bluuebunny/crossref_metadata_2025 huggingface dataset:
Morphometric analysis of airways in pre-COPD and mild COPD lungs using continuous surface representations of the bronchial lumen
Authors: Ortiz-Puerta David , Diaz Orlando , Retamal Jaime , Hurtado Daniel E.
Published: December 2023

Introduction: Chronic Obstructive Pulmonary Disease (COPD) is a prevalent respiratory disease that presents a high rate of underdiagnosis during onset and early stages. Studies have shown that in mild COPD patients, remodeling of the small airways occurs concurrently with morphological changes in the proximal airways. Despite this evidence, the geometrical study of the airway tree from computed tomography (CT) lung images remains underexplored due to poor representations and limited tools to characterize the airway structure.

Methods: We perform a comprehensive morphometric study of the proximal airways based on geometrical measures associated with the different airway generations. To this end, we leverage the geometric flexibility of the Snakes IsoGeometric Analysis method to accurately represent and characterize the airway luminal surface and volume informed by CT images of the respiratory tree. Based on this framework, we study the airway geometry of smoking pre-COPD and mild COPD individuals.

Results: Our results show a significant difference between groups in airway volume, length, luminal eccentricity, minimum radius, and surface-area-to-volume ratio in the most distal airways.

Discussion: Our findings suggest a higher degree of airway narrowing and collapse in COPD patients when compared to pre-COPD patients. We envision that our work has the potential to deliver a comprehensive tool for assessing morphological changes in airway geometry that take place in the early stages of COPD.
Level-set based adaptive-active contour segmentation technique with long short-term memory for diabetic retinopathy classification
Authors: Bhansali Ashok , Patra Rajkumar , Abouhawwash Mohamed , Askar S. S. , Awasthy Mohan , Rao K. B. V. Brahma
Published: December 2023

Diabetic Retinopathy (DR) is a major type of eye defect that is caused by abnormalities in the blood vessels within the retinal tissue. Early detection by automatic approach using modern methodologies helps prevent consequences like vision loss. So, this research has developed an effective segmentation approach known as Level-set Based Adaptive-active Contour Segmentation (LBACS) to segment the images by improving the boundary conditions and detecting the edges using Level Set Method with Improved Boundary Indicator Function (LSMIBIF) and Adaptive-Active Counter Model (AACM). For evaluating the DR system, the information is collected from the publically available datasets named as Indian Diabetic Retinopathy Image Dataset (IDRiD) and Diabetic Retinopathy Database 1 (DIARETDB 1). Then the collected images are pre-processed using a Gaussian filter, edge detection sharpening, Contrast enhancement, and Luminosity enhancement to eliminate the noises/interferences, and data imbalance that exists in the available dataset. After that, the noise-free data are processed for segmentation by using the Level set-based active contour segmentation technique. Then, the segmented images are given to the feature extraction stage where Gray Level Co-occurrence Matrix (GLCM), Local ternary, and binary patterns are employed to extract the features from the segmented image. Finally, extracted features are given as input to the classification stage where Long Short-Term Memory (LSTM) is utilized to categorize various classes of DR. The result analysis evidently shows that the proposed LBACS-LSTM achieved better results in overall metrics. The accuracy of the proposed LBACS-LSTM for IDRiD and DIARETDB 1 datasets is 99.43% and 97.39%, respectively which is comparably higher than the existing approaches such as Three-dimensional semantic model, Delimiting Segmentation Approach Using Knowledge Learning (DSA-KL), K-Nearest Neighbor (KNN), Computer aided method and Chronological Tunicate Swarm Algorithm with Stacked Auto Encoder (CTSA-SAE).
Therapeutic targeting of p90 ribosomal S6 kinase
Authors: Wright Eric B. , Lannigan Deborah A.
Published: December 2023

The Serine/Threonine protein kinase family, p90 ribosomal S6 kinases (RSK) are downstream effectors of extracellular signal regulated kinase 1/2 (ERK1/2) and are activated in response to tyrosine kinase receptor or G-protein coupled receptor signaling. RSK contains two distinct kinase domains, an N-terminal kinase (NTKD) and a C-terminal kinase (CTKD). The sole function of the CTKD is to aid in the activation of the NTKD, which is responsible for substrate phosphorylation. RSK regulates various homeostatic processes including those involved in transcription, translation and ribosome biogenesis, proliferation and survival, cytoskeleton, nutrient sensing, excitation and inflammation. RSK also acts as a major negative regulator of ERK1/2 signaling. RSK is associated with numerous cancers and has been primarily studied in the context of transformation and metastasis. The development of specific RSK inhibitors as cancer therapeutics has lagged behind that of other members of the mitogen-activated protein kinase signaling pathway. Importantly, a pan-RSK inhibitor, PMD-026, is currently in phase I/1b clinical trials for metastatic breast cancer. However, there are four members of the RSK family, which have overlapping and distinct functions that can vary in a tissue specific manner. Thus, a problem for transitioning a RSK inhibitor to the clinic may be the necessity to develop isoform specific inhibitors, which will be challenging as the NTKDs are very similar to each other. CTKD inhibitors have limited use as therapeutics as they are not able to inhibit the activity of the NTKD but could be used in the development of proteolysis-targeting chimeras.
Enhancing knowledge discovery from unstructured data using a deep learning approach to support subsurface modeling predictions
Authors: Hoover Brendan , Zaengle Dakota , Mark-Moser MacKenzie , Wingo Patrick , Suhag Anuj , Rose Kelly
Published: December 2023

Subsurface interpretations and models rely on knowledge from subject matter experts who utilize unstructured information from images, maps, cross sections, and other products to provide context to measured data (e. g., cores, well logs, seismic surveys). To enhance such knowledge discovery, we advanced the National Energy Technology Laboratory's (NETL) Subsurface Trend Analysis (STA) workflow with an artificial intelligence (AI) deep learning approach for image embedding. NETL's STA method offers a validated science-based approach of combining geologic systems knowledge, statistical modeling, and datasets to improve predictions of subsurface properties. The STA image embedding tool quickly extracts images from unstructured knowledge products like publications, maps, websites, and presentations; categorically labels the images; and creates a repository for geologic domain postulation. Via a case study on geographic and subsurface literature of the Gulf of Mexico (GOM), results show the STA image embedding tool extracts images and correctly labels them with ~90 to ~95% accuracy.
How to teach about sustainable development in physical education? Examples from the perspectives of certified teachers in Sweden
Authors: Fröberg Andreas , Wiklander Petter , Baena-Morales Salvador , Lundvall Suzanne
Published: December 2023

Introduction

Teachers have a vital role in educating and empowering students to become informed and active agents of change in promoting sustainable development (SD). Little is known what PE teachers teach about SD. The aim of the present study was to explore what certified compulsory school and upper-secondary school physical education (PE) teachers in Sweden teach about SD within their practice.

Methods

An online survey was used to collect data about background information and what the PE teachers had taught about SD in PE. Data from 653 PE teachers was used and the teaching examples were analyzed through thematic analysis.

Results

The analysis resulted in eight themes: Equality, inclusion, and norms, Exploring the local environment, Outdoor education and care of nature, Interdisciplinary projects, Picking waste and recycling, Sustainable bodies, Sustainable lifestyles, health and well-being, and Sustainable use of products and consumption.

Discussion

The findings suggest that PE can have distinct subject-specific contribution to aspects of the SD agenda, but also a role to empower students of how movement, exercise, and sport can be embedded within a broader ecological perspective. Furthermore, the described themes may open for research about what competences that are particularly relevant for PE teachers in the context of SD.
Activation of sperm Toll-like receptor 2 induces hyperactivation to enhance the penetration to mucus and uterine glands: a trigger for the uterine inflammatory cascade in cattle
Authors: Akthar Ihshan , Kim Yejin , Umehara Takashi , Kanno Chihiro , Sasaki Motoki , Marey Mohamed Ali , Yousef Mohamed Samy , Haneda Shingo , Shimada Masayuki , Miyamoto Akio
Published: December 2023

It is known that sperm and seminal plasma (SP) affect uterine immunity. In cattle, artificial insemination enables breeding by depositing frozen and largely diluted sperm with a negligible amount of SP into the uterus. Thus, the present study focused on the impact of frozen-thawed sperm on bovine uterine immunity. We have previously shown that in the bovine uterus, sperm swim smoothly over the luminal epithelium and some sperm interact with uterine glands to induce a weak inflammatory response mainly via the endometrial Toll-like receptor 2 (TLR2) signaling. However, the process by which sperm is encountered in the uterine glands is not completely clear. The present study intended to evaluate the role of sperm-TLR2 in sperm-uterine mucus penetration for reaching the glandular epithelium to induce the uterine immune response. To activate and block sperm-TLR2, they were treated with TLR2 agonist and antagonist, respectively. TLR2 activation enhanced sperm hyperactivation and improved its capacity to penetrate the artificial viscoelastic fluid and estrous-uterine-mucus. In contrast, TLR2-blocked sperm showed completely opposite effects. It is noteworthy, that the TLR2-activated sperm that penetrated the uterine mucus exhibited increased motile activity with hyperactivation. In the sperm-endometrial ex-vivo model, a greater amount of TLR2-activated sperm entered the uterine glands with an immune response, which was seen as the upregulation of mRNA expression for TNFA, IL1B, IL8, PGES, and TLR2 similar to those in control sperm. On the other hand, a lesser amount of TLR2-blocked sperm entered the uterine glands and weakened the sperm-induced increase only in PGES, suggesting that penetration of a certain number of sperm in the uterine gland is necessary enough to trigger the inflammatory response. Altogether, the present findings indicate that activation of sperm-TLR2 promotes their hyperactivation and mucus penetration with greater motility, allowing them to enter into the uterine glands more. This further suggests that the hyperactivated sperm contributes to triggering the pro-inflammatory cascade partly via TLR2 in the uterus.
Magmatism at an ultra-slow spreading rift: high-resolution geomorphological studies of a Red Sea Rift segment in Hadarba Deep
Authors: Le Saout Morgane , van der Zwan Froukje M. , Schiebener Cora K. , Augustin Nico
Published: December 2023

The mid-ocean rift in the Red Sea is one of the youngest rifting systems on Earth. Only recently, state-of-the-art methods and modern deep-sea instruments have been used to explore this young and unique volcanic system. During the first autonomous underwater vehicle surveys of the Red Sea Rift in Spring 2022, we collected multibeam bathymetry, backscatter, sub-bottom profiler data, and water column data over a 9 km long ridge segment in the Hadarba Deep between 22.49°N and 22.56°N to investigate the volcano-tectonic processes of this ultra-slow spreading segment (12 mm/year spreading rate). The high-resolution hydroacoustic data was used to (1) delineate and quantify the geometry of tectonic structures and individual lava flows, (2) define lava flow morphology and eruption style, (3) estimate relative ages of flows and features, and (4) retrace the evolution of the volcanic activity. In addition, the geochemistry of several young lava flows provides information on the relation between the different magma that supply these eruptions. About 90 eruptive units with variable sedimentary cover have been identified within the 43 km2mapped region. The oldest lava flows are buried under 3 to 4.2 m of sediment, indicating ages of up to ~30 ka based on average sedimentation rate estimates (~14 cm/ka), while the youngest eruptions are covered by<10 cm of sediment, and are thus younger than 700 years. Three volcanic phases have been identified based on changes in flow morphology and distribution, and tectonic pattern. All three axial phases have an average eruptive frequency of ~100-250 years. The segment displays an overall low tectonic extension (<10% of the total extension) and low vertical offset. Our geomorphological maps, analyses, and statistics reveal a moderately faulted, ultra-slow spreading MOR segment in the Red Sea with a surprisingly large amount of magmatic extension, implying that the segment has been underlined by a large magma supply for at least 15 ka. All these observations provide valuable implications for the formation history of the Red Sea Rift and the formation of ultra-slow spreading crust.
Solar radiation stimulates release of semi-labile dissolved organic matter from microplastics
Authors: Wang Jun , Cai Ruanhong
Published: December 2023

Microplastics can release dissolved organic matter (DOM) into seawater under solar radiation exposure. However, the molecular composition and bioavailability of this DOM remain to be investigated. Here, two popular microplastics, low-density polyethylene (LDPE) and polystyrene (PS), were exposed to solar radiation in an artificial seawater for 10 days. The solar-induced LDPE-DOM and PS-DOM were molecularly characterized using ultra-high-resolution mass spectrometry, and were further incubated in a coastal microbial assemblage to examine their bioavailability. Results showed that solar radiation stimulated release of DOM from the microplastics. Dissolved organic carbon concentration analysis indicated that approximately 19.03 µg C L–1 and 3.85 µg C L–1 were released from each gram of LDPE and PS per day, respectively. Molecular composition analysis showed that both the LDPE-DOM and PS-DOM comprised a proportion of nitrogen- and sulfur-bearing molecules, and that the LDPE-DOM molecules were associated with lower molecular abundance and values of double-equivalent-bond and aromatic-index, but higher average hydrogen-to-carbon ratio than that in the PS-DOM. In addition, a proportion of the assigned formulas in LDPE-DOM (22.3%) and PS-DOM (55.8%) could be found in a coastal-DOM sample, suggesting their potential contribution to coastal DOM pool. The further incubation experiment showed that nearly 18.7% of LDPE-DOM and 9.5% of PS-DOM were utilized or transformed within 30 days. Still, a fraction of the solar-induced LDPE-DOM and PS-DOM resisted rapid microbial utilization, remained as semi-labile DOM. These results underlined unaccounted consequences of microplastic-derived DOM in coastal DOM pool.
Freshwater resources around the reclaimed new land on the Eastern Hengsha Shoal in the Changjiang estuary
Authors: Wu Tong , Zhu Jianrong , Ma Rui , Qiu Wei , Yuan Rui
Published: December 2023

Reclaiming estuarine tidal flats is practiced to meet the growing demand for land. The reclaimed new land (RNL) on the Eastern Hengsha Shoal in the Changjiang Estuary is for agricultural production in Shanghai. Whether freshwater resources exist around the RNL has become a critical issue \caused by estuarine saltwater intrusion. In this study, the spatiotemporal saltwater intrusion and freshwater distribution around the RNL at different guarantee rates of river discharge using the improved 3D numerical model ECOM-si was investigated. Three water intakes on Hengsha Island and the northern edge of the RNL were set. The results showed that at different guarantee rates of river discharge during the dry season, there is a relatively sufficient suitable water intake time in the upper RNL. Nevertheless, there is a very limited suitable water intake time in the middle and lower RNL as the guarantee rate increases, especially in January and February. During the flood season, three water intakes can ensure sufficient suitable water intake time. The salinity around the RNL significantly increases under the combined effect of 50% and 95% guarantee rates with a 12 m/s northerly wind in February, resulting in a significant threat to the three water intakes. At the 50% guarantee rate, the suitable water intake times in February are 14.86, 9.78 and 3.53 days at three water intakes, respectively. At the 95% guarantee rate, the suitable water intake time in February is only 0.31 days in the upper RNL, and there is no freshwater in the middle and lower RNL. Overall, there is sufficient freshwater in the flood season and limited freshwater in the dry season for agriculture along the northern edge of the RNL.
In-pile performance of end plug with different structure for SiC cladding
Authors: Yue Huifang , Liu Shichao , Xin Yong , Li Yuanming , Chen Ping , Qiu Xi
Published: December 2023

The in-pile performance of SiC cladding with different kinds of end plug were studied. The effect of end plug structure on the mechanical performance of cladding was investigated. The results indicated that obvious stress concentration appeared on the corner between the cladding and end plug for all kinds of cladding. The cladding with a scarf end plug possessed the lowest hoop, axial, and radial stress, which ensured the structural integrity of the fuel element. The cladding with a butted lap end plug suffered rather large axial stress, the maximum valve of which was up to 450 MPa at the end of life, which was higher than the yield strength of SiC ceramics. A scarf end plug can meet the requirements of the cladding, which may be used as an end plug for fuel rods in the future.
A qualitative examination on the implementation of participatory “A”rt-based activity on “Health” of older community-dwellers: what worked for the Singapore A-Health Intervention?
Authors: Ma Stephanie Hilary Xinyi , Tan Michael Koon Boon , Goh Shannon Shuet Ning , Yeo Gabriellia , Teng Alicia , Yang Yilin , Galéry Kévin , Beauchet Olivier , Ho Andy Hau Yan
Published: December 2023

Introduction

Art and museum-based interventions are gaining increasing recognition for their potential as low-risk activities for older adults, offering numerous physical, cognitive, and emotional benefits. However, there remains a dearth of knowledge regarding the science of implementation as well as the factors and processes that contribute to their effectiveness from the perspectives of intervention participants.

Methods

The current research draws on the qualitative evaluation data obtained from a larger mixed-method randomized control trial that evaluated a standardized Participatory “A”rt-Based Activity On “Health” of Older Community-Dwellers—the Singapore A-Health Intervention. Adopting a participatory action research approach, the primary objective is to critically examine the lived experiences and health impact of the Singapore A-Health Intervention with a secondary objective to uncover strategies for optimized implementation outcomes. All 56 participants who completed the intervention filled out a program evaluation survey and a nested sample of 30 participants completed a series of acceptability focus groups.

Results

Descriptive analyses of the program evaluation survey data revealed that 96.2% of participants were satisfied with the overall experience of the Singapore A-Health intervention (M = 9.00, SD = 1.76), reported that the intervention positively impacted their quality of life (M = 8.90, SD = 1.43), and social wellbeing (M = 8.92, SD = 1.43). Thematic analysis with a grounded theory approach on the qualitative focus group data revealed three interrelated themes detailing how the Singapore A-Health Intervention contributed to positive health and wellbeing outcomes (1. A-Health Experience, 2. Wellbeing Outcomes, 3. Enabling Factors) and nine subthemes (1a. Intellectual Stimulation, 1b. Positive Stress, 1c. Peer Interaction, 2a. Interpersonal Bonds, 2b. Personal Growth, 2c. Mindful Living, 3a. Integrated Support, 3b. Session Design, 3c. Mode of Engagement).

Discussion

This investigation provides important insights to the Singapore A-Health intervention’s effectiveness for enhancing wellbeing among older adults, as well as the factors that enable successful program implementation. These findings offer a culturally unique perspective on the benefits of art and museum interventions, while underscoring the imperative need for strong partnership and collaborations among community stakeholders in supporting the health and wellbeing of ageing populations.
Comparing technology and regulatory landscape of probiotics as food, dietary supplements and live biotherapeutics
Authors: Spacova Irina , Binda Sylvie , ter Haar Jessica Anne , Henoud Solange , Legrain-Raspaud Sophie , Dekker James , Espadaler-Mazo Jordi , Langella Philippe , Martín Rebeca , Pane Marco , Ouwehand Arthur C.
Published: December 2023

Application of beneficial microorganisms as probiotics targets a broad range of intended uses, from maintaining health and supporting normal bodily functions to curing and preventing diseases. Currently, three main regulatory fields of probiotic products can be defined depending on their intended use: the more similar probiotic foods and probiotic dietary supplements, and live biotherapeutic products. However, it is not always straightforward to classify a probiotic product into one of these categories. The regulatory nuances of developing, manufacturing, investigating and applying each category of probiotic products are not universal, and not always apparent to those unfamiliar with the various global probiotic regulatory guidelines. Various global markets can be significantly different regarding legislation, possible claims, market value and quality requirements for the development and commercialization of probiotic products. Furthermore, different probiotic product categories are also linked with variable costs at different stages of product development. This review outlines the current landscape comparing probiotic foods, probiotic dietary supplements, and live biotherapeutics as probiotic products from a regulatory lens, focusing on product development, manufacturing and production, and clinical research agenda. The aim is to inform and promote a better understanding among stakeholders by outlining the expectations and performance for each probiotic product category, depending on their intended use and targeted geographical region.
Ecophysiological performance of terrestrial diatoms isolated from biocrusts of coastal sand dunes
Authors: Glaser Karin , Kammann Sandra , Plag Niklas , Dressler Mirko
Published: December 2023

Terrestrial diatoms are widespread in a large variety of habitats and are regularly recorded in biocrusts. Although diatoms have long been known to live in terrestrial habitats, only a few studies have focused on their diversity of ecophysiology. Here we present a study on the ecophysiological performance of five terrestrial diatom cultures from biocrusts, which were collected in sand dunes of the German coast of the Baltic Sea. The sampling sites were selected along a gradient of human impacts on the dunes. The richness of diatom species, roughly estimated from permanent slides, was around 30 species per sampling site. The species abundance was calculated in the same way revealing a high proportion of broken diatom frustules. All diatom cultures established in the laboratory showed no photoinhibition and high oxygen production along a light gradient. The desiccation tolerance differed among the strains, with high recovery observed for Hantzschia abundans and Achnanthes coarctata and low to no recovery for Pinnularia borealis and Pinnularia intermedia. The maximum growth rate for most strains was between 25 and 30°C. These temperatures can be easily reached in their natural environments. Nevertheless, during short-term exposure to elevated temperatures, oxygen production was recorded up to 35°C. Interestingly, two of five diatom cultures (Hantzschia abundans and Pinnularia borealis) produced mycosporine-like amino acids. These UV-protective substances are known from marine diatoms but not previously reported in terrestrial diatoms.
Copper and cuproptosis: new therapeutic approaches for Alzheimer’s disease
Authors: Li Xiao , Chen Xinwang , Gao Xiyan
Published: December 2023

Copper (Cu) plays a crucial role as a trace element in various physiological processes in humans. Nonetheless, free copper ions accumulate in the brain over time, resulting in a range of pathological changes. Compelling evidence indicates that excessive free copper deposition contributes to cognitive decline in individuals with Alzheimer’s disease (AD). Free copper levels in the serum and brain of AD patients are notably elevated, leading to reduced antioxidant defenses and mitochondrial dysfunction. Moreover, free copper accumulation triggers a specific form of cell death, namely copper-dependent cell death (cuproptosis). This article aimed to review the correlation between copper dysregulation and the pathogenesis of AD, along with the primary pathways regulating copper homoeostasis and copper-induced death in AD. Additionally, the efficacy and safety of natural and synthetic agents, including copper chelators, lipid peroxidation inhibitors, and antioxidants, were examined. These treatments can restore copper equilibrium and prevent copper-induced cell death in AD cases. Another aim of this review was to highlight the significance of copper dysregulation and promote the development of pharmaceutical interventions to address it.
Cross-species conservation in the regulation of parvalbumin by perineuronal nets
Authors: Wang Angela S. , Wan Xinghaoyun , Storch Daria-Salina , Li Vivian Y. , Cornez Gilles , Balthazart Jacques , Cisneros-Franco J. Miguel , de Villers-Sidani Etienne , Sakata Jon T.
Published: December 2023

Parvalbumin (PV) neurons play an integral role in regulating neural dynamics and plasticity. Therefore, understanding the factors that regulate PV expression is important for revealing modulators of brain function. While the contribution of PV neurons to neural processes has been studied in mammals, relatively little is known about PV function in non-mammalian species, and discerning similarities in the regulation of PV across species can provide insight into evolutionary conservation in the role of PV neurons. Here we investigated factors that affect the abundance of PV in PV neurons in sensory and motor circuits of songbirds and rodents. In particular, we examined the degree to which perineuronal nets (PNNs), extracellular matrices that preferentially surround PV neurons, modulate PV abundance as well as how the relationship between PV and PNN expression differs across brain areas and species and changes over development. We generally found that cortical PV neurons that are surrounded by PNNs (PV+PNN neurons) are more enriched with PV than PV neurons without PNNs (PV-PNN neurons) across both rodents and songbirds. Interestingly, the relationship between PV and PNN expression in the vocal portion of the basal ganglia of songbirds (Area X) differed from that in other areas, with PV+PNN neurons having lower PV expression compared to PV-PNN neurons. These relationships remained consistent across development in vocal motor circuits of the songbird brain. Finally, we discovered a causal contribution of PNNs to PV expression in songbirds because degradation of PNNs led to a diminution of PV expression in PV neurons. These findings reveal a conserved relationship between PV and PNN expression in sensory and motor cortices and across songbirds and rodents and suggest that PV neurons could modulate plasticity and neural dynamics in similar ways across songbirds and rodents.
Research on prognostic risk assessment model for acute ischemic stroke based on imaging and multidimensional data
Authors: Liang Jiabin , Feng Jie , Lin Zhijie , Wei Jinbo , Luo Xun , Wang Qing Mei , He Bingjie , Chen Hanwei , Ye Yufeng
Published: December 2023

Accurately assessing the prognostic outcomes of patients with acute ischemic stroke and adjusting treatment plans in a timely manner for those with poor prognosis is crucial for intervening in modifiable risk factors. However, there is still controversy regarding the correlation between imaging-based predictions of complications in acute ischemic stroke. To address this, we developed a cross-modal attention module for integrating multidimensional data, including clinical information, imaging features, treatment plans, prognosis, and complications, to achieve complementary advantages. The fused features preserve magnetic resonance imaging (MRI) characteristics while supplementing clinical relevant information, providing a more comprehensive and informative basis for clinical diagnosis and treatment. The proposed framework based on multidimensional data for activity of daily living (ADL) scoring in patients with acute ischemic stroke demonstrates higher accuracy compared to other state-of-the-art network models, and ablation experiments confirm the effectiveness of each module in the framework.
Investigating functional brain connectivity patterns associated with two hypnotic states
Authors: de Matos Nuno M. P. , Staempfli Philipp , Seifritz Erich , Preller Katrin , Bruegger Mike
Published: December 2023

While there’s been clinical success and growing research interest in hypnosis, neurobiological underpinnings induced by hypnosis remain unclear. In this fMRI study (which is part of a larger hypnosis project) with 50 hypnosis-experienced participants, we analyzed neural and physiological responses during two hypnosis states, comparing them to non-hypnotic control conditions and to each other. An unbiased whole-brain analysis (multi-voxel- pattern analysis, MVPA), pinpointed key neural hubs in parieto-occipital-temporal areas, cuneal/precuneal and occipital cortices, lingual gyri, and the occipital pole. Comparing directly both hypnotic states revealed depth-dependent connectivity changes, notably in left superior temporal/supramarginal gyri, cuneus, planum temporale, and lingual gyri. Multi-voxel- pattern analysis (MVPA) based seeds were implemented in a seed-to-voxel analysis unveiling region-specific increases and decreases in functional connectivity patterns. Physiologically, the respiration rate significantly slowed during hypnosis. Summarized, these findings foster fresh insights into hypnosis-induced functional connectivity changes and illuminate further knowledge related with the neurobiology of altered consciousness.
Multiomics insights on the onset, progression, and metastatic evolution of breast cancer
Authors: Alvarez-Frutos Lucia , Barriuso Daniel , Duran Mercedes , Infante Mar , Kroemer Guido , Palacios-Ramirez Roberto , Senovilla Laura
Published: December 2023

Breast cancer is the most common malignant neoplasm in women. Despite progress to date, 700,000 women worldwide died of this disease in 2020. Apparently, the prognostic markers currently used in the clinic are not sufficient to determine the most appropriate treatment. For this reason, great efforts have been made in recent years to identify new molecular biomarkers that will allow more precise and personalized therapeutic decisions in both primary and recurrent breast cancers. These molecular biomarkers include genetic and post-transcriptional alterations, changes in protein expression, as well as metabolic, immunological or microbial changes identified by multiple omics technologies (e.g., genomics, epigenomics, transcriptomics, proteomics, glycomics, metabolomics, lipidomics, immunomics and microbiomics). This review summarizes studies based on omics analysis that have identified new biomarkers for diagnosis, patient stratification, differentiation between stages of tumor development (initiation, progression, and metastasis/recurrence), and their relevance for treatment selection. Furthermore, this review highlights the importance of clinical trials based on multiomics studies and the need to advance in this direction in order to establish personalized therapies and prolong disease-free survival of these patients in the future.
Clinical and molecular profiling of EGFR-mutant lung adenocarcinomas transformation to small cell lung cancer during TKI treatment
Authors: Chen Yongxia , He Mengye , Dai Zhengfeng , Wang Yina , Chen Jing , Wang Xiaoting , Dong Xiao , Huang Jianfei , Ruan Jian , Zhang Xiaochen , Shen Peng , Jia Yunlu
Published: December 2023

Introduction

Small cell lung cancer (SCLC) transformation serves as a significant mechanism of resistance to tyrosine kinase inhibitors (TKIs) in advanced non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) mutations. To address this clinical challenge, we conducted a retrospective analysis at Zhejiang University School of Medicine, the First Affiliated Hospital, focusing on patients with EGFR sensitizing mutations.

Methods

A total of 1012 cases were included in this retrospective analysis. The cohort primarily consisted of patients with EGFR sensitizing mutations. Biopsy-confirmed small cell transformation was observed in seven patients, accounting for 0.7% of the cases. All patients in this subset were initially diagnosed with stage IV adenocarcinoma (ADC), with four cases classified as poorly differentiated and three as moderately to poorly differentiated ADC. EGFR exon 19 deletions were identified in five of these cases. Next-generation sequencing (NGS) was performed on seven cases, revealing mutations in the tumor protein p53 (TP53) gene in four cases and loss of the retinoblastoma1 (RB1) gene in three cases.

Results

The median duration from the initial diagnosis to small cell transformation was 35.9 months (interquartile range: 12.1–84 months). Following small cell transformation during EGFR inhibition, all patients received etoposide/platinum-based treatment, leading to a median progression-free survival (PFS) of 4.7 months (interquartile range: 2.7–10.1 months). Notably, most patients in this series had poorly differentiated adenocarcinomas at the outset. TP53 mutations and RB1 loss were common genetic alterations observed in patients with small cell transformation in this cohort.

Discussion

The findings underscore the clinical significance of SCLC transformation as a resistance mechanism to EGFR TKIs in NSCLC with EGFR mutations. The observed genetic alterations, including TP53 mutations and RB1 loss, suggest potential associations with the transformation process and warrant further investigation. Understanding the genetic landscape and clinical outcomes in patients experiencing small cell transformation can contribute to improved strategies for managing resistance in EGFR-mutant NSCLC.
Gender and authorship of publications from Pediatric Acute Lung Injury and Sepsis Investigators (PALISI)
Authors: Jeyapalan Asumthia S. , Brown Stephanie R. , Gaspers Mary G. , Haliani Brittany , Kudchadkar Sapna R. , Rowan Courtney M. , Gertz Shira J.
Published: December 2023

Introduction

Pediatric Acute Lung Injury and Sepsis Investigators (PALISI) is a network fostering clinical research to optimize care for critically ill children. We aim to examine the efforts of the PALISI Network to increase gender parity in research, as evidenced by authorship.

Methods

The first and senior authors of all published PALISI articles from 2002 to 2021 were analyzed for gender of presentation. Funding sources, impact factors, professional roles, and location were extracted.

Results

We identified 303 articles, 61 published from 2002 to 2011, and 242 from 2012 to 2021. There were 302 first authors, representing 188 unique individuals, and 283 senior authors, representing 119 unique individuals. Over half (55.6%, n = 168) of the first authors were women. More women were first authors from 2012 to 2021 (n = 145, 60.2%) as compared to the years 2002–2011 [37.7%, n = 23, OR = 2.50 (95% CI: 1.40, 4.45, p = 0.002)]. Senior authors were 36.0% (n = 102) women, with no change over time. Women senior authors had a higher proportion of women first authors (67.7% vs. 32.4%, p = 0.017). No gender differences were noted based on article type or impact factor. The majority of authors came from institutions in the United States. Women had comparatively more NIH and CDC funding but received less funding from foundations and AHRQ.

Discussion

In PALISI publications, first authorship by women has increased over time, such that it now exceeds both the proportion of women pediatric intensivists and women first authors in critical care publications. Senior authorship by women has been stagnant. A multifactorial approach by individuals, institutions, networks, and journals is needed to bring senior women authors to parity.
Metabolic reprogramming in the tumor microenvironment: unleashing T cell stemness for enhanced cancer immunotherapy
Authors: Liu Youhan , Wang Tao , Ma Wen , Jia Zixuan , Wang Qinglu , Zhang Maoling , Luo Ying , Sun Hongmei
Published: December 2023

T cells play a pivotal role in the immune system by distinguishing between various harmful pathogens and cancerous cells within the human body and initiating an immune response. Within the tumor microenvironment (TME), immune effector T cells encounter both immunosuppressive cells and factors that hinder their functionality. Additionally, they endure robust and persistent antigenic stimulation, often leading to exhaustion and apoptosis. However, the stemness of T cells, characterized by their ability to survive and self-renew over extended periods, represents a primary target in immune checkpoint therapies such as anti-PD-1 therapy. T cell stemness encompasses specific memory T cell subsets and progenitor-exhausted T cells with stem cell-like properties. Therefore, understanding the impact of the TME on T cell stemness, including factors like K+, lactate, and H+, holds significant importance and can facilitate the mitigation of terminal T-cell depletion, the identification of potential resilient biomarkers or therapeutic targets resistant to immune checkpoint therapies, and ultimately lead to sustained anti-tumor effects. Thus, it offers a novel perspective for advancing tumor immunotherapy.
A systematic review on the effects of exercise on gut microbial diversity, taxonomic composition, and microbial metabolites: identifying research gaps and future directions
Authors: Cullen John M. A. , Shahzad Shahim , Dhillon Jaapna
Published: December 2023

The gut microbiome, hosting a diverse microbial community, plays a pivotal role in metabolism, immunity, and digestion. While the potential of exercise to influence this microbiome has been increasingly recognized, findings remain incongruous. This systematic review examined the effects of exercise on the gut microbiome of human and animal models. Databases (i.e., PubMed, Cochrane Library, Scopus, and Web of Science) were searched up to June 2022. Thirty-two exercise studies, i.e., 19 human studies, and 13 animal studies with a minimum of two groups that discussed microbiome outcomes, such as diversity, taxonomic composition, or microbial metabolites, over the intervention period, were included in the systematic review (PROSPERO registration numbers for human review: CRD42023394223). Results indicated that over 50% of studies found no significant exercise effect on human microbial diversity. When evident, exercise often augmented the Shannon index, reflecting enhanced microbial richness and evenness, irrespective of disease status. Changes in beta-diversity metrics were also documented with exercise but without clear directionality. A larger percentage of animal studies demonstrated shifts in diversity compared to human studies, but without any distinct patterns, mainly due to the varied effects of predominantly aerobic exercise on diversity metrics. In terms of taxonomic composition, in humans, exercise usually led to a decrease in the Firmicutes/Bacteroidetes ratio, and consistent increases with Bacteroides and Roseburia genera. In animal models, Coprococcus, another short chain fatty acid (SCFA) producer, consistently rose with exercise. Generally, SCFA producers were found to increase with exercise in animal models. With regard to metabolites, SCFAs emerged as the most frequently measured metabolite. However, due to limited human and animal studies examining exercise effects on microbial-produced metabolites, including SCFAs, clear patterns did not emerge. The overall risk of bias was deemed neutral. In conclusion, this comprehensive systematic review underscores that exercise can potentially impact the gut microbiome with indications of changes in taxonomic composition. The significant variability in study designs and intervention protocols demands more standardized methodologies and robust statistical models. A nuanced understanding of the exercise-microbiome relationship could guide individualized exercise programs to optimize health.

Systematic Review Registration:https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=394223, identifier CRD42023394223.
Membrane-anchored calpains – hidden regulators of growth and development beyond plants?
Authors: Šafranek Martin , Shumbusho Alain , Johansen Wenche , Šarkanová Júlia , Voško Stanislav , Bokor Boris , Jásik Ján , Demko Viktor
Published: December 2023

Calpains are modulatory proteases that modify diverse cellular substrates and play essential roles in eukaryots. The best studied are animal cytosolic calpains. Here, we focus on enigmatic membrane-anchored calpains, their structural and functional features as well as phylogenetic distribution. Based on domain composition, we identified four types of membrane-anchored calpains. Type 1 and 2 show broad phylogenetic distribution among unicellular protists and streptophytes suggesting their ancient evolutionary origin. Type 3 and 4 diversified early and are present in brown algae and oomycetes. The plant DEK1 protein is the only representative of membrane-anchored calpains that has been functionally studied. Here, we present up to date knowledge about its structural features, putative regulation, posttranslational modifications, and biological role. Finally, we discuss potential model organisms and available tools for functional studies of membrane-anchored calpains with yet unknown biological role. Mechanistic understanding of membrane-anchored calpains may provide important insights into fundamental principles of cell polarization, cell fate control, and morphogenesis beyond plants.
Interaction with the entomopathogenic fungus Beauveria bassiana influences tomato phenome and promotes resistance to Botrytis cinerea infection
Authors: Russo Assunta , Winkler Jana Barbro , Ghirardo Andrea , Monti Maurilia M. , Pollastri Susanna , Ruocco Michelina , Schnitzler Jörg-Peter , Loreto Francesco
Published: December 2023

Plants are central to complex networks of multitrophic interactions. Increasing evidence suggests that beneficial microorganisms (BMs) may be used as plant biostimulants and pest biocontrol agents. We investigated whether tomato (Solanum lycopersicum) plants are thoroughly colonized by the endophytic and entomopathogenic fungus Beauveria bassiana, and how such colonization affects physiological parameters and the phenotype of plants grown under unstressed conditions or exposed to the pathogenic fungus Botrytis cinerea. As a positive control, a strain of the well-known biocontrol agent and growth inducer Trichoderma afroharzianum was used. As multitrophic interactions are often driven by (or have consequences on) volatile organic compounds (VOCs) released by plants constitutively or after induction by abiotic or biotic stresses, VOC emissions were also studied. Both B. bassiana and T. afroharzianum induced a significant but transient (one to two-day-long) reduction of stomatal conductance, which may indicate rapid activation of defensive (rejection) responses, but also limited photosynthesis. At later stages, our results demonstrated a successful and complete plant colonization by B. bassiana, which induced higher photosynthesis and lower respiration rates, improved growth of roots, stems, leaves, earlier flowering, higher number of fruits and yield in tomato plants. Beauveria bassiana also helped tomato plants fight B. cinerea, whose symptoms in leaves were almost entirely relieved with respect to control plants. Less VOCs were emitted when plants were colonized by B. bassiana or infected by B. cinerea, alone or in combination, suggesting no activation of VOC-dependent defensive mechanisms in response to both fungi.
Individual characteristics on multicultural team performance: does the role played by leaders and team members matter?
Authors: Guzmán-Rodríguez Laura Esmeralda , Arizkuren-Eleta Amaia , Agarwala Tanuja , Bornay-Barrachina Mar
Published: December 2023

The main purpose of this study was to analyze the impact of individual characteristics of cultural sensitivity, adaptability, cohesion, and cultural diversity on the multicultural team performance. Also, we analyzed the moderating effect of being a team member or a team leader on the relationships mentioned above. To test out hipotheses, data were collected from 415 members of multicultural teams specifically, from 304 team members and 111 leaders. The findings provided evidence to support a positive relationship between cultural sensitivity, adaptability, cohesion, and team performance. Cultural diversity did not show a significant impact on team performance. The study also showed that the leaders and members had different perceptions about the factors that influence team performance. For instance, team members consider that cohesion influences team performance, while leaders consider adaptability as the key factor to achieve performance. Main implications from findings are discussed.