bluuebunny/crossref_metadata_2025 huggingface dataset:
Turn-based Spatiotemporal Coherence for GPUs
Authors: Puthoor Sooraj , Lipasti Mikko H.
Published: May 2023

This article introduces turn-based spatiotemporal coherence. Spatiotemporal coherence is a novel coherence implementation that assigns write permission to epochs (or turns) as opposed to a processor core. This paradigm shift in the assignment of write permissions satisfies all conditions of a coherence protocol with virtually no coherence overhead. We discuss the implementation of this coherence mechanism on a baseline GPU. The evaluation shows that spatiotemporal coherence achieves a speedup of 7.13% for workloads with read data reuse across kernels compared to the baseline software-managed GPU coherence implementation while also providing write atomicity and avoiding the need for software inserted acquire-release operations.

1
Alabib-65: A Realistic Dataset for Algerian Sign Language Recognition
Authors: Khellas Kenza , Seghir Rachid
Published: May 2023

Sign language recognition (SLR) is a promising research field that aims to blur boundaries between Deaf and hearing people by creating a system that can transcribe signs into a written or vocal language. There is a growing body of literature that investigates the recognition of different sign languages, especially American sign language. So far, to the best of our knowledge, no study has considered the Algerian SLR. This is mainly due to the lack of datasets. To address this issue, we created the Alabib-65, the first Algerian Sign Language dataset. It consists of up to 6,238 Videos recorded from 41 native signers under realistic settings. This dataset is challenging due to a variety of reasons. First, there is a little inter-class variability. The 65 sign classes are similar in terms of hands’ configuration, placement, or movement and can share the same sub-parts. Second, there is a large intra-class variability. Furthermore, compared to other SL datasets that were collected from an indoor environment with a static and simple background, our videos were recorded from both indoor and outdoor environments with 22 backgrounds varying from simple to cluttered, and from static to dynamic. To underpin future research, we provided baseline results on this new dataset using state-of-the-art machine learning methods, namely: IDTFs with Fisher vector and SVM-classifier, VGG16-GRU, I3D, I3D-GRU, and I3D-GRU-Attention. The results show the validity and the challenges of our dataset.
Pathophysiology of Retinopathy of Prematurity
Authors: Hartnett M. Elizabeth
Published: May 2023

Retinopathy of prematurity (ROP) is a complex disease involving development of the neural retina, ocular circulations, and other organ systems of the premature infant. The external stresses of the ex utero environment also influence the pathophysiology of ROP through interactions among retinal neural, vascular, and glial cells. There is variability among individual infants and presentations of the disease throughout the world, making ROP challenging to study. The methods used include representative animal models, cell culture, and clinical studies. This article describes the impact of maternal–fetal interactions; stresses that the preterm infant experiences; and biologic pathways of interest, including growth factor effects and cell–cell interactions, on the complex pathophysiology of ROP phenotypes in developed and emerging countries.
Improving Durability of Fuel Cells with Platinum-rich Alloy Cathode Catalysts
Authors: Ramaswamy Nagappan , Kumaraguru Swami , Jarvis Karalee , Ferreira Paulo
Published: May 2023

Pt3Co-alloy based nanoparticle catalysts are very active for oxygen reduction reaction (ORR) thereby enabling high performance of proton exchange membrane fuel cells (PEMFC) for automotive propulsion. However, these catalyst materials degrade due to a combination of electrochemical surface area (ECSA) loss and dissolution of cobalt-alloying element from the nanoparticles. Dissolution of cobalt has a two-fold impact on the durability of fuel cells—i) a loss in the low-current density kinetic region due to a decrease in specific activity and ii) a loss in the high-current density transport region due to Co2+ contamination of the ionomer phase. Cobalt dissolution-contamination needs to be mitigated as it limits fuel cell performance and lifetime for heavy-duty automotive applications. In this article, we study the use of PtCo-alloy catalysts with Pt-rich compositions using catalyst-specific accelerated stress test measurement in membrane electrode assemblies to decrease the amount of dissolved Co and mitigate its subsequent contamination effects. We demonstrate Pt5Co and Pt7Co compositions to enable significant improvements in durability (∼50 mV and ∼100 mV with respect to Pt3Co after 30,000 voltage cycles) with a minor but acceptable compromise in the initial specific activity of the catalyst.
Au-wrapped CuS-Interlaced Chain Structure for Ultrafast Response and High Sensitive Non-Enzymatic Glucose Sensor
Authors: Zhang Yan , Gao Yumeng , Zhang Shan , Huang Yaoyao , Wei Yuan , Cai Huishan , Jia Zhenfu , Su Xiaodong
Published: May 2023

We report the fabrication and testing of ultrafast response nonenzymatic glucose sensor based on the use of interlaced chain structure Au@CuS nanomaterial. The new Au@CuS nanomaterial was synthesized by a facile solvothermal method from L-cysteine、Cu(NO3)2·3H2O and Au Seeds without using additional surfactants or templates. The combination of Au and CuS solves the problems of poor electrical conductivity of CuS and the susceptibility of Au to toxicity, while the interlaced chain structure exposes more active sites to facilitate the diffusion of glucose molecules with a low resistance to increase the inter-electron transfer rate. The non-enzymatic Au@CuS-based glucose sensor showed a wide linear range with excellent sensitivity (5817.37 and 3629.78 μA mM−1cm−2), ultrafast response time (<0.1 s), excellent selectivity and outstanding long-term stability. Further, the designed glucose sensor was used to determine glucose in human blood serum sample with satisfactory result.
Gate-Bias-Induced Threshold Voltage Shifts in GaN FATFETs
Authors: Irokawa Yoshihiro , Mitsuishi Kazutaka , Izumi Takatomi , Nishii Junya , Nabatame Toshihide , Koide Yasuo
Published: May 2023

The threshold voltage (V
TH) stability in GaN fat field-effect transistors (FATFETs) with a large channel area of ∼6.2 × 104
μm2 was studied using drain current vs gate voltage (I
D–V
G) characteristics. Each measurement was found to positively shift the previous I
D–V
G curve, and V
TH eventually saturated with increasing number of measurements. The saturated V
TH was ∼0.8 V for measurements in which V
G ranged from −10 to 25 V and was ∼8 V for measurements in which the V
G ranged from −10 to 40 V. Moreover, the positive gate bias stress increased V
TH to 12.3 V. These shifts of V
TH can be explained by electron trapping; according to charge-pumping measurements, the traps cannot exist in the oxide or the oxide/p-GaN interface but can exist near the surface region in p-GaN layers in GaN FATFETs. Scanning transmission electron microscopy and electron energy-loss spectroscopy analyses revealed the presence of oxygen within several atomic layers of p-GaN from the oxide/p-GaN interface. This intermixed oxygen might be the origin of the n-type behavior of the p-GaN surface; furthermore, the oxygen is speculated to be related to the traps. Surprisingly, similar incorporated oxygen was observed even in the surface region of as-grown p-GaN layers.
Correlation of Structural and Mechanical Properties for Ultrasonically Stir Casted Al6061 Reinforced SiC-AlN Hybrid Metal Matrix Composites
Authors: Singh Anil Kumar , Yadav Gaurav , Gupta Pallav
Published: May 2023

In our current investigation, Al6061-SiC-AlN composites were manufactured using the ultrasonic stir casting method. As reinforcement, silicon carbide (SiC) and aluminium nitride (AlN) [both 3 percent and 6 percent by wt.] were used to provide mechanical properties including tensile, compressive, and hardness. Al6061-SiC-AlN hybrid composite samples’ tensile strength, compressive strength, and hardness were measured. Al6061-SiC-AlN hybrid composites’ tensile, compressive, and hardness properties are calculated and compared to those of the matrix i.e. Al 6061 alloy. The tensile strength, compressive strength, and hardness all rose from 328 to 385 MPa, 145 to 178 MPa, and 302 to 724 VHN, respectively, with the addition of SiC and AlN nano-reinforcements. The suggested composite is compared to unreinforced Al6061 in terms of density and mechanical qualities such ultimate tensile strength, yield strength, impact strength, hardness, and wear characteristics. The results of the experimental examination showed that the produced hybrid composite, which contains 20% of the total reinforcing material, has no appreciable increase in impact strength but displays high hardness, high yield strength, and low wear rate.
Highly Sensitive Isopropanol Gas Sensor based on SnO2 Nano-Flowers on Gold, Silver, and Aluminum Interdigitated Electrodes
Authors: Moayedi Mehdi , Ansari Hamid Reza , Kordrostami Zoheir
Published: May 2023

In this research we have proposed a high selectivity Isopropanol gas sensor. The sensor shows significant resistance change only to Isopropanol gas. The synthesis method of flower-like SnO2 nanostructures, the electrode material and design, and the optimized working temperature provide the high selectivity and high response of the sensor. The SnO2 nanoflowers (NFs) have been synthesized in a two-step process as the gas sensitive layer. The sensor shows its best performance on Au interdigitated electrodes. The optimized working temperature is obtained at 150 °C. The proposed sensor has a high sensitivity, good repeatability, long-term stability and remarkable selectivity. The responses of the sensor to 100 ppm of isopropanol at 150 °C is 71 and the sensor is capable of keeping almost 96% of the initial response in a 40 d period.
Inhibited postprandial retrograde cyclic motor pattern in the distal colon of patients with diarrhea-predominant irritable bowel syndrome
Authors: Wiklendt Lukasz , Mohd Rosli Reizal , Kumar Raghu , Paskaranandavadivel Niranchan , Bampton Peter A. , Maslen Lyn , Costa Marcello , Brookes Simon J. , O’Grady Greg , Dinning Phil G.
Published: May 2023

Compared with healthy adults this study has shown a significant reduction in the prevalence of the postprandial retrograde cyclic motor pattern in the distal colon of patients with diarrhea-predominant irritable bowel syndrome. We hypothesize that this altered motility may allow for premature rectal filling which contributes to the postprandial urgency and diarrhea experienced by these patients.
MicroRNA-200b deficiency is not sufficient to increase susceptibility to allergen-induced airway inflammation and dysfunction in mice
Authors: Kahnamoui Shana , Basu Sujata , Lei Yubin , Patel Daywin , Keijzer Richard , Pascoe Christopher D.
Published: May 2023

MicroRNA-200b regulates the abundance of key asthma-related genes. However, loss of miR-200b does not potentiate allergic asthma in a mouse model, suggesting that miR-200b deficiency may not be sufficient to drive of asthma pathogenesis.
Acute effects of neuromuscular electrical stimulation on cortical dynamics and reflex activation
Authors: Borzuola Riccardo , Quinzi Federico , Scalia Martina , Pitzalis Sabrina , Di Russo Francesco , Macaluso Andrea
Published: May 2023

Neuromuscular electrical stimulation superimposed on voluntary contractions (NMES+) is effective to improve motor performance in several populations. Here, we investigated the changes in cortical activation and reflex response following three acute conditions, including NMES+. Our results show that NMES+ has a greater excitatory effect at both spinal and cortical levels compared with passive stimulation and voluntary exercise alone. These results open up original perspectives for the implementation of NMES+ in neurorehabilitation and training environments.
Strength-duration properties and excitability of motor and sensory axons across different target thresholds
Authors: Shimatani Yoshimitsu , Lin Cindy Shin-Yi , Matamala José Manuel , Kiernan Matthew C.
Published: May 2023

This study provides a comprehensive assessment concerning the strength-duration behavior of motor and sensory axons at differing target levels of the compound nerve response. Strength-duration time constant was increased at lower target response levels particularly for sensory axons, whereas threshold change at 0.2 ms and passive membrane properties were not different. The results have established templates for axonal behavior in normal human axons, demonstrating altered adaptive responses, presumably secondary to different patterns of nerve activation.
Voluntary muscle coactivation in quiet standing elicits reciprocal rather than coactive agonist-antagonist control of reactive balance
Authors: Martino Giovanni , Beck Owen N. , Ting Lena H.
Published: May 2023

Feedforward and feedback muscle coactivation are commonly observed in older and mobility impaired adults and are considered strategies to improve stability by increasing body stiffness prior to and in response to perturbations. In young adults, voluntary feedforward coactivation does not necessarily increase feedback coactivation in response to perturbations. Instead, feedforward coactivation enabled faster ankle torques through reciprocal agonist-antagonist muscle activity. As such, coactivation may promote either agility or stability depending on the behavioral context.
Application of Wearable Technologies in Fall Risk Assessment and Improvement in Patients with Peripheral Neuropathy: A Systematic Review
Authors: Pan Qiyang , Chen Yungu , Ma Xin , Wang Chen , Chen Wenming
Published: May 2023

Background. Peripheral neuropathy is regarded as one of the leading causes of fatal and nonfatal falls. Wearable sensors, due to their increasing availability and flexibility of setting and space, are used widely to obtain wearer’s kinematic data to analyze one’s balance capacities for the evaluation of risk of fall. There is yet to have a review study focusing on the application of wearable sensors in the scope of fall risk for patients with peripheral neuropathy. Objective. To investigate the methods by which researchers adopt to assess risk of fall in peripheral neuropathy patients and potentially shed light on future researches. Methods. A systematic review design was used to identify articles on fall risk assessment and balance training using wearable sensors in patients with peripheral neuropathy. The study is aimed at extracting the following information: the type of sensors, the type of signal and data processing employed, the scales and tests used in the study, and the type of application. Results. We identified 351 studies, from which 8 were included. An average sample size of 35.6 patients enrolled the studies. The accelerometer was the most common wearable sensor used. 10‐meter walk test was the preferable procedure for assessing risk of fall. Conclusion. This review examined several key components in studies on assessing and improving the risk of fall using wearable sensors. We identified the preferred functional test (10‐meter walk test), sensor technology (accelerometer), locations (torso and lower legs), and fall risk improvement methods (prostheses). However, due to the limited number of articles specializing in this field of research, a consensus on patient sample size and procedures is not reached. We would recommend future researches to examine more parameters and adopt a fusion sensor setup.
Jammer Location‐Aware Method in Wireless Sensor Networks Based on Fibonacci Branch Search
Authors: Yang Fang , Shu Nina , Hu Chenxi , Huang Jun , Niu Zhao
Published: May 2023

Due to the sharing and open‐access characteristics of the wireless medium, wireless sensor networks (WSNs) can be easily attacked by jammers. To mitigate the effects of a jamming attack, one reliable solution is to locate and remove the jammer from the deployed area within the WSN. To realize the jammer’s localization in the WSN, many range‐free methods have been proposed. However, most of these methods are sensitive to the distribution of nodes and the parameters of the jammer. For this reason, a jammer location‐aware method based on Fibonacci branch search (FBS) is proposed in this article. First, the interference region is estimated by using the interference region mapping service of sensors in wireless sensor networks. Then, the search point is selected in the jamming area and the fitness function is designed according to the average distance from the search point to the boundary sensor. According to the basic branch structure and interactive search rules, the global optimal solution is obtained in the jamming area. Finally, the position of the search point with the best fitness value is used as the estimation of the jammer position. Compared with the existing typical range‐free methods, rich simulation experiments demonstrate that the FBS algorithm is superior in the location‐aware method for jammers with a higher precision and a lower sensitivity to the distribution of nodes and the parameters of the jammer, respectively.
M-Hazy Module and Its Homomorphism Theorem
Authors: Huo Donghua , Liu Hongyu
Published: May 2023

Based on a completely distributive lattice

M

, we propose a new fuzzification approach to a module, which leads to the concept of an

M

-hazy module. Different from the traditional fuzzification approach that defines a fuzzy algebra as a fuzzy subset of a classical algebra, we introduce an

M

-hazy module by fuzzifications of algebraic operations. Then, we investigate the fundamental properties of

M

-hazy modules and

M

-hazy submodules. In particular, we present the

M

-hazy module homomorphism theorem.
A Signal Optimization Model of Adjacent Closely Spaced Intersections Which Optimizes Pedestrian Crossing
Authors: Wang Jiawen , Chen Hao , Hang Jiayu , Xu Mingjie , Han Yin
Published: May 2023

Adjacent closely spaced intersections with characteristics of short link distance and high pedestrian flow are primarily located in high-density urban areas. To address the problems of queue overflow, poor traffic operation, and high pedestrian travel delays, a pedestrian-motor vehicle signal optimization method for adjacent closely spaced intersections was proposed in this paper. First, the traffic flow entering the closely spaced intersections is divided into nonarterial and arterial flow categories to establish a delay model of pedestrian crossing. Then, a pedestrian crossing delay model based on pedestrian demand is constructed according to pedestrian crossing time and a space diagram. An optimization model for pedestrians and vehicles at adjacent closely spaced intersections is established, and an artificial intelligence algorithm is used to optimize this model. Finally, a selected case intersection is optimized. The results show that compared with a traditional single optimization method, vehicle delay decreased about 4%, 13.8%, 17.1%, and 25.9% and total pedestrian delay decreased by 3%, 15%, 25%, and 31%, respectively, for the four proposed scenarios.
Application of Serum Mid‐Infrared Spectroscopy Combined with Machine Learning in Rapid Screening of Breast Cancer and Lung Cancer
Authors: Zhu Kejing , Shen Jie , Xu Wen , Yue Keyu , Zhu Liying , Niu Yulin , Wu Qing , Pan Wei
Published: May 2023

Cancer is an increasing burden on global health. Breast and lung cancers are the two tumors with the highest incidence rates. The study shows that early detection and early diagnosis are important prognostic factors for breast and lung cancers. Due to the great advantages of artificial intelligence in feature extraction, the combination of infrared analysis technology may have great potential in clinical applications. This study explores the potential application of mid‐infrared spectroscopy combined with machine learning for the differentiation of breast and lung cancers. The experiment collects blood samples from clinical sources, separates serum, trains classification models, and finally predicts unknown sample categories. We use k‐fold cross‐validation to determine the training set of 301 cases and the test set of 50 cases. Through differential spectrum analysis, we found that the intervals of 1318.59–1401.03 cm−1, 1492.15–1583.27 cm−1, and 1597.25–1721.64 cm−1 have significant differences, which may reflect the absorption of key chemical bonds in protein molecules. We use a total of 24 models such as decision trees, discriminant analysis, support vector machines, and K‐nearest neighbor to train, identify, and distinguish spectra. The results show that under the same conditions, the prediction model trained based on fine KNN has the best performance and can perform 100% prediction on the test set samples. This also shows that our model has important potential for auxiliary diagnosis of serum breast cancer and lung cancer. This method may help to further achieve comprehensive screening of associated cancers in underserved areas, thereby reducing the cancer burden through early detection of cancer and appropriate treatment and care of cancer patients.
A Dynamic Product Evaluation Model Based on Online Customer Reviews from the Perspective of the Elaboration Likelihood Model
Authors: Li Yang , Xu Zeshui , Zhang Yixin
Published: May 2023

Plenty of online customer reviews (OCRs) provide consumers with an abundant source of word‐of‐mouth (WOM). It makes potential customers evaluate alternative products or services more conveniently. Thus, relative studies have been arising. Considering that existing research is almost deployed from the perspective of reviewers, the study proposes an evaluation model based on the OCRs from the view of potential customers. In the model, the OCRs in text form are translated into probabilistic linguistic term sets from the perspective of the cognitive process model, namely, the elaboration likelihood model, for further evaluation. Meanwhile, the influence of the OCRs’ published time is also taken into consideration, and then, the model is transformed into a dynamic evaluation model. In general, we propose a dynamic product evaluation model to simulate the cognitive process of the potential consumers disposing of OCRs. In addition, an evaluation of 6 hotels in Chengdu, Sichuan Province, is developed based on the proposed dynamic product evaluation model, and some discussions, as well as conclusions, are also carried out.
Protective Effects of Artemisia selengensis Turcz. Leaf Extract on Caenorhabditis elegans under High Glucose Diet
Authors: Li Rong , Tao Mingfang , Xu Tingting , Wang Jinsong , Duan Rui , Wu Ting , Pan Siyi , Xu Xiaoyun
Published: May 2023

Artemisia selengensis Turcz. (AST), as a common edible and medicinal herb, exerts multiple biological activities including antioxidant, antihyperuricemia, and inhibition of α-glucosidase activities. However, limited information is available about its beneficial effects on high glucose toxicity in Caenorhabditis elegans (C. elegans). In the current study, Artemisia selengensis Turcz. leaf extract (ASTE), rich in caffeoylquinic acids, was found to alleviate high glucose-induced damages in C. elegans by extending the lifespan, increasing the body bending and pharyngeal pumping rates, and by reducing glucose and lipid accumulation and oxidative stress. Further results demonstrated that ASTE extended the lifespan of C. elegans on high glucose diet by inhibiting the insulin/IGF-1 signaling (IIS), and activating SKN-1 and AAK-2 signaling pathways. In conclusion, our findings reveal the direct evidence for the protective effects of ASTE against high glucose toxicity.
Comprehensive Analysis of ZVS Operation Range and Deadband Conditions of a Dual H-Bridge Bidirectional DC-DC Converter with Phase Shift Control
Authors: Adam Ahmed Hamed Ahmed , Chen Jiawei , Kamel Salah , Zeinoddini‐Meymand Hamed
Published: May 2023

This study offers a thorough examination of the zero voltage switching (ZVS) operation range and deadband conditions for a bidirectional DC-DC converter with phase shift control, featuring dual H-bridge. The analysis considers the soft switching range of the DAB converter, accounting for the impact of the headband and the ZVS capacitor. By applying the differential equation of the circuit during deadband time, a sufficient constraint for the input and output bridges can be calculated. The findings indicate that as the output voltage increases, the minimum phase shift value required to achieve ZVS decreases, and expanding the phase shift value will expand the ZVS range and reduce switching losses. The study provides simulation results for various operating conditions, validating the theoretical analysis of the proposed system. In addition, the results furnish information about the circuit behavior during the deadband and waveforms. Finally, MATLAB/SIMULINK verifies the simulation results for different operating stages.
An Efficient Pairing-Free Certificateless Signature Scheme with KGC Trust Level 3 for Wireless Sensor Network
Authors: Zhao Hong , Zhang Xinyu , Li Zhaobin , Wei Zhanzhen
Published: May 2023

With the widespread adoption of wireless sensor networks (WSN), the security of the WSN has been a wide concern. Certificateless signature eliminates the certificate management problem and key escrow problem and is considered a feasible solution to solve the data integrity and authentication of WSN. Recently, Thumbur et al. proposed an efficient pairing-free certificateless signature scheme, and Xu et al. pointed out that their scheme is not resistant to signature forgery attacks and proposed an improved scheme. Based on the trust hierarchy defined by Girault, we find that Xu et al.’s scheme is still only able to achieve security under KGC trust level 2. Moreover, Thumbur et al.’s scheme uses the Schnorr signature algorithm form, which makes it favorable for scaling, while Xu et al.’s scheme breaks this advantage. Therefore, we propose a pairing-free certificateless scheme capable of reaching KGC trust level 3, still using the Schnorr signature algorithm form, and prove the security of the new scheme under the random oracle model. The final efficiency analysis shows that the new scheme has shorter public key length and higher computational efficiency.
Supplementary Video S2A from First-in-Human Study of the Radioligand 68Ga-N188 Targeting Nectin-4 for PET/CT Imaging of Advanced Urothelial Carcinoma
Authors: Duan Xiaojiang , Xia Lei , Zhang Zhuochen , Ren Yanan , Pomper Martin G. , Rowe Steven P. , Li Xuesong , Li Nan , Zhang Ning , Zhu Hua , Yang Zhi , Sheng Xinan , Yang Xing
Published: May 2023

40 min full dynamic Total-body PET imaging of Patient 1
Supplementary Figures S1-S15 from First-in-Human Study of the Radioligand 68Ga-N188 Targeting Nectin-4 for PET/CT Imaging of Advanced Urothelial Carcinoma
Authors: Duan Xiaojiang , Xia Lei , Zhang Zhuochen , Ren Yanan , Pomper Martin G. , Rowe Steven P. , Li Xuesong , Li Nan , Zhang Ning , Zhu Hua , Yang Zhi , Sheng Xinan , Yang Xing
Published: May 2023

Figure S1. Synthesis of N188. Figure S2. Mass spectrometry characterization of N188.Figure S3. SPR characterization of N188.Figure S4. Radio-HPLC characterization of 68Ga-N188.Figure S5. Stability of 68Ga-N188 in serum and normal saline. Figure S6. Synthesis of FITC-N188. Figure S7. Mass spectrometry characterization of FITC-N188. Figure S8. Blood routine safety test. Figure S9. Toxicity test of 68Ga-N188. Figure S10. Results of PET/CT dynamic imaging studies in one healthy subject. Figure S11. Pharmacokinetics of 68Ga-N188 in mouse blood. Figure. S12 68Ga-N188 PET/CT imaging with maximum intensity projection (MIP) reconstruction of 12 advanced UC patients with obtained pathological sections. Figure S13. Representative PET/CT images of a patient (No. 3) with advanced urothelial carcinoma. Figure. S14 Comparison of brain metastasis imaging of patient No. 4 using 68Ga-N188, 18F-FDG PET/CT and MRI. Figure. S15 Nectin-4 IHC staining in 12 mUC patients with pathological sections of primary focus.
Supplementary Figure 1 from Antitumor Efficacy of Dual Blockade with Encorafenib + Cetuximab in Combination with Chemotherapy in Human BRAFV600E-Mutant Colorectal Cancer
Authors: Napolitano Stefania , Woods Melanie , Lee Hey Min , De Falco Vincenzo , Martini Giulia , Della Corte Carminia Maria , Martinelli Erika , Famiglietti Vincenzo , Ciardiello Davide , Anderson Amanda , Fowlkes Natalie Wall , Villareal Oscar Eduardo , Sorokin Alexey , Kanikarla Preeti , Coker Olu , Morris Van , Altucci Lucia , Tabernero Josep , Troiani Teresa , Ciardiello Fortunato , Kopetz Scott
Published: May 2023

Differentially enriched hallmark gene sets after cytotoxic chemotherapy and targeted therapy of B1003b PDX tumor samples.
Data from Phase II Investigation of TVB-2640 (Denifanstat) with Bevacizumab in Patients with First Relapse High-Grade Astrocytoma
Authors: Kelly William , Diaz Duque Adolfo Enrique , Michalek Joel , Konkel Brandon , Caflisch Laura , Chen Yidong , Pathuri Sarath Chand , Madhusudanannair-Kunnuparampil Vinu , Floyd John , Brenner Andrew
Published: May 2023

AbstractPurpose:
Glioblastoma represents the most common primary brain tumor. Although antiangiogenics are used in the recurrent setting, they do not prolong survival. Glioblastoma is known to upregulate fatty acid synthase (FASN) to facilitate lipid biosynthesis. TVB-2640, a FASN inhibitor, impairs this activity.
Experimental Design:
We conducted a prospective, single-center, open-label, unblinded, phase II study of TVB-2640 plus bevacizumab in patients with recurrent high-grade astrocytoma. Patients were randomly assigned to TVB-2640 (100 mg/m2 oral daily) plus bevacizumab (10 mg/kg i.v., D1 and D15) or bevacizumab monotherapy for cycle 1 only (28 days) for biomarker analysis. Thereafter, all patients received TVB-2640 plus bevacizumab until treatment-related toxicity or progressive disease (PD). The primary endpoint was progression-free survival (PFS).
Results:
A total of 25 patients were enrolled. The most frequently reported adverse events (AE) were palmar–plantar erythrodysesthesia, hypertension, mucositis, dry eye, fatigue, and skin infection. Most were grade 1 or 2 in intensity. The overall response rate (ORR) for TVB-2640 plus bevacizumab was 56% (complete response, 17%; partial response, 39%). PFS6 for TVB-2640 plus bevacizumab was 31.4%. This represented a statistically significant improvement in PFS6 over historical bevacizumab monotherapy (BELOB 16%; P = 0.008) and met the primary study endpoint. The observed OS6 was 68%, with survival not reaching significance by log-rank test (P = 0.56).
Conclusions:
In this phase II study of relapsed high-grade astrocytoma, TVB-2640 was found to be a well-tolerated oral drug that could be safely combined with bevacizumab. The favorable safety profile and response signals support the initiation of a larger multicenter trial of TVB-2640 plus bevacizumab in astrocytoma.
Figure S3 from Dynamic Intestinal Stem Cell Plasticity and Lineage Remodeling by a Nutritional Environment Relevant to Human Risk for Tumorigenesis
Authors: Choi Jiahn , Zhang Xusheng , Li Wenge , Houston Michele , Peregrina Karina , Dubin Robert , Ye Kenny , Augenlicht Leonard
Published: May 2023

The western diet suppresses expression of a large number of genes encoding subunits of each of the 5 complexes of mitochondrial electron transport.
Supplementary Tables 1-7 from Combinatorial BCL2 Family Expression in Acute Myeloid Leukemia Stem Cells Predicts Clinical Response to Azacitidine/Venetoclax
Authors: Waclawiczek Alexander , Leppä Aino-Maija , Renders Simon , Stumpf Karolin , Reyneri Cecilia , Betz Barbara , Janssen Maike , Shahswar Rabia , Donato Elisa , Karpova Darja , Thiel Vera , Unglaub Julia M. , Grabowski Susanna , Gryzik Stefanie , Vierbaum Lisa , Schlenk Richard F. , Röllig Christoph , Hundemer Michael , Pabst Caroline , Heuser Michael , Raffel Simon , Müller-Tidow Carsten , Sauer Tim , Trumpp Andreas
Published: May 2023

7 Tables showing: molecular and clinical patient data, cell line info, antibody panels and overview of assays used
Supplementary Figure 2 from Combinatorial BCL2 Family Expression in Acute Myeloid Leukemia Stem Cells Predicts Clinical Response to Azacitidine/Venetoclax
Authors: Waclawiczek Alexander , Leppä Aino-Maija , Renders Simon , Stumpf Karolin , Reyneri Cecilia , Betz Barbara , Janssen Maike , Shahswar Rabia , Donato Elisa , Karpova Darja , Thiel Vera , Unglaub Julia M. , Grabowski Susanna , Gryzik Stefanie , Vierbaum Lisa , Schlenk Richard F. , Röllig Christoph , Hundemer Michael , Pabst Caroline , Heuser Michael , Raffel Simon , Müller-Tidow Carsten , Sauer Tim , Trumpp Andreas
Published: May 2023

Transcriptomic and functional characterization of LSC-like cells
Data from Targeted MDM2 Degradation Reveals a New Vulnerability for p53-Inactivated Triple-Negative Breast Cancer
Authors: Adams Clare M. , Mitra Ramkrishna , Xiao Youcai , Michener Peter , Palazzo Juan , Chao Allen , Gour Jitendra , Cassel Joel , Salvino Joseph M. , Eischen Christine M.
Published: May 2023

Abstract
Triple-negative breast cancers (TNBC) frequently inactivate p53, increasing their aggressiveness and therapy resistance. We identified an unexpected protein vulnerability in p53-inactivated TNBC and designed a new PROteolysis TArgeting Chimera (PROTAC) to target it. Our PROTAC selectively targets MDM2 for proteasome-mediated degradation with high-affinity binding and VHL recruitment. MDM2 loss in p53 mutant/deleted TNBC cells in two-dimensional/three-dimensional culture and TNBC patient explants, including relapsed tumors, causes apoptosis while sparing normal cells. Our MDM2-PROTAC is stable in vivo, and treatment of TNBC xenograft-bearing mice demonstrates tumor on-target efficacy with no toxicity to normal cells, significantly extending survival. Transcriptomic analyses revealed upregulation of p53 family target genes. Investigations showed activation and a required role for TAp73 to mediate MDM2-PROTAC–induced apoptosis. Our data, challenging the current MDM2/p53 paradigm, show MDM2 is required for p53-inactivated TNBC cell survival, and PROTAC-targeted MDM2 degradation is an innovative potential therapeutic strategy for TNBC and superior to existing MDM2 inhibitors.
Significance:
p53-inactivated TNBC is an aggressive, therapy-resistant, and lethal breast cancer subtype. We designed a new compound targeting an unexpected vulnerability we identified in TNBC. Our MDM2-targeted degrader kills p53-inactivated TNBC cells, highlighting the requirement for MDM2 in TNBC cell survival and as a new therapeutic target for this disease.

See related commentary by Peuget and Selivanova, p. 1043.

This article is highlighted in the In This Issue feature, p. 1027
Single-Cell Profiling of CD8+ T Cells in Acute Myeloid Leukemia Reveals a Continuous Spectrum of Differentiation and Clonal Hyperexpansion
Authors: Desai Poonam N. , Wang Bofei , Fonseca Andre , Borges Pamella , Jelloul Fatima Zahra , Reville Patrick K. , Lee Eric , Ly Christopher , Basi Akshay , Root Jessica , Baran Natalia , Post Sean M. , Deng Qing , Sun Hanxiao , Harmanci Arif O. , Burks Jared K. , Gomez Javier A. , DiNardo Courtney D. , Daver Naval G. , Alatrash Gheath , Konopleva Marina , Green Michael R. , Antunes Dinler A. , Futreal Andrew , Hao Dapeng , Abbas Hussein A.
Published: May 2023

Comprehensive investigation of CD8+ T cells in acute myeloid leukemia (AML) is essential for developing immunotherapeutic strategies beyond immune checkpoint blockade. Herein, we performed single-cell RNA profiling of CD8+ T cells from 3 healthy bone marrow donors and 23 newly diagnosed (NewlyDx) and 8 relapsed/refractory (RelRef) patients with AML. Cells coexpressing canonical exhaustion markers formed a cluster constituting <1% of all CD8+ T cells. We identified two effector CD8+ T-cell subsets characterized by distinct cytokine and metabolic profiles that were differentially enriched in NewlyDx and RelRef patients. We refined a 25-gene CD8-derived signature correlating with therapy resistance, including genes associated with activation, chemoresistance, and terminal differentiation. Pseudotemporal trajectory analysis supported enrichment of a terminally differentiated state in CD8+ T cells with high CD8-derived signature expression at relapse or refractory disease. Higher expression of the 25-gene CD8 AML signature correlated with poorer outcomes in previously untreated patients with AML, suggesting that the bona fide state of CD8+ T cells and their degree of differentiation are clinically relevant. Immune clonotype tracking revealed more phenotypic transitions in CD8 clonotypes in NewlyDx than in RelRef patients. Furthermore, CD8+ T cells from RelRef patients had a higher degree of clonal hyperexpansion associated with terminal differentiation and higher CD8-derived signature expression. Clonotype-derived antigen prediction revealed that most previously unreported clonotypes were patient-specific, suggesting significant heterogeneity in AML immunogenicity. Thus, immunologic reconstitution in AML is likely to be most successful at earlier disease stages when CD8+ T cells are less differentiated and have greater capacity for clonotype transitions.
TABLE 2 from Phase I Trial of Autologous RNA-electroporated cMET-directed CAR T Cells Administered Intravenously in Patients with Melanoma and Breast Carcinoma
Authors: Shah Payal D. , Huang Alexander C. , Xu Xiaowei , Orlowski Robert , Amaravadi Ravi K. , Schuchter Lynn M. , Zhang Paul , Tchou Julia , Matlawski Tina , Cervini Amanda , Shea Joanne , Gilmore Joan , Lledo Lester , Dengel Karen , Marshall Amy , Wherry E. John , Linette Gerald P. , Brennan Andrea , Gonzalez Vanessa , Kulikovskaya Irina , Lacey Simon F. , Plesa Gabriela , June Carl H. , Vonderheide Robert H. , Mitchell Tara C.
Published: May 2023

Adverse events, clinically relevant (# subjects includes those with the given toxicity at least possibly related to study treatment)
Supplementary Figure 1 from Phase I Trial of Autologous RNA-electroporated cMET-directed CAR T Cells Administered Intravenously in Patients with Melanoma and Breast Carcinoma
Authors: Shah Payal D. , Huang Alexander C. , Xu Xiaowei , Orlowski Robert , Amaravadi Ravi K. , Schuchter Lynn M. , Zhang Paul , Tchou Julia , Matlawski Tina , Cervini Amanda , Shea Joanne , Gilmore Joan , Lledo Lester , Dengel Karen , Marshall Amy , Wherry E. John , Linette Gerald P. , Brennan Andrea , Gonzalez Vanessa , Kulikovskaya Irina , Lacey Simon F. , Plesa Gabriela , June Carl H. , Vonderheide Robert H. , Mitchell Tara C.
Published: May 2023

Supplementary Figure 1.: Representative immunohistochemical staining for Subject 74 with metastatic melanoma; lymph node biopsy. Panel A: pS6 staining prior to infusion; Panel B: pS6 staining at post-infusion biopsy; Panel C: Ki-67 staining prior to infusion; Panel D: Ki-67 staining at post-infusion biopsy.
Figure S7 from Dissecting the Origin of Heterogeneity in Uterine and Ovarian Carcinosarcomas
Authors: Sertier Anne-Sophie , Ferrari Anthony , Pommier Roxane M. , Treilleux Isabelle , Boyault Sandrine , Devouassoux-Shisheboran Mojgan , Kielbassa Janice , Thomas Emilie , Tonon Laurie , Le Texier Vincent , Charreton Amandine , Morel Anne-Pierre , Floquet Anne , Joly Florence , Berton-Rigaud Dominique , Ferron Gwenaël , Arnould Laurent , Croce Sabrina , Bataillon Guillaume , Saintigny Pierre , Mery-Lamarche Eliane , Sagan Christine , Senaratne Aruni P. , Gut Ivo G. , Calvo Fabien , Viari Alain , Ouzounova Maria , Ray-Coquard Isabelle , Puisieux Alain
Published: May 2023

Alteration of chromatin remodeling genes in uterine and ovarian CS.
Figure S5 from Dissecting the Origin of Heterogeneity in Uterine and Ovarian Carcinosarcomas
Authors: Sertier Anne-Sophie , Ferrari Anthony , Pommier Roxane M. , Treilleux Isabelle , Boyault Sandrine , Devouassoux-Shisheboran Mojgan , Kielbassa Janice , Thomas Emilie , Tonon Laurie , Le Texier Vincent , Charreton Amandine , Morel Anne-Pierre , Floquet Anne , Joly Florence , Berton-Rigaud Dominique , Ferron Gwenaël , Arnould Laurent , Croce Sabrina , Bataillon Guillaume , Saintigny Pierre , Mery-Lamarche Eliane , Sagan Christine , Senaratne Aruni P. , Gut Ivo G. , Calvo Fabien , Viari Alain , Ouzounova Maria , Ray-Coquard Isabelle , Puisieux Alain
Published: May 2023

BRCAness feature: tandem duplicator phenotype.
Figure S3 from Dissecting the Origin of Heterogeneity in Uterine and Ovarian Carcinosarcomas
Authors: Sertier Anne-Sophie , Ferrari Anthony , Pommier Roxane M. , Treilleux Isabelle , Boyault Sandrine , Devouassoux-Shisheboran Mojgan , Kielbassa Janice , Thomas Emilie , Tonon Laurie , Le Texier Vincent , Charreton Amandine , Morel Anne-Pierre , Floquet Anne , Joly Florence , Berton-Rigaud Dominique , Ferron Gwenaël , Arnould Laurent , Croce Sabrina , Bataillon Guillaume , Saintigny Pierre , Mery-Lamarche Eliane , Sagan Christine , Senaratne Aruni P. , Gut Ivo G. , Calvo Fabien , Viari Alain , Ouzounova Maria , Ray-Coquard Isabelle , Puisieux Alain
Published: May 2023

Clustering of CS mutational signatures with COSMIC signatures.
Figure S2 from Dissecting the Origin of Heterogeneity in Uterine and Ovarian Carcinosarcomas
Authors: Sertier Anne-Sophie , Ferrari Anthony , Pommier Roxane M. , Treilleux Isabelle , Boyault Sandrine , Devouassoux-Shisheboran Mojgan , Kielbassa Janice , Thomas Emilie , Tonon Laurie , Le Texier Vincent , Charreton Amandine , Morel Anne-Pierre , Floquet Anne , Joly Florence , Berton-Rigaud Dominique , Ferron Gwenaël , Arnould Laurent , Croce Sabrina , Bataillon Guillaume , Saintigny Pierre , Mery-Lamarche Eliane , Sagan Christine , Senaratne Aruni P. , Gut Ivo G. , Calvo Fabien , Viari Alain , Ouzounova Maria , Ray-Coquard Isabelle , Puisieux Alain
Published: May 2023

Heterogeneity of genomic rearrangements in carcinosarcoma.
Figure S14 from Dissecting the Origin of Heterogeneity in Uterine and Ovarian Carcinosarcomas
Authors: Sertier Anne-Sophie , Ferrari Anthony , Pommier Roxane M. , Treilleux Isabelle , Boyault Sandrine , Devouassoux-Shisheboran Mojgan , Kielbassa Janice , Thomas Emilie , Tonon Laurie , Le Texier Vincent , Charreton Amandine , Morel Anne-Pierre , Floquet Anne , Joly Florence , Berton-Rigaud Dominique , Ferron Gwenaël , Arnould Laurent , Croce Sabrina , Bataillon Guillaume , Saintigny Pierre , Mery-Lamarche Eliane , Sagan Christine , Senaratne Aruni P. , Gut Ivo G. , Calvo Fabien , Viari Alain , Ouzounova Maria , Ray-Coquard Isabelle , Puisieux Alain
Published: May 2023

Complete clonal evolution of P05 tumor.
Figure S10 from Dissecting the Origin of Heterogeneity in Uterine and Ovarian Carcinosarcomas
Authors: Sertier Anne-Sophie , Ferrari Anthony , Pommier Roxane M. , Treilleux Isabelle , Boyault Sandrine , Devouassoux-Shisheboran Mojgan , Kielbassa Janice , Thomas Emilie , Tonon Laurie , Le Texier Vincent , Charreton Amandine , Morel Anne-Pierre , Floquet Anne , Joly Florence , Berton-Rigaud Dominique , Ferron Gwenaël , Arnould Laurent , Croce Sabrina , Bataillon Guillaume , Saintigny Pierre , Mery-Lamarche Eliane , Sagan Christine , Senaratne Aruni P. , Gut Ivo G. , Calvo Fabien , Viari Alain , Ouzounova Maria , Ray-Coquard Isabelle , Puisieux Alain
Published: May 2023

Analysis of common genomic events between paired tumor samples.
FIGURE 2 from Dissecting the Origin of Heterogeneity in Uterine and Ovarian Carcinosarcomas
Authors: Sertier Anne-Sophie , Ferrari Anthony , Pommier Roxane M. , Treilleux Isabelle , Boyault Sandrine , Devouassoux-Shisheboran Mojgan , Kielbassa Janice , Thomas Emilie , Tonon Laurie , Le Texier Vincent , Charreton Amandine , Morel Anne-Pierre , Floquet Anne , Joly Florence , Berton-Rigaud Dominique , Ferron Gwenaël , Arnould Laurent , Croce Sabrina , Bataillon Guillaume , Saintigny Pierre , Mery-Lamarche Eliane , Sagan Christine , Senaratne Aruni P. , Gut Ivo G. , Calvo Fabien , Viari Alain , Ouzounova Maria , Ray-Coquard Isabelle , Puisieux Alain
Published: May 2023

Key gene alterations in uterine and ovarian CS. Oncoprint of alterations identified in the 50 most altered genes from TCGA cancer pathways and custom lists of CRG. The type of genomic alteration (deletion, amplification, fusion, broken by SV, missense, truncated) is described in the legend. Number and proportions of alteration types are summarized by gene (horizontal bars on right) and by sample (vertical bars on top). The samples are classified into MSI and CN-high according to TCGA endometrial carcinoma classification.
FIGURE 1 from Dissecting the Origin of Heterogeneity in Uterine and Ovarian Carcinosarcomas
Authors: Sertier Anne-Sophie , Ferrari Anthony , Pommier Roxane M. , Treilleux Isabelle , Boyault Sandrine , Devouassoux-Shisheboran Mojgan , Kielbassa Janice , Thomas Emilie , Tonon Laurie , Le Texier Vincent , Charreton Amandine , Morel Anne-Pierre , Floquet Anne , Joly Florence , Berton-Rigaud Dominique , Ferron Gwenaël , Arnould Laurent , Croce Sabrina , Bataillon Guillaume , Saintigny Pierre , Mery-Lamarche Eliane , Sagan Christine , Senaratne Aruni P. , Gut Ivo G. , Calvo Fabien , Viari Alain , Ouzounova Maria , Ray-Coquard Isabelle , Puisieux Alain
Published: May 2023

Genomic landscape of CS. A, Tissue origin and histological subtypes for each tumor (from P01 to P15). B, Main component and detailed percentage content for both samples (a and b) derived from the same tumor. C, CNA analysis: tumor purity (%), ploidy, FGA, and CNA breakpoints number. D, SV number, classified as deletion, duplication, inversion, and interchromosomal translocation. E, SNV and small indel number. F, Proportion of each of four mutational signatures deciphered in the whole cohort. G, MSI phenotype: MSI score (representing the percentage of unstable microsatellite loci), MLH1 promoter methylation (beta-value), and mRNA expression level (TPM – transcripts per million). H, Kataegis number illustrating APOBEC error-prone DNA repair process. I, BRCAness phenotype: number of LST, (white stars highlight samples with LST number ≥20), BRCA1 promoter methylation level (beta-value), BRCA1/2 genes alterations and TDP score, collectively summarized by the HRD status track.
Supplementary Methods 1 from A novel class of Ribosome Modulating Agents (RMAs) exploits cancer ribosome heterogeneity to selectively target the CMS2 subtype of colorectal cancer
Authors: Terzo Esteban , Apte Shruti A , Padhye Simran , Rashed Saleh , Austin Wesley , Caponegro Michael , Reddy Anupama , Shi Shuhao , Wang Christy , Clark Roger B , Sidransky David , Modur Vijay , Badarinarayana Vasudeo
Published: May 2023

Supplementary methods
Supplementary Data 1 from A novel class of Ribosome Modulating Agents (RMAs) exploits cancer ribosome heterogeneity to selectively target the CMS2 subtype of colorectal cancer
Authors: Terzo Esteban , Apte Shruti A , Padhye Simran , Rashed Saleh , Austin Wesley , Caponegro Michael , Reddy Anupama , Shi Shuhao , Wang Christy , Clark Roger B , Sidransky David , Modur Vijay , Badarinarayana Vasudeo
Published: May 2023

ZKN-157- chemical characterization