bluuebunny/crossref_metadata_2025 huggingface dataset:
Defect Identification of Power Line Insulators Based on a MobileViT‐Yolo Deep Learning Algorithm
Authors: Zan Weidong , Dong Chaoyi , Zhang Zhiming , Chen Xiaoyan , Zhao Jianfei , Hao Fu
Published: May 2023

Power line insulator defect identification usually suffers from complex backgrounds, small defect target sizes, and inconspicuous defect features. Traditional identification methods based on image processing, image analysis, and pattern classification have many limitations in solving the aforementioned problems. In recent decades, deep learning classification methods have gradually replaced traditional identification methods in the task of power line insulator defect identification. To accurately identify the locations of insulator defects, this paper proposes an insulator defect detection algorithm using an improved lightweight YOLOv4‐tiny network (ILYTN). First, the CBL (Conv‐BN‐LeakyReLU) modules of the backbone network are replaced with MobileViT blocks to enhance the feature extraction capability of the backbone network. Second, coordinate attention (CA) is introduced in the feature fusion part to improve the network's ability to focus on the location of defects. Finally, an EIOU (efficient intersection over union) loss function, instead of the original CIOU loss function, is used so that the convergence speed of the network can be improved. To verify the effectiveness of the proposed algorithm in this paper, the mViT‐yolo algorithm is compared with the mainstream Faster‐RCNN algorithm, SSD algorithm, YOLOv3 algorithm, and YOLOv4‐tiny algorithm. The experimental results show that the algorithm proposed in this paper outperforms all the above algorithms in terms of detection accuracy. Compared with the traditional YOLOv4‐tiny algorithm, the proposed algorithm increases the mean average precision (mAP) by 1.64%, the average precision (AP) of missing insulator defects by 0.32%, and the average precision (AP) of broken insulator defects by 4.96%. © 2023 The Authors. IEEJ Transactions on Electrical and Electronic Engineering published by Institute of Electrical Engineer of Japan and Wiley Periodicals LLC.
Long-Time Dynamics in Quantum Spin Lattices: Ergodicity and Hydrodynamic Projections at All Frequencies and Wavelengths
Authors: Ampelogiannis Dimitrios , Doyon Benjamin
Published: May 2023

Obtaining rigorous and general results about the non-equilibrium dynamics of extended many-body systems is a difficult task. In quantum lattice models with short-range interactions, the Lieb–Robinson bound tells us that the spatial extent of operators grows at most linearly in time. But what happens within this light-cone? We discuss rigorous results on ergodicity and the emergence of the Euler hydrodynamic scale in correlation functions, which establish fundamental principles at the root of non-equilibrium physics. One key idea of the present work is that general structures of Euler hydrodynamics, obtained under ballistic scaling, follow independently from the details of the microscopic dynamics, and in particular do not necessitate chaos; they are consequences of “extensivity”. Another crucial observation is that these apply at arbitrary frequencies and wavelengths. That is, long-time, persistent oscillations of correlation functions over ballistic regions of spacetime, which may be of microscopic frequencies and wavelengths, are predicted by a general Euler-hydrodynamic theory that takes the same form as that for smoothed-out correlation functions. This involves a natural extension of notions of conserved quantities and hydrodynamic projection and shows that the Euler hydrodynamic paradigm covers the full frequency-wavelength plane.
NLS ground states on the half-line with point interactions
Authors: Boni Filippo , Carlone Raffaele
Published: May 2023

We investigate the existence and the uniqueness of NLS ground states of fixed mass on the half-line in the presence of a point interaction at the origin. The nonlinearity is of power type, and the regime is either $$L^{2}$$

L
2

-subcritical or $$L^{2}$$

L
2

-critical, while the point interaction is either attractive or repulsive. In the $$L^{2}$$

L
2

-subcritical case, we prove that ground states exist for every mass value if the interaction is attractive, while ground states exist only for sufficiently large masses if the interaction is repulsive. In the latter case, if the power is less or equal to four, ground states coincide with the only bound state. If instead, the power is greater than four, then there are values of the mass for which two bound states exist, and neither of the two is a ground state, and values of the mass for which two bound states exist, and one of them is a ground state. In the $$L^{2}$$

L
2

-critical case, we prove that ground states exist for masses strictly below a critical mass value in the attractive case, while ground states never exist in the repulsive case.
Comparing surgical outcomes of approaches to adrenalectomy — a systematic review and network meta-analysis of randomised clinical trials
Authors: Davey Matthew G. , Ryan Éanna J. , Donlon Noel E. , Ryan Odhrán K. , Al Azzawi Mohammed , Boland Michael R. , Kerin Michael J. , Lowery Aoife J.
Published: May 2023

Background

No randomised clinical trials (RCTs) have simultaneously compared the safety of open (OA), transperitoneal laparoscopic (TLA), posterior retroperitoneal (PRA), and robotic adrenalectomy (RA) for resecting adrenal tumours.

Aim

To evaluate outcomes for OA, TLA, PRA, and RA from RCTs.

Methods

A NMA was performed according to PRISMA-NMA guidelines. Analysis was performed using R packages and Shiny.

Results

Eight RCTs with 488 patients were included (mean age: 48.9 years). Overall, 44.5% of patients underwent TLA (217/488), 37.3% underwent PRA (182/488), 16.4% underwent RA (80/488), and just 1.8% patients underwent OA (9/488). The mean tumour size was 35 mm in largest diameter with mean sizes of 44.3 mm for RA, 40.9 mm for OA, 35.5 mm for TLA, and 34.4 mm for PRA (P < 0.001). TLA had the lowest blood loss (mean: 50.6 ml), complication rates (12.4%, 14/113), and conversion to open rates (1.3%, 2/157), while PRA had the shortest intra-operative duration (mean: 94 min), length of hospital stay (mean: 3.7 days), lowest visual analogue scale pain scores post-operatively (mean: 3.7), and was most cost-effective (mean: 1728 euros per case). At NMA, there was a significant increase in blood loss for OA (mean difference (MD): 117.00 ml (95% confidence interval (CI): 1.41–230.00)) with similar blood loss observed for PRA (MD: − 10.50 (95% CI: − 83.40–65.90)) compared to TLA.

Conclusion

LTA and PRA are important contemporary options in achieving favourable outcomes following adrenalectomy. The next generation of RCTs may be more insightful for comparison surgical outcomes following RA, as this approach is likely to play a future role in minimally invasive adrenalectomy.

PROSPERO registration

CRD42022301005.
National Evaluation of HIV Service Resource Allocation in Tanzania
Authors: McBain Ryan K. , Jordan Monica , Mann Carlyn , Ruhago George M. , Lee Bryant , Forsythe Steven , Stewart Kaylee , Brown Jessica , Nandakumar Allyala
Published: May 2023

Using time-driven activity-based costing (TDABC), we examined resource allocation and costs for HIV services throughout Tanzania at patient and facility levels. This national, cross-sectional analysis of 22 health facilities quantified costs and resources associated with 886 patients receiving care for five HIV services: antiretroviral therapy, prevention of mother-to-child transmission, HIV testing and counseling, voluntary medical male circumcision, and pre-exposure prophylaxis. We also documented total provider-patient interaction time, the cost of services with and without inclusion of consumables, and conducted fixed-effects multivariable regression analyses to examine patient- and facility-level correlates of costs and provider-patient time. Findings showed that resources and costs for HIV care varied significantly throughout Tanzania, including as a function of patient- and facility-level characteristics. While some variation may be preferable (e.g., needier patients received more resources), other areas suggested a lack of equity (e.g., wealthier patients received more provider time) and presented opportunities to optimize care delivery protocols.
Analysis of the Cryptographic Algorithms in IoT Communications
Authors: Silva Catarina , Cunha Vitor A. , Barraca João P. , Aguiar Rui L.
Published: May 2023

The advances on recent communication paradigms brings new security and privacy challenges, mainly about personal data collection by smart devices. Resource constrained devices face serious issues to run complex cryptographic algorithms. Trying to evaluate the performance impact of those algorithms in usual and common devices used in smart homes, in this paper we tested the impact of different cryptographic algorithms in low computational devices, typically used in smart devices applied in smart homes, testing different security configurations and using the two most used transport protocols (HTTP and MQTT). The experiment measures their effects on six commonly used embedded devices in IoT WSNs: ESP8622, ESP32, and Raspberry Pi (RPi) from 1 to 4. The experiment measured the power consumption, message delay, and additional message length (bytes). Moreover, the analysis was also used to model security algorithms. The experimental results from long runs (72 hours) reveal the cryptographic solution choice is significant for the message delay and additional message length.
The pro- and antineoplastic effects of deoxycholic acid in pancreatic adenocarcinoma cell models
Authors: Schwarcz Szandra , Kovács Patrik , Kovács Tünde , Ujlaki Gyula , Nyerges Petra , Uray Karen , Bai Péter , Mikó Edit
Published: May 2023

Background

Commensal bacteria secrete metabolites that reach distant cancer cells through the circulation and influence cancer behavior. Deoxycholic acid (DCA), a hormone-like metabolite, is a secondary bile acid specifically synthesized by intestinal microbes. DCA may have both pro- and antineoplastic effects in cancers.

Methods and results

The pancreatic adenocarcinoma cell lines, Capan-2 and BxPC-3, were treated with 0.7 µM DCA, which corresponds to the reference concentration of DCA in human serum. DCA influenced the expression of epithelial to mesenchymal transition (EMT)-related genes, significantly decreased the expression level of the mesenchymal markers, transcription factor 7- like 2 (TCF7L2), snail family transcriptional repressor 2 (SLUG), CLAUDIN-1, and increased the expression of the epithelial genes, zona occludens 1 (ZO-1) and E-CADHERIN, as shown by real-time PCR and Western blotting. Consequently, DCA reduced the invasion capacity of pancreatic adenocarcinoma cells in Boyden chamber experiments. DCA induced the protein expression of oxidative/nitrosative stress markers. Moreover, DCA reduced aldehyde dehydrogenase 1 (ALDH1) activity in an Aldefluor assay and ALDH1 protein level, suggesting that DCA reduced stemness in pancreatic adenocarcinoma. In Seahorse experiments, DCA induced all fractions of mitochondrial respiration and glycolytic flux. The ratio of mitochondrial oxidation and glycolysis did not change after DCA treatment, suggesting that cells became hypermetabolic.

Conclusion

DCA induced antineoplastic effects in pancreatic adenocarcinoma cells by inhibiting EMT, reducing cancer stemness, and inducing oxidative/nitrosative stress and procarcinogenic effects such as hypermetabolic bioenergetics.
Stakeholder Perspectives on the Impact of COVID-19 on the Implementation of a Community-Clinic Linkage Model in New York City
Authors: Onakomaiya Deborah , Ali Shahmir H. , Islam Tanzeela , Mohaimin Sadia , Kaur Jagjit , Pillai Shaaranya , Monir Afsana , Mehdi Aasma , Mehmood Rehan , Mammen Shinu , Hussain Sarah , Zanowiak Jennifer , Wyatt Laura C. , Alam Gulnahar , Lim Sahnah , Islam Nadia S.
Published: May 2023

Community-clinical linkage models (CCLM) have the potential to reduce health disparities, especially in underserved communities; however, the COVID-19 pandemic drastically impacted their implementation. This paper explores the impact of the pandemic on the implementation of CCLM intervention led by community health workers (CHWs) to address diabetes disparities among South Asian patients in New York City. Guided by the Consolidated Framework for Implementation Research (CFIR), 22 stakeholders were interviewed: 7 primary care providers, 7 CHWs, 5 community-based organization (CBO) representatives, and 3 research staff. Semi-structured interviews were conducted; interviews were audio-recorded and transcribed. CFIR constructs guided the identification of barriers and adaptations made across several dimensions of the study’s implementation context. We also explored stakeholder-identified adaptations used to mitigate the challenges in the intervention delivery using the Model for Adaptation Design and Impact (MADI) framework. (1) Communication and engagement refers to how stakeholders communicated with participants during the intervention period, including difficulties experienced staying connected with intervention activities during the lockdown. The study team and CHWs developed simple, plain-language guides designed to enhance digital literacy. (2) Intervention/research process describes intervention characteristics and challenges stakeholders faced in implementing components of the intervention during the lockdown. CHWs modified the health curriculum materials delivered remotely to support engagement in the intervention and health promotion. (3) community and implementation context pertains to the social and economic consequences of the lockdown and their effect on intervention implementation. CHWs and CBOs enhanced efforts to provide emotional/mental health support and connected community members to resources to address social needs. Study findings articulate a repository of recommendations for the adaptation of community-delivered programs in under-served communities during a time of public health crises.
Evaluating the Use of Online Self-Report Questionnaires as Clinically Valid Mental Health Monitoring Tools in the Clinical Whitespace
Authors: Arrow Kaitlyn , Resnik Philip , Michel Hanna , Kitchen Christopher , Mo Chen , Chen Shuo , Espy-Wilson Carol , Coppersmith Glen , Frazier Colin , Kelly Deanna L.
Published: May 2023

Although digital health solutions are increasingly popular in clinical psychiatry, one application that has not been fully explored is the utilization of survey technology to monitor patients outside of the clinic. Supplementing routine care with digital information collected in the “clinical whitespace” between visits could improve care for patients with severe mental illness. This study evaluated the feasibility and validity of using online self-report questionnaires to supplement in-person clinical evaluations in persons with and without psychiatric diagnoses. We performed a rigorous in-person clinical diagnostic and assessment battery in 54 participants with schizophrenia (N = 23), depressive disorder (N = 14), and healthy controls (N = 17) using standard assessments for depressive and psychotic symptomatology. Participants were then asked to complete brief online assessments of depressive (Quick Inventory of Depressive Symptomatology) and psychotic (Community Assessment of Psychic Experiences) symptoms outside of the clinic for comparison with the ground-truth in-person assessments. We found that online self-report ratings of severity were significantly correlated with the clinical assessments for depression (two assessments used: R = 0.63, p < 0.001; R = 0.73, p < 0.001) and psychosis (R = 0.62, p < 0.001). Our results demonstrate the feasibility and validity of collecting psychiatric symptom ratings through online surveys. Surveillance of this kind may be especially useful in detecting acute mental health crises between patient visits and can generally contribute to more comprehensive psychiatric treatment.
The experience of dysmenorrhea
Authors: Serrahima Carlota , Martínez Manolo
Published: May 2023

Dysmenorrhea, or menstrual pain, is regularly suffered by 45 to 95% of menstruating women. Despite its prevalence, and despite the philosophical importance of pain as a general phenomenon, dysmenorrhea has been all but completely overlooked in contemporary analytic philosophy of mind. This paper aims at rectifying this situation. We single out three properties of what is often considered the paradigmatic case of painful experience, what we call injury-centered pains, and argue that dysmenorrhea does not have any of them, and hence that it does not neatly conform to the injury-centered model of pain. This calls into question the centrality of the injury-centered model, and suggests novel research avenues within theoretical debates on affectivity.
A long lead time forecast model applying an ensemble approach for managing the great Karun multi-reservoir system
Authors: Mostaghimzadeh Ehsan , Ashrafi Seyed Mohammad , Adib Arash , Geem Zong Woo
Published: May 2023

Flow prediction is regarded as a major computational process in strategic water resources planning. Prediction’s lead time has an inverse relationship with results’ accuracy and certainty. This research studies the impact of climate-atmospheric indices on surface runoff predictions with a long lead time. To this end, the correlation of 36 long-distance climate indices with runoff was examined at 10 key nodes of the Great Karun multi-reservoir system in Iran, and indices with higher correlation are divided into 4 different groups. Then, using Artificial Neural Network (ANN) and Ensemble Learning to combine the input variables, flow is predicted in 6-month horizons, and results are compared with observed values. To assess the impact of extending the prediction lead time, results from the proposed model are compared with those of a monthly prediction model. The performed comparison shows that using an ensemble approach improves the final results significantly. Moreover, Tropical Pacific SST EOF, Caribbean SST, and Nino1 + 2 indices are found to be influential parameters to the basin’s inflow. It is observed that the performance of the prediction process varies in different hydrological conditions and the best results are obtained for dry seasons.
Calculation method of equivalent permeability of dual-porosity media considering fractal characteristics and fracture stress sensitivity
Authors: Luo Xiang , Cheng Youyou , Tan Chengqian
Published: May 2023

In the petroleum industry, the accurate calculation of equivalent permeability of dual medium is very important for the estimation of reserves and the design of oil and gas production. At present, there are many methods to calculate the equivalent permeability of dual medium. These methods have their own advantages and disadvantages, and are suitable for different medium characteristics and physical problems, but they cannot calculate the equivalent permeability of dual medium under reservoir conditions. Thus, the emergence of fractal theory provides a theoretical basis for us to study the law of fluid transport in randomly distributed pores and fractures. Many scholars have deduced the analytical solution of the fractal model of double-porosity media, and the fractal dimension of the rock matrix and fracture network has been widely used in the permeability model of dual-porosity media. It has been proven that fracture permeability and pore matrix permeability considering fractal properties can be realistically applied. In this work, the fractal dimension of the rock matrix and fracture network aperture surface tortuosity are introduced to establish a dual-permeability calculation model considering the fracture closure effect. Taking the Yanchi Chang 8 area of the Ordos Basin as an example, comparing the results of the numerical simulation model and fractal model, the proposed two-porosity medium model considering the stress closure effect is more accurate. The sensitivity analysis of each parameter in the equivalent permeability model shows that considering the effect of stress closure reduced the fracture and pore aperture. The equivalent permeability is significantly influenced by the fracture inclination, the fractal dimension of the fracture aperture, and the fractal dimension of the matrix pore diameter. The rougher fracture surface and more tortuous capillary path forces particles to move longer distances, thereby reducing the permeability of the fracture network.
A new weighted extreme learning machine based on elastic net regularization embedded exponential regularized discriminative dictionary learning for image classification
Authors: Wu Di , Zhao PinYi , Wan Qin
Published: May 2023

It is well known that discriminative sparse representation can significantly improve the performance of image classification. However, there remain several tricky issues to be addressed due to the unsatisfied performance and high time consumption. In this paper, a novel classification framework called weighted extreme learning machine exponential regularized discriminative dictionary learning (WELM-ERDDL) is proposed to address these issues. The main contributions of this paper include (1) the WELM is embedded with ERDDL via exponential regularized linear discriminative analysis (ERLDA) for feature mappings while enabling nonlinear and diverse feature representation; (2) in the ELM learning process, the elastic net regularization is utilized to optimize more robust and meaningful output weights; (3) an effective weight update rule is designed for WELM. To verify the effectiveness of the proposed method, several experiments are conducted on real-world image classification databases. The results show that the proposed WELM-ERDDL framework is even more efficient than other state-of-the-art algorithms in general.
Carbon dioxide laser for treating pediatric facial papillomatosis: a case study
Authors: Xu Tianshu , Huang Zixian , Wang Yan , Wang Yuepeng , He Yilin , Cai Yongkang , Huang Zhiquan
Published: May 2023

Purpose

Carbon dioxide (CO2) lasers enable precise vaporization of lesions with minimal bleeding and have been widely used to excise a wide variety of lesions with good results. Papillomatosis is a disorder characterized by a wart-like growth that tends to recur relentlessly after surgical removal or medical treatment. Treatment of pediatric facial papillomatosis by utilizing a CO2 laser is a viable alternative strategy. This paper presents a case of an 8-month-old child with facial papilloma, that we treated by ablation using a CO2 laser, and discusses the efficacy of this treatment modality.

Methods

A case of pediatric facial papilloma treated with CO2 laser ablation was reported, and the benefits of this treatment modality were reviewed and analyzed in the context of the existing literature.

Results

Under general anesthesia, the lesional tissue of the left lip was excised, and the pathological diagnosis was confirmed to be maxillofacial papilloma. The lesions were surgically ablated in stages using a CO2 laser, and erythromycin ointment was applied to the treated areas after surgery. A total of three rounds of CO2 laser treatment were performed. The child had no complications during or after the operations; the child’s facial appearance was significantly improved, and there was no sign of recurrence during the 6-month follow-up.

Conclusions

The CO2 laser was useful for resection of this patient who had pediatric facial papillomatosis, and it can restore an aesthetic facial soft tissue profile without significant residual facial deformity. The CO2 laser can achieve precise vaporization resection of diseased tissue with minimal blood loss and a good cosmetic result.
Literary Adaptations in Spanish Cinema
Authors: Faulkner Sally
Published: May 2023

New readings of twentieth-century literary cinematic texts are presented here in historical context, informed by cultural theory.
The Welsh Trust, 1674–1681: a Charitable Proposal for Comprehension
Authors: WANG CHRISTY
Published: May 2023

The Welsh Trust (1674–81), established by Thomas Gouge, an ejected Presbyterian minister, brought together clergy and laity across emerging denominational divides who shared a desire to unite English Protestants against the perceived resurgence of Catholicism. The enterprise serves as a miniature of the tension among many Presbyterians between the reality of their dissent and the desire for church comprehension, challenging the traditional binary of ‘Dons’ and ‘Ducklings’. Furthermore, it reveals the creative ways in which mobilisers of comprehension pursued their ideals, which profoundly shaped the many godly reformations of the English Church after the Glorious Revolution.
The settlement of tax disputes by the International Court of Justice
Authors: Braumann Céline
Published: May 2023

This article analyses the ICJ, one of the most eminent actors of the international legal regime, as an actor of the international tax regime. So far, the ICJ’s role in tax dispute resolution has been a blind spot in the literature.

The descriptive part of this article first discusses the case law of the PCIJ and ICJ that considers – albeit incidentally – questions of taxation. These tax-related cases are categorized as (i) ‘wrongful taxation’ constituting the subject matter of the dispute; (ii) taxation as evidence for a ‘genuine link’ between the state and a national; or (iii) taxation as an ‘effectivité’ to prove the de facto exercise of state authority over a given territory.

The second half of the descriptive analysis assesses the Court’s jurisdiction over tax disputes. Tax treaties usually lack compromissory clauses. Yet, there are a number of jurisdictional bases that vest the Court with the competence to sit over hypothetical tax treaty disputes, although certain reservations may render the Court’s jurisdiction residual to other means of tax dispute settlement. Further, Article 344 TFEU possibly precludes EU member states from initiating ICJ proceedings concerning tax treaty disputes with other EU states.

The second, normative part of this article contemplates the Court as a future ‘World Tax Court’. It briefly addresses (i) possible effects of the ICJ’s hypothetical involvement in tax disputes; (ii) whether the ICJ might have a future role in tax dispute settlement in light of recent developments; and (iii) whether it is even desirable to involve the Court in tax disputes.
Effects of High‐Frequency Flow Variability on the Pathways of the Indonesian Throughflow
Authors: Iskandar Mochamad Riza , Jia Yanli , Sasaki Hideharu , Furue Ryo , Kida Shinichiro , Suga Toshio , Richards Kelvin J.
Published: May 2023

Previous studies have shown the presence of strong mesoscale eddy activities in the Indonesian Seas and their influence on the transport and water mass properties of the Indonesian Throughflow (ITF), a mean flow from the Pacific Ocean to the Indian Ocean through the Indonesian Archipelago. This study explores the effects of these eddy activities, or high‐frequency flow variability (HFFV), on residence time and pathway of the ITF by conducting Lagrangian particle tracking experiments using a velocity field from an eddy‐resolving ocean general circulation model. Particles are released at key locations in the western and eastern routes of the ITF and tracked both backward and forward in time. To assess the effects of flow variability that has a time scale longer than a day but shorter than a month, the definition of HFFV in this study, we conduct parallel experiments using daily and monthly averaged velocity fields. Particle trajectories reveal the contrasting circulation characteristics of the Sulawesi and Banda Seas. HFFV in the Sulawesi Sea (in the western route) is high, causing water to circulate longer over a broader area. The longer residence time in the Sulawesi Sea helps the upwelling of the inflowing Pacific waters, especially the intermediate water masses, to rise above 300 m at the Makassar Strait, and also has the potential to allow mixing processes to modify the water mass properties of the ITF. In contrast, HFFV is much lower in the Banda Sea and has minimal effects on the ITF.
Tree Rings Hint at the Fall of the Hittite Empire
Authors: Basilio Humberto
Published: May 2023

The Bronze Age civilization adapted to changes in climate but suffered during a prolonged crisis.
Probabilistic Assessment of Antarctic Thermomechanical Structure: Impacts on Ice Sheet Stability
Authors: Hazzard James A. N. , Richards Fred D. , Goes Saskia D. B. , Roberts Gareth G.
Published: May 2023

Uncertainty in present‐day glacial isostatic adjustment (GIA) rates represents at least 44% of the total gravity‐based ice mass balance signal over Antarctica. Meanwhile, physical couplings between solid Earth, sea level and ice dynamics enhance the dependency of the spatiotemporally varying GIA signal on three‐dimensional variations in mantle rheology. Improved knowledge of thermomechanical mantle structure is therefore required to refine estimates of current and projected ice mass balance. Here, we present a Bayesian inverse method for self‐consistently mapping shear‐wave velocities from high‐resolution adjoint tomography into thermomechanical structure using calibrated parameterisations of anelasticity at seismic frequency. We constrain the model using regional geophysical data sets containing information on upper mantle temperature, attenuation and viscosity structure. Our treatment allows formal quantification of parameter covariances, and naturally permits propagation of material parameter uncertainties into thermomechanical structure estimates. We find that uncertainty in steady‐state viscosity structure at 150 km depth can be reduced by 4–5 orders of magnitude compared with a forward‐modeling approach neglecting covariance between viscoelastic parameters. By accounting for the dependence of apparent viscosity on loading timescale, we find good agreement between our estimates of mantle viscosity beneath West Antarctica, and those derived from satellite GPS. Direct access to temperature structure allows us to estimate lateral variations in lithosphere‐asthenosphere boundary (LAB) depth, geothermal heat flow (GHF), and associated uncertainties. We find evidence for shallow LAB depths (63 ± 13 km), and high GHF (76 ± 7 mW m−2) beneath West Antarctica that, combined with low asthenospheric viscosities, indicate a highly dynamic response to ice mass loss.
Vortioxetine hydrobromide inhibits the growth of gastric cancer cells in vivo and in vitro by targeting JAK2 and SRC
Authors: Li Mingzhu , Duan Lina , Wu Wenjie , Li Wenjing , Zhao Lili , Li Ang , Lu Xuebo , He Xinyu , Dong Zigang , Liu Kangdong , Jiang Yanan
Published: May 2023

Gastric cancer is the fourth leading cause of cancer deaths worldwide. Most patients are diagnosed in the advanced stage. Inadequate therapeutic strategies and the high recurrence rate lead to the poor 5-year survival rate. Therefore, effective chemopreventive drugs for gastric cancer are urgently needed. Repurposing clinical drugs is an effective strategy for discovering cancer chemopreventive drugs. In this study, we find that vortioxetine hydrobromide, an FDA-approved drug, is a dual JAK2/SRC inhibitor, and has inhibitory effects on cell proliferation of gastric cancer. Computational docking analysis, pull-down assay, cellular thermal shift assay (CETSA) and in vitro kinase assays are used to illustrate vortioxetine hydrobromide directly binds to JAK2 and SRC kinases and inhibits their kinase activities. The results of non-reducing SDS-PAGE and Western blotting indicate that vortioxetine hydrobromide suppresses STAT3 dimerization and nuclear translocation activity. Furthermore, vortioxetine hydrobromide inhibits the cell proliferation dependent on JAK2 and SRC and suppresses the growth of gastric cancer PDX model in vivo. These data demonstrate that vortioxetine hydrobromide, as a novel dual JAK2/SRC inhibitor, curbs the growth of gastric cancer in vitro and in vivo by JAK2/SRC-STAT3 signaling pathways. Our results highlight that vortioxetine hydrobromide has the potential application in the chemoprevention of gastric cancer.
Multi-trait genome-wide association analyses leveraging alcohol use disorder findings identify novel loci for smoking behaviors in the Million Veteran Program
Authors: Cheng Youshu , Dao Cecilia , Zhou Hang , Li Boyang , Kember Rachel L. , Toikumo Sylvanus , Zhao Hongyu , Gelernter Joel , Kranzler Henry R. , Justice Amy C. , Xu Ke
Published: May 2023

Smoking behaviors and alcohol use disorder (AUD), both moderately heritable traits, commonly co-occur in the general population. Single-trait genome-wide association studies (GWAS) have identified multiple loci for smoking and AUD. However, GWASs that have aimed to identify loci contributing to co-occurring smoking and AUD have used small samples and thus have not been highly informative. Applying multi-trait analysis of GWASs (MTAG), we conducted a joint GWAS of smoking and AUD with data from the Million Veteran Program (N = 318,694). By leveraging GWAS summary statistics for AUD, MTAG identified 21 genome-wide significant (GWS) loci associated with smoking initiation and 17 loci associated with smoking cessation compared to 16 and 8 loci, respectively, identified by single-trait GWAS. The novel loci for smoking behaviors identified by MTAG included those previously associated with psychiatric or substance use traits. Colocalization analysis identified 10 loci shared by AUD and smoking status traits, all of which achieved GWS in MTAG, including variants onSIX3, NCAM1, and nearDRD2. Functional annotation of the MTAG variants highlighted biologically important regions onZBTB20, DRD2, PPP6C, andGCKRthat contribute to smoking behaviors. In contrast, MTAG of smoking behaviors and alcohol consumption (AC) did not enhance discovery compared with single-trait GWAS for smoking behaviors. We conclude that using MTAG to augment the power of GWAS enables the identification of novel genetic variants for commonly co-occuring phenotypes, providing new insights into their pleiotropic effects on smoking behavior and AUD.
Survival improvement of patients with FLT3 mutated acute myeloid leukemia: results from a prospective 9 years cohort
Authors: Oñate Guadalupe , Pratcorona Marta , Garrido Ana , Artigas-Baleri Alicia , Bataller Alex , Tormo Mar , Arnan Montserrat , Vives Susana , Coll Rosa , Salamero Olga , Vall-Llovera Ferran , Sampol Antònia , Garcia Antoni , Cervera Marta , Avila Sara Garcia , Bargay Joan , Ortín Xavier , Nomdedéu Josep F. , Esteve Jordi , Sierra Jorge ,   Spanish Cooperative Group for the Study and Treatment of Acute Leukemias and Myelodysplasias (CETLAM)
Published: May 2023

Midostaurin added to intensive chemotherapy is the standard of care for acute myeloid leukemia (AML) with FLT3 mutations (FLT3mut). We analyzed the impact of midostaurin in 227 FLT3mut-AML patients included in the AML-12 prospective trial for fit patients ≤70 years (#NCT04687098). Patients were divided into an early (2012–2015) and late (2016–2020) cohorts. They were uniformly treated except for the addition of midostaurin in 71% of late group patients. No differences were observed in response rates or the number of allotransplants between groups. Outcome was improved in the late period: 2-year relapse incidence decreased from 42% vs 29% in early vs late group (p = 0.024) and 2-year overall survival (OS) improved from 47% vs 61% (p = 0.042), respectively. The effect of midostaurin was evident in NPM1mut patients (n = 151), with 2-yr OS of 72% (exposed) vs 50% (naive) patients (p = 0.011) and mitigated FLT3-ITD allelic ratio prognostic value: 2-yr OS with midostaurin was 85% and 58% in low and high ratio patients (p = 0.049) vs 67% and 39% in naive patients (p = 0.005). In the wild-type NPM1 subset (n = 75), we did not observe significant differences between both study periods. In conclusion, this study highlights the improved outcome of FLT3mut AML fit patients with the incorporation of midostaurin.
Clarifying the effect of biodiversity on productivity in natural ecosystems with longitudinal data and methods for causal inference
Authors: Dee Laura E. , Ferraro Paul J. , Severen Christopher N. , Kimmel Kaitlin A. , Borer Elizabeth T. , Byrnes Jarrett E. K. , Clark Adam Thomas , Hautier Yann , Hector Andrew , Raynaud Xavier , Reich Peter B. , Wright Alexandra J. , Arnillas Carlos A. , Davies Kendi F. , MacDougall Andrew , Mori Akira S. , Smith Melinda D. , Adler Peter B. , Bakker Jonathan D. , Brauman Kate A. , Cowles Jane , Komatsu Kimberly , Knops Johannes M. H. , McCulley Rebecca L. , Moore Joslin L. , Morgan John W. , Ohlert Timothy , Power Sally A. , Sullivan Lauren L. , Stevens Carly , Loreau Michel
Published: May 2023

Causal effects of biodiversity on ecosystem functions can be estimated using experimental or observational designs — designs that pose a tradeoff between drawing credible causal inferences from correlations and drawing generalizable inferences. Here, we develop a design that reduces this tradeoff and revisits the question of how plant species diversity affects productivity. Our design leverages longitudinal data from 43 grasslands in 11 countries and approaches borrowed from fields outside of ecology to draw causal inferences from observational data. Contrary to many prior studies, we estimate that increases in plot-level species richness caused productivity to decline: a 10% increase in richness decreased productivity by 2.4%, 95% CI [−4.1, −0.74]. This contradiction stems from two sources. First, prior observational studies incompletely control for confounding factors. Second, most experiments plant fewer rare and non-native species than exist in nature. Although increases in native, dominant species increased productivity, increases in rare and non-native species decreased productivity, making the average effect negative in our study. By reducing the tradeoff between experimental and observational designs, our study demonstrates how observational studies can complement prior ecological experiments and inform future ones.
Neutrophil metabolomics in severe COVID-19 reveal GAPDH as a suppressor of neutrophil extracellular trap formation
Authors: Li Yafeng , Hook Jessica S. , Ding Qing , Xiao Xue , Chung Stephen S. , Mettlen Marcel , Xu Lin , Moreland Jessica G. , Agathocleous Michalis
Published: May 2023

Severe COVID-19 is characterized by an increase in the number and changes in the function of innate immune cells including neutrophils. However, it is not known how the metabolome of immune cells changes in patients with COVID-19. To address these questions, we analyzed the metabolome of neutrophils from patients with severe or mild COVID-19 and healthy controls. We identified widespread dysregulation of neutrophil metabolism with disease progression including in amino acid, redox, and central carbon metabolism. Metabolic changes in neutrophils from patients with severe COVID-19 were consistent with reduced activity of the glycolytic enzyme GAPDH. Inhibition of GAPDH blocked glycolysis and promoted pentose phosphate pathway activity but blunted the neutrophil respiratory burst. Inhibition of GAPDH was sufficient to cause neutrophil extracellular trap (NET) formation which required neutrophil elastase activity. GAPDH inhibition increased neutrophil pH, and blocking this increase prevented cell death and NET formation. These findings indicate that neutrophils in severe COVID-19 have an aberrant metabolism which can contribute to their dysfunction. Our work also shows that NET formation, a pathogenic feature of many inflammatory diseases, is actively suppressed in neutrophils by a cell-intrinsic mechanism controlled by GAPDH.
Probing excitations and cooperatively rearranging regions in deeply supercooled liquids
Authors: Ortlieb Levke , Ingebrigtsen Trond S. , Hallett James E. , Turci Francesco , Royall C. Patrick
Published: May 2023

Upon approaching the glass transition, the relaxation of supercooled liquids is controlled by activated processes, which become dominant at temperatures below the so-called dynamical crossover predicted by Mode Coupling theory (MCT). Two of the main frameworks rationalising this behaviour are dynamic facilitation theory (DF) and the thermodynamic scenario which give equally good descriptions of the available data. Only particle-resolved data from liquids supercooled below the MCT crossover can reveal the microscopic mechanism of relaxation. By employing state-of-the-art GPU simulations and nano-particle resolved colloidal experiments, we identify the elementary units of relaxation in deeply supercooled liquids. Focusing on the excitations of DF and cooperatively rearranging regions (CRRs) implied by the thermodynamic scenario, we find that several predictions of both hold well below the MCT crossover: for the elementary excitations, their density follows a Boltzmann law, and their timescales converge at low temperatures. For CRRs, the decrease in bulk configurational entropy is accompanied by the increase of their fractal dimension. While the timescale of excitations remains microscopic, that of CRRs tracks a timescale associated with dynamic heterogeneity, $${t}^{*} \sim {\tau }_{\alpha }^{0.8}$$

t

*

~

τ

α

0.8

. This timescale separation of excitations and CRRs opens the possibility of accumulation of excitations giving rise to cooperative behaviour leading to CRRs.
Paired immunoglobulin-like receptor B is an entry receptor for mammalian orthoreovirus
Authors: Shang Pengcheng , Simpson Joshua D. , Taylor Gwen M. , Sutherland Danica M. , Welsh Olivia L. , Aravamudhan Pavithra , Natividade Rita Dos Santos , Schwab Kristina , Michel Joshua J. , Poholek Amanda C. , Wu Yijen , Rajasundaram Dhivyaa , Koehler Melanie , Alsteens David , Dermody Terence S.
Published: May 2023

Mammalian orthoreovirus (reovirus) infects most mammals and is associated with celiac disease in humans. In mice, reovirus infects the intestine and disseminates systemically to cause serotype-specific patterns of disease in the brain. To identify receptors conferring reovirus serotype-dependent neuropathogenesis, we conducted a genome-wide CRISPRa screen and identified paired immunoglobulin-like receptor B (PirB) as a receptor candidate. Ectopic expression of PirB allowed reovirus binding and infection. PirB extracelluar D3D4 region is required for reovirus attachment and infectivity. Reovirus binds to PirB with nM affinity as determined by single molecule force spectroscopy. Efficient reovirus endocytosis requires PirB signaling motifs. In inoculated mice, PirB is required for maximal replication in the brain and full neuropathogenicity of neurotropic serotype 3 (T3) reovirus. In primary cortical neurons, PirB expression contributes to T3 reovirus infectivity. Thus, PirB is an entry receptor for reovirus and contributes to T3 reovirus replication and pathogenesis in the murine brain.
Analysis of PPI networks of transcriptomic expression identifies hub genes associated with Newcastle disease virus persistent infection in bladder cancer
Authors: Ahmad Umar , Abdullah Syahril , Chau De Ming , Chia Suet Lin , Yusoff Khatijah , Chan Soon Choy , Ong Teng Aik , Razack Azad Hassan , Veerakumarasivam Abhi
Published: May 2023

Bladder cancer cells can acquire persistent infection of oncolytic Newcastle disease virus (NDV) but the molecular mechanism(s) remain unelucidated. This poses a major barrier to the effective clinical translation of oncolytic NDV virotherapy of cancers. To improve our understanding of the molecular mechanism(s) associated with the development of NDV persistent infection in bladder cancer, we used mRNA expression profiles of persistently infected bladder cancer cells to construct PPI networks. Based on paths and modules in the PPI network, the bridges were found mainly in the upregulated mRNA-pathways of p53 signalling, ECM-receptor interaction, and TGF-beta signalling and downregulated mRNA-pathways of antigen processing and presentation, protein processing in endoplasmic reticulum, completement and coagulation cascades in persistent TCCSUPPi cells. In persistent EJ28Pi cells, connections were identified mainly through upregulated mRNA-pathways of renal carcinoma, viral carcinogenesis, Ras signalling and cell cycle and the downregulated mRNA-pathways of Wnt signalling, HTLV-I infection and pathways in cancers. These connections were mainly dependent on RPL8-HSPA1A/HSPA4 in TCCSUPPi cells and EP300, PTPN11, RAC1—TP53, SP1, CCND1 and XPO1 in EJ28Pi cells. Oncomine validation showed that the top hub genes identified in the networks that include RPL8, THBS1, F2 from TCCSUPPi and TP53 and RAC1 from EJ28Pi are involved in the development and progression of bladder cancer. Protein-drug interaction networks identified several putative drug targets that could be used to disrupt the linkages between the modules and prevent bladder cancer cells from acquiring NDV persistent infection. This novel PPI network analysis of differentially expressed mRNAs of NDV persistently infected bladder cancer cell lines provide an insight into the molecular mechanisms of NDV persistency of infection in bladder cancers and the future screening of drugs that can be used together with NDV to enhance its oncolytic efficacy.
E. coli allantoinase is activated by the downstream metabolic enzyme, glycerate kinase, and stabilizes the putative allantoin transporter by direct binding
Authors: Rodionova Irina A. , Hosseinnia Ali , Kim Sunyoung , Goodacre Norman , Zhang Li , Zhang Zhongge , Palsson Bernhard , Uetz Peter , Babu Mohan , Saier Milton H.
Published: May 2023

Allantoin is a good source of ammonium for many organisms, and in Escherichia coli it is utilized under anaerobic conditions. We provide evidence that allantoinase (AllB) is allosterically activated by direct binding of the allantoin catabolic enzyme, glycerate 2-kinase (GlxK) in the presence of glyoxylate. Glyoxylate is known to be an effector of the AllR repressor which regulates the allantoin utilization operons in E. coli. AllB has low affinity for allantoin, but its activation by GlxK leads to increased affinity for its substrate. We also show that the predicted allantoin transporter YbbW (re-named AllW) has allantoin specificity and the protein–protein interaction with AllB. Our results show that the AllB-dependent allantoin degradative pathway is subject to previously unrecognized regulatory mechanisms involving direct protein–protein interactions.
Perceptions of intelligence & sentience shape children’s interactions with robot reading companions
Authors: Caruana Nathan , Moffat Ryssa , Miguel-Blanco Aitor , Cross Emily S.
Published: May 2023

The potential for robots to support education is being increasingly studied and rapidly realised. However, most research evaluating education robots has neglected to examine the fundamental features that make them more or less effective, given the needs and expectations of learners. This study explored how children’s perceptions, expectations and experiences are shaped by aesthetic and functional features during interactions with different robot ‘reading buddies’. We collected a range of quantitative and qualitative measures of subjective experience before and after children read a book with one of three different robots. An inductive thematic analysis revealed that robots have the potential offer children an engaging and non-judgemental social context to promote reading engagement. This was supported by children’s perceptions of robots as being intelligent enough to read, listen and comprehend the story, particularly when they had the capacity to talk. A key challenge in the use of robots for this purpose was the unpredictable nature of robot behaviour, which remains difficult to perfectly control and time using either human operators or autonomous algorithms. Consequently, some children found the robots’ responses distracting. We provide recommendations for future research seeking to position seemingly sentient and intelligent robots as an assistive tool within and beyond education settings.