bluuebunny/crossref_metadata_2025 huggingface dataset:
Impact of immunotherapy time-of-day infusion on survival and immunologic correlates in patients with metastatic renal cell carcinoma: a multicenter cohort analysis
Authors: Patel Jimmy S , Woo Yena , Draper Amber , Jansen Caroline S , Carlisle Jennifer W , Innominato Pasquale F , Lévi Francis A , Dhabaan Layla , Master Viraj A , Bilen Mehmet A , Khan Mohammad K , Lowe Michael C , Kissick Haydn , Buchwald Zachary S , Qian David C
Published: March 2024

Background

Recent studies have demonstrated that earlier time-of-day infusion of immune checkpoint inhibitors (ICIs) is associated with longer progression-free survival (PFS) and overall survival (OS) among patients with metastatic melanoma and non-small cell lung cancer. These data are in line with growing preclinical evidence that the adaptive immune response may be more effectively stimulated earlier in the day. We sought to determine the impact of time-of-day ICI infusions on outcomes among patients with metastatic renal cell carcinoma (mRCC).

Methods

The treatment records of all patients with stage IV RCC who began ICI therapy within a multicenter academic hospital system between 2015 and 2020 were reviewed. The associations between the proportion of ICI infusions administered prior to noon (denoting morning infusions) and PFS and OS were evaluated using univariate and multivariable Cox proportional hazards regression.

Results

In this study, 201 patients with mRCC (28% women) received ICIs and were followed over a median of 18 months (IQR 5–30). The median age at the time of ICI initiation was 63 years (IQR 56–70). 101 patients (50%) received ≥20% of their ICI infusions prior to noon (Group A) and 100 patients (50%) received <20% of infusions prior to noon (Group B). Across the two comparison groups, initial ICI agents consisted of nivolumab (58%), nivolumab plus ipilimumab (34%), and pembrolizumab (8%). On univariate analysis, patients in Group A had longer PFS and OS compared with those in Group B (PFS HR 0.67, 95% CI 0.48 to 0.94, Punivar=0.020; OS HR 0.57, 95% CI 0.34 to 0.95, Punivar=0.033). These significant findings persisted following multivariable adjustment for age, sex, performance status, International Metastatic RCC Database Consortium risk score, pretreatment lactate dehydrogenase, histology, and presence of bone, brain, and liver metastases (PFS HR 0.70, 95% CI 0.50 to 0.98, Pmultivar=0.040; OS HR 0.57, 95% CI 0.33 to 0.98, Pmultivar=0.043).

Conclusions

Patients with mRCC may benefit from earlier time-of-day receipt of ICIs. Our findings are consistent with established mechanisms of chrono-immunology, as well as with preceding analogous studies in melanoma and lung cancer. Additional prospective randomized trials are warranted.
Cost-effectiveness of treating advanced melanoma with tumor-infiltrating lymphocytes based on an international randomized phase 3 clinical trial
Authors: ten Ham Renske M T , Rohaan Maartje W , Jedema Inge , Kessels Rob , Stegeman Wim , Scheepmaker Walter , Nuijen Bastiaan , Nijenhuis Cynthia , Lindenberg Melanie , Borch Troels Holz , Monberg Tine , Donia Marco , Marie Svane Inge , van Harten Wim , Haanen John , Retel Valesca P
Published: March 2024

Introduction

In a multicenter, open-label randomized phase 3 clinical trial conducted in the Netherlands and Denmark, treatment with ex vivo-expanded tumor-infiltrating lymphocytes (TIL-NKI/CCIT) from autologous melanoma tumor compared with ipilimumab improved progression-free survival in patients with unresectable stage IIIC–IV melanoma after failure of first-line or second-line treatment. Based on this trial, we conducted a cost-utility analysis.

Methods

A Markov decision model was constructed to estimate expected costs (expressed in 2021€) and outcomes (quality-adjusted life years (QALYs)) of TIL-NKI/CCIT versus ipilimumab in the Netherlands. The Danish setting was assessed in a scenario analysis. A modified societal perspective was applied over a lifetime horizon. TIL-NKI/CCIT production costs were estimated via activity-based costing. Through sensitivity analyses, uncertainties and their impact on the incremental cost-effectiveness ratio (ICER) were assessed.

Results

Mean total undiscounted lifetime benefits were 4.47 life years (LYs) and 3.52 QALYs for TIL-NKI/CCIT and 3.33 LYs and 2.46 QALYs for ipilimumab. Total lifetime undiscounted costs in the Netherlands were €347,168 for TIL-NKI/CCIT (including €67,547 for production costs) compared with €433,634 for ipilimumab. Undiscounted lifetime cost in the Danish scenario were €337,309 and €436,135, respectively. This resulted in a dominant situation for TIL-NKI/CCIT compared with ipilimumab in both countries, meaning incremental QALYs were gained at lower costs. Survival probabilities, and utility in progressive disease affected the ICER most.

Conclusion

Based on the data of a randomized phase 3 trial, treatment with TIL-NKI/CCIT in patients with unresectable stage IIIC–IV melanoma is cost-effective and cost-saving, both in the current Dutch and Danish setting. These findings led to inclusion of TIL-NKI/CCIT as insured care and treatment guidelines. Publicly funded development of the TIL-NKI/CCIT cell therapy shows realistic promise to further explore development of effective personalized treatment while warranting economic sustainability of healthcare systems.
Superior cortical venous anatomy for endovascular device implantation: a systematic review
Authors: Brannigan Jamie , McClanahan Alexander , Hui Ferdinand , Fargen Kyle M , Pinter Nandor , Oxley Thomas J
Published: March 2024

Endovascular electrode arrays provide a minimally invasive approach to access intracranial structures for neural recording and stimulation. These arrays are currently used as brain–computer interfaces (BCIs) and are deployed within the superior sagittal sinus (SSS), although cortical vein implantation could improve the quality and quantity of recorded signals. However, the anatomy of the superior cortical veins is heterogenous and poorly characterised. MEDLINE and Embase databases were systematically searched from inception to December 15, 2023 for studies describing the anatomy of the superior cortical veins. A total of 28 studies were included: 19 cross-sectional imaging studies, six cadaveric studies, one intraoperative anatomical study and one review. There was substantial variability in cortical vein diameter, length, confluence angle, and location relative to the underlying cortex. The mean number of SSS branches ranged from 11 to 45. The vein of Trolard was most often reported as the largest superior cortical vein, with a mean diameter ranging from 2.1 mm to 3.3 mm. The mean vein of Trolard was identified posterior to the central sulcus. One study found a significant age-related variability in cortical vein diameter and another identified myoendothelial sphincters at the base of the cortical veins. Cortical vein anatomical data are limited and inconsistent. The vein of Trolard is the largest tributary vein of the SSS; however, its relation to the underlying cortex is variable. Variability in cortical vein anatomy may necessitate individualized pre-procedural planning of training and neural decoding in endovascular BCI. Future focus on the relation to the underlying cortex, sulcal vessels, and vessel wall anatomy is required.
PERSPECTIVES OF PERSONS WITH APHASIA, CAREGIVERS, AND SPEECH THERAPISTS TOWARD COVID-INDUCED CHANGES IN APHASIA SERVICES: A RETROSPECTIVE REPORT
Authors: KONG ANTHONY PAK-HIN , CHANG VICTOR WAI-TAT
Published: March 2024

Aphasia is an acquired language disorder caused by damage in a specific area of the brain that controls language use and understanding. This retroactive report aimed to summarize the influence of the COVID-19 pandemic on the lived experience of people with aphasia (PWA) and caregivers. Their perceptions of the quality and effectiveness of these services were compared with service providers (speech therapists). About half of the PWA received speech-and-language therapy during phase 1 of COVID-19 (first half of 2020), but this issue of missing therapy sessions improved in phase 2 (the third and fourth waves of infection between July 2020 and October 2021). The pandemic reduced PWA’s social interactions and increased negative emotions in PWA and caregivers. Most speech therapists only commenced telepractice after the first COVID-19 outbreak, but in-person sessions resumed in phase 2. While most service receivers were in favor of teletherapy, therapists identified limitations and recommended suggestions for future implementation.
A reinterpretation of the mineralization processes involved in the formation of the Tomnadashan sulfide deposit, Loch Tay, Scotland, UK
Authors: Webb S. , Torvela T. , Chapman R. , Selby D. , Gooday R.
Published: March 2024

The Tomnadashan sulfide deposit, which is located on the southern margin of Loch Tay (Scotland, UK), was mined for copper during the 19th century. The genetic processes at Tomnadashan remain poorly understood, and the mineralization has never been dated. To gain an improved understanding of this mineral system, we have dated the molybdenite at Tomnadashan using the Re–Os chronometer. Furthermore, we have contextualized these ages within a paragenetic interpretation. Our results show that the age of the molybdenite is
c.
423–419 Ma, and it occurs early in the paragenesis (the second stage out of six). Based on the paragenesis of molybdenite, this age is likely to reflect the initial Caledonian mineralization event at Loch Tay. Our new data and literature review suggest that although Tomnadashan is a magmatic-related ore deposit, the porphyry that crops out is unlikely to have provided the mineralizing fluids associated with the mineralization. A concealed intrusion or granitic dykes within the porphyry may be the source of the magmatic–hydrothermal fluids. The age data indicate that the Tomnadashan mineralization is coeval with gold mineralization at Cavanacaw in Northern Ireland, giving rise to the possibility of a previously unrecognized mid-Silurian magmatic–hydrothermal episode of gold and base metal mineralization throughout the Grampian Terrane.

Thematic collection:
This article is part of the Early Career Research collection available at:
https://www.lyellcollection.org/topic/collections/early-career-research
Recovery from Adversarial Attacks in Cyber-physical Systems: Shallow, Deep, and Exploratory Works
Authors: Lu Pengyuan , Zhang Lin , Liu Mengyu , Sridhar Kaustubh , Sokolsky Oleg , Kong Fanxin , Lee Insup
Published: March 2024

Cyber-physical systems (CPS) have experienced rapid growth in recent decades. However, like any other computer-based systems, malicious attacks evolve mutually, driving CPS to undesirable physical states, and potentially causing catastrophes. Although the current state-of-the-art is well aware of this issue, the majority of researchers have not focused on CPS recovery, the procedure we defined as restoring a CPS’s physical state back to a target condition under adversarial attacks. To call for attention on CPS recovery and identify existing efforts, we have surveyed a total of 30 relevant papers. We identify a major partition of the proposed recovery strategies: shallow recovery vs. deep recovery, where the former does not use a dedicated recovery controller while the latter does. Additionally, we surveyed exploratory research on topics that facilitate recovery. From these publications, we discuss the current state-of-the-art of CPS recovery, with respect to applications, attack type, attack surfaces, and system dynamics. Then, we identify untouched sub-domains in this field and suggest possible future directions for researchers.
An Ontology-Based Framework for Supporting Decision-Making in Conservation and Restoration Interventions for Cultural Heritage
Authors: Moraitou Efthymia , Christodoulou Yannis , Kotis Konstantinos , Caridakis George
Published: March 2024

Decision-making (DM) is the backbone of the Conservation and Restoration (CnR) of Cultural Heritage (CH). The demands of the DM process for information organization and management have raised issues that the CnR community attempts to solve by creating DM-support tools and systems, which, among others, exploit Semantic Web (SW) technologies. Regarding the tools and systems that focus on the DM process of selecting an intervention option (CnR-DM-I), they present benefits, as well as limitations, regarding the (1) completeness of representation of the relevant knowledge in a unified manner, (2) facilitation of recording the CnR-DM-I process
per se
, in terms of the problem at hand as well as the intervention parameters, requirements, and criteria, and (3) recommendation and further exploration of CnR intervention options in a systematic manner. This work proposes an ontology-based framework as a means to overcome those limitations. The proposed framework (DS-CnRI) sets at its core a formal ontology which provides the necessary entities to represent expert knowledge related to CnR-DM-I. The ontology also includes rules which provide useful inferences to assist the CnR-DM-I process. The proposed framework has been deployed and evaluated in collaboration with conservators. Initial evaluation results show that the framework assists conservators in CnR-DM-I to detect and select the most suitable intervention options, to better understand the limitations of different options, and to document the process of reaching their decision.
Real-Time Attentive Dilated U-Net for Extremely Dark Image Enhancement
Authors: Huang Junjian , Ren Hao , Liu Shulin , Liu Yong , Lv Chuanlu , Lu Jiawen , Xie Changyong , Lu Hong
Published: March 2024

Images taken under low-light conditions suffer from poor visibility, color distortion, and graininess, all of which degrade the image quality and hamper the performance of downstream vision tasks, such as object detection and instance segmentation in the field of autonomous driving, making low-light enhancement an indispensable basic component of high-level visual tasks. Low-light enhancement aims to mitigate these issues, and has garnered extensive attention and research over several decades. The primary challenge in low-light image enhancement arises from the low signal-to-noise ratio caused by insufficient lighting. This challenge becomes even more pronounced in near-zero lux conditions, where noise overwhelms the available image information. Both traditional image signal processing pipeline and conventional low-light image enhancement methods struggle in such scenarios. Recently, deep neural networks have been used to address this challenge. These networks take unmodified RAW images as input and produce the enhanced sRGB images, forming a deep learning based image signal processing pipeline. However, most of these networks are computationally expensive and thus far from practical use. In this article, we propose a lightweight model called
attentive dilated U-Net
(ADU-Net) to tackle this issue. Our model incorporates several innovative designs, including an asymmetric U-shape architecture, dilated residual modules for feature extraction, and attentive fusion modules for feature fusion. The dilated residual modules provide strong representative capability, whereas the attentive fusion modules effectively leverage low-level texture information and high-level semantic information within the network. Both modules employ a lightweight design but offer significant performance gains. Extensive experiments demonstrate that our method is highly effective, achieving an excellent balance between image quality and computational complexity—that is, taking less than 4ms for a high-definition 4K image on a single GTX 1080Ti GPU and yet maintaining competitive visual quality. Furthermore, our method exhibits pleasing scalability and generalizability, highlighting its potential for widespread applicability.
High Porous Activated Carbon Electrode Derived from Watermelon Peel Biomass Exposed with DC Glow Discharge Plasma Applied for Super Capacitors
Authors: K C Sowmiya , K A Vijayalakshmi
Published: March 2024

The growing demand for sustainable and environmentally-friendly technologies has spurred the exploration of innovative methods for waste management and resource utilization. Among the various bio-wastes generated globally, watermelon peel emerges as a significant contributor. To characterize carbon materials in the presence of functional groups, for morphological analysis, and intensity, we subjected activated fruit peel carbon to X-ray diffraction, Fourier-transform infrared spectroscopy, field-emission scanning electron microscopy, X-ray photoelectron spectroscopy, and Raman studies. Furthermore, we examined its electrochemical performance. Another method used to assess wettability is the contact angle. Watermelon-rind-activated carbon was exposed to a DC glow discharge oxygen and air plasma with a 450 V applied potential. The air-treated carbon demonstrated a noteworthy capacitance of 1669 F g−1 at 0.5 mA g−1 in a 2 M KOH electrolyte. Our study found that the properties of the activated carbon were enhanced through cold plasma treatment. This research provides valuable insights into the potential resources of fruit peels and proposes a novel adsorbent with cost-effective advantages in supercapacitors, which could provide effective energy storage for portable gadgets, electric cars, and renewable energy systems, thus presenting a solution for sustainable waste management.
Analysis of CNT and rGO Mediation for an Efficient Super-Capacitive Response in Cr-Doped Co3O4 Based Composites
Authors: Faryad Umar , Imran Muhammad , Zawar Sidra , Yaqub Muhammad Atif , Murtaza Ghulam , Ramay Shahid M. , Atiq Shahid
Published: March 2024

The synthesis of novel and high capacitance electrode materials has attracted much attention over the last few decades to meet the needs of electrode materials in supercapacitors. Cobalt oxide, one of several vanadium oxides, has recently gained popularity due to its unique layered structure, phase transition, and applications in supercapacitors. Here, we present structural, morphological, and electrochemical analysis of Cr-doped Co3O4 nanostructures and their carbon nanotubes/reduced graphene oxide (CNT/rGO) based composites. Hydrothermal and solvothermal routes are followed to prepare the samples. The active material is developed via a polymer-based binder and is used as the electrode in a three-electrode electrochemical system. X-ray diffraction confirms the spinel-type cubic crystal structure, while the stoichiometric elemental contents are verified via an energy dispersive X-ray spectroscopy. Well-shaped layered growth of the nanocomposites is revealed by field emission scanning electron microscopy. The electrochemical analysis is performed using a 2 M KOH electrolyte solution and a three-electrode electrochemical setup. The pure and Cr-doped nanocomposite samples reveal a pseudo capacitive behavior in all samples. The systematic capacitive and resistive response of the samples has also been presented in this report. The aforementioned attributes make the synthesized specimen a potential candidate for an electrode material.
Evaluations of artificial intelligence and machine learning algorithms in neurodiagnostics
Authors: Williams Kristin S.
Published: March 2024

This article evaluates the ethical implications of utilizing artificial intelligence (AI) algorithms in neurological diagnostic examinations. Applications of AI technology have been utilized to aid in the determination of pharmacological dosages of gadolinium for brain lesion detection, localization of seizure foci, and the characterization of large vessel occlusion in ischemic stroke patients. Multiple subtypes of AI/machine learning (ML) algorithms are analyzed, as AI-assisted neurology utilizes supervised, unsupervised, artificial neural network (ANN), and deep neural network (DNN) learning models. As ANN and DNN analyses can be applied to data with an unknown clinical diagnosis, these algorithms are evaluated according to Bayesian statistical analyses. Bayesian neural network analyses are incorporated, as these algorithms indicate that the predictive accuracy and model performance are dependent upon accurate configurations of the model’s hyperparameters and neural inputs. Thus, mathematical evaluations of AI algorithms are comprehensively explored to examine their clinical utility, as underperformance of AI/ML models may have deleterious consequences that affect patient outcomes due to misdiagnosis and false-negative test results.
Bézier Cubics and Neural Network Agreement along a Moderate Geomagnetic Storm
Authors: Eroglu Emre , Koksal Mehmet Emir
Published: March 2024

The discussion models the IRI‐2012 TEC map over a moderate geomagnetic storm period (5 days) in February 2015 and compares the yield of the models. The models are constructed with the help of cubic Bézier curves and machine learning. In a sense, the comparison of a classical and mechanical approach with a modern and computer‐based one is a considerable experience for the paper. The parametric curve approach governs models of piecewise continuous Bézier cubics, while the models employ only the TEC map. The design is separated into curve components at every five‐hour curvature point, and each component is handled independently. Instead of the traditional least squares method for finding control points of cubics, it utilizes the mean of every five‐hour of the piecewise curves of the TEC data. Accordingly, the prediction error can be controlled at a rate that can compete with the modern network approach. In the network model, 120 hours of the solar wind parameters and the TEC map of the storm are processed. The reliability of the network model is assessed by the (R) correlation coefficient and mean square error. In modeling the TEC map with the classical approach, the mean absolute error is 0.0901% and the correlation coefficient (R) score is 99.9%. The R score of the network model is 99.6%, and the mean square error is 0.71958 (TECU) (at epoch 47). The results agree with the literature.
First Report of Myocastor coypus Infected with Staphylococcus cohnii
Authors: Dong Wei , Peng Nana , Yang Lei , Ning Huimin , Fan Jie , Li Xinying , Chen Yuhao , Han Xu , Ge Meng
Published: March 2024

In December 2021, a wildlife conservation base in Hunan, China, reported illness and death among its captive Myocastor coypus population. A gram‐positive pathogen was isolated from the affected animals. The 16S rDNA sequence of the isolated strain was approximately 1,500 bp long and exhibited 98.4% homogeneity with Staphylococcus cohnii found in sea cucumbers. Interestingly, the biochemical reactions of the isolated strain were consistent with the characteristics of S. cohnii. The LD100 for BALB/c mice was 1.2 × 107 CFU/g, while the MLD was 0.6 × 107 CFU/g. Inflammatory cell infiltration was observed in the liver, spleen, and kidneys of infected mice, accompanied by widespread systemic bacteremia and focal hepatic and splenic necrosis. Moreover, mycelium was detected in the liver and kidney. The isolated strain possessed both HLB and PVL virulence genes. To the best of our knowledge, this is the first study to report a highly pathogenic strain of S. cohnii isolated from M. coypus, possessing both HLB and PVL virulence genes. The findings contribute to yielding a better understanding of the pathogenic mechanisms of S. cohnii and have significant implications for disease control in M. coypus, as well as for public health safety and the prevention of zoonotic diseases.
ACP-Based Space Systems: Design, Development, and Operation
Authors: Cai Yingkai , Meng Qingliang , Wang Zhaokui
Published: March 2024

In the context of the rapid advancements in space technology and the increasing complexity of space missions, there is a growing need for efficient and effective approaches to tackle the multifaceted challenges faced by space systems. Traditional methods often fall short in providing comprehensive support throughout the entire life cycle of space systems. To address these challenges, this paper presents a novel parallel space system architecture based on ACP (artificial systems, computational experiments, and parallel execution) and explores its applications in the design, development, and operation of space systems. The proposed architecture integrates artificial systems with actual space systems and employs computational experiments to generate extensive sample data. This approach enhances the accuracy of the artificial systems’ model and optimizes the performance of the real systems, facilitating parallel advancements between the two. The design, development, and operation processes of Q-Sat, implemented using the ACP framework, serve as a case study to illustrate the advantages of parallel space systems. Following adjustments made to the discrepancies between parallel systems under the ACP-based space system framework, the accuracy of missing orbit compensation improved by 86.5%, and the 24-hour forecast positional error was reduced by approximately 65 m. Furthermore, this paper discusses future trends, emphasizing the increasing efficiency and reliability of digitized, integrated, and adaptive space systems. The findings contribute to the understanding of parallel space systems and provide valuable insights for further advancements in the field.
Red Yeast Rice and Optimal Fermentation Periods Improve the Quality of Esan Fermented Fish Sausage
Authors: Gawborisut Somsamorn , Muengkratok Suprawee
Published: March 2024

Esan fermented fish sausage (EFFS) has an unappealing off-white color. The incorporation of an appropriate amount of red yeast rice (RYR) and the selection of an optimal fermentation period may yield visually appealing, high-quality sausages. This study is aimed at investigating the effects of different RYR levels (0, 0.35, and 0.7%) and fermentation periods (0, 2, 4, and 6 days) on the quality parameters of EFFS. The following parameters were examined for raw EFFS: CIE color values (L∗, a∗, and b∗), microbial analyses (total viable count, lactic acid bacteria, and yeast and mold counts), titratable acidity (TA), pH, weight loss, cooking loss, texture profile analysis (TPA), and sensory evaluation (color, odor, hand-feel texture, overall acceptability, and overall preference ranking). The quality parameters of the cooked EFFS were CIE color values and sensory evaluation (color, odor, mouthfeel, texture, flavor, overall acceptability, and overall preference ranking). The results showed that 0.35 and 0.7% RYR increased the a∗ (red/green) values of raw and cooked EFFS but decreased the L∗ (lightness) and b∗ (yellow/blue) values. These RYR levels significantly improved the sensory color, overall acceptability, and overall preference ranking of the raw and cooked EFFSs. However, no statistical differences were observed between the effects of 0.35 and 0.7% RYR. RYR levels did not affect the microbial analyses, TA, pH, weight loss, cooking loss, or TPA. Moreover, they had no effect on the odor and hand-feel texture of raw EFFS, or the odor, mouthfeel texture, or flavor of cooked EFFS. Therefore, RYR supplementation improved the color quality of the EFFSs without altering the other quality parameters, with 0.35% RYR deemed optimal. Moreover, the fermentation period significantly influenced most quality parameters, except CIE color values and sensory color perception of raw and cooked EFFSs. Most sensory parameters improved by day 2, remained unchanged until day 4, and then deteriorated on day 6.
A Hybrid Expert System for Estimation of the Manufacturability of a Notional Design
Authors: Sommers Alexander , Rahimi Shahram , McCall Tonya , Wall Emily , Henslee Althea , Dalton Larry , Babin Paul D. , Watson Nathan , Sharma Gehendra , Parmar Milan D.
Published: March 2024

The more “manufacturable” a product is, the “easier” it is to manufacture. For two different product designs targeting the same role, one may be more manufacturable than the other. Evaluating manufacturability requires experts in the processes of manufacturing, “manufacturing process engineers” (MPEs). Human experts are expensive to train and employ, while a well‐designed expert system (ES) could be quicker, more reliable, and provide higher performance and superior accuracy. In this work, a group of MPEs (“Team A”) externalized a portion of their expertise into a rule‐based expert system in cooperation with a group of ES knowledge engineers and developers. We produced a large ES with 113 total rules and 94 variables. The ES comprises a crisp ES which constructs a Fuzzy ES, thus producing a two‐stage ES. Team A then used the ES and a derivation of it (the “MAKE A”) to conduct assessments of the manufacturability of several “notional” designs, providing a sanity check of the rule‐base. A provisional assessment used a first draft of the rule‐base, and MAKE A, and was of notional wing designs. The primary assessment, using an updated rule‐base and MAKE A, was of notional rotor blade designs. We describe the process by which this ES was made and the assessments that were conducted and conclude with insights gained from constructing the ES. These insights can be summarized as follows: build a bridge between expert and user, move from general features to specific features, do not make the user do a lot of work, and only ask the user for objective observations. We add the product of our work to the growing library of tools and methodologies at the disposal of the U.S. Army Engineer Research and Development Center (ERDC). The primary findings of the present work are (1) an ES that satisfied the experts, according to their expressed performance expectations, and (2) the insights gained on how such a system might best be constructed.
Goaf Site Stability Detection in the Overlap Area of Coal Mining Subsidence and Urban Construction
Authors: Dai Guangli , Li Hongjia , Liu Chao , Li Huaizhan , Chang Youwei , Chen Yu , Gao Yandong , Yuan Yafei , Huo Wenqi
Published: March 2024

The contradiction between coal mining and urban construction in coal resource‐based cities is prominent, which greatly limits the sustainable development of these cities. Pan’an New City is a key mining‐induced subsidence area in Xuzhou City, which presents significant challenges to the construction of the new city. Therefore, in order to ensure the safe construction of Pan’an New City, the residual deformation and stability of the goaf sites must be monitored and evaluated. Under such background, based on the measured leveling data of the mining‐induced surface deformation in a coal mine near Pan’an New City, this paper first analyzed the accuracy of InSAR monitoring of surface deformation in coal mining subsidence area by SBAS‐InSAR technology. Then, the SBAS‐InSAR technology was used to monitor the surface subsidence rate and cumulative subsidence in the coal mining subsidence area of Pan’an New City, based on the 29 scene SAR data during Dec. 2020 and Jan. 2022. The results showed that the goaf site in the north and northwest of Pan’an New City is unstable, while the other areas are stable. Finally, according to the monitoring results, the suggestions have been put forward for the construction of Pan’an New Town on the goaf site. The research results have important theoretical and practical significance for the reuse of goaf sites in Pan’an New City and similar areas in Xuzhou.
Antidiabetic Potential of Phytochemicals Found in Vernonia amygdalina
Authors: Talwar Archna , Chakraborty Neha , Zahera Manaal , Anand Shruti , Ahmad Irshad , Siddiqui Samra , Nayyar Avni , Haque Ashanul , Saeed Mohd
Published: March 2024

Type 2 diabetes mellitus (T2DM), or “insulin-independent diabetes mellitus,” is a worldwide health concern. Diabetes affects roughly 415 million individuals worldwide, with 193 million undiagnosed cases. The number of people afflicted in the following decades is predicted to double. Although various synthetic medications are currently available to treat/manage T2DM, their side effects compel researchers to seek novel treatment options. Because of their affinity for biological receptors and broad bioactivity, nature has long been a source of innovative medication. V. amygdalina is one of the numerous natural productswith antidiabetic properties. Several studies have shown that the extracts have antidiabetic effects in vitro and in vivo. This review examined the antidiabetic and pharmacokinetic characteristics of phytoconstituents found in V. amygdalina.
Effect of Tunable Dielectric Core on Optical Bistability in Cylindrical Core–Shell Nanocomposites
Authors: Getachew Shewa
Published: March 2024

In this paper, the effect of a tunable dielectric core on local field enhancement, induced optical bistability, and the optical bistability domain in cylindrical core–shell nanoparticle composites are studied. The local field enhancement factor increases significantly at two resonant frequencies. The results demonstrate that the local field enhancement factor in the cylindrical core–shell nanoparticle increases when the natural attribute of the dielectric function of the dielectric core is varied by adding a dielectric function to it. Furthermore, we demonstrated that the magnitude of the imaginary part of the active dielectric core increases as the onset and offset input intensities increase. This indicates that the optical bistability or threshold width range widens as the imaginary part of the dielectric function of the dielectric core increases, thereby enlarging the threshold domain to improve system activation.
NPEPPS Is a Druggable Driver of Platinum Resistance
Authors: Jones Robert T. , Scholtes Mathijs , Goodspeed Andrew , Akbarzadeh Maryam , Mohapatra Saswat , Feldman Lily Elizabeth , Vekony Hedvig , Jean Annie , Tilton Charlene B. , Orman Michael V. , Romal Shahla , Deiter Cailin , Kan Tsung Wai , Xander Nathaniel , Araki Stephanie P. , Joshi Molishree , Javaid Mahmood , Clambey Eric T. , Layer Ryan , Laajala Teemu D. , Parker Sarah J. , Mahmoudi Tokameh , Zuiverloon Tahlita C.M. , Theodorescu Dan , Costello James C.
Published: March 2024

There is an unmet need to improve the efficacy of platinum-based cancer chemotherapy, which is used in primary and metastatic settings in many cancer types. In bladder cancer, platinum-based chemotherapy leads to better outcomes in a subset of patients when used in the neoadjuvant setting or in combination with immunotherapy for advanced disease. Despite such promising results, extending the benefits of platinum drugs to a greater number of patients is highly desirable. Using the multiomic assessment of cisplatin-responsive and -resistant human bladder cancer cell lines and whole-genome CRISPR screens, we identified puromycin-sensitive aminopeptidase (NPEPPS) as a driver of cisplatin resistance. NPEPPS depletion sensitized resistant bladder cancer cells to cisplatin in vitro and in vivo. Conversely, overexpression of NPEPPS in sensitive cells increased cisplatin resistance. NPEPPS affected treatment response by regulating intracellular cisplatin concentrations. Patient-derived organoids (PDO) generated from bladder cancer samples before and after cisplatin-based treatment, and from patients who did not receive cisplatin, were evaluated for sensitivity to cisplatin, which was concordant with clinical response. In the PDOs, depletion or pharmacologic inhibition of NPEPPS increased cisplatin sensitivity, while NPEPPS overexpression conferred resistance. Our data present NPEPPS as a druggable driver of cisplatin resistance by regulating intracellular cisplatin concentrations.

Significance:

Targeting NPEPPS, which induces cisplatin resistance by controlling intracellular drug concentrations, is a potential strategy to improve patient responses to platinum-based therapies and lower treatment-associated toxicities.
Regular Use of Aspirin and Statins Reduces the Risk of Cancer in Individuals with Systemic Inflammatory Diseases
Authors: Lin Jia-Run , Han Duan-Duan , Wei Wei , Zeng Qin , Rong Zi-Xuan , Bai Xue , Zhang Yan-Pei , Wang Jian , Cai Xiao-Ting , Rao Xu-Guang , Ma Si-Cong , Dong Zhong-Yi
Published: March 2024

Aspirin has shown potential for cancer prevention, but a recent large randomized controlled trial found no evidence for a reduction in cancer risk. Given the anti-inflammatory effects of aspirin, systemic inflammatory diseases (SID), such as osteoporosis, cardiovascular diseases, and metabolic diseases, could potentially modify the aspirin-cancer link. To investigate the impact of aspirin in people with SIDs, we conducted an observational study on a prospective cohort of 478,615 UK Biobank participants. Individuals with at least one of the 41 SIDs displayed a higher cancer risk than those without SIDs. Regular aspirin use showed protective effects exclusively in patients with SID, contrasting an elevated risk among their non-SID counterparts. Nonetheless, aspirin use demonstrated preventative potential only for 9 of 21 SID-associated cancer subtypes. Cholesterol emerged as another key mediator linking SIDs to cancer risk. Notably, regular statin use displayed protective properties in patients with SID but not in their non-SID counterparts. Concurrent use of aspirin and statins exhibited a stronger protective association in patients with SID, covering 14 common cancer subtypes. In summary, patients with SIDs may represent a population particularly responsive to regular aspirin and statin use. Promoting either combined or individual use of these medications within the context of SIDs could offer a promising chemoprevention strategy.

Significance:

Individuals with systemic inflammatory diseases derive chemoprotective benefits from aspirin and statins, providing a precision cancer prevention approach to address the personal and public challenges posed by cancer.
Cancer Cells Hijack Physiologic Metabolic Signals to Seed Liver Metastasis
Authors: Rettig Andres R. , Ganesh Karuna
Published: March 2024

Metastasis arises from cancer cell–intrinsic adaptations and permissive tumor microenvironments (TME) that are distinct across different organs. Deciphering the mechanisms underpinning organotropism could provide novel preventive and therapeutic strategies for patients with cancer. Rogava and colleagues identified Pip4k2c as a driver of liver metastasis, acting by sensitizing cancer cells to insulin-dependent PI3K/AKT signaling, which could be reversed by dual pharmacologic inhibition of PI3K and SGLT2 or a ketogenic diet. The study highlights the importance of tumor microenvironment communication in the context of systemic physiology and points toward potential combination therapies.
TABLE 2 from High-resolution Diffusion-weighted Imaging to Detect Changes in Tumor Size and ADC, and Predict Adverse Biopsy Histology during Prostate Cancer Active Surveillance
Authors: Saouaf Rola , Xie Yibin , Kim Sungjin , Raphael Yaniv , Nguyen Christopher , Luthringer Daniel , Daskivich Timothy J. , Lo Eric , Tighiouart Mourad , Li Debiao , Kim Hyung L.
Published: March 2024

Size progression or ADC progressiona as predictor of adverse biopsy histologyb
TABLE 1 from High-resolution Diffusion-weighted Imaging to Detect Changes in Tumor Size and ADC, and Predict Adverse Biopsy Histology during Prostate Cancer Active Surveillance
Authors: Saouaf Rola , Xie Yibin , Kim Sungjin , Raphael Yaniv , Nguyen Christopher , Luthringer Daniel , Daskivich Timothy J. , Lo Eric , Tighiouart Mourad , Li Debiao , Kim Hyung L.
Published: March 2024

Baseline demographics
Data from High-resolution Diffusion-weighted Imaging to Detect Changes in Tumor Size and ADC, and Predict Adverse Biopsy Histology during Prostate Cancer Active Surveillance
Authors: Saouaf Rola , Xie Yibin , Kim Sungjin , Raphael Yaniv , Nguyen Christopher , Luthringer Daniel , Daskivich Timothy J. , Lo Eric , Tighiouart Mourad , Li Debiao , Kim Hyung L.
Published: March 2024

AbstractPurpose:
Majority of men with low-risk prostate cancer can be managed with active surveillance (AS). This study evaluates a high-resolution diffusion-weighted imaging (HR-DWI) technique to predict adverse biopsy histology (AH), defined as Gleason score ≥7 on any biopsy or ≥3 increase in number of positive biopsy cores on systematic biopsies. We test the hypothesis that high-grade disease and progressing disease undergo subtle changes during even short intervals that can be detected by HR-DWI.
Experimental Design:
In a prospective clinical trial, serial multiparametric MRIs, incorporating HR-DWI and standard DWI (S-DWI) were performed approximately 12 months apart prior to prostate biopsy (n = 59). HR-DWI, which uses reduced field-of-view and motion compensation techniques, was compared with S-DWI.
Results:
HR-DWI had a 3-fold improvement in spacial resolution compared with S-DWI as confirmed using imaging phantoms. For detecting AH, multiparametric MRI using HR-DWI had a sensitivity of 75% and specificity of 83.9%, and MRI using S-DWI had a sensitivity of 71.4% and specificity of 54.8%. The AUC for HR-DWI was significantly higher (0.794 vs. 0.631, P = 0.014). Secondary analyses of univariable predictors of AH showed tumor size increase [OR 16.8; 95% confidence interval (CI): 4.06–69.48; P < 0.001] and apparent diffusion coefficient (ADC) decrease (OR 5.06; 95% CI: 1.39–18.38; P = 0.014) on HR-DWI were significant predictors of AH.
Conclusion:
HR-DWI outperforms S-DWI in predicting AH. Patient with AH have tumors that change in size and ADC that could be detected using HR-DWI. Future studies with longer follow-up should assess HR-DWI for predicting disease progression during AS.
Significance:
We report on a prospective clinical trial using a MRI that has three times the resolution of standard MRI. During AS for prostate cancer, two high-resolution MRIs performed approximately a year apart can detect tumor changes that predict the presence of aggressive cancers that should be considered for curative therapy such as prostatectomy or radiation.
Evaluation of 3D C-Arm Fluoroscopy versus Diagnostic CT for Deep Brain Stimulation Stereotactic Registration and Post-Operative Lead Localization
Authors: Manfield James , Martin Sean , Green Alexander L. , FitzGerald James J.
Published: March 2024

Introduction: DBS efficacy depends on accuracy. CT-MRI fusion is established for both stereotactic registration and electrode placement verification. The desire to streamline DBS workflows, reduce operative time, and minimize patient transfers has increased interest in portable imaging modalities such as the Medtronic O-arm® and mobile CT. However, these remain expensive and bulky. 3D C-arm fluoroscopy (3DXT) units are a smaller and less costly alternative, albeit incompatible with traditional frame-based localization and without useful soft tissue resolution. We aimed to compare fusion of 3DXT and CT with pre-operative MRI to evaluate if 3DXT-MRI fusion alone is sufficient for accurate registration and reliable targeting verification. We further assess DBS targeting accuracy using a 3DXT workflow and compare radiation dosimetry between modalities. Methods: Patients underwent robot-assisted DBS implantation using a workflow incorporating 3DXT which we describe. Two intra-operative 3DXT spins were performed for registration and accuracy verification followed by conventional CT post-operatively. Post-operative 3DXT and CT images were independently fused to the same pre-operative MRI sequence and co-ordinates generated for comparison. Registration accuracy was compared to 15 consecutive controls who underwent CT-based registration. Radial targeting accuracy was calculated and radiation dosimetry recorded. Results: Data were obtained from 29 leads in 15 consecutive patients. 3DXT registration accuracy was significantly superior to CT with mean error 0.22 ± 0.03 mm (p < 0.0001). Mean Euclidean electrode tip position variation for CT to MRI versus 3DXT to MRI fusion was 0.62 ± 0.40 mm (range 0.0 mm–1.7 mm). In comparison, direct CT to 3DXT fusion showed electrode tip Euclidean variance of 0.23 ± 0.09 mm. Mean radial targeting accuracy assessed on 3DXT was 0.97 ± 0.54 mm versus 1.15 ± 0.55 mm on CT with differences insignificant (p = 0.30). Mean patient radiation doses were around 80% lower with 3DXT versus CT (p < 0.0001). Discussion: Mobile 3D C-arm fluoroscopy can be safely incorporated into DBS workflows for both registration and lead verification. For registration, the limited field of view requires the use of frameless transient fiducials and is highly accurate. For lead position verification based on MRI co-registration, we estimate there is around a 0.4 mm discrepancy between lead position seen on 3DXT versus CT when corrected for brain shift. This is similar to that described in O-arm® or mobile CT series. For units where logistical or financial considerations preclude the acquisition of a cone beam CT or mobile CT scanner, our data support portable 3D C-arm fluoroscopy as an acceptable alternative with significantly lower radiation exposure.
Oncogenic MTOR Signaling Axis Compensates BTK Inhibition in a Chronic Lymphocytic Leukemia Patient with Richter Transformation: A Case Report and Review of the Literature
Authors: Parigger Thomas , Drothler Stephan , Scherhäufl Christian , Gassner Franz Josef , Schubert Maria , Steiner Markus , Höpner Jan Philip , Hödlmoser Alexandra , Schultheis Lena , Bakar Aryunni Abu , Neureiter Daniel , Pleyer Lisa , Egle Alexander , Greil Richard , Geisberger Roland , Zaborsky Nadja
Published: March 2024

Introduction: Targeting the B-cell receptor pathway via ibrutinib, a specific inhibitor of Bruton’s tyrosine kinase, has shown marked clinical efficacy in treatment of patients with chronic lymphocytic leukemia (CLL), thus becoming a preferred first line option independent of risk factors. However, acquired resistance to ibrutinib poses a major clinical problem and requires the development of novel treatment combinations to increase efficacy and counteract resistance development and clinical relapse rates. Case Presentation: In this study, we performed exome and transcriptome analyses of an ibrutinib resistant CLL patient in order to investigate genes and expression patterns associated with ibrutinib resistance. Here, we provide evidence that ibrutinib resistance can be attributed to aberrant mammalian target of rapamycin (MTOR) signaling. Conclusion: Thus, our study proposes that combined use of MTOR inhibitors with ibrutinib could be a possible option to overcome therapy resistance in ibrutinib treated patients.
Neuropil Variation in the Prefrontal, Motor, and Visual Cortex of Six Felids
Authors: Nelson Jacob , Woeste Erin M. , Oba Ken , Bitterman Kathleen , Billings Brendon K. , Sacco James , Jacobs Bob , Sherwood Chet C. , Manger Paul R. , Spocter Muhammad A.
Published: March 2024

Introduction: Felids have evolved a specialized suite of morphological adaptations for obligate carnivory. Although the musculoskeletal anatomy of the Felidae has been studied extensively, the comparative neuroanatomy of felids is relatively unexplored. Little is known about how variation in the cerebral anatomy of felids relates to species-specific differences in sociality, hunting strategy, or activity patterns. Methods: We quantitatively analyzed neuropil variation in the prefrontal, primary motor, and primary visual cortices of six species of Felidae (Panthera leo, Panthera uncia, Panthera tigris, Panthera leopardus, Acinonyx jubatus, Felis sylvestris domesticus) to investigate relationships with brain size, neuronal cell parameters, and select behavioral and ecological factors. Neuropil is the dense, intricate network of axons, dendrites, and synapses in the brain, playing a critical role in information processing and communication between neurons. Results: There were significant species and regional differences in neuropil proportions, with African lion, cheetah, and tiger having more neuropil in all three cortical regions in comparison to the other species. Based on regression analyses, we find that the increased neuropil fraction in the prefrontal cortex supports social and behavioral flexibility, while in the primary motor cortex, this facilitates the neural activity needed for hunting movements. Greater neuropil fraction in the primary visual cortex may contribute to visual requirements associated with diel activity patterns. Conclusion: These results provide a cross-species comparison of neuropil fraction variation in the Felidae, particularly the understudied Panthera, and provide evidence for convergence of the neuroanatomy of Panthera and cheetahs.