bluuebunny/crossref_metadata_2025 huggingface dataset:
A phenomenology and epistemology of large language models: transparency, trust, and trustworthiness
Authors: Heersmink Richard , de Rooij Barend , Clavel Vázquez María Jimena , Colombo Matteo
Published: June 2024

This paper analyses the phenomenology and epistemology of chatbots such as ChatGPT and Bard. The computational architecture underpinning these chatbots are large language models (LLMs), which are generative artificial intelligence (AI) systems trained on a massive dataset of text extracted from the Web. We conceptualise these LLMs as multifunctional computational cognitive artifacts, used for various cognitive tasks such as translating, summarizing, answering questions, information-seeking, and much more. Phenomenologically, LLMs can be experienced as a “quasi-other”; when that happens, users anthropomorphise them. For most users, current LLMs are black boxes, i.e., for the most part, they lack data transparency and algorithmic transparency. They can, however, be phenomenologically and informationally transparent, in which case there is an interactional flow. Anthropomorphising and interactional flow can, in some users, create an attitude of (unwarranted) trust towards the output LLMs generate. We conclude this paper by drawing on the epistemology of trust and testimony to examine the epistemic implications of these dimensions. Whilst LLMs generally generate accurate responses, we observe two epistemic pitfalls. Ideally, users should be able to match the level of trust that they place in LLMs to the degree that LLMs are trustworthy. However, both their data and algorithmic opacity and their phenomenological and informational transparency can make it difficult for users to calibrate their trust correctly. The effects of these limitations are twofold: users may adopt unwarranted attitudes of trust towards the outputs of LLMs (which is particularly problematic when LLMs hallucinate), and the trustworthiness of LLMs may be undermined.
Brain perfusion SPECT in dementia: what radiologists should know
Authors: Imokawa Tomoki , Yokoyama Kota , Takahashi Kanae , Oyama Jun , Tsuchiya Junichi , Sanjo Nobuo , Tateishi Ukihide
Published: June 2024

The findings of brain perfusion single-photon emission computed tomography (SPECT), which detects abnormalities often before changes manifest in morphological imaging, mainly reflect neurodegeneration and contribute to dementia evaluation. A major shift is about to occur in dementia practice to the approach of diagnosing based on biomarkers and treating with disease-modifying drugs. Accordingly, brain perfusion SPECT will be required to serve as a biomarker of neurodegeneration. Hypoperfusion in Alzheimer’s disease (AD) is typically seen in the posterior cingulate cortex and precuneus early in the disease, followed by the temporoparietal cortices. On the other hand, atypical presentations of AD such as the posterior variant, logopenic variant, frontal variant, and corticobasal syndrome exhibit hypoperfusion in areas related to symptoms. Additionally, hypoperfusion especially in the precuneus and parietal association cortex can serve as a predictor of progression from mild cognitive impairment to AD. In dementia with Lewy bodies (DLB), the differentiating feature is the presence of hypoperfusion in the occipital lobes in addition to that observed in AD. Hypoperfusion of the occipital lobe is not a remarkable finding, as it is assumed to reflect functional loss due to impairment of the cholinergic and dopaminergic systems rather than degeneration per se. Moreover, the cingulate island sign reflects the degree of AD pathology comorbid in DLB. Frontotemporal dementia is characterized by regional hypoperfusion according to the three clinical types, and the background pathology is diverse. Idiopathic normal pressure hydrocephalus shows apparent hypoperfusion around the Sylvian fissure and corpus callosum and apparent hyperperfusion in high-convexity areas. The cortex or striatum with diffusion restriction on magnetic resonance imaging in prion diseases reflects spongiform degeneration and brain perfusion SPECT reveals hypoperfusion in the same areas. Brain perfusion SPECT findings in dementia should be carefully interpreted considering background pathology.
Targeting IL-11R/EZH2 signaling axis as a therapeutic strategy for osteosarcoma lung metastases
Authors: Devarajan Eswaran , Davis R. Eric , Beird Hannah C. , Wang Wei-Lien , Jensen V. Behrana , Jayakumar Arumugam , Leung Cheuk Hong , Lin Heather Y. , Wu Chia-Chin , Ihezie Stephanie A. , Tsai Jen-Wei , Futreal P. Andrew , Lewis Valerae O.
Published: June 2024

Lung metastases are the primary cause of death for osteosarcoma (OS) patients. We recently validated interleukin-11 receptor α (IL-11Rα) as a molecular target for the inhibition of OS lung metastases. Since there is no clinically approved antibody against this receptor, we sought to identify downstream targets that mediate the effects of IL-11Rα signaling. We used shRNA to deplete IL-11Rα from OS cells; as a complementary approach, we added IL-11 exogenously to OS cells. The resulting changes in gene expression identified EZH2 as a downstream candidate. This was confirmed by knockdown of IL-11Rα in OS cells, which led to increased expression of genes repressed by histone methyltransferase EZH2, including members of the WNT pathway, a known target pathway of EZH2. Exogenous IL-11 increased the global levels of histone H3 lysine 27 trimethylation, evidence of EZH2 activation. Treatment with the EZH2 inhibitor GSK126 significantly reduced in vitro proliferation and increased cell-cycle arrest and apoptosis, which were partially mediated through the WNT pathway. In vivo, treatment of an orthotopic nude mouse model of OS with GSK126 inhibited lung metastatic growth and prolonged survival. In addition, significantly shorter recurrence-free survival was seen in OS patients with high levels of EZH2 in their primary tumors (P < .05). This suggests that IL-11Rα promotes OS lung metastasis via activation of EZH2. Thus, blocking EZH2 activity may be an effective strategy for inhibiting OS lung metastasis and improving prognosis.
Multi-parameter modeling for prediction of gas–water production in tight sandstone reservoirs
Authors: Mo Chaoping , Zhang Guangdong , Tang Yong , Zeng Difeng
Published: June 2024

Tight sandstone reservoirs are significant sources of natural gas reserves. As traditional reserves become increasingly scarce and costly, optimizing the development of these reservoirs becomes crucial. This study introduces a novel two-phase gas–water flow model for single wells, incorporating both Darcy and non-Darcy flow equations. These equations are derived from mass conservation and momentum principles for both gas and water phases. Using data from a real tight gas well, our model, which includes stress-sensitive phases for gas and water, outperforms traditional Darcy flow models. Specifically, the average relative deviations in daily production rates were 0.1815% for gas and − 0.2677% for water, which are significantly smaller compared to traditional Darcy flow models. Further application of the non-Darcy flow model reveals strategies to enhance well performance. For example, mitigating liquid lock damage within a 2 m radius near the well could restore the permeability from 0.045 to 0.143 mD, thereby tripling the daily gas production. This non-Darcy flow model is easy to implement and shows significant potential in forecasting production yields in tight sandstone reservoirs, highlighting its importance in the petroleum and natural gas industry.
Antitumor activity of afatinib in EGFR T790M-negative human oral cancer therapeutically targets mTOR/Mcl-1 signaling axis
Authors: Han Jung-Min , Oh Kyu-Young , Choi Su-Jung , Lee Won-Woo , Jin Bo-Hwan , Kim Ji-Hoon , Yu Hyun-Ju , Kim Ryan Jin Young , Yoon Hye-Jung , Lee Jae-Il , Hong Seong-Doo , Cho Sung-Dae
Published: June 2024

Purpose

This study investigates the role and effectiveness of the epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) in oral cancer, focusing on the clinical relevance of EGFR and myeloid cell leukemia-1 (Mcl-1) in head and neck cancers (HNCs). It aims to explore the molecular mechanism of afatinib, a TKI, in treating human oral cancer.

Methods

We conducted an in silico analysis using databases like The Cancer Genome Atlas, Gene Expression Omnibus, and Clinical Proteomic Tumor Analysis Consortium, along with immunohistochemistry staining, to study EGFR and Mcl-1 expression in HNCs. For investigating afatinib’s anticancer properties, we performed various in vitro and in vivo analyses, including trypan blue exclusion assay, Western blotting, 4′-6-diamidino-2-phenylindole staining, flow cytometry, quantitative real-time PCR, Mitochondrial membrane potential assay, overexpression vector construction, transient transfection, and a tumor xenograft model.

Results

Higher expression levels of EGFR and Mcl-1 were observed in HNC patient tissues compared to normal tissues, with their co-expression significantly linked to poor prognosis. There was a strong correlation between EGFR and Mcl-1 expressions in oral cancer patients. Afatinib treatment induced apoptosis and suppressed Mcl-1 in oral cancer cell lines without the EGFR T790M mutation. The mechanism of afatinib-induced apoptosis involved the EGFR/mTOR/Mcl-1 axis, as shown by the effects of mTOR activator MHY1485 and inhibitor rapamycin. Afatinib also increased Bim expression, mitochondrial membrane permeabilization, and cytochrome c release. It significantly lowered tumor volume without affecting body, liver, and kidney weights.

Conclusion

Afatinib, targeting the EGFR/mTOR/Mcl-1 axis, shows promise as a therapeutic strategy for oral cancer, especially in patients with high EGFR and Mcl-1 expressions.
A Comprehensive Students-as-Teachers Program: Developing and Empowering Future Medical Educators
Authors: Noramly Selina , Waggoner-Fountain Linda , Keeley Meg , Barry Deborah
Published: June 2024

We describe the development of two formats of a Students as Teachers (SaT) program that was designed to train fourth-year medical students as near-peer teachers in the pre-clinical classroom. This program has served 191 students since its inception in 2017 through a 2-week credit bearing elective or an evening workshop series. We describe key elements of the courses and positive outcomes of our program within a learning communities’ framework. We present these data for other institutions interested in creating their own SaT program.
MDSTF: a multi-dimensional spatio-temporal feature fusion trajectory prediction model for autonomous driving
Authors: Wang Xing , Wu Zixuan , Jin Biao , Lin Mingwei , Zou Fumin , Liao Lyuchao
Published: June 2024

In the field of autonomous driving, trajectory prediction of traffic agents is an important and challenging problem. Fully capturing the complex spatio-temporal features in trajectory data is crucial for accurate trajectory prediction. This paper proposes a trajectory prediction model called multi-dimensional spatio-temporal feature fusion (MDSTF), which integrates multi-dimensional spatio-temporal features to model the trajectory information of traffic agents. In the spatial dimension, we employ graph convolutional networks (GCN) to capture the local spatial features of traffic agents, spatial attention mechanism to capture the global spatial features, and LSTM combined with spatial attention to capture the full-process spatial features of traffic agents. Subsequently, these three spatial features are fused using a gate fusion mechanism. Moreover, during the modeling of the full-process spatial features, LSTM is capable of capturing short-term temporal dependencies in the trajectory information of traffic agents. In the temporal dimension, we utilize a Transformer-based encoder to extract long-term temporal dependencies in the trajectory information of traffic agents, which are then fused with the short-term temporal dependencies captured by LSTM. Finally, we employ two temporal convolutional networks (TCN) to predict trajectories based on the fused spatio-temporal features. Experimental results on the ApolloScape trajectory dataset demonstrate that our proposed method outperforms state-of-the-art methods in terms of weighted sum of average displacement error (WSADE) and weighted sum of final displacement error (WSFDE) metrics. Compared to the best baseline model (S2TNet), our method achieves reductions of 4.37% and 6.23% respectively in these metrics.
Complementary In Situ Characterization of Superelasticity in Fe–Mn–Al–Ni–Ti Shape Memory Alloys by Acoustic Emission, Digital Image Correlation and Infrared Thermography
Authors: Müller M. , Lehnert R. , Motylenko M. , Krooß P. , Vollmer M. , Niendorf T. , Biermann H. , Weidner A.
Published: June 2024

Coupled in situ investigations were conducted on a Fe–Mn–Al–Ni–Ti single crystal deformed in compression and two Fe–Mn–Al–Ni–Ti oligo-crystals deformed in tension. Acoustic emission measurements were employed to monitor the degradation of superelasticity and the stabilization of martensite due to dislocation processes. These observations were corroborated by the application of digital image correlation and infrared thermography measurements. A poor strain reversibility and a premature plastification of the parent phase were observed in case of the single crystal due to an unfavourable crystal orientation. A contradictory transformation behaviour of the two oligo-crystals was observed, with one specimen showing a promising strain reversibility and characterisitic signs of degradation, and the other specimen exhibiting a limited strain reversibility due to an unusual confinement of the martensitic phase transformation to an unfavourably oriented grain. In the former case, an increase in the dislocation density within five cycles was detected through a shift of the acoustic signals’ median frequencies. In the latter case, a strong coupling between martensite nucleation and dislocation generation led to a pronounced martensite stabilization after one loading cycle. For all specimens, temporal sequence effects related to the coupling of martensite nucleation and dislocation generation were detected by means of acoustic emission.
The Effect of Composition and Temperature on the Hydrogen Reduction Behavior of Sintered Pellets of Bauxite Residue-Lime Mixtures
Authors: Kar Manish Kumar , van der Eijk Casper , Safarian Jafar
Published: June 2024

This study explores the isothermal hydrogen reduction of sintered pellets made of a mixture of bauxite residue and calcite with varying compositions at different reduction temperatures. Sintered pellets with varying compositions show three primary iron-containing oxide phases including brownmillerite, srebrodolskite, and fayalite; however, brownmillerite is the major phase in all the sintered pellets. The sintered pellets were reduced in a thermogravimetry furnace to establish instantaneous weight reduction with respect to time. Phases and microstructural analysis were carried out using X-ray diffraction and scanning electron microscopy, respectively. Mercury intrusion porosimeter and pycnometer were utilized to assess the porosity and density of the reduced pellets. Thermochemistry calculations were performed using the thermodynamics software FactSage 8.2. The reduction rate is most pronounced at a temperature of 1000 °C for all pellet compositions. It is intriguing to note that the rate of reduction shows minimal variance across pellets with different compositions; however, the higher calcite pellets exhibit a higher initial rate of reduction. Various kinetic models were examined to determine the activation energies for three different composition pellets, and the three-dimensional diffusion model has been well suited for this process. Close activation energies in the range of 84.6 to 94.8 kJ were obtained. A slightly higher activation energy was obtained for lower CaCO3 added pellets, and it was attributed to their reduced porosity and increased sintering, impeding the reaction kinetics. There were no significant differences in the formation of mayenite with varying the calcite amount; however, higher calcite pellets indicated more mayenite formation.

Graphical Abstract
A survey on recent advances in the computation of asymptotes
Authors: Magdalena-Benedicto R. , de Sevilla M. A. Fernández , Pérez-Díaz S.
Published: June 2024

In this paper, we summarize two algorithms for computing all the generalized asymptotes of a plane algebraic curve implicitly or parametrically defined. The approach is based on the notion of perfect curve introduced from the concepts and results presented in Blasco and Pérez-Díaz (Comput Aided Geom Des 31(2):81–96, 2014), Blasco and Pérez-Díaz (Comput Aided Geom Des 31(7-8):345–357, 2014), and Blasco and Pérez-Díaz (J Comput Appl Math 278:231–247, 2015). From these results, we derive a new method that allow to easily compute horizontal and vertical asymptotes.
Optimal Power and Battery Storage Dispatch Architecture for Microgrids: Implementation in a Campus Microgrid
Authors: Escobar Eros D. , Betancur Daniel , Isaac Idi A.
Published: June 2024

The expansion of electric microgrids has led to the incorporation of new elements and technologies into the power grids, carrying power management challenges and the need of a well-designed control architecture to provide efficient and economic access to electricity. This paper presents the development of a flexible hourly day-ahead power dispatch architecture for distributed energy resources in microgrids, with cost-based or demand-based operation, built up in a multi-class Python environment with SQLExpress and InfluxDB databases storing the dispatcher and microgrid data, and its experimental implementation using Modbus communication. The experimental power dispatch architecture is described and each operation stage is detailed, including the considered mathematical models of the energy resources, the database management, the linear-programming optimization of power dispatch, and the Modbus setpoint writing. Validation studies of the proposed control system are presented for real-time digital-simulated devices and physical resources as a real application at the Universidad Pontificia Bolivariana (UPB) campus microgrid. The simulated and physical microgrid characteristics are described and the hourly dispatch results for generation, storage and load devices are presented, standing out as a reliable power management architecture for economic commitment and load peak shaving in simulated and real microgrids. The proposed architecture demonstrates its readiness for present and future electrical system challenges, effectively incorporating meteorological variations, renewable energy sources, and power demand fluctuations into the control framework, with a strong dependence on the quality of the meteorological forecast.
Insight on molecular interactions in shrinkage of Na-montmorillonite clay by molecular dynamics simulation
Authors: Feng Wei-Qiang , Al-Zaoari Kamal , Chen Ze-Jian
Published: June 2024

Expansive soils are known to be hazardous materials for infrastructure due to their high shrinking or swelling potential. Understanding the shrinking factors of expansive soils such as montmorillonite (MMT) is essential for predicting their mechanical properties. The interactions between the components of Na-MMT clays, e.g., MMT layer–layer (LL), layer–cation (LC), layer–water (LW) and water–cation (WC), are responsible for its shrinking behavior. In this study, molecular dynamics simulation and grand canonical Monte Carlo simulations are used to investigate the interaction energy evolution in the layered structure of Na-MMT for the shrinkage mechanisms analysis of clay. The results of simulation indicate that the magnitude of the interaction energy contributed by the interlayer cations dehydration is the driving force of the interlayer shrinkage. Furthermore, in the hydrated state, with one water layer, two water layers and three water layers, the attractive interactions between WC and LW, maintain the stability of the clay layers. However, at the dry state, the interaction energy between layers and cations appears to be the most essential component in holding the stacked layers together, which provides structural stability to the clay sheets. Finally, the study reveals that intermolecular interactions contribute to the mechanical properties of clays such as cohesive and elastic properties.
Graph-Enhanced Prompt Learning for Personalized Review Generation
Authors: Qu Xiaoru , Wang Yifan , Li Zhao , Gao Jun
Published: June 2024

Personalized review generation is significant for e-commerce applications, such as providing explainable recommendation and assisting the composition of reviews. With the success of pre-trained language models (PLMs), prompt learning-based approaches have been employed to handle this task. However, the existing approach neglects the historical user-item interactions as well as the diverse semantics of the reviews (including semantically relevant reviews and semantically irrelevant reviews). In this paper, we propose GRAPA, a graph-enhanced prompt learning approach for personalized review generation. Specifically, GRAPA extracts topic-level information for each review to address the semantic diversity of reviews. Moreover, GRAPA employs a heterogeneous graph neural network (GNN) to explore the collaborative information hidden in historical user-item interactions. User and item representations generated by the GNN module as well as their ID embeddings are used as prompts and fed into a PLM to guide the generation process. To alleviate the interference of semantically irrelevant reviews, GRAPA further proposes a contrastive learning module to distinguish them. Experimental results on public datasets show that GRAPA outperforms existing methods by up to 4.3% in BLEU-4 and 5.4% in ROUGE2-F.
Comparison of thresholds for a convolutional neural network classifying medical images
Authors: Rainio Oona , Tamminen Jonne , Venäläinen Mikko S. , Liedes Joonas , Knuuti Juhani , Kemppainen Jukka , Klén Riku
Published: June 2024

Our aim is to compare different thresholds for a convolutional neural network (CNN) designed for binary classification of medical images. We consider six different thresholds, including the default threshold of 0.5, Youden’s threshold, the point on the ROC curve closest to the point (0,1), the threshold of equal sensitivity and specificity, and two sensitivity-weighted thresholds. We test these thresholds on the predictions of a CNN with InceptionV3 architecture computed from five datasets consisting of medical images of different modalities related to either cancer or lung infections. The classifications of each threshold are evaluated by considering their accuracy, sensitivity, specificity, F1 score, and net benefit. According to our results, the best thresholds are Youden’s threshold, the point on the ROC curve closest to the point (0,1), and the threshold of equal sensitivity and specificity, all of which work significantly better than the default threshold in terms of accuracy and F1 score. If higher values of sensitivity are desired, one of the two sensitivity-weighted could be of interest.
Emerging pathogens and disease dynamics threatening avocado production in southern Türkiye
Authors: Çalış Özer , Çelik Sefanur , Fidan Hakan , Tek Mumin Ibrahim , Shah Mehraj , Tozlu Ilhami , Wani Shabir Hussain
Published: June 2024

Avocado (Persea americana Milll.) holds a pivotal position in global fruit crops, contributing significantly to the economies of tropical and subtropical regions. However, the rising incidence of diseases poses a substantial risk to avocado production. This comprehensive study investigated the disease landscape in Antalya, the largest avocado cultivation area in the Türkiye. A survey of 2537 avocado trees across 11 regions from 2020 to 2021 revealed alarming disease incidences, particularly in the eastern regions of Gazipasa and Alanya. Dieback, branch canker, anthracnose, and soil-borne root rot were identified as the primary diseases affecting tree canopies, twigs, and branches. Morphological and molecular analyzes unveiled a spectrum of pathogens, with Colletotrichum gloeosporioides dominating in the Mediterranean region. Notably, Phytophthora cinnamomi emerged as a severe threat, causing root rot and decline in avocado trees. Fusarium solani and Fusarium oxysporum, known for their association with tropical fruit crops, were identified in the western parts of Antalya. Additionally, we have detected Neofusicoccum parvum, Lasiodiplodia theobromae, and Neopestalotiopsis rosae in collected samples from avocado trees. The identified pathogens exhibited varying levels of severity in branch canker and anthracnose on avocado branches and leaves. Furthermore, pathogenicity evaluations shed light on the potential of these pathogens to induce severe symptoms, emphasizing the urgency for effective control measures. The exploration of cultural and biological control strategies are crucial for mitigating the impact of branch canker, dieback, and anthracnose diseases, ensuring the sustainability of avocado cultivation in the region.
Determination of tolerance to Erwinia amylovora of intergeneric hybrid genus: Cydomalus
Authors: Şahin Müge
Published: June 2024

A greater genetic diversity is essential for disease resistance in particular, and intergeneric hybridization makes this possible. The genus Cydomalus (syn: Cydolus), which is frequently used as rootstock, was derived from intergeneric hybridization between Cydonia oblonga Mill. and Malus domestica Borkh in Moldova and Bulgaria. It is known that hybrids from this genus exhibit quince and/or apple characteristics and some of them have been identified with reddish fruit skin color in Türkiye in the last decade. Erwinia amylovora Burril. is the most devastating bacterial disease in the Rosaceae family, and there have been no reports of Cydomalus. In this study, fire blight susceptibility index of three Cydomalus genotypes, were collected from İzmir and Manisa provinces, and two important quince rootstocks were determined by artificial inoculations with the most virulent Erwinia amylovora strain of our collection, under greenhouse conditions for two consecutive years. In addition, susceptibility levels of two Cydomalus genotypes were observed under natural disease pressure habitats. In line with the results of artificial inoculations, two of Cydomalus genotypes were determined to be more tolerant to fire blight disease than quince rootstocks and these genotypes could be used in breeding studies. Moreover, Cydomalus genus was identified as the new host for Erwinia amylovora.
In vitro biological evaluation of a novel folic acid-targeted receptor quantum dot−β−cyclodextrin carrier for C−2028 unsymmetrical bisacridine in the treatment of human lung and prostate cancers
Authors: Pilch Joanna , Potęga Agnieszka , Kowalik Patrycja , Kowalczyk Agata , Bujak Piotr , Kasprzak Artur , Paluszkiewicz Ewa , Nowicka Anna Maria
Published: June 2024

Background

Traditional small-molecule chemotherapeutics usually do not distinguish tumors from healthy tissues. However, nanotechnology creates nanocarriers that selectively deliver drugs to their site of action. This work is the next step in the development of the quantum dot−β−cyclodextrin−folic acid (QD−β−CD−FA) platform for targeted and selected delivery of C−2028 unsymmetrical bisacridine in cancer therapy.

Methods

Herein, we report an initial biological evaluation (using flow cytometry and light microscopy) as well as cell migration analysis of QD−β−CD(C−2028)−FA nanoconjugate and its components in the selected human lung and prostate cancer cells, as well as against their respective normal cells.

Results

C−2028 compound induced apoptosis, which was much stronger in cancer cells compared to normal cells. Conjugation of C−2028 with QDgreen increased cellular senescence, while the introduction of FA to the conjugate significantly decreased this process. C−2028 nanoencapsulation also reduced cell migration. Importantly, QDgreen and QDgreen−β−CD−FA themselves did not induce any toxic responses in studied cells.

Conclusions

In conclusion, the results demonstrate the high potential of a novel folic acid-targeted receptor quantum dot−β−cyclodextrin carrier (QDgreen−β−CD−FA) for drug delivery in cancer treatment. Nanoplatforms increased the amount of delivered compounds and demonstrated high suitability.
Anforderungen, Ressourcen und Arbeitsengagement von Pflegemanager_innen der unteren und mittleren Ebene
Authors: Forster Andrea , Koob Clemens
Published: June 2024

Zusammenfassung. Hintergrund: Pflegemanager_innen im unteren und mittleren Management kommt eine zentrale Rolle im Gesundheitswesen zu. Für ihre Leistungsfähigkeit und Gesundheit ist insbesondere ihr Arbeitsengagement bedeutsam, das gemäß Job-Demands-Resources-Modell von arbeitsbezogenen Anforderungen und Ressourcen abhängt. Bisher mangelt es an Untersuchungen zu Anforderungen, Ressourcen und Arbeitsengagement von Pflegemanager_innen in Deutschland. Ziel: Ziel war es, die Arbeitsanforderungen und -ressourcen sowie das Arbeitsengagement von Pflegemanager_innen der unteren und mittleren Führungsebene in Krankenhäusern und Altenpflegeeinrichtungen in Deutschland zu beschreiben. Zudem sollten mögliche Unterschiede in diesen Bereichen zwischen verschiedenen Gruppen, insbesondere im Hinblick auf Geschlecht, Alter und Führungsebene, exploriert werden. Methoden: Die Studie wurde im Querschnittdesign durchgeführt. Die Daten wurden per Online-Fragebogen erhoben. Es konnten N = 408 Fälle ausgewertet werden. Ergebnisse: Arbeitsüberlastung ist die am stärksten ausgeprägte Anforderung, gefolgt von emotionalen Anforderungen. Ressourcenseitig können Pflegemanager_innen vor allem auf positive soziale Beziehungen zurückgreifen. Kritisch werden vor allem die verfügbaren professionellen Ressourcen bewertet. Das Arbeitsengagement ist moderat. Schlussfolgerungen: Die Studie zeigt klaren Handlungsbedarf bezüglich einer Verbesserung des Arbeitsengagements. Insbesondere Arbeitsüberlastung und professionelle Ressourcen sind durch geeignete systemweite und organisationsbezogene Maßnahmen zu adressieren.
Seawater Intrusion in the Observed Grounding Zone of Petermann Glacier Causes Extensive Retreat
Authors: Ehrenfeucht Shivani , Rignot Eric , Morlighem Mathieu
Published: June 2024

Understanding grounding line dynamics is critical for projecting glacier evolution and sea level rise. Observations from satellite radar interferometry reveal rapid grounding line migration forced by oceanic tides that are several kilometers larger than predicted by hydrostatic equilibrium, indicating the transition from grounded to floating ice is more complex than previously thought. Recent studies suggest seawater intrusion beneath grounded ice may play a role in driving rapid ice loss. Here, we investigate its impact on the evolution of Petermann Glacier, Greenland, using an ice sheet model. We compare model results with observed changes in grounding line position, velocity, and ice elevation between 2010 and 2022. We match the observed retreat, speed up, and thinning using 3‐km‐long seawater intrusion that drive peak ice melt rates of 50 m/yr; but we cannot obtain the same agreement without seawater intrusion. Including seawater intrusion in glacier modeling will increase the sensitivity to ocean warming.
Reduced Geostatistical Approach With a Fourier Neural Operator Surrogate Model for Inverse Modeling of Hydraulic Tomography
Authors: Guo Quan , He Yu , Liu Ming , Zhao Yue , Liu Yuzheng , Luo Jian
Published: June 2024

In this study, we propose a new approach for inverse modeling of hydraulic tomography (HT) using the Fourier neural operator (FNO) as a surrogate forward model. FNO is a deep learning model that directly parameterizes the integral kernel in Fourier space to learn solution operators for parametric partial differential equations (PDEs). We trained a highly accurate FNO to learn the solution operators of PDEs in HT, which can efficiently generate multiple channels of hydraulic head fields corresponding to specific pumping tests in new parameter fields through a single forward pass. The trained FNO surrogate model is integrated with the reduced geostatistical approach (RGA) to provide a powerful tool, named RGA‐FNO, for inverse modeling of Gaussian random fields. RGA utilizes principal components to effectively reduce problem dimensions and encode geostatistical information. FNO benefits from deep learning automatic differentiation, enabling efficient backpropagation of gradients during inverse modeling. Our results show that RGA‐FNO can efficiently produce satisfactory estimations for random transmissivity fields with an exponential covariance function, which is non‐differentiable and visually non‐smooth. The RGA‐FNO application on steady‐state multi‐well HT is better than the single‐well transient pumping test for inverse modeling. The data required for inverse modeling applications of RGA‐FNO increases with the variance of the random transmissivity fields. FNO and other neural operator models have the potential to play an important role in groundwater modeling, especially in inverse modeling and experimental design, which often requires a large number of forward simulations.
One in Four US Households Likely Exceed New Soil Lead Guidance Levels
Authors: Filippelli Gabriel M. , Dietrich Matthew , Shukle John , Wood Leah , Margenot Andrew , Egendorf S. Perl , Mielke Howard W.
Published: June 2024

Lead exposure has blighted communities across the United States (and the globe), with much of the burden resting on lower income communities, and communities of color. On 17 January 2024, the US Environmental Protection Agency (USEPA) lowered the recommended screening level of lead in residential soils from 400 to 200 parts per million. Our analysis of tens of thousands of citizen‐science collected soil samples from cities and communities around the US indicates that nearly one quarter of households may contain soil lead that exceed the new screening level. Extrapolating across the nation, that equates to nearly 30 million households needing to mitigate potential soil lead hazards, at a potential total cost of 290 billion to $1.2 trillion. We do not think this type of mitigation is feasible at the massive scale required and we have instead focused on a more immediate, far cheaper strategy: capping current soils with clean soils and/or mulch. At a fraction of the cost and labor of disruptive conventional soil mitigation, it yields immediate and potentially life‐changing benefits for those living in these environments.
Comparison of Lightning Channel Luminosity Versus Time Profiles in the Infrared and Visible Ranges
Authors: Ding Z. , Rakov V. A. , Zhu Y. , Kereszy I. , Chen S. , Tran M. D.
Published: June 2024

Infrared (IR) luminosity of lightning channel in the 3–5 μm range usually persisted throughout the entire interstroke interval, which is in contrast to the simultaneously recorded visible (0.4–0.8 μm) luminosity that always decayed to an undetectable level prior to a subsequent return stroke pulse. A longer visible luminosity period at the end of flash tended to be associated with a longer IR afterglow period following the decay of visible luminosity (and by inference current) to an undetectable level. At the end of flash, the IR luminosity persisted up to about 1 s, and the median IR afterglow duration was a factor of 10 longer than the median visible luminosity duration. The IR luminosity often exhibited a hump when the visible luminosity was monotonically decaying or undetectable, with the corresponding channel temperature being likely around 3400 K.
Enhanced Modulation of Streamflow Flash Droughts by Reservoir Operations in India
Authors: Singh Rajesh , Mishra Vimal
Published: June 2024

Streamflow flash droughts (SFDs) occur due to a rapid decline in streamflow and cause major challenges associated with water availability for downstream ecosystems, hydropower generation, and irrigation water demand. Human interventions such as reservoir operations and reservoir storage can considerably influence streamflow variability. However, the crucial role of dams/reservoirs on the occurrence of SFDs in India remains unexamined. Using a combination of hydrological and hydrodynamical models, we examined the role of reservoirs on SFDs in India during 1971–2020. Reservoirs play a considerable role in the occurrence of SFDs during the summer monsoon season (June‐September) in India. The frequency and severity of SFDs in the presence of reservoirs are substantially lesser than in the absence of them. In addition, high and low antecedent reservoir storage conditions before meteorological flash droughts (MFDs) do not support the rapid decline of streamflow (i.e., SFDs) downstream of reservoirs, while the medium reservoir storage conditions prior to MFDs favor the development of SFDs. Similar to conventional (or long‐term) streamflow droughts (SDs), SFDs are more frequent in the El Nino phase than in the La Nina phase. Unlike the long‐term streamflow droughts, the implementation of dams considerably reduces the frequency of SFDs during both the negative and positive phases of El Nino Southern Oscillation. Overall, our findings demonstrate the considerable role of human interventions in flash drought occurrence, as SFDs are triggered by MFDs but modulated by reservoir storage and operations.
Model Diagnostic Analysis in a Cold Basin Influenced by Frozen Soils With the Aid of Stable Isotope
Authors: Nan Yi , Tian Fuqiang , Li Zongxing
Published: June 2024

Understanding the hydrological processes on the Tibetan Plateau (TP) under climate change is an important scientific question. The frequent multiphase transfer exacerbates the complexity of hydrological processes on the TP, which brings equifinality problem to hydrological models and causes large uncertainties in quantifying the contributions of runoff components. Tracer‐aided hydrological models are helpful for improving model performances and have been adopted in cryospheric regions, but the influence of frozen soil has yet to be considered. This study adopted the Tracer‐aided Tsinghua Representative Elementary Watershed model (THREW‐T) in a typical cold basin with widespread frozen soil on the TP. The model structure was diagnosed with isotope by identifying the influences of frozen soil. A simplified catchment‐scale frozen soil module was incorporated into the model. Results showed that: (a) The THREW‐T model cannot simultaneously simulate baseflow and stream water isotope well. The imbalance of simulations on two objectives could be attributed to the influence of frozen soil, resulting in seasonal variation of soil‐related parameters, which was not considered in the model. (b) Incorporating the frozen soil module significantly improved the balance of baseflow and isotope simulation, simultaneously producing low baseflow and high contribution of subsurface runoff during wet seasons. (c) The frozen soil had little influence on the annual streamflow, but changed the runoff seasonality by reducing baseflow during dry seasons and increasing subsurface runoff during wet seasons. The frozen soil module was still simplified, and further work is needed to improve the physical representation of soil freeze‐thaw process. This study highlights the value of tracer‐aided hydrological modeling method on diagnosing model structure by identifying the influence of specific processes such as frozen soil.
Optically levitated micro gyroscopes with an MHz rotational vaterite rotor
Authors: Zeng Kai , Xu Xiangming , Wu Yulie , Wu Xuezhong , Xiao Dingbang
Published: June 2024

The field of levitated optomechanics has experienced significant advancements in manipulating the translational and rotational dynamics of optically levitated particles and exploring their sensing applications. The concept of using optically levitated particles as gyroscopes to measure angular motion has long been explored but has not yet been proven either theoretically or experimentally. In this study, we present the first rotor gyroscope based on optically levitated high-speed rotating particles. The gyroscope is composed of a micrometer-size ellipsoidal vaterite particle that is driven to rotate at MHz frequencies in a vacuum environment. When an external angular velocity is input, the optical axis deviates from its initial position, resulting in changes in the frequency and amplitude of the rotational signal. By analyzing these changes, the angular velocity of the input can be accurately detected, making it the smallest rotor gyroscope in the world. The angular rate bias instability of the gyroscope is measured to be 0.08°/s and can be further improved to as low as 10−9°/h theoretically by cooling the motion and increasing the angular moment of the levitated particle. Our work opens a new application paradigm for levitated optomechanical systems and may pave the way for the development of quantum rotor gyroscopes.
Penpulimab, an anti-PD-1 antibody, for heavily pretreated metastatic nasopharyngeal carcinoma: a single-arm phase II study
Authors: Chen Xiaozhong , Wang Wei , Zou Qingfeng , Zhu Xiaodong , Lin Qin , Jiang Yi , Sun Yan , Shen Liangfang , Wang Lin , Zou Guorong , Lin Xiaoyan , Lin Shaojun , Li Minying , Wang Ying , Xu Ruilian , Ao Rui , Wang Rensheng , Lin Haifeng , Huang Shuang , Xu Tingting , Li Wenting , Xia Mengying , Xia Yu , Wang Zhongmin , Li Baiyong , Li Jingao , Hu Chaosu
Published: June 2024

Penpulimab is an anti-programmed cell death-1 (PD-1) IgG1 antibody with no Fc gamma receptor (FcγR) binding activity, and thus theoretically reduced immune-related adverse events (irAEs) while maintaining efficacy. This single-arm, phase II trial conducted across 20 tertiary care centers in China enrolled adult patients with metastatic nasopharyngeal carcinoma (NPC) who had failed two or more lines of previous systemic chemotherapy. Patients received 200-mg penpulimab intravenously every 2 weeks (4 weeks per cycle) until disease progression or intolerable toxicities. The primary endpoint was objective response rate (ORR) per RECIST (version 1.1), as assessed by an independent radiological review committee. The secondary endpoints included progression-free survival (PFS) and overall survival (OS). One hundred thirty patients were enrolled and 125 were efficacy evaluable. At the data cutoff date (September 28, 2022), 1 patient achieved complete response and 34 patients attained partial response. The ORR was 28.0% (95% CI 20.3–36.7%). The response was durable, with 66.8% still in response at 9 months. Thirty-three patients (26.4%) were still on treatment. The median PFS and OS were 3.6 months (95% CI = 1.9–7.3 months) and 22.8 months (95% CI = 17.1 months to not reached), respectively. Ten (7.6%) patients experienced grade 3 or higher irAEs. Penpulimab has promising anti-tumor activities and acceptable toxicities in heavily pretreated metastatic NPC patients, supporting further clinical development as third-line treatment of metastatic NPC.
Caries preventing efficacy of new Isomalt-containing mouthrinse formulations: a microbial study
Authors: Amaechi Bennett T. , AbdulAzees Parveez Ahamed , Mohseni Sahar , Luong Minh N. , Lin Chun-Yen , Restrepo-Ceron Maria Camila , Kataoka Yuko , Omosebi Temitope O. , Kanthaiah Kannan
Published: June 2024

Objectives

The effectiveness of an Isomalt-containing mouthrinse to prevent caries development was investigated.

Methods

Human enamel blocks were randomly assigned to five groups (n = 30/group): De-ionized distilled water (DDW), and mouthrinse containing either (IFC) 1% Isomalt, 225 ppm fluoride, and 0.05% cetylpyridinium chloride (CPC), (IF) 1% Isomalt and 225ppm fluoride, (FC) 225 ppm fluoride and 0.05% CPC or (F) 225 ppm fluoride. During 7-day demineralization in a Microbial Caries Model, mouthrinses were applied once daily for 1 min. Demineralization was assessed using Surface Microhardness testing for percentage change in SMH (%ΔSMH) and Transverse Microradiography for mineral loss (ΔZ). Data analysis (α = 0.05) used paired t-test (Intra-group comparison using SMH) and ANOVA/Tukey’s for inter-group comparisons (%ΔSMH and ΔZ).

Results

With SMH, relative to sound enamel baseline, demineralization was significant (P < 0.001) in all groups, except in IFC. Intergroup comparison with %ΔSMH showed significantly (p < 0.001) greater demineralization in DDW compared to other groups, and in IF, FC, and F compared to IFC (P < 0.001). With ΔZ, relative to DDW, all groups significantly (p < 0.0001) inhibited demineralization at varying percentages.

Conclusions

Mouthrinse containing Isomalt, fluoride, and CPC inhibited demineralization amidst cariogenic biofilm; thus, highlighting its potential as a more effective caries control tool than mouthrinse with only fluoride.
The miR-29 family facilitates the activation of NK-cell immune responses by targeting the B7-H3 immune checkpoint in neuroblastoma
Authors: Pathania Anup S. , Chava Haritha , Chaturvedi Nagendra K. , Chava Srinivas , Byrareddy Siddappa N. , Coulter Don W. , Challagundla Kishore B.
Published: June 2024

Neuroblastoma (NB) is a highly aggressive pediatric cancer that originates from immature nerve cells, presenting significant treatment challenges due to therapy resistance. Despite intensive treatment, approximately 50% of high-risk NB cases exhibit therapy resistance or experience relapse, resulting in poor outcomes often associated with tumor immune evasion. B7-H3 is an immune checkpoint protein known to inhibit immune responses. MicroRNAs (miRNAs) are small non-coding RNAs involved in post-transcriptional gene regulation. Our study aims to explore the impact of miRNAs on B7-H3 regulation, the anti-tumor immune response, and tumorigenicity in NB. Analysis of NB patients and patient-derived xenograft tumors revealed a correlation between higher B7-H3 expression and poorer patient survival. Notably, deceased patients exhibited a depletion of miR-29 family members (miR-29a, miR-29b, and miR-29c), which displayed an inverse association with B7-H3 expression in NB patients. Overexpression and knockdown experiments demonstrated that these miRNAs degrade B7-H3 mRNA, resulting in enhanced NK cell activation and cytotoxicity. In vivo, experiments provided further evidence that miR-29 family members reduce tumorigenicity, macrophage infiltration, and microvessel density, promote infiltration and activation of NK cells, and induce tumor cell apoptosis. These findings offer a rationale for developing more effective combination treatments that leverage miRNAs to target B7-H3 in NB patients.
TMC6 functions as a GPCR-like receptor to sense noxious heat via Gαq signaling
Authors: Zhang Chen , Tong Fang , Zhou Bin , He Mingdong , Liu Shuai , Zhou Xiaomeng , Ma Qiang , Feng Tianyu , Du Wan-Jie , Yang Huan , Xu Hao , Xiao Lei , Xu Zhen-Zhong , Zhu Cheng , Wu Ruiqi , Wang Yan-Qing , Han Qingjian
Published: June 2024

Thermosensation is vital for the survival, propagation, and adaption of all organisms, but its mechanism is not fully understood yet. Here, we find that TMC6, a membrane protein of unknown function, is highly expressed in dorsal root ganglion (DRG) neurons and functions as a Gαq-coupled G protein-coupled receptor (GPCR)-like receptor to sense noxious heat. TMC6-deficient mice display a substantial impairment in noxious heat sensation while maintaining normal perception of cold, warmth, touch, and mechanical pain. Further studies show that TMC6 interacts with Gαq via its intracellular C-terminal region spanning Ser780to Pro810. Specifically disrupting such interaction using polypeptide in DRG neurons, genetically ablating Gαq, or pharmacologically blocking Gαq-coupled GPCR signaling can replicate the phenotype of TMC6 deficient mice regarding noxious heat sensation. Noxious heat stimulation triggers intracellular calcium release from the endoplasmic reticulum (ER) of TMC6- but not control vector-transfected HEK293T cell, which can be significantly inhibited by blocking PLC or IP3R. Consistently, noxious heat-induced intracellular Ca2+release from ER and action potentials of DRG neurons largely reduced when ablating TMC6 or blocking Gαq/PLC/IP3R signaling pathway as well. In summary, our findings indicate that TMC6 can directly function as a Gαq-coupled GPCR-like receptor sensing noxious heat.