating Different Data Modalities for the Classification of Alzheimer’s Disease Stages
Authors: Maddalena Lucia , Granata Ilaria , Giordano Maurizio , Manzo Mario , Guarracino Mario Rosario
Published: March 2023

Alzheimer’s disease (AD) is the most common form of dementia with physical, psychological, social, and economic impacts on patients, their carers, and society. Its early diagnosis allows clinicians to initiate the treatment as early as possible to arrest or slow down the disease progression more effectively. We consider the problem of classifying AD patients through a machine learning approach using different data modalities acquired by non-invasive techniques. We perform an extensive evaluation of a machine learning classification procedure using omics, imaging, and clinical features, extracted by the ANMerge dataset, taken alone or combined together. Experimental results suggest that integrating omics and imaging features leads to better performance than any of them taken separately. Moreover, clinical features consisting of just two cognitive test scores always lead to better performance than any of the other types of data or their combinations. Since these features are usually involved in the clinician diagnosis process, our results show how their adoption as classification features positively biases the results.
A Deep Learning Framework for Generation and Analysis of Driving Scenario Trajectories
Authors: Demetriou Andreas , Alfsvåg Henrik , Rahrovani Sadegh , Haghir Chehreghani Morteza
Published: March 2023

We propose a unified deep learning framework for the generation and analysis of driving scenario trajectories, and validate its effectiveness in a principled way. To model and generate scenarios of trajectories with different lengths, we develop two approaches. First, we adapt the Recurrent Conditional Generative Adversarial Networks (RC-GAN) by conditioning on the length of the trajectories. This provides us the flexibility to generate variable-length driving trajectories, a desirable feature for scenario test case generation in the verification of autonomous driving. Second, we develop an architecture based on Recurrent Autoencoder with GANs to obviate the variable length issue, wherein we train a GAN to learn/generate the latent representations of original trajectories. In this approach, we train an integrated feed-forward neural network to estimate the length of the trajectories to be able to bring them back from the latent space representation. In addition to trajectory generation, we employ the trained autoencoder as a feature extractor, for the purpose of clustering and anomaly detection, to obtain further insights into the collected scenario dataset. We experimentally investigate the performance of the proposed framework on real-world scenario trajectories obtained from in-field data collection.
Identification of Clinical Features Associated with Mortality in COVID-19 Patients
Authors: Eskandarian Rahimeh , Alizadehsani Roohallah , Behjati Mohaddeseh , Zahmatkesh Mehrdad , Sani Zahra Alizadeh , Haddadi Azadeh , Kakhi Kourosh , Roshanzamir Mohamad , Shoeibi Afshin , Hussain Sadiq , Khozeimeh Fahime , Darbandy Mohammad Tayarani , Joloudari Javad Hassannataj , Lashgari Reza , Khosravi Abbas , Nahavandi Saeid , Islam Sheikh Mohammed Shariful
Published: March 2023

Understanding clinical features and risk factors associated with COVID-19 mortality is needed to early identify critically ill patients, initiate treatments and prevent mortality. A retrospective study on COVID-19 patients referred to a tertiary hospital in Iran between March and November 2020 was conducted. COVID-19-related mortality and its association with clinical features including headache, chest pain, symptoms on computerized tomography (CT), hospitalization, time to infection, history of neurological disorders, having a single or multiple risk factors, fever, myalgia, dizziness, seizure, abdominal pain, nausea, vomiting, diarrhoea and anorexia were investigated. Based on the investigation outcome, decision tree and dimension reduction algorithms were used to identify the aforementioned risk factors. Of the 3008 patients (mean age 59.3 ± 18.7 years, 44% women) with COVID-19, 373 died. There was a significant association between COVID-19 mortality and old age, headache, chest pain, low respiratory rate, oxygen saturation < 93%, need for a mechanical ventilator, having symptoms on CT, hospitalization, time to infection, neurological disorders, cardiovascular diseases and having a risk factor or multiple risk factors. In contrast, there was no significant association between mortality and gender, fever, myalgia, dizziness, seizure, abdominal pain, nausea, vomiting, diarrhoea and anorexia. Our results might help identify early symptoms related to COVID-19 and better manage patients according to the extracted decision tree. The proposed ML models identified a number of clinical features and risk factors associated with mortality in COVID-19 patients. These models if implemented in a clinical setting might help to early identify patients needing medical attention and care. However, more studies are needed to confirm these findings.
EMA-FDA Parallel Scientific Advice: Optimizing Development of Medicines in the Global Age
Authors: Thor Shannon , Vetter Thorsten , Marcal Anabela , Kweder Sandra
Published: March 2023

As medicines development continues towards a globalized approach, both the pharmaceutical industry and regulatory agencies increasingly seek opportunities to proactively engage early in product development. The parallel scientific advice program shared by the European Medicines Agency (EMA) and the US Food and Drug Administration (FDA) provides a mechanism for experts to concurrently engage in scientific discourse with sponsors on key issues during the development phase of new medicinal products (drugs, biologicals, vaccines, and advanced therapies).
A new approach to controlling a hydraulic indirect elevator with a variable-speed pump
Authors: Stawiński Łukasz , Kosucki Andrzej , Morawiec Adrian , Skowrońska Justyna
Published: March 2023

The paper describes a new approach to the issue of controlling an indirect elevator with a bidirectional variable-speed pump and a simple controller based on the position sensor. The aim of this paper is to present a method of controlling the speed of the elevator to ensure smooth movement and proper positioning of the car on the floor, regardless of its load and ropes rigidity. The main feature of the proposed solution is the use of a frequency inverter in vector mode to control the speed of the car in both directions. The control function is based on virtual cams comparing actual measurements from the car position sensor. The proposed control strategy has been experimentally verified on the existing indirect elevator drive, and the obtained results indicate a very high accuracy in maintaining and shaping the speed and positioning of the car. The conducted research confirms the possibility of using a new method of controlling hydraulic and indirect elevators. The benefits of this method include a less complex hydraulic system, the control of overloads in the car and vibrations in the rope system, and the possibility of energy recovery.
The Creative Response
Authors: Antonelli Cristiano , Colombelli Alessandra
Published: March 2023

This Element combines the advances of the economics of knowledge and innovation implementing the Schumpeterian notion of creative response to understand the determinants and the effects of the rate and direction of technological and organizational change and its variance across time and space, firms, and industries. The notion of creative response provides an inclusive framework that enables to highlight the crucial role of knowledge in assessing the rate and direction of technological change and to clarify that no innovation is possible without the generation of new knowledge, while the generation of new knowledge augments the chances of innovation but does not automatically yield the introduction of innovation. Firms thus are faced with several strategic decisions to make the creative response possible. The Element elaborates on the analytical core of the notion of creative response and articulates its implications for economic policy and strategic management.
Shifts in Above‐ Versus Below‐Ground Carbon Gains to Terrestrial Ecosystems Carbon Sinks Under Excess Nitrogen Inputs
Authors: Lu Xiaofei , Gilliam Frank S. , Yue Xu , Wang Bin , Kuang Yuanwen
Published: March 2023

Although elevated atmospheric nitrogen (N) deposition can increase terrestrial carbon (C) sinks, the persistence of this C acquisition depends partly on the responses of plant biomass and soil organic carbon (SOC) to long‐term exogenous N input. Experiments with N‐additions show increases in above‐ground biomass (AGB), although C dynamics between above‐ and below‐ground under N enrichment are unconnected in many studies. Here, we meta‐analyzed data from 362 N‐addition experiments globally and found that both AGB (+34%) and below‐ground biomass (BGB, +13%) positively but root‐to‐shoot ratios negatively (−15%) responded to N addition. These responses were reversed, however, when the experimental duration was over 20 years, wherein BGB increased and AGB was unchanged or even declined, during which time plants invested more C into roots. The effects of increased AGB were weak and negative, whereas those of increased BGB were robust and positive on SOC. Under chronic N deposition, the significant increase in SOC (5%) was associated with the increased root C inputs and decreased soil C losses rather than with increased above‐ground C inputs. The results suggest that the sequestration of below‐ground C exceeds that of above‐ground C to sustain terrestrial C gain during long‐term N deposition.
Influence of Seasonal Post‐Depositional Processes on the Remanent Magnetization in Varved Sediments From Glacial Lake Ojibway (Canada)
Authors: Philippe Édouard G. H. , St‐Onge Guillaume , Valet Jean‐Pierre , Godbout Pierre‐Marc , Egli Ramon , Francus Pierre , Roy Martin
Published: March 2023

The natural remanent magnetization (NRM) of high sedimentation rate sediments provides significant information about paleomagnetic secular variation of the Earth's magnetic field and can also potentially be used for stratigraphy. However, NRM acquisition depends on conditions inherent to the depositional environment. In addition to recording a precise annual chronology, varved sediments reflect marked annual sedimentary changes. The Earth's magnetic field does not vary significantly over such a short period, so magnetic changes recorded by varves are expected to reflect the influence of depositional parameters on the recording process. We focus here on a sequence of 27 ± 1 varves from the former proglacial Lake Ojibway (∼8.5 ka cal BP) from which individual cm‐thick summer and winter beds were sampled. Paleomagnetic, granulometric and geochemical analyses were conducted on each bed. A mean inclination shallowing of 24.3° is observed in winter beds, along with an 11.3° shallowing in summer beds. Magnetic declinations follow, on average, the expected field direction, but differences of up to 20° occur between successive beds. Summer beds are thicker than winter beds and have stronger magnetic susceptibility, higher Ca/Fe ratios and coarser sedimentary and magnetic grains. This grain size pattern reflects the input of coarser detrital particles during summer, while the finer fraction remained in suspension until it was deposited in winter. A combination of differential compaction between the winter and summer beds, seasonally varying physical and magnetic properties of sediments, and delayed NRM acquisition explains the variable and coercivity‐dependent inclination shallowing.
Strategies for Successful Collaborative Writing
Authors: Baer Eric , Layou Karen , Macdonald R. , Zuber Sharon
Published: March 2023

Lessons learned and applied during a recent workshop can help authors, from students to seasoned professionals, work together to produce more equitable and effective writing.
How Wine’s Origin Was Shaped by the Last Glacial Maximum
Authors: Duncombe Jenessa
Published: March 2023

The harsh climate of the ice age influenced grapevine cultivation at the dawn of agriculture.
Why Tropical Forests Are Important for Our Well-Being
Authors: Borma Laura
Published: March 2023

Tropical forests play a critical role in supporting human well-being, food security, and the maintenance of biodiversity.
Myelofibrosis-type megakaryocyte dysplasia (MTMD) as a distinct category of BCR::ABL-negative myeloproliferative neoplasms. Challenges and perspectives
Authors: Barosi Giovanni , Rosti Vittorio , Gale Robert Peter
Published: March 2023

In this Perspective, we discuss criteria for defining a new disease entity or variant of a recognized disease or disorder. We do so in the context of the current topography of the BCR::ABL-negative myeloproliferative neoplasms (MPNs) where two new variants are reported: clonal megakaryocyte dysplasia with normal blood values (CMD-NBV) and clonal megakaryocyte dysplasia with isolated thrombocytosis (CMD-IT). The cardinal feature of these variants is bone marrow megakaryocyte hyperplasia and atypia corresponding the WHO histological criteria for primary myelofibrosis (myelofibrosis-type megakaryocyte dysplasia-MTMD). Persons with these new variants have a different disease course and features from others in the MPN domain. In a broader context we suggest myelofibrosis-type megakaryocyte dysplasia defines a spectrum of related MPN variants including CMD-NBV, CMD-IT, pre-fibrotic myelofibrosis and overt myelofibrosis, which differ from polycythemia vera and essential thrombocythemia. Our proposal needs external validation and we stress the need for a consensus definition of the megakaryocyte dysplasia which is the hallmark of these disorders.
Fabrication of practical deformable displays: advances and challenges
Authors: Kim Dong Wook , Kim Seong Won , Lee Gyujeong , Yoon Jangyeol , Kim Sangwoo , Hong Jong-Ho , Jo Sung-Chan , Jeong Unyong
Published: March 2023

Display form factors such as size and shape have been conventionally determined in consideration of usability and portability. The recent trends requiring wearability and convergence of various smart devices demand innovations in display form factors to realize deformability and large screens. Expandable displays that are foldable, multi-foldable, slidable, or rollable have been commercialized or on the edge of product launches. Beyond such two-dimensional (2D) expansion of displays, efforts have been made to develop three dimensional (3D) free-form displays that can be stretched and crumpled for use in realistic tactile sensation, artificial skin for robots, and on-skin or implantable displays. This review article analyzes the current state of the 2D and 3D deformable displays and discusses the technological challenges to be achieved for industrial commercialization.
Upconversion time-stretch infrared spectroscopy
Authors: Hashimoto Kazuki , Nakamura Takuma , Kageyama Takahiro , Badarla Venkata Ramaiah , Shimada Hiroyuki , Horisaki Ryoich , Ideguchi Takuro
Published: March 2023

High-speed measurement confronts the extreme speed limit when the signal becomes comparable to the noise level. In the context of broadband mid-infrared spectroscopy, state-of-the-art ultrafast Fourier-transform infrared spectrometers, in particular dual-comb spectrometers, have improved the measurement rate up to a few MSpectra s−1, which is limited by the signal-to-noise ratio. Time-stretch infrared spectroscopy, an emerging ultrafast frequency-swept mid-infrared spectroscopy technique, has shown a record-high rate of 80 MSpectra s−1 with an intrinsically higher signal-to-noise ratio than Fourier-transform spectroscopy by more than the square-root of the number of spectral elements. However, it can measure no more than ~30 spectral elements with a low resolution of several cm−1. Here, we significantly increase the measurable number of spectral elements to more than 1000 by incorporating a nonlinear upconversion process. The one-to-one mapping of a broadband spectrum from the mid-infrared to the near-infrared telecommunication region enables low-loss time-stretching with a single-mode optical fiber and low-noise signal detection with a high-bandwidth photoreceiver. We demonstrate high-resolution mid-infrared spectroscopy of gas-phase methane molecules with a high resolution of 0.017 cm−1. This unprecedentedly high-speed vibrational spectroscopy technique would satisfy various unmet needs in experimental molecular science, e.g., measuring ultrafast dynamics of irreversible phenomena, statistically analyzing a large amount of heterogeneous spectral data, or taking broadband hyperspectral images at a high frame rate.
Evaluation of Cow’s Milk Related Symptom Score [CoMiSS] accuracy in cow’s milk allergy diagnosis
Authors: El-Shafie Ali M. , Omar Zein A. , El Zefzaf Heba M. S. , Basma Elsayedamr M. , Al Sabbagh Nahla M. , Bahbah Wael A.
Published: March 2023

Background

Cow’s Milk-related Symptom Score (CoMiSS) is an awareness tool to recognize cow’s milk allergy (CMA) symptoms in infants. We aimed to assess the best cut-off point of CoMiSS in our country and investigate other parameters suggested to raise the strength of CoMiSS in CMA diagnosis.

Methods

We enrolled 100 infants with CMA-suggestive symptoms with documentation of CoMiSS initially and 4 weeks after cow milk-free diet (CMFD) followed by an open food challenge (OFC) test. Infants with symptom recurrence upon challenge were diagnosed with confirmed CMA.

Results

Initial mean CoMiSS was 15.76 ± 5.29, being higher in the confirmed CMA group (84% of infants). Following CMFD, median CoMiSS significantly reduced to 1.5 in the confirmed CMA group compared to 6.5 in the negative group. Receiver operation characteristic (ROC) curve identified a CoMiSS score of ≥12 as the best cut-off value with 76.19% sensitivity, 62.50% specificity and overall accuracy of 74.00%. Mucoid stool, bloody stool and faltering growth were reported in 80, 41 and 52% of confirmed CMA infants, respectively, with considerable improvement following CMFD.

Conclusions

Our study revealed a CoMiSS score of ≥12 to be the best cut-off point. However, CoMiSS cannot be used alone for accurate diagnosis of CMA.

Impact

CoMiSS ≥12 can predict a positive response to CMFD; nevertheless, CoMiSS is a good awareness tool and cannot be regarded as a stand-alone CMA diagnostic test.

CoMiSS reduction following CMFD was predictive of a reaction to OFC to diagnose CMA as well as for monitoring symptom improvement.

Symptoms commonly associated with CMA as mucoid stool, bloody stool, marked abdominal distention not responding to medical treatment and faltering growth, in addition to their improvements in response to CMA are suggested parameters to be added to CoMiSS to improve its accuracy.
Safety, tolerability, and pharmacokinetics of Aurora kinase B inhibitor AZD2811: a phase 1 dose-finding study in patients with advanced solid tumours
Authors: Johnson Melissa L. , Wang Judy S. , Falchook Gerald , Greenlees Carol , Jones Suzanne , Strickland Donald , Fabbri Giulia , Kennedy Caroline , Elizabeth Pease J. , Sainsbury Liz , MacDonald Alexander , Schalkwijk Stein , Szekeres Philip , Cosaert Jan , Burris Howard
Published: March 2023

Background

AZD2811 is a potent, selective Aurora kinase B inhibitor. We report the dose-escalation phase of a first-in-human study assessing nanoparticle-encapsulated AZD2811 in advanced solid tumours.

Methods

AZD2811 was administered in 12 dose-escalation cohorts (2-h intravenous infusion; 15‒600 mg; 21-/28-day cycles) with granulocyte colony-stimulating factor (G-CSF) at higher doses. The primary objective was determining safety and maximum tolerated/recommended phase 2 dose (RP2D).

Results

Fifty-one patients received AZD2811. Drug exposure was sustained for several days post-dose. The most common AZD2811-related adverse events (AEs) were fatigue (27.3%) at ≤200 mg/cycle and neutropenia (37.9%) at ≥400 mg/cycle. Five patients had dose-limiting toxicities: grade (G)4 decreased neutrophil count (n = 1, 200 mg; Days 1, 4; 28-day cycle); G4 decreased neutrophil count and G3 stomatitis (n = 1 each, both 400 mg; Day 1; 21-day cycle); G3 febrile neutropenia and G3 fatigue (n = 1 each, both 600 mg; Day 1; 21-day cycle +G-CSF). RP2D was 500 mg; Day 1; 21-day cycle with G-CSF on Day 8. Neutropenia/neutrophil count decrease were on-target AEs. Best overall responses were partial response (n = 1, 2.0%) and stable disease (n = 23, 45.1%).

Conclusions

At RP2D, AZD2811 was tolerable with G-CSF support. Neutropenia was a pharmacodynamic biomarker.

Clinical trial registration

NCT02579226.
CDK4/6 inhibition triggers ICAM1-driven immune response and sensitizes LKB1 mutant lung cancer to immunotherapy
Authors: Bai Xue , Guo Ze-Qin , Zhang Yan-Pei , Fan Zhen-zhen , Liu Li-Juan , Liu Li , Long Li-Li , Ma Si-Cong , Wang Jian , Fang Yuan , Tang Xin-Ran , Zeng Yu-Jie , Pan Xinghua , Wu De-Hua , Dong Zhong-Yi
Published: March 2023

Liver kinase B1 (LKB1) mutation is prevalent and a driver of resistance to immune checkpoint blockade (ICB) therapy for lung adenocarcinoma. Here leveraging single cell RNA sequencing data, we demonstrate that trafficking and adhesion process of activated T cells are defected in genetically engineered Kras-driven mouse model with Lkb1 conditional knockout. LKB1 mutant cancer cells result in marked suppression of intercellular adhesion molecule-1 (ICAM1). Ectopic expression of Icam1 in Lkb1-deficient tumor increases homing and activation of adoptively transferred SIINFEKL-specific CD8+ T cells, reactivates tumor-effector cell interactions and re-sensitises tumors to ICB. Further discovery proves that CDK4/6 inhibitors upregulate ICAM1 transcription by inhibiting phosphorylation of retinoblastoma protein RB in LKB1 deficient cancer cells. Finally, a tailored combination strategy using CDK4/6 inhibitors and anti-PD-1 antibodies promotes ICAM1-triggered immune response in multiple Lkb1-deficient murine models. Our findings renovate that ICAM1 on tumor cells orchestrates anti-tumor immune response, especially for adaptive immunity.
Robust flexural performance and fracture behavior of TiO2 decorated densified bamboo as sustainable structural materials
Authors: Ba Ziyu , Luo Hongyun , Guan Juan , Luo Jun , Gao Jiajia , Wu Sujun , Ritchie Robert O.
Published: March 2023

High-performance, fast-growing natural materials with sustainable and functional features currently arouse significant attention. Here, facile processing, involving delignification, in situ hydrothermal synthesis of TiO2 and pressure densification, is employed to transform natural bamboo into a high-performance structural material. The resulting TiO2-decorated densified bamboo exhibits high flexural strength and elastic stiffness, with both properties more than double that of natural bamboo. Real-time acoustic emission reveals the key role of the TiO2 nanoparticles in enhancing the flexural properties. The introduction of nanoscale TiO2 is found to markedly increase the degree of oxidation and the formation of hydrogen bonds in bamboo materials, leading to extensive interfacial failure between the microfibers, a micro-fibrillation process that results in substantial energy consumption and high fracture resistance. This work furthers the strategy of the synthetic reinforcement of fast-growing natural materials, which could lead to the expanded applications of sustainable materials for high-performance structural applications.
Engineered hypermutation adapts cyanobacterial photosynthesis to combined high light and high temperature stress
Authors: Sun Huili , Luan Guodong , Ma Yifan , Lou Wenjing , Chen Rongze , Feng Dandan , Zhang Shanshan , Sun Jiahui , Lu Xuefeng
Published: March 2023

Photosynthesis can be impaired by combined high light and high temperature (HLHT) stress. Obtaining HLHT tolerant photoautotrophs is laborious and time-consuming, and in most cases the underlying molecular mechanisms remain unclear. Here, we increase the mutation rates of cyanobacterium Synechococcus elongatus PCC 7942 by three orders of magnitude through combinatory perturbations of the genetic fidelity machinery and cultivation environment. Utilizing the hypermutation system, we isolate Synechococcus mutants with improved HLHT tolerance and identify genome mutations contributing to the adaptation process. A specific mutation located in the upstream non-coding region of the gene encoding a shikimate kinase results in enhanced expression of this gene. Overexpression of the shikimate kinase encoding gene in both Synechococcus and Synechocystis leads to improved HLHT tolerance. Transcriptome analysis indicates that the mutation remodels the photosynthetic chain and metabolism network in Synechococcus. Thus, mutations identified by the hypermutation system are useful for engineering cyanobacteria with improved HLHT tolerance.
DNA replication initiation factor RECQ4 possesses a role in antagonizing DNA replication initiation
Authors: Xu Xiaohua , Chang Chou-Wei , Li Min , Omabe Kenneth , Le Nhung , Chen Yi-Hsuan , Liang Feng , Liu Yilun
Published: March 2023

Deletion of the conserved C-terminus of the Rothmund-Thomson syndrome helicase RECQ4 is highly tumorigenic. However, while the RECQ4 N-terminus is known to facilitate DNA replication initiation, the function of its C-terminus remains unclear. Using an unbiased proteomic approach, we identify an interaction between the RECQ4 N-terminus and the anaphase-promoting complex/cyclosome (APC/C) on human chromatin. We further show that this interaction stabilizes APC/C co-activator CDH1 and enhances APC/C-dependent degradation of the replication inhibitor Geminin, allowing replication factors to accumulate on chromatin. In contrast, the function is blocked by the RECQ4 C-terminus, which binds to protein inhibitors of APC/C. A cancer-prone, C-terminal-deleted RECQ4 mutation increases origin firing frequency, accelerates G1/S transition, and supports abnormally high DNA content. Our study reveals a role of the human RECQ4 C-terminus in antagonizing its N-terminus, thereby suppressing replication initiation, and this suppression is impaired by oncogenic mutations.